Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

PubMed Central

2010-01-01

Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304

Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus.

PubMed

Hallén, Jonas; Johansen, Odd Erik; Birkeland, Kåre I; Gullestad, Lars; Aakhus, Svend; Endresen, Knut; Tjora, Solve; Jaffe, Allan S; Atar, Dan

2010-09-15

The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if available (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). One-hundred thirteen (90%) had detectable cTnT at baseline and of those, 22 (18% of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r=0.92, p>0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p=0.058). Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

PubMed Central

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, Christophe; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

2014-01-01

Background ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established. Methods and Results We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017). Conclusions In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction. PMID:18378613

Baseline glucocorticoids are drivers of body mass gain in a diving seabird

USGS Publications Warehouse

Hennin, Holly; Berlin, Alicia; Love, Oliver P.

2016-01-01

Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic–pituitary–adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

Baseline glucocorticoids are drivers of body mass gain in a diving seabird.

PubMed

Hennin, Holly L; Wells-Berlin, Alicia M; Love, Oliver P

2016-03-01

Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic-pituitary-adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Large-baseline InSAR for precise topographic mapping: a framework for TanDEM-X large-baseline data

NASA Astrophysics Data System (ADS)

Pinheiro, Muriel; Reigber, Andreas; Moreira, Alberto

2017-09-01

The global Digital Elevation Model (DEM) resulting from the TanDEM-X mission provides information about the world topography with outstanding precision. In fact, performance analysis carried out with the already available data have shown that the global product is well within the requirements of 10 m absolute vertical accuracy and 2 m relative vertical accuracy for flat to moderate terrain. The mission's science phase took place from October 2014 to December 2015. During this phase, bistatic acquisitions with across-track separation between the two satellites up to 3.6 km at the equator were commanded. Since the relative vertical accuracy of InSAR derived elevation models is, in principle, inversely proportional to the system baseline, the TanDEM-X science phase opened the doors for the generation of elevation models with improved quality with respect to the standard product. However, the interferometric processing of the large-baseline data is troublesome due to the increased volume decorrelation and very high frequency of the phase variations. Hence, in order to fully profit from the increased baseline, sophisticated algorithms for the interferometric processing, and, in particular, for the phase unwrapping have to be considered. This paper proposes a novel dual-baseline region-growing framework for the phase unwrapping of the large-baseline interferograms. Results from two experiments with data from the TanDEM-X science phase are discussed, corroborating the expected increased level of detail of the large-baseline DEMs.

Relations of Depressive Symptoms and Antidepressant Use to Body Mass Index and Selected Biomarkers for Diabetes and Cardiovascular Disease

PubMed Central

Balasubramanian, Raji; Pagoto, Sherry L.; Schneider, Kristin L.; Hébert, James R.; Phillips, Lawrence S.; Goveas, Joseph S.; Culver, Annie L.; Olendzki, Barbara C.; Beck, James; Smoller, Jordan W.; Sepavich, Deidre M.; Ockene, Judith K.; Uebelacker, Lisa; Zorn, Martha; Liu, Simin

2013-01-01

Objectives. We investigated whether depressive symptoms and antidepressant use are associated with biomarkers for glucose dysregulation and inflammation, body mass index (BMI), and waist circumference. Methods. Postmenopausal women were recruited into the Women’s Health Initiative from 1993 to 1998, and data were collected at regular intervals through 2005. We used multiple linear regression models to examine whether depressive symptoms and antidepressant use are associated with BMI, waist circumference, and biomarkers. Results. Analysis of data from 71 809 women who completed all relevant baseline and year 3 assessments showed that both elevated depressive symptoms and antidepressant use were significantly associated with higher BMI and waist circumference. Among 1950 women, elevated depressive symptoms were significantly associated with increased insulin levels and measures of insulin resistance. Analyses of baseline data from 2242 women showed that both elevated depressive symptoms and antidepressant use were associated with higher C-reactive protein levels. Conclusions. Monitoring body habitus and other biomarkers among women with elevated depression symptoms or taking antidepressant medication may be prudent to prevent diabetes and cardiovascular disease. PMID:23763394

The association between C-reactive protein levels and the risk for chronic kidney disease hospitalizations in adults of a remote Indigenous Australian community - A prospective cohort study.

PubMed

Arnold, Luke W; Hoy, Wendy E; Wang, Zhiqiang

2017-09-01

Indigenous Australians are significantly burdened by chronic kidney disease (CKD). Elevated levels of C-reactive protein (CRP) have been associated with diabetes and cardiovascular incidence in previous studies. Elevated CRP has been associated with albuminuria and reduced eGFR in cross-sectional studies. This study investigated the long-term predictive association between CRP measured at a baseline exam and the incidence of a CKD-related hospitalization. Health screening examinations were conducted in individuals of a remote indigenous Australian community between 1992 and 1998. The risk of subsequent CKD hospitalisations, documented through Northern Territory hospital records up to 2010, was estimated with Cox proportional hazard models in people aged over 18 years at the baseline screen and who had albumin-creatinine ratios (ACRs) less than 34g/mol. 546 participants were eligible for our study. Individuals in the highest CRP tertile at baseline had increased levels of traditional cardiovascular risk factors. They also had almost 4 times the risk of a CKD-related hospitalisation compared with participants in the lowest CRP tertile (HR=3.91, 95%CI 1.01-15.20, P=0.049) after adjustment for potential confounding factors. Participants with CRP concentrations greater than 3mg/L had almost 3 times the risk of CKD hospitalisations than those ≤3mg/L (HR=2.84, 95%CI 1.00-8.00, P=0.049). Furthermore, risk of CKD hospitalisations increased 34% per doubling of baseline CRP (HR=1.34, 95%CI 1.04-1.74, P=0.024). In individuals in this remote indigenous community without overt albuminuria at baseline the risk for incident CKD related hospitalisations was predicted by elevated C-reactive protein levels almost a decade earlier. Further research is needed to understand the roles that CRP and systemic inflammation play in CKD risk. © 2016 Asian Pacific Society of Nephrology.

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

PubMed

Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

2018-04-17

Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable (P interaction =0.002). Conclusions -In the EXCEL trial, elevated baseline BNP levels in patients with LMCAD undergoing revascularization were independently associated with long-term mortality but not non-fatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI vs. CABG for revascularization of LMCAD may be conditioned by the baseline BNP level. Clinical Trial Registration -URL: http://www.clinicaltrials.gov. Unique identifier: NCT01205776.

Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy.

PubMed

Yang, Sung Wook; Kim, Gi Hyun; Chung, Jung Wha; Sohn, Hyung Rae; Lee, Sang Soo; Hong, Sukho; Chung, Seong Min; Jang, Eun Sun; Jeong, Sook-Hyang; Kim, Jin-Wook

2015-07-01

Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. Delayed AFP response to ETV may serve as an indicator of high HCC risk. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Postprandial gastrointestinal blood flow, oxygen consumption and heart rate in rainbow trout (Oncorhynchus mykiss).

PubMed

Eliason, Erika J; Higgs, David A; Farrell, Anthony P

2008-04-01

The present study is the first to simultaneously and continuously measure oxygen consumption (MO(2)) and gastrointestinal blood flow (q(gi)) in fish. In addition, while it is the first to compare the effects of three isoenergetic diets on q(gi) in fish, no significant differences among diets were found for postprandial MO(2), q(gi) or heart rate (f(H)) in rainbow trout, Oncorhynchus mykiss. Postprandial q(gi), f(H) and MO(2) were significantly elevated above baseline levels by 4 h. Postprandial q(gi) peaked at 136% above baseline after 11 h, f(H) peaked at 110% above baseline after 14 h and MO(2) peaked at 96% above baseline after 27 h. Moreover, postprandial MO(2) remained significantly elevated above baseline longer than q(gi) (for 41 h and 30 h, respectively), perhaps because most of the increase in MO(2) associated with feeding is due to protein handling, a process that continues following the absorption of nutrients which is thought to be the primary reason for the elevation of q(gi). In addition to the positive relationships found between postprandial MO(2) and q(gi) and between postprandial MO(2) and f(H), we discovered a novel relationship between postprandial q(gi) and f(H).

Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks

USGS Publications Warehouse

Kitaysky, A.S.; Kitaiskaia, E.V.; Wingfield, J.C.; Piatt, John F.

2001-01-01

Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.

Identification and prediction of group-based glycemic control trajectories during the transition to adolescence.

PubMed

Rohan, Jennifer M; Rausch, Joseph R; Pendley, Jennifer Shroff; Delamater, Alan M; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis

2014-10-01

To identify trajectories of glycemic control over a period of 3 years in a pediatric sample of youth diagnosed with Type 1 diabetes transitioning to adolescence. A second aim was to examine a set of modifiable individual and family level baseline predictors of glycemic control group membership. This multisite, prospective study included 239 children and adolescents (ages 9-11 years at baseline) diagnosed with Type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c (HbA1c) collected at 6-month intervals over a period of 3 years. Predictors of glycemic control membership included baseline global executive functioning, diabetes self-management, diabetes-specific family conflict, blood glucose monitoring frequency, and relevant individual and family level covariates. Group-based trajectory analyses were used to describe patterns of glycemic control from baseline to 36 months and 3 trajectories were identified: low risk (42.9%), elevated risk (44.6%), and high risk (12.1%) subgroups. Baseline maternal-reported family conflict, blood glucose monitoring frequency, and gender were significant predictors of glycemic control group membership. Higher levels of baseline family conflict, lower frequency of blood glucose monitoring, and female gender were associated with elevated and high-risk group membership. These findings underscore the importance of examining trajectories of HbA1c across time. These results suggest that problematic trajectories of glycemic control are evident during the transition to adolescence. Furthermore, there are modifiable individual and family level characteristics that predict group membership and hence could be targeted in interventions to ensure adequate glycemic control is maintained over time and that risks for diabetes-related complications are reduced.

Identification and Prediction of Group-Based Glycemic Control Trajectories during the Transition to Adolescence

PubMed Central

Rohan, Jennifer M.; Rausch, Joseph R.; Pendley, Jennifer Shroff; Delamater, Alan M.; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis

2014-01-01

Objective To identify trajectories of glycemic control over a period of three years in a pediatric sample of youth diagnosed with type 1 diabetes transitioning to adolescence. A second aim was to examine a set of modifiable individual and family-level baseline predictors of glycemic control group membership. Methods This multisite, prospective study included 239 children and adolescents (ages 9–11 years at baseline) diagnosed with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c (HbA1c) collected at six month intervals over a period of three years. Predictors of glycemic control membership included baseline global executive functioning, diabetes self-management, diabetes-specific family conflict, blood glucose monitoring frequency, and relevant individual and family level covariates. Results Group-based trajectory analyses were used to describe patterns of glycemic control from baseline to 36 months and three trajectories were identified: low risk (42.9%), elevated risk (44.6%), and high risk (12.1%) subgroups. Baseline maternal-reported family conflict, blood glucose monitoring frequency, and gender were significant predictors of glycemic control group membership. Higher levels of baseline family conflict, lower frequency of blood glucose monitoring, and female gender were associated with elevated and high risk group membership. Conclusions These findings underscore the importance of examining trajectories of HbA1c across time. These results suggest that problematic trajectories of glycemic control are evident during the transition to adolescence. Furthermore, there are modifiable individual and family-level characteristics that predict group membership and hence could be targeted in interventions to ensure adequate glycemic control is maintained over time and that risks for diabetes-related complications are reduced. PMID:24274797

The relationship between maternal fear of hypoglycaemia and adherence in children with type-1 diabetes.

PubMed

Freckleton, Evril; Sharpe, Louise; Mullan, Barbara

2014-01-01

Regular blood glucose monitoring is important for children with type-1 diabetes; however, the relationship between maternal fear of hypoglycaemia and glycaemic control is not well understood. The relationship between maternal beliefs about diabetes, concerns about glycaemic control and adherence to recommended blood glucose levels in young children with type-1 diabetes were examined in this study. Seventy-one mothers with children under 13 were recruited, and a prospective design was used. Demographics, maternal self-reported hypoglycaemic fear and illness perceptions were measured at baseline. Self-report daily blood sugar levels were recorded over 1 week, and glycosylated haemoglobin (HbA1c) blood glucose levels were collected at baseline and 3 months later. High maternal fears of hypoglycaemia were predictive of suboptimal daily glycaemic control (elevated blood glucose levels), irrespective of illness duration or age at diagnosis. The results suggest that mothers who worry most about hypoglycaemia compensate by maintaining their child's blood glucose levels above recommended levels. Elevated blood glucose levels have important consequences for long-term health, and further research could explore ways to target maternal fear of hypoglycaemia.

Characterization of liver function parameter alterations after transjugular intrahepatic portosystemic shunt creation and association with early mortality.

PubMed

Casadaban, Leigh C; Parvinian, Ahmad; Couture, Patrick M; Minocha, Jeet; Knuttinen, M Grace; Bui, James T; Gaba, Ron C

2014-12-01

The purpose of this article is to characterize the temporal evolution and clinical impact of laboratory liver function parameters after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, 157 patients (98 men and 59 women; median age, 55 years) underwent TIPS between 2000 and 2012 and had 1-month hepatobiliary laboratory follow-up. Medical record review was used to compare baseline, peak, and low bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and international normalized ratio (INR) levels within 30 days after TIPS in surviving and dying patients to assess laboratory responses to shunt creation. TIPSs were created with a hemodynamic success rate of 98%, with median pressure gradient reduction of 13 mm Hg. Ninety-day mortality was 21%. Hepatobiliary laboratory values showed significant increases in the days after TIPS compared with baseline levels (bilirubin, 1.6 vs 3.5 mg/dL; AST, 49 vs 149 U/L; ALT, 26 vs 90 U/L; alkaline phosphatase, 97 vs 177 U/L; and INR, 1.5 vs 2.0; p<0.05 in all cases). Patients surviving to 90 days experienced statistically significant but transient laboratory value elevations-up to twofold over baseline-within days of TIPS, whereas patients dying within 90 days experienced three-to fourfold increases over a longer period that did not return to baseline. Differences in laboratory evolution were statistically significant in surviving versus dying patients. TIPS results in acute transient elevation of hepatobiliary enzymes, which may be more pronounced in patients with early mortality. An exaggerated laboratory elevation in excess of threefold greater than baseline or a prolonged increase exceeding 1 week may herald poorer clinical outcome.

Increased follistatin levels after oral contraceptive treatment in obese and non-obese women with polycystic ovary syndrome.

PubMed

Chen, Mei-Jou; Yang, Wei-Shiung; Chen, Hsin-Fu; Kuo, Jahn-Jahn; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Shee-Uan

2010-03-01

Follistatin levels have recently been considered as a marker for inflammation. Our objective was to evaluate the level of circulating follistatin and high-sensitivity C-reactive protein (hsCRP) in women with polycystic ovary syndrome (PCOS) after oral contraceptive (OC) treatment. A total of 56 Taiwanese women with PCOS were enrolled in this prospective observational study in which they were treated for 3 months with OCs (ethinyl estradiol-cyproterone acetate). Blood samples were taken at baseline after treatment during the withdrawal bleed. Body mass index (BMI), lipid profiles, plasma follistatin, hsCRP, fasting glucose, insulin for the homeostasis model assessment of insulin resistance (HOMA-IR) and hormone profiles were measured and analyzed. Total testosterone, free androgen index (FAI), dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels were significantly lower, but total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, circulating follistatin and hsCRP were significantly higher than baseline in women with PCOS after treatment with OCs. An elevation of fasting insulin, HOMA-IR and hsCRP after OC treatment was more evident in non-obese than obese women, whereas the elevation of follistatin was significant in both obese and non-obese women. Follistatin and hsCRP levels all showed significant correlations with each other at baseline and after treatment. The differences in follistatin and hsCRP levels from baseline to after OC treatment were significantly associated with the difference in triglyceride levels. Both hsCRP and follistatin levels increase after OC treatment in women with PCOS. Follistatin seems more sensitive than hsCRP alone to represent the aggravated low-grade inflammatory status after OC treatment in obese and non-obese women with PCOS.

Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents.

PubMed

Tricò, Domenico; Prinsen, Hetty; Giannini, Cosimo; de Graaf, Robin; Juchem, Christoph; Li, Fangyong; Caprio, Sonia; Santoro, Nicola; Herzog, Raimund I

2017-07-01

Traditional risk factors for type 2 diabetes mellitus are weak predictors of changes in glucose tolerance and insulin sensitivity in youth. To identify early metabolic features of insulin resistance (IR) in youth and whether they predict deterioration of glycemic control. A cross-sectional and longitudinal study was conducted at the Yale Pediatric Obesity Clinic. Concentrations of α-hydroxybutyrate, β-hydroxybutyrate, lactate, and branched-chain amino acids (BCAAs) were measured by nuclear magnetic resonance spectroscopy in 78 nondiabetic adolescents during an oral glucose tolerance test (OGTT). Associations between baseline metabolic alterations and longitudinal changes in glucose control were tested in 16 subjects after a mean follow-up of 2.3 years. The relationship between metabolite levels, parameters of IR, and glycemic control, and their progression over time. Elevated fasting α-hydroxybutyrate levels were observed in adolescents with reduced insulin sensitivity after adjusting for age, sex, ethnicity, Tanner stage, and body mass index z-score (P = 0.014). Plasma α-hydroxybutyrate and BCAAs were increased throughout the course of the OGTT in this group (P < 0.03). Notably, borderline IR was associated with a progressive α-hydroxybutyrate decrease from elevated baseline concentrations to normal levels (P = 0.02). Increased baseline α-hydroxybutyrate concentrations were further associated with progressive worsening of glucose tolerance and disposition index. α-Hydroxybutyrate and BCAA concentrations during an OGTT characterize insulin-resistant youth and predict worsening of glycemic control. These findings provide potential biomarkers for risk assessment of type 2 diabetes and new insights into IR pathogenesis. Copyright © 2017 Endocrine Society

The relationship between dominance, corticosterone, memory, and food caching in mountain chickadees (Poecile gambeli).

PubMed

Pravosudov, Vladimir V; Mendoza, Sally P; Clayton, Nicola S

2003-08-01

It has been hypothesized that in avian social groups subordinate individuals should maintain more energy reserves than dominants, as an insurance against increased perceived risk of starvation. Subordinates might also have elevated baseline corticosterone levels because corticosterone is known to facilitate fattening in birds. Recent experiments showed that moderately elevated corticosterone levels resulting from unpredictable food supply are correlated with enhanced cache retrieval efficiency and more accurate performance on a spatial memory task. Given the correlation between corticosterone and memory, a further prediction is that subordinates might be more efficient at cache retrieval and show more accurate performance on spatial memory tasks. We tested these predictions in dominant-subordinate pairs of mountain chickadees (Poecile gambeli). Each pair was housed in the same cage but caching behavior was tested individually in an adjacent aviary to avoid the confounding effects of small spaces in which birds could unnaturally and directly influence each other's behavior. In sharp contrast to our hypothesis, we found that subordinate chickadees cached less food, showed less efficient cache retrieval, and performed significantly worse on the spatial memory task than dominants. Although the behavioral differences could have resulted from social stress of subordination, and dominant birds reached significantly higher levels of corticosterone during their response to acute stress compared to subordinates, there were no significant differences between dominants and subordinates in baseline levels or in the pattern of adrenocortical stress response. We find no evidence, therefore, to support the hypothesis that subordinate mountain chickadees maintain elevated baseline corticosterone levels whereas lower caching rates and inferior cache retrieval efficiency might contribute to reduced survival of subordinates commonly found in food-caching parids.

Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

PubMed

Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

2017-04-01

This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, P<0.001). When HR of the 1st quartile was regarded as the reference, HRs for abdominal obesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend <0.001]. Although the risk of incident abdominal obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

Pretreatment data is highly predictive of liver chemistry signals in clinical trials.

PubMed

Cai, Zhaohui; Bresell, Anders; Steinberg, Mark H; Silberg, Debra G; Furlong, Stephen T

2012-01-01

The goal of this retrospective analysis was to assess how well predictive models could determine which patients would develop liver chemistry signals during clinical trials based on their pretreatment (baseline) information. Based on data from 24 late-stage clinical trials, classification models were developed to predict liver chemistry outcomes using baseline information, which included demographics, medical history, concomitant medications, and baseline laboratory results. Predictive models using baseline data predicted which patients would develop liver signals during the trials with average validation accuracy around 80%. Baseline levels of individual liver chemistry tests were most important for predicting their own elevations during the trials. High bilirubin levels at baseline were not uncommon and were associated with a high risk of developing biochemical Hy's law cases. Baseline γ-glutamyltransferase (GGT) level appeared to have some predictive value, but did not increase predictability beyond using established liver chemistry tests. It is possible to predict which patients are at a higher risk of developing liver chemistry signals using pretreatment (baseline) data. Derived knowledge from such predictions may allow proactive and targeted risk management, and the type of analysis described here could help determine whether new biomarkers offer improved performance over established ones.

Elevated serum uric acid level predicts rapid decline in kidney function

PubMed Central

Kuwabara, Masanari; Bjornstad, Petter; Hisatome, Ichiro; Niwa, Koichiro; Roncal-Jimenez, Carlos A; Andres-Hernando, Ana; Jensen, Thomas; Milagres, Tamara; Sato, Yuka; Garcia, Gabriela; Ohno, Minoru; Lanaspa, Miguel A; Johnson, Richard J

2018-01-01

Background While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease (CKD), it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5-years in a general Japanese population. Methods This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30–85 years) in our analyses whose data were available at 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73m2 at baseline. In addition to examining the entire cohort (n=12,578), we stratified our analyses by baseline eGFR groups; 60–90 mL/min/1.73m2, 90–120 mL/min/1.73m2, and ≥120 mL/min/1.73m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR and rapid eGFR decline (defined as the highest quantile of change in eGFR), adjusted for age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. Results After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR: 1.27, 95% CI: 1.17–1.38), and 1 mg/dL increase in SUA over 5-years was associated with 3.77-fold greater odds of rapid eGFR decline (OR: 3.77, 95% CI: 3.35–4.26). Conclusions Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5-years. PMID:28285309

Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.

PubMed

Belhomme, Nicolas; Jouneau, Stéphane; Bouzillé, Guillaume; Decaux, Olivier; Lederlin, Mathieu; Guillot, Stéphanie; Perlat, Antoinette; Jégo, Patrick

2018-01-01

Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis. We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients. Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years. There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

Role of Soluble ST2 Levels and Beta-Blockers Dosage on Cardiovascular Events of Patients with Unselected ST-Segment Elevation Myocardial Infarction

PubMed Central

Huang, Wei-Ping; Zheng, Xuan; He, Lei; Su, Xi; Liu, Cheng-Wei; Wu, Ming-Xiang

2018-01-01

Background: Serum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown. Methods: A total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI. Results: Baseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = −0.243, P = 0.009) and LV ejection fraction (r = −0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201–8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084–3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI. Conclusions: High baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology. PMID:29786039

DEM corrections on series of wrapped interferograms as a tool to improve deformation monitoring around Siling Co lake in Tibet.

NASA Astrophysics Data System (ADS)

Ducret, Gabriel; Doin, Marie-Pierre; Lasserre, Cécile; Guillaso, Stéphane; Twardzik, Cedric

2010-05-01

In order to increase our knowledge on the lithosphere rheological structure under the Tibetan plateau, we study the loading response due to lake Siling Co water level changes. The challenge here is to measure the deformation with an accuracy good enough to obtain a correct sensivity to model parameters. InSAR method in theory allow to observe the spatio-temporal pattern of deformation, however its exploitation is limited by unwrapping difficulties linked with temporal decorrelation and DEM errors in sloppy and partially incoherent areas. This lake is a large endhoreic lake at 4500~m elevation located North of the strike-slip right lateral Gyaring Co fault, and just to the south of the Bangong Nujiang suture zone, on which numerous left-lateral strike slip are branching. The Siling Co lake water level has strongly changed in the past, as testified by numerous traces of palaeo-shorelines, clearly marked until 60 m above present-day level. In the last years, the water level in this lake increased by about 1~m/yr, a remarkably fast rate given the large lake surface (1600~km2). The present-day ground subsidence associated to the water level increase is studied by InSAR using all ERS and Envisat archived data on track 219, obtained through the Dragon cooperation program. We chose to compute 750~km long differential interferograms centered on the lake to provide a good constraint on the reference. A redundant network of small baseline interferograms is computed with perpendicular baseline smaller than 500~m. The coherence is quickly lost with time (over one year), particularly to the North of the lake because of freeze-thaw cycles. Unwrapping thus becomes hazardous in this configuration, and fails on phase jumps created by DEM contrasts. The first work is to improve the simulated elevation field in radar geometry from the Digital Elevation Model (here SRTM) in order to exploit the interferometric phase in layover areas. Then, to estimate DEM error, we mix the Permanent Scattered and Small Baseline methods. The aim is to improve spatial and temporal coherence. We use as a reference strong and stable amplitude points or spatially coherent areas, scattered within the SAR scene. We calculate the relative elevation error of every point in the neighbourhood of reference points. A global inversion allows to perform spatial integration of local errors at the radar image scale. Finally, we evaluate how the DEM correct ion of wrapped interferograms improves the unwrapping step. Furthermore, to help unwrapping we also compute and then remove from the wrapped interferograms the residual orbital trend and the phase-elevation relationship due variations in atmospheric stratification. Stack of unwrapped small baseline interferograms show clearly the average subsidence rate around the lake of about 4 mm/yr associated to the present-day water level increase. To compare the observed deformation to the water level elevation changes, we extract from satellite images in the period 1972 to 2009 the water level changes. The deformation signal is discussed in terms of end-members visco-elastic models of the lithosphere and uppermost mantle.

Concentrations and annual fluxes of sediment-associated chemical constituents from conterminous US coastal rivers using bed sediment data

USGS Publications Warehouse

Horowitz, Arthur J.; Stephens, Verlin C.; Elrick, Kent A.; Smith, James J.

2012-01-01

Coastal rivers represent a significant pathway for the delivery of natural and anthropogenic sediment-associated chemical constituents to the Atlantic, Pacific and Gulf of Mexico coasts of the conterminous USA. This study entails an accounting segment using published average annual suspended sediment fluxes with published sediment-associated chemical constituent concentrations for (1) baseline, (2) land-use distributions, (3) population density, and (4) worldwide means to estimate concentrations/annual fluxes for trace/major elements and total phosphorus, total organic and inorganic carbon, total nitrogen, and sulphur, for 131 coastal river basins. In addition, it entails a sampling and subsequent chemical analysis segment that provides a level of ‘ground truth’ for the calculated values, as well as generating baselines for sediment-associated concentrations/fluxes against which future changes can be evaluated. Currently, between 260 and 270 Mt of suspended sediment are discharged annually from the conterminous USA; about 69% is discharged from Gulf rivers (n = 36), about 24% from Pacific rivers (n = 42), and about 7% from Atlantic rivers (n = 54). Elevated sediment-associated chemical concentrations relative to baseline levels occur in the reverse order of sediment discharges:Atlantic rivers (49%)>Pacific rivers (40%)>Gulf rivers (23%). Elevated trace element concentrations (e.g. Cu, Hg, Pb, Zn) frequently occur in association with present/former industrial areas and/or urban centres, particularly along the northeast Atlantic coast. Elevated carbon and nutrient concentrations occur along both the Atlantic and Gulf coasts but are dominated by rivers in the urban northeast and by southeastern and Gulf coast (Florida) ‘blackwater’ streams. Elevated Ca, Mg, K, and Na distributions tend to reflect local petrology, whereas elevated Ti, S, Fe, and Al concentrations are ubiquitous, possibly because they have substantial natural as well as anthropogenic sources. Almost all the elevated sediment-associated chemical concentrations found in conterminous US coastal rivers are lower than worldwide averages.

Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

PubMed

Wiegers, Evita C; Rooijackers, Hanne M; Tack, Cees J; Groenewoud, Hans J M M; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

2017-12-01

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-induced hyperlacticacidemia on brain lactate during hypoglycemia between 1 ) patients with type 1 diabetes and IAH, 2 ) patients with type 1 diabetes and normal awareness of hypoglycemia, and 3 ) healthy participants without diabetes ( n = 6 per group). All participants underwent a hypoglycemic (2.8 mmol/L) clamp after performing a bout of HIIT on a cycle ergometer. Before HIIT (baseline) and during hypoglycemia, brain lactate levels were determined continuously with J-difference-editing 1 H-MRS, and time curves were analyzed using nonlinear mixed-effects modeling. At the beginning of hypoglycemia (after HIIT), brain lactate levels were elevated in all groups but most pronounced in patients with IAH. During hypoglycemia, brain lactate decreased ∼30% below baseline in patients with IAH but returned to baseline levels and remained there in the other two groups. Our results support the concept of enhanced lactate transport as well as increased lactate oxidation in patients with type 1 diabetes and IAH. © 2017 by the American Diabetes Association.

Continued cannabis use at one year follow up is associated with elevated mood and lower global functioning in bipolar I disorder.

PubMed

Kvitland, Levi Roestad; Melle, Ingrid; Aminoff, Sofie Ragnhild; Demmo, Christine; Lagerberg, Trine Vik; Andreassen, Ole Andreas; Ringen, Petter Andreas

2015-02-05

There is limited knowledge about how environmental factors affect the course of bipolar disorder (BD). Cannabis has been proposed as a potential risk factor for poorer course of illness, but the role of cannabis use has not been studied in a first treatment BD I sample. The present study examines the associations between course of illness in first treatment BD I and continued cannabis use, from baseline to one year follow up. Patients (N = 62) with first treatment DSM-IV BD I were included as part of the Thematically Organized Psychosis study (TOP), and completed interviews and self-report questionnaires at both baseline and follow up. Cannabis use within the last six months at baseline and use between baseline and follow up ("continued use") was recorded. After controlling for confounders, continued cannabis use was significantly associated with elevated mood (YMRS) and inferior global functioning (GAF-F) at follow up. Elevated mood mediated the effect of cannabis use on global functioning. These results suggest that cannabis use has clinical implications for the early course of BD by increasing mood level. More focus on reducing cannabis use in clinical settings seems to be useful for improving outcome in early phase of the disorder.

Effectiveness of a Cognitive Behavioral Therapy-Based Indicated Prevention Program for Children with Elevated Anxiety Levels: a Randomized Controlled Trial.

PubMed

van Starrenburg, Manon L A; Kuijpers, Rowella C M W; Kleinjan, Marloes; Hutschemaekers, Giel J M; Engels, Rutger C M E

2017-01-01

Childhood anxiety is a problem not only because of its negative consequences on the well-being of children but also because of its adverse effects on society and its role in mental disorders later in life. Adequate prevention might be the key in tackling this problem. The effectiveness of Coping Cat, as an indicated CBT-based prevention program in Dutch primary school children, was assessed by means of a randomized controlled trial. In total, 141 children aged 7-13 with elevated levels of anxiety and their mothers were included and randomly assigned to an intervention group and a waiting list control group. After screening, all participants completed baseline, post-intervention, and 3-month follow-up assessments. The results showed that Coping Cat, as an indicated prevention program, reduces children's self-reported anxiety symptoms, with Cohen's effect size d of 0.66 at the 3-month follow-up. A moderating effect was found for baseline anxiety level; specifically, children with high levels of baseline anxiety who received the Coping Cat program had lower anxiety levels at follow-up compared to children with high levels of anxiety in the control condition. No moderating effects of gender or age were found. An unexpected decline in anxiety levels from screening to pre-assessment was found in both groups, and this decline was stronger in the experimental group. These promising results warrant the implementation of Coping Cat as an indicated prevention program.

Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs.

PubMed

Broussard, Josiane L; Kolka, Cathryn M; Castro, Ana V B; Asare Bediako, Isaac; Paszkiewicz, Rebecca L; Szczepaniak, Edward W; Szczepaniak, Lidia S; Knutson, Kristen L; Kim, Stella P; Bergman, Richard N

2015-11-01

A normal consequence of increased energy intake and insulin resistance is compensatory hyperinsulinaemia through increased insulin secretion and/or reduced insulin clearance. Failure of compensatory mechanisms plays a central role in the pathogenesis of type 2 diabetes mellitus; consequently, it is critical to identify in vivo signal(s) involved in hyperinsulinaemic compensation. We have previously reported that high-fat feeding leads to an increase in nocturnal NEFA concentration. We therefore designed this study to test the hypothesis that elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation for insulin resistance. Blood sampling was conducted in male dogs to determine 24 h profiles of NEFA at baseline and during high-fat feeding with and without acute nocturnal NEFA suppression using a partial A1 adenosine receptor agonist. High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIR(g)). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIR(g) with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIR(g). This relationship indicates that the hyperinsulinaemic compensation induced in response to high-fat feeding was prevented when the nocturnal NEFA pattern was returned to baseline. Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.

[Relationship between inflammatory markers and the risk of colorectal cancer in Kailuan male cohort].

PubMed

Wang, G; Xu, W G; Li, F; Su, K; Li, N; Lü, Z Y; Feng, X S; Wei, L P; Chen, H D; Chen, Y H; Guo, L W; Cui, H; Yang, W J; Li, Z F; Ren, J S; Wu, S L; Shi, J F; Dai, M; He, J

2017-10-31

Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios ( HR ) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P =0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer ( HR =1.38, 95% CI: 1.05-1.81, P =0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Ludwig, D. A.; Gray, B. D.; Vernikos, J.

1998-01-01

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory.

PubMed

Pravosudov, Vladimir V

2003-12-22

It is widely assumed that chronic stress and corresponding chronic elevations of glucocorticoid levels have deleterious effects on animals' brain functions such as learning and memory. Some animals, however, appear to maintain moderately elevated levels of glucocorticoids over long periods of time under natural energetically demanding conditions, and it is not clear whether such chronic but moderate elevations may be adaptive. I implanted wild-caught food-caching mountain chickadees (Poecile gambeli), which rely at least in part on spatial memory to find their caches, with 90-day continuous time-release corticosterone pellets designed to approximately double the baseline corticosterone levels. Corticosterone-implanted birds cached and consumed significantly more food and showed more efficient cache recovery and superior spatial memory performance compared with placebo-implanted birds. Thus, contrary to prevailing assumptions, long-term moderate elevations of corticosterone appear to enhance spatial memory in food-caching mountain chickadees. These results suggest that moderate chronic elevation of corticosterone may serve as an adaptation to unpredictable environments by facilitating feeding and food-caching behaviour and by improving cache-retrieval efficiency in food-caching birds.

Prognosis of patients with non-ST-segment-elevation myocardial infarction and nonobstructive coronary artery disease: propensity-matched analysis from the Acute Catheterization and Urgent Intervention Triage Strategy trial.

PubMed

Planer, David; Mehran, Roxana; Ohman, E Magnus; White, Harvey D; Newman, Jonathan D; Xu, Ke; Stone, Gregg W

2014-06-01

Troponin elevation is a risk factor for mortality in patients with non-ST-segment-elevation acute coronary syndromes. However, the prognosis of patients with troponin elevation and nonobstructive coronary artery disease (CAD) is unknown. Our objective was therefore to evaluate the impact of nonobstructive CAD in patients with non-ST-segment-elevation acute coronary syndromes and troponin elevation enrolled in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. In the ACUITY trial, 3-vessel quantitative coronary angiography was performed in a formal substudy of 6921 patients presenting with non-ST-segment-elevation acute coronary syndromes. Patients with elevated admission troponin levels were stratified by the presence or absence of obstructive CAD (any lesion with quantitative diameter stenosis >50%). Propensity score matching was performed to adjust for baseline characteristics. Of 2442 patients with elevated troponin, 197 (8.8%) had nonobstructive CAD. Maximum diameter stenosis was 87.4 (73.2, 100.0) versus 22.6 (19.2, 25.7; P<0.0001) in patients with versus without obstructive CAD, respectively. Propensity matching yielded 117 patients with nonobstructive CAD and 331 patients with obstructive CAD, with no significant baseline differences between groups. In the matched cohort, overall 1-year mortality was significantly higher in patients with nonobstructive CAD (5.2% versus 1.6%; hazard ratio [95% confidence interval]=3.44 [1.05, 11.28]; P=0.04), driven by greater noncardiac mortality. Conversely, recurrent myocardial infarction and unplanned revascularization rates were significantly higher in patients with obstructive CAD. Patients with non-ST-segment-elevation acute coronary syndromes and elevated troponin levels but without obstructive CAD, while having low rates of subsequent myocardial infarction and unplanned revascularization, are still at considerable risk for 1-year mortality from noncardiac causes. http://www.clinicaltrials.gov. Unique identifier: NCT00093158. © 2014 American Heart Association, Inc.

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

PubMed

Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

The relationship among psychological and psychophysiological characteristics of fibromyalgia patients.

PubMed

Thieme, Kati; Turk, Dennis C; Gracely, Richard H; Maixner, William; Flor, Herta

2015-02-01

This study examined the relationship of psychophysiological response patterns in fibromyalgia with psychological characteristics and comorbid mental disorders. Surface electromyographic data, systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels were recorded continuously during baseline, stress, and relaxation tasks. Cluster analysis revealed 4 subgroups of patients who differed on pain characteristics and cognitive, affective, and behavioral responses to pain and stress. The largest group (46.7%) was characterized by elevated blood pressure levels and stress reactivity (a disposition assumed to be a vulnerability factor for the development of diseases) associated with pain, anxiety, physical interference, low activity, and pain behaviors. A second group (41.6%) showed low baseline blood pressure and reactivity, and high activity and stress. A third group (9.2%) displayed high baseline skin conductance level, reactivity, and depression, and a fourth small group (2.5%) displayed elevated baseline electromyographic response and reactivity with high levels of anxiety and depression. These data suggest that unique psychophysiological response patterns are associated with psychological coping and mental disorders in fibromyalgia patients. The identification of the mechanisms that contribute to these group differences will further our understanding of the mechanisms involved in the development and maintenance of fibromyalgia and suggest differential treatment strategies. This article presents psychological characteristics and comorbidity with mental disorders of psychophysiological subgroups of fibromyalgia patients. This mechanistic analysis will assist scientific identification of systems-based pathways that contribute to autonomic and stress mechanisms that mediate chronic pain. Demonstration of distinct, homogeneous subgroups is an important step towards personalized, mechanism-oriented treatments. Copyright © 2015 American Pain Society. All rights reserved.

Pretreatment data is highly predictive of liver chemistry signals in clinical trials

PubMed Central

Cai, Zhaohui; Bresell, Anders; Steinberg, Mark H; Silberg, Debra G; Furlong, Stephen T

2012-01-01

Purpose The goal of this retrospective analysis was to assess how well predictive models could determine which patients would develop liver chemistry signals during clinical trials based on their pretreatment (baseline) information. Patients and methods Based on data from 24 late-stage clinical trials, classification models were developed to predict liver chemistry outcomes using baseline information, which included demographics, medical history, concomitant medications, and baseline laboratory results. Results Predictive models using baseline data predicted which patients would develop liver signals during the trials with average validation accuracy around 80%. Baseline levels of individual liver chemistry tests were most important for predicting their own elevations during the trials. High bilirubin levels at baseline were not uncommon and were associated with a high risk of developing biochemical Hy’s law cases. Baseline γ-glutamyltransferase (GGT) level appeared to have some predictive value, but did not increase predictability beyond using established liver chemistry tests. Conclusion It is possible to predict which patients are at a higher risk of developing liver chemistry signals using pretreatment (baseline) data. Derived knowledge from such predictions may allow proactive and targeted risk management, and the type of analysis described here could help determine whether new biomarkers offer improved performance over established ones. PMID:23226004

Iron Status and the Acute Post-Exercise Hepcidin Response in Athletes

PubMed Central

Peeling, Peter; Sim, Marc; Badenhorst, Claire E.; Dawson, Brian; Govus, Andrew D.; Abbiss, Chris R.; Swinkels, Dorine W.; Trinder, Debbie

2014-01-01

This study explored the relationship between serum ferritin and hepcidin in athletes. Baseline serum ferritin levels of 54 athletes from the control trial of five investigations conducted in our laboratory were considered; athletes were grouped according to values <30 μg/L (SF<30), 30–50 μg/L (SF30–50), 50–100 μg/L (SF50–100), or >100 μg/L (SF>100). Data pooling resulted in each athlete completing one of five running sessions: (1) 8×3 min at 85% vVO2peak; (2) 5×4 min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous at 75% vVO2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each running session were represented amongst all four groups; hence, the mean exercise duration and intensity were not different (p>0.05). Venous blood samples were collected pre-, post- and 3 h post-exercise, and were analysed for serum ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise serum ferritin levels were different between groups (p<0.05). There were no group differences for pre- or post-exercise serum iron or IL-6 (p>0.05). Post-exercise IL-6 was significantly elevated compared to baseline within each group (p<0.05). Pre- and 3 h post-exercise hepcidin-25 was sequentially greater as the groups baseline serum ferritin levels increased (p<0.05). However, post-exercise hepcidin levels were only significantly elevated in three groups (SF30–50, SF50–100, and SF>100; p<0.05). An athlete's iron stores may dictate the baseline hepcidin levels and the magnitude of post-exercise hepcidin response. Low iron stores suppressed post-exercise hepcidin, seemingly overriding any inflammatory-driven increases. PMID:24667393

Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia.

PubMed

Whittington, Hannah J; McAndrew, Debra J; Cross, Rebecca L; Neubauer, Stefan; Lygate, Craig A

2016-01-01

Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia. CrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates (76% of baseline vs. 59%, respectively, P = 0.02). Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia (104% of baseline vs. 67%, P = 0.0007). The cardioprotective effect of hypothermic high K+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts (76% of baseline vs. 55% of baseline as seen in WT hearts, P = 0.02). These observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury.

CryoSat Ice Processor: High-Level Overview of Baseline-C Data and Quality-Control

NASA Astrophysics Data System (ADS)

Mannan, R.; Webb, E.; Hall, A.; Bouffard, J.; Femenias, P.; Parrinello, T.; Bouffard, J.; Brockley, D.; Baker, S.; Scagliola, M.; Urien, S.

2016-08-01

Since April 2015, the CryoSat ice products have been generated with the new Baseline-C Instrument Processing Facilities (IPFs). This represents a major upgrade to the CryoSat ice IPFs and is the baseline for the second CryoSat Reprocessing Campaign. Baseline- C introduces major evolutions with respect to Baseline- B, most notably the release of freeboard data within the L2 SAR products, following optimisation of the SAR retracker. Additional L2 improvements include a new Arctic Mean Sea Surface (MSS) in SAR; a new tuneable land ice retracker in LRM; and a new Digital Elevation Model (DEM) in SARIn. At L1B new attitude fields have been introduced and existing datation and range biases reduced. This paper provides a high level overview of the changes and evolutions implemented at Baseline-C in order to improve CryoSat L1B and L2 data characteristics and exploitation over polar regions. An overview of the main Quality Control (QC) activities performed on operational Baseline-C products is also presented.

Blood Glucose Levels in Diabetic Patients Following Corticosteroid Injections into the Subacromial Space of the Shoulder.

PubMed

Aleem, Alexander W; Syed, Usman Ali M; Nicholson, Thema; Getz, Charles L; Namdari, Surena; Beredjiklian, Pedro K; Abboud, Joseph A

2017-09-01

Corticosteroid injections are used to treat a variety of orthopedic conditions with the goal of decreasing pain and inflammation. Administration of systemic or local corticosteroids risks temporarily increasing blood glucose levels, especially diabetic patients. The purpose of this study is to quantify the effects of corticosteroid injections on blood glucose levels in diabetic patients with shoulder pathology. Diabetic patients who regularly monitored their blood glucose levels and were indicated for a subacromial corticosteroid injection were included in this prospective investigation. The typical normal morning fasting glucose and most recent hemoglobin A1c level was recorded for each patient. After injection, patients were contacted daily to confirm their fasting morning glucose level for 10 days post-injection. Seventeen consecutive patients were enrolled. Patients with hemoglobin A1c of <7% had an average rise in blood glucose of 38 mg/dL compared to 98 mg/dL in the poorly controlled group after injection ( P <0.001). Well-controlled patients' glucose levels returned to near baseline levels around post-injection day 8, while poorly controlled patients levels remained elevated. Similarly, insulin-dependent diabetic patients had an average increase in fasting glucose level of 99 mg/dL versus 50 mg/dL in non-insulin-dependent diabetic patients ( P <0.001). After corticosteroid injection, patients with well-controlled diabetes experience smaller elevations and faster return to baseline glucose levels than patients with poor control. Insulin dependent diabetics experienced similar findings as patients with poor control. Future studies are needed to evaluate dosing to optimize the risks of blood glucose elevation while maintaining therapeutic benefit.

Using signage to promote stair use on a university campus in hidden and visible stairwells.

PubMed

Grimstvedt, Megan E; Kerr, Jacqueline; Oswalt, Sara B; Fogt, Donovan L; Vargas-Tonsing, Tiffanye M; Yin, Zenong

2010-03-01

This study tested the effectiveness of a stair use promotion strategy in visible and hidden stairwells during intervention and post intervention follow up. A quasi-experimental study design was used with a 1 week baseline, a 3 week intervention, and post intervention at 2 and 4 weeks in 4 university buildings in San Antonio, Texas with stairwells varying in visibility. Participants were students, faculty, staff, and visitors to the 4 buildings. A total of 8431 observations were made. The intervention incorporated motivational signs with direction to nearby stairwells placed by elevators to promote stair use. Stair and elevator use was directly observed and recorded. Logistic regression analyses were used to test whether stair versus elevator use varied by intervention phase and stairwell visibility. Stair use increased significantly (12% units) during the intervention period and remained above baseline levels during post intervention follow-up. At baseline, visible stairs were 4 times more likely to be used than hidden stairs; however, the increase in stair use during intervention was similar in both types of stairwells. Motivational and directional signage can significantly increase stair use on a university campus. Furthermore, stairwell visibility is an important aspect of stair use promotion.

Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

PubMed

Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

2017-09-01

Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1)

PubMed Central

Kunde, Dale A.; Taylor, Robyn L.; Pyecroft, Stephen B.; Sohal, Sukhwinder Singh; Snow, Elizabeth T.

2017-01-01

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1’s cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild. PMID:28591206

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

PubMed

Sun, Bing; Xie, Yuan; Jiang, Jinfa; Wang, Yiping; Xu, Xiaolin; Zhao, Cuimei; Huang, Feifei

2015-04-14

Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

Effect of a marathon run on serum lipoproteins, creatine kinase, and lactate dehydrogenase in recreational runners.

PubMed

Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A

2005-12-01

The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride level was significantly elevated postrace, then fell 30% below baseline 1 day after the run, and returned to baseline after 1 week. Total cholesterol responded less dramatically but with a similar pattern. High-density lipoprotein cholesterol remained significantly elevated and low-density lipoprotein cholesterol was transiently reduced for 3 days after the run. The total cholesterol/high-density cholesterol ratio was significantly lowered for 3 days. Serum lactate dehydrogenase activity significantly doubled postrace and then declined but remained elevated for 2 weeks. Serum creatine kinase activity peaked 24 hr after the run, with a 15-fold rise, and returned to baseline after 1 week. The rise of these enzymes reflects mechanically damaged muscle cells leaking contents into the interstitial fluid. It is concluded that a prolonged strenuous exercise bout in recreational runners, such as a marathon, produces beneficial changes in lipid blood profiles that are significant for only 3 days. However, muscle damage is also evident for 1 week or more from the dramatic and long-lasting effect on enzyme levels. Laboratory values for these runners were outside normal ranges for some days after the race.

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

PubMed

Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

1984-03-01

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Stress regulation and incision in borderline personality disorder--a pilot study modeling cutting behavior.

PubMed

Reitz, Sarah; Krause-Utz, Annegret; Pogatzki-Zahn, Esther M; Ebner-Priemer, Ulrich; Bohus, Martin; Schmahl, Christian

2012-08-01

Emotion dysregulation in Borderline Personality Disorder (BPD) is characterized by high baseline negative intensity, high reactivity, and slow return to baseline. Patients with BPD often engage in self-injurious behavior because it leads to immediate relief of stress levels. We aimed to assess stress regulation as well as the influence of tissue damage on subjective (aversive tension) and objective (heart rate) stress correlates in BPD. In 14 unmedicated patients with BPD and 18 healthy controls, a stress induction was followed by an incision into the forearm conducted by an investigator. For aversive tension, we found elevated baseline levels as well as slower return to baseline in BPD. In controls, incision resulted in a short-term increase of aversive tension, whereas tension and heart rate decreased in the BPD group. Our preliminary results support the hypothesis that tissue damage may play a role in disturbed stress regulation in BPD.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

Testosterone and Haemosporidian Parasites Along a Tropical Elevational Gradient in Rufous-Collared Sparrows (Zonotrichia capensis).

PubMed

Escallón, Camilo; Weinstein, Nicole M; Tallant, James A; Wojtenek, Winfried; Rodríguez-Saltos, Carlos A; Bonaccorso, Elisa; Moore, Ignacio T

2016-10-01

Elevation has been proposed as a dominant ecological variable shaping life history traits and subsequently their underlying hormonal mechanisms. In an earlier meta-analysis of tropical birds, elevation was positively related to testosterone levels. Furthermore, parasitism by avian haemosporidians should vary with elevation as environmental conditions affect vector abundance, and while testosterone is needed for breeding, it is hypothesized to be immunosuppressive and thus could exacerbate haemosporidian infection. Our objective in this study was to examine the relationships between elevation, testosterone levels, and parasitism by avian haemosporidians. We surveyed breeding male rufous-collared sparrows (Zonotrichia capensis) across a wide elevational range along the equator. We measured baseline testosterone levels, haemosporidian infection at four elevations spanning the species' natural range in the Ecuadorian Andes (600, 1500, 2100, 3300 m). Testosterone levels from breeding males were not related to elevation, but there was high intrapopulation variability. Testosterone levels were not related to the probability of parasitism, but our results from one population suggested that the likelihood of being infected by haemosporidian parasites was greater when in breeding condition. In conclusion, even though there is variation in life history strategies among the studied populations, wider divergence in seasonality and life history traits would probably be needed to detect an effect of elevation on testosterone if one exists. Additionally, our results show that variation in testosterone is not related to infection risk of haemosporidians, thus other factors that take a toll on energetic resources, such as reproduction, should be looked at more closely. © 2016 Wiley Periodicals, Inc.

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

PubMed

Saad, Ahmed; Wang, Wei; Herrmann, Sandra M S; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Bjarnason, Haraldur; Lerman, Lilach O; Textor, Stephen C

2016-11-01

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Association of admission testosterone level with ST-segment resolution in male patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Separham, Ahmad; Ghaffari, Samad; Sohrabi, Bahram; Aslanabadi, Naser; Hadavi Bavil, Mozhgan; Lotfollahi, Hasanali

2017-01-01

Low level of testosterone may be associated with cardiovascular diseases in men, as some evidence suggests a protective role for testosterone in cardiovascular system. Little is known about the possible role of serum testosterone in response to reperfusion therapy in ST-elevation myocardial infarction (STEMI) and its relationship with ST-segment recovery. The present study was conducted to evaluate the association of serum testosterone levels with ST-segment resolution following primary percutaneous coronary intervention (PPCI) in male patients with acute STEMI. Forty-eight men (mean age 54.55 ± 12.20) with STEMI undergoing PPCI were enrolled prospectively. Single-lead ST segment resolution in the lead with maximum baseline ST-elevation was measured and patients were divided into two groups according to the degree of ST-segment resolution: complete (> or =50%) or incomplete (<50%). The basic and demographic data of all patients, their left ventricular ejection fraction (LVEF) and laboratory findings including serum levels of free testosterone and cardiac enzymes were recorded along with angiographic finding and baseline TIMI (Thrombolysis in Myocardial Infarction) flow and also in-hospital complications and then these variables were compared between two groups. A complete ST-resolution (≥50%) was observed in 72.9% of the patients. The serum levels of free testosterone ( P  = 0.04), peak cardiac troponin ( P  = 0.03) were significantly higher and hs-CRP ( P  = 0.02) were lower in patients with complete ST-resolution compared to those with incomplete ST-resolution. In-hospital complications were observed in 31.2% of patients. The patients with a lower baseline TIMI flow ( P  = 0.03) and those who developed complications ( P  = 0.04) had lower levels of free testosterone. A significant positive correlation was observed between the left ventricular function and serum levels of free testosterone ( P  = 0.01 and r = +0.362). This study suggests that in men with STEMI undergoing PPCI, higher serum levels of testosterone are associated with a better reperfusion response, fewer complications and a better left ventricular function.

Comparison of the effects of metoprolol or carvedilol on serum gamma-glutamyltransferase and uric acid levels among patients with acute coronary syndrome without ST segment elevation.

PubMed

Aşkın, Lütfü; Karakelleoğlu, Şule; Değirmenci, Hüsnü; Demirelli, Selami; Şimşek, Ziya; Taş, Muhammed Hakan; Topçu, Selim; Lazoğlu, Zakir

2016-01-01

Serum gamma-glutamyltransferase (GGT) and uric acid levels measured in patients with acute coronary syndrome without ST segment elevation (NSTEMI) are important in diagnosis and in predicting the prognosis of the disease. There is a limited number of clinical studies investigating the effects of beta-blockers on GGT and uric acid levels in these patients. In our study, we aimed to investigate the effects of beta-blocker therapy on GGT and uric acid levels. We conducted a randomized, prospective clinical study. Hundred patients with NSTEMI were included in this study, and they were divided into two groups. Fifty patients were administered metoprolol succinate treatment (1 x 50 mg), whereas the remaining 50 patients were administered carvedilol treatment (2 x 12.5 mg). Thereafter, all of the patients underwent coronary angiography. Blood samples were taken at the time of admission, at the 1st month, and 3rd month to detect GGT and uric acid levels. There was no statistically significant difference among the metoprolol or carvedilol groups in terms of the GGT levels measured at the baseline, 1st month, and 3rd month (p=0.904 and p=0.573, respectively). In addition, there was no statistically significant difference among the metoprolol or carvedilol groups in terms of uric acid levels measured at the baseline, 1st month, and 3rd month (p=0.601 and p=0.601, respectively). We found that GGT and uric acid levels did not show any change compared to the baseline values, with metoprolol and carvedilol treatment initiated in the early period in patients with NSTEMI.

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

PubMed Central

Miyake, Teruki; Kumagi, Teru; Furukawa, Shinya; Hirooka, Masashi; Kawasaki, Keitarou; Koizumi, Mitsuhito; Todo, Yasuhiko; Yamamoto, Shin; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

2014-01-01

Background It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. Methods We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period. Results In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041). Conclusions Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose. PMID:25237894

Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

PubMed

Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

2009-04-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Markers of Oxidative Stress and Inflammation in Ascites and Plasma in Patients with Platinum-Sensitive, Platinum-Resistant, and Platinum-Refractory Epithelial Ovarian Cancer.

PubMed

Cantón-Romero, Juan Carlos; Miranda-Díaz, Alejandra Guillermina; Bañuelos-Ramírez, Jose Luis; Carrillo-Ibarra, Sandra; Sifuentes-Franco, Sonia; Castellanos-González, José Alberto; Rodríguez-Carrizalez, Adolfo Daniel

2017-01-01

Diverse proinflammatory biomarkers and oxidative stress are strongly associated with advanced epithelial ovarian cancer (EOC). Objective . To determine the behavior of markers of oxidative stress and inflammation in plasma and ascites fluid in patients with platinum-sensitive, platinum-resistant, and platinum-refractory EOC. Methods . A prospective cohort study. The colorimetric method was used to determine levels of the markers 8-isoprostanes (8-IP), lipid peroxidation products (LPO), and total antioxidant capacity (TAC) in plasma and ascites fluid; and with ELISA, the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF- α ) were determined in patients with EOC. Results . In ascites fluid, a significant increase in 8-IP versus baseline plasma levels was found ( p = 0.002). There was an important leakage of the TAC levels in ascites fluid versus baseline plasma levels ( p < 0.001). The IL-6 was elevated in ascites fluid versus baseline plasma levels ( p = 0.003), and there were diminished levels of TNF- α in ascites fluid versus baseline plasma levels ( p = 0.001). Discussion . We hypothesize that the ascites fluid influences the behavior and dissemination of the tumor. Deregulation between oxidants, antioxidants, and the proinflammatory cytokines was found to vary among platinum-sensitive, platinum-resistant, and platinum-refractory patients.

The effects of elevated endogenous GABA levels on movement-related network oscillations.

PubMed

Muthukumaraswamy, S D; Myers, J F M; Wilson, S J; Nutt, D J; Lingford-Hughes, A; Singh, K D; Hamandi, K

2013-02-01

The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated. Copyright © 2012 Elsevier Inc. All rights reserved.

Prevalence and predictors of alanine aminotransferase elevation among normal weight, overweight and obese youth in Mexico.

PubMed

Purcell, Maura; Flores, Yvonne N; Zhang, Zuo-Feng; Denova-Gutiérrez, Edgar; Salmeron, Jorge

2013-09-01

This study aimed to determine the prevalence of and risk factors associated with elevated alanine aminotransferase (ALT) levels among a sample of normal weight, overweight and obese youth from two urban populations in Central Mexico. Baseline data from 1262 youth aged 8-19 years who participated in the Mexican Health Worker Cohort Study from March 2004 to April 2006 were reviewed, including 680 girls and 582 boys, with a total of 83 participants with elevated ALT level (>40 U/L). Information was obtained from self-administered questionnaires, anthropometric results and clinical measurements. Associations of interest were examined using multivariate logistic regression models. A total of 3.8% of girls and 9.8% of boys had elevated ALT levels. Elevated ALT was observed in 28.9% of the obese and 14.2% of the overweight participants. Metabolic syndrome (MS) occurred in 6.1% of the study population and those with MS had a high percentage of elevated ALT (14.5% of girls and 40.0% of boys, respectively). Abdominal obesity and insulin resistance were also associated with a greater risk of elevated ALT. Obesity and certain metabolic risk factors are important predictors for elevated ALT. Screening for ALT levels in obese youth could help to identify those at risk and reduce the possibility of future liver diseases. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Effect of 6-min Walk Test on pro-BNP Levels in Patients with Pulmonary Arterial Hypertension.

PubMed

Pathak, Vikas; Aris, Robert; Jensen, Brian C; Huang, Wei; Ford, Hubert James

2018-06-01

Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions. Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30 days or more were enrolled. After resting the patient for 30 min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2 h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student's paired t tests. There were 17 females and 3 male subjects. The mean age was 53 ± 11 years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50 ± 15 mmHg with a mean pulmonary vascular resistance of 10 ± 4 Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377 ± 140 m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1 h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2 h post 6MWT. There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1 h. Pro-BNP levels then return to baseline at 2 h post 6MWT.

Argon laser irradiation of rabbits' eyes-changes in prostaglandin E2 levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naveh, N.; Peer, J.; Bartov, E.

1991-02-01

Laser irradiation of the eye is a widely used therapeutic measure in various ocular disorders. We investigated in laser-treated rabbits' eyes the changes in prostaglandin E2 (PGE2) levels of the tissue affected by the laser (the retina/choroid) and of its adjacent vitreous over a two-week period. The parameters studied were; PGE2 in vitro production by the retina/choroid, as well as PGE2 and protein levels in the vitreous, the latter indicative of a break in the blood retinal barrier (BRB). The effect of noncoherent light exposure used for illumination, and that of the mechanical manipulation involved (sham exposure) were also studied.more » Following laser exposure vitreal PGE2 levels were increased two-fold above baseline (days three and 14), whereas light exposure resulted in a single peak. PGE2 in vitro production by the retina/choroid in the laser-exposed group was elevated throughout the observation period, peaking twice (days 3 and 14), in the light-exposed group the enhanced production was evident during a shorter period, whereas in the sham group it remained unchanged from baseline. An elevation in vitreal protein levels to above baseline levels occurred in both the laser- and, to a lesser degree, in the noncoherent light-exposed groups, but not in the sham group. Our study demonstrated an enhanced PGE2 in vitro production by retina/choroid of laser-exposed eyes, which might be attributable to the additive effect of the laser induced trauma, and the noncoherent light photochemical changes; the clinical significance of the recurrent increase in vitreal PGE2 levels in laser-treated eyes might be related to its anti-inflammatory properties.« less

The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle.

PubMed

Carroll, Chad C; O'Connor, Devin T; Steinmeyer, Robert; Del Mundo, Jonathon D; McMullan, David R; Whitt, Jamie A; Ramos, Jahir E; Gonzales, Rayna J

2013-07-01

This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein(-1)·min(-1)). COX-2 activity was elevated at 4 and 24 h after RE (P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein(-1)·min(-1)). The protein level of COX-1 was not altered (P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Geodesy by radio interferometry - Effects of atmospheric modeling errors on estimates of baseline length

NASA Technical Reports Server (NTRS)

Davis, J. L.; Herring, T. A.; Shapiro, I. I.; Rogers, A. E. E.; Elgered, G.

1985-01-01

Analysis of very long baseline interferometry data indicates that systematic errors in prior estimates of baseline length, of order 5 cm for approximately 8000-km baselines, were due primarily to mismodeling of the electrical path length of the troposphere and mesosphere ('atmospheric delay'). Here observational evidence for the existence of such errors in the previously used models for the atmospheric delay is discussed, and a new 'mapping' function for the elevation angle dependence of this delay is developed. The delay predicted by this new mapping function differs from ray trace results by less than approximately 5 mm, at all elevations down to 5 deg elevation, and introduces errors into the estimates of baseline length of less than about 1 cm, for the multistation intercontinental experiment analyzed here.

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

PubMed Central

Lv, Guo-Cai; Ma, Wen-Jiang; Ying, Lin-Jung; Jin, Xi; Zheng, Lin; Yang, Yi-Da

2010-01-01

AIM: To evaluate the efficacy and safety of telbivudine (LDT) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who have high baseline alanine aminotransferase (ALT) levels between 10 and 20 times the upper limit of normal. METHODS: Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk. Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls. We compared the virological, biochemical, serological and side effect profiles between the two groups at 52 wk. RESULTS: By week 52, the mean decrease in hepatitis B virus (HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group, respectively (P < 0.05). The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group, respectively (P < 0.05). In addition, 45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative, and 37.5% of those in the high baseline group and 22.5% of controls, respectively, had HBeAg seroconversion (P < 0.05) at week 52. Moreover, in the high baseline group, 4 out of 40 patients (10%) became hepatitis B surface antigen (HBsAg)-negative and 3 (7.5%) of them seroconverted (became HBsAg-positive). Only 1 patient in the control group became HBsAg-negative, but had no seroconversion. The ALT normalization rate, viral breakthrough, genotypic resistance to LDT, and elevations in creatine kinase levels were similar in the two groups over the 52 wk. CONCLUSION: High baseline ALT level is a strong predictor for optimal results during LDT treatment. PMID:20731026

N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes.

PubMed

Heeschen, Christopher; Hamm, Christian W; Mitrovic, Veselin; Lantelme, Nicte-Ha; White, Harvey D

2004-11-16

Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date. NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non-ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels >250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P<0.001). In troponin T-negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P<0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T-positive patients (9.8%; P=0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; -24%; 72 hours, -49%; both P<0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (< or =250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P<0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to >250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P<0.001). Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more rapidly identify patients suitable for early discharge or more intensive therapy deserves future prospective studies.

Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system

PubMed Central

Tan, Bingyao; MacLellan, Benjamin; Mason, Erik

2018-01-01

Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely. PMID:29509807

The Renin-Angiotensin System, Not the Kinin-Kallikrein System, Affects Post-Exercise Proteinuria.

PubMed

Koçer, Günnur; Basralı, Filiz; Kuru, Oktay; Şentürk, Ümit Kemal

2018-05-17

Temporary proteinuria post-exercise is common and is caused predominantly by renal haemodynamic alterations. One reason is up-regulation of angiotensin II (Ang II) due to the reducing effect of angiotensin-converting enzyme (ACE) inhibitors. However, another, ignored, reason could be the kininase effect of ACE inhibition. This study investigated how ACE inhibition reduces post-exercise proteinuria: by either Ang II up-regulation inhibition or bradykinin elevation due to kininase activity inhibition. Our study included 10 volunteers, who completed 3 high-intensity exercise protocols involving cycling at 1-week intervals. The first protocol was a control arm, the second evaluated the effect of ACE inhibition and the third examined the effect of angiotensin type 1 receptor blockade. Upon application, both agents reduced systolic and diastolic blood pressure; however, there were no statistically significant -differences. In addition, total protein, microalbumin and -β2-microglobulin excretion levels in urine specimens were analysed before, 30 min after and 120 min after the exercise protocols. Total protein levels in urine samples were elevated in all 3 protocols after 30 min of high-intensity exercise, compared to baseline levels. However, both ACE inhibition and angiotensin type 1 receptor blockade suppressed total protein in the 30th min. In each protocol, total protein levels returned to the baseline after 120 min. Urinary microalbumin and β2-microglobulin levels during the control protocol were significantly higher 30 min post-exercise; however, only angiotensin type 1 receptor blockade suppressed microalbumin levels. The results indicated Ang II up-regulation, not bradykinin elevation, plays a role in post-exercise proteinuria. © 2018 S. Karger AG, Basel.

Evidence for baseline glucocorticoids as mediators of reproductive investment in a wild bird.

PubMed

Love, Oliver P; Madliger, Christine L; Bourgeon, Sophie; Semeniuk, Christina A D; Williams, Tony D

2014-04-01

Determining the mechanisms that mediate investment decisions between current and future reproductive attempts is still a key goal of life-history studies. Since baseline levels of stress hormones (glucocorticoids - GCs) act as predictive and labile regulators of daily energetic balance in vertebrates they remain excellent candidates for mediating investment decisions both within and across reproductive attempts. Using free-living female European starlings (Sturnus vulgaris) we experimentally reduced investment in current reproduction (number of offspring raised in the first brood) to examine whether baseline corticosterone (CORT) acted as a hormonal mediator preparing individuals for a predictable increase in future investment (number of offspring raised in the second brood). Although treatment and control birds raised the same total amount of offspring across two broods, the experimental birds increased reproductive investment in second broods to compensate for the reduced investment in the first brood. Data on both mean and intra-individual changes in baseline CORT support the idea that an increase in baseline CORT between the incubation stages in treatment birds strongly predicted this increase in investment. Importantly, we measured the increase in baseline CORT during late incubation prior to the increase in energetic demand associated with increased reproductive investment in offspring, indicating that flexible within-individual changes in baseline GCs can act as a labile mechanism preparing individuals for predictable increases in reproductive investment. As such, our experimental results indicate that elevated baseline GCs can prepare individuals for investment in energetically expensive life-history stages, rather than simply being elevated as a consequence of increased effort or demand. This suggests that short-term preparative increases in baseline GCs benefit individuals by successfully allowing them to maximize fitness under varying environmental conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Markers of Oxidative Stress and Inflammation in Ascites and Plasma in Patients with Platinum-Sensitive, Platinum-Resistant, and Platinum-Refractory Epithelial Ovarian Cancer

PubMed Central

Cantón-Romero, Juan Carlos; Bañuelos-Ramírez, Jose Luis; Sifuentes-Franco, Sonia; Castellanos-González, José Alberto

2017-01-01

Diverse proinflammatory biomarkers and oxidative stress are strongly associated with advanced epithelial ovarian cancer (EOC). Objective. To determine the behavior of markers of oxidative stress and inflammation in plasma and ascites fluid in patients with platinum-sensitive, platinum-resistant, and platinum-refractory EOC. Methods. A prospective cohort study. The colorimetric method was used to determine levels of the markers 8-isoprostanes (8-IP), lipid peroxidation products (LPO), and total antioxidant capacity (TAC) in plasma and ascites fluid; and with ELISA, the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were determined in patients with EOC. Results. In ascites fluid, a significant increase in 8-IP versus baseline plasma levels was found (p = 0.002). There was an important leakage of the TAC levels in ascites fluid versus baseline plasma levels (p < 0.001). The IL-6 was elevated in ascites fluid versus baseline plasma levels (p = 0.003), and there were diminished levels of TNF-α in ascites fluid versus baseline plasma levels (p = 0.001). Discussion. We hypothesize that the ascites fluid influences the behavior and dissemination of the tumor. Deregulation between oxidants, antioxidants, and the proinflammatory cytokines was found to vary among platinum-sensitive, platinum-resistant, and platinum-refractory patients. PMID:28848618

Early Dynamic Risk Stratification with Baseline Troponin Levels and 90-minute ST Segment Resolution to Predict 30 Day Cardiovascular Mortality in STEMI: Analysis from CLARITY TIMI-28

PubMed Central

Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Bode, Christoph; Rifai, Nader; Gerszten, Robert E.; Gibson, C. Michael; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.

2010-01-01

Background Troponin is the preferred biomarker for risk stratification in non-ST-elevation ACS. The incremental prognostic utility of the initial magnitude of troponin elevation and its value in conjunction with ST segment resolution (STRes) in STEMI is less well-defined. Methods Troponin T (TnT) was measured in 1250 patients at presentation undergoing fibrinolysis for STEMI in CLARITY-TIMI 28. STRes was measured at 90 minutes. Multivariable logistic regression was used to examine the independent association between TnT levels, STRes, and 30-day cardiovascular (CV) mortality. Results Patients were classified into undetectable TnT at baseline (n=594), detectable but below the median of 0.12 ng/ml (n=330), and above the median (n=326). Rates of 30-day CV death were 1.5%, 4.5%, and 9.5% respectively (P<0.0001). Compared with those with undetectable levels and adjusting for baseline factors, the odds ratios for 30-day CV death were 4.56 (1.72-12.08, P=0.002) and 5.81 (2.29-14.73, P=0.0002) for those below and above the median, respectively. When combined with STRes, there was a significant gradient of risk, and in a multivariable model both baseline TnT (P=0.004) and STRes (P=0.003) were significant predictors of 30-day CV death. The addition of TnT and STRes to clinical risk factors significantly improved the C-statistic (0.86 to 0.90, P=0.02) and the integrated discriminative improvement 7.1% (P=0.0009). Conclusions Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI. Use of these two simple, readily available tools can aid clinicians in early risk stratification. PMID:20569707

Circulating intestinal fatty acid-binding protein (I-FABP) levels in acute decompensated heart failure.

PubMed

Kitai, Takeshi; Kim, Yong-Hyun; Kiefer, Kathryn; Morales, Rommel; Borowski, Allen G; Grodin, Justin L; Tang, W H Wilson

2017-06-01

Venous congestion has become increasingly recognized as a potential contributor to end-organ dysfunction in heart failure. Elevated I-FABP, which is excreted specifically from damaged intestinal epithelial cells, has been found in patients with abdominal hypertension and intestinal ischemia. We hypothesize that elevated intestinal fatty acid-binding protein (I-FABP) levels would identify patients with more advanced heart failure who have venous and intestinal congestion. Baseline serum I-FABP levels were measured in 69 acute decompensated heart failure (ADHF) patients admitted to the intensive care unit for invasive hemodynamic monitoring and tailored medical therapy. Comprehensive echocardiography examinations were performed in all study patients, and clinical outcomes (death, cardiac transplant or left ventricular assist device placement) were assessed. The median circulating I-FABP level was 853pg/ml (interquartile range: 533 to 1448pg/ml). Age, gender, race, and baseline comorbidities were comparable between patients with low and high I-FABP levels. Although there were no significant correlations between I-FABP levels and invasively-measured hemodynamic parameters nor echocardiographic parameters, patients with higher I-FABP levels (≥853g/ml) had significantly worse clinical outcomes compared to those with lower I-FABP levels (<853pg/ml, P=0.025). Circulating I-FABP levels had no association with invasively-measured hemodynamic parameters, but were associated with adverse clinical outcomes in patients with ADHF with systolic dysfunction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

An Analysis of Department of Defense Instruction 8500.2 'Information Assurance (IA) Implementation.'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, Philip LaRoche

2012-01-01

The Department of Defense (DoD) provides its standard for information assurance in its Instruction 8500.2, dated February 6, 2003. This Instruction lists 157 'IA Controls' for nine 'baseline IA levels.' Aside from distinguishing IA Controls that call for elevated levels of 'robustness' and grouping the IA Controls into eight 'subject areas' 8500.2 does not examine the nature of this set of controls, determining, for example, which controls do not vary in robustness, how this set of controls compares with other such sets, or even which controls are required for all nine baseline IA levels. This report analyzes (1) the IAmore » Controls, (2) the subject areas, and (3) the Baseline IA levels. For example, this report notes that there are only 109 core IA Controls (which this report refers to as 'ICGs'), that 43 of these core IA Controls apply without variation to all nine baseline IA levels and that an additional 31 apply with variations. This report maps the IA Controls of 8500.2 to the controls in NIST 800-53 and ITGI's CoBIT. The result of this analysis and mapping, as shown in this report, serves as a companion to 8500.2. (An electronic spreadsheet accompanies this report.)« less

Natural history of allergic sensitization in infants with early-onset atopic dermatitis: results from ORCA Study.

PubMed

Just, Jocelyne; Deslandes-Boutmy, Emmanuelle; Amat, Flore; Desseaux, Kristell; Nemni, Ariane; Bourrat, Emmanuelle; Sahraoui, Fatia; Pansé, Isabelle; Bagot, Martine; Fouéré, Sébastien

2014-11-01

Early-onset atopic dermatitis (AD) is a particular phenotype that may convey a risk of developing multiple sensitizations to allergens but little is known about the pathway of sensitization. The aims of this study were to describe the natural history of sensitization to allergens for this phenotype and to identify the most predictive marker associated with the risk of developing sensitization to inhaled allergens in a well-selected cohort of infants with AD. Infants with active AD were enrolled and prospectively explored for biological markers of atopy every year until the age of 6 yr. Allergic sensitization was defined as the presence of positive specific IgEs to allergens and multiple sensitizations as being sensitized to ≥2 allergens. Elevated blood eosinophilia was defined as an eosinophil blood count ≥470 eosinophils/mm(3) and elevated total IgE as a serum IgE level ≥45 kU/l. Two hundred and twenty-nine infants were included. Elevated blood eosinophilia was observed at baseline in 60 children (26.2%) and elevated total IgE in 85 (37.1%). When elevated at baseline, eosinophilia and IgE levels remained significantly higher during the follow-up period. Sensitization to food allergens decreased from 58% to 34%, whereas sensitization to inhaled allergens increased over time from 17% to 67%. Initial multiple sensitizations to food allergens were the most predictive factor for the risk of developing sensitization to inhaled allergens at 6 yr (OR 3.72 [1.68-8.30] p < 0.001). In the early-onset AD phenotype, multiple sensitization to food allergens conveys a higher risk of sensitization to inhaled allergens than single sensitization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level.

PubMed

Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung

2014-01-01

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding.

The Construction and Validation of All-Atom Bulk-Phase Models of Amorphous Polymers Using the TIGER2/TIGER3 Empirical Sampling Method

PubMed Central

Li, Xianfeng; Murthy, Sanjeeva; Latour, Robert A.

2011-01-01

A new empirical sampling method termed “temperature intervals with global exchange of replicas and reduced radii” (TIGER3) is presented and demonstrated to efficiently equilibrate entangled long-chain molecular systems such as amorphous polymers. The TIGER3 algorithm is a replica exchange method in which simulations are run in parallel over a range of temperature levels at and above a designated baseline temperature. The replicas sampled at temperature levels above the baseline are run through a series of cycles with each cycle containing four stages – heating, sampling, quenching, and temperature level reassignment. The method allows chain segments to pass through one another at elevated temperature levels during the sampling stage by reducing the van der Waals radii of the atoms, thus eliminating chain entanglement problems. Atomic radii are then returned to their regular values and re-equilibrated at elevated temperature prior to quenching to the baseline temperature. Following quenching, replicas are compared using a Metropolis Monte Carlo exchange process for the construction of an approximate Boltzmann-weighted ensemble of states and then reassigned to the elevated temperature levels for additional sampling. Further system equilibration is performed by periodic implementation of the previously developed TIGER2 algorithm between cycles of TIGER3, which applies thermal cycling without radii reduction. When coupled with a coarse-grained modeling approach, the combined TIGER2/TIGER3 algorithm yields fast equilibration of bulk-phase models of amorphous polymer, even for polymers with complex, highly branched structures. The developed method was tested by modeling the polyethylene melt. The calculated properties of chain conformation and chain segment packing agreed well with published data. The method was also applied to generate equilibrated structural models of three increasingly complex amorphous polymer systems: poly(methyl methacrylate), poly(butyl methacrylate), and DTB-succinate copolymer. Calculated glass transition temperature (Tg) and structural parameter profile (S(q)) for each resulting polymer model were found to be in close agreement with experimental Tg values and structural measurements obtained by x-ray diffraction, thus validating that the developed methods provide realistic models of amorphous polymer structure. PMID:21769156

Irisin in response to acute and chronic whole-body vibration exercise in humans.

PubMed

Huh, Joo Young; Mougios, Vassilis; Skraparlis, Athanasios; Kabasakalis, Athanasios; Mantzoros, Christos S

2014-07-01

Irisin is a recently identified myokine, suggested to mediate the beneficial effects of exercise by inducing browning of white adipocytes and thus increasing energy expenditure. In humans, the regulation of irisin by exercise is not completely understood. We investigated the effect of acute and chronic whole-body vibration exercise, a moderate-intensity exercise that resembles shivering, on circulating irisin levels in young healthy subjects. Healthy untrained females participated in a 6-week program of whole-body vibration exercise training. Blood was drawn before and immediately after an acute bout of exercise at baseline (week 0) and after 6 weeks of training. The resting irisin levels were not different at baseline (week 0) and after 6 weeks of training. At both 0 and 6 weeks of training, an acute bout of vibration exercise significantly elevated circulating irisin levels by 9.5% and 18.1%, respectively (p=0.05 for the percent change of irisin levels). Acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury

PubMed Central

Kuster, Diederik W. D.; Cardenas-Ospina, Adriana; Miller, Lawson; Liebetrau, Christoph; Troidl, Christian; Nef, Holger M.; Möllmann, Helge; Hamm, Christian W.; Pieper, Karen S.; Mahaffey, Kenneth W.; Kleiman, Neal S.; Stuyvers, Bruno D.; Marian, Ali J.

2013-01-01

Diagnosis of myocardial infarction (MI) is based on ST-segment elevation on electrocardiographic evaluation and/or elevated plasma cardiac troponin (cTn) levels. However, troponins lack the sensitivity required to detect the onset of MI at its earliest stages. Therefore, to confirm its viability as an ultra-early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C (cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 days after coronary occlusion, with use of a custom-made immunoassay. cMyBP-C plasma levels were increased from baseline (76 ± 68 ng/l) at 3 h (767 ± 211 ng/l) and peaked at 6 h (2,418 ± 780 ng/l) after coronary ligation. Plasma cTnI, cTnT, and myosin light chain-3 levels were all increased 6 h after ligation. In a cohort of patients (n = 12) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy, cMyBP-C was significantly increased from baseline (49 ± 23 ng/l) in a time-dependent manner, peaking at 4 h (560 ± 273 ng/l). In a cohort of patients with non-ST segment elevation MI (n = 176) from the SYNERGY trial, cMyBP-C serum levels were significantly higher (7,615 ± 4,514 ng/l) than those in a control cohort (416 ± 104 ng/l; n = 153). cMyBP-C is released in the blood rapidly after cardiac damage and therefore has the potential to positively mark the onset of MI. PMID:24337456

Total homocysteine and cognition in a tri-ethnic cohort

PubMed Central

Wright, C.B.; Lee, H.-S.; Paik, M.C.; Stabler, S.P.; Allen, R.H.; Sacco, R.L.

2005-01-01

Objective: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. Method: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. Results: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI −3.6, −0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE −2.2 points; 95% CI −3.5, −0.9). Conclusions: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors. PMID:15277617

The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

PubMed

Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

2018-03-15

Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

A Prospective Examination of the Relations between Emotional Abuse and Anxiety: Moderation by Distress Tolerance

PubMed Central

Banducci, Anne N.; Lejuez, C.W.; Dougherty, Lea R.; MacPherson, Laura

2016-01-01

Objective Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across five years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Method Community youth (N = 244) were annually assessed across five years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Results Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Conclusions Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time. PMID:27501698

A Prospective Examination of the Relations Between Emotional Abuse and Anxiety: Moderation by Distress Tolerance.

PubMed

Banducci, Anne N; Lejuez, C W; Dougherty, Lea R; MacPherson, Laura

2017-01-01

Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across 5 years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Community youth (N = 244) were annually assessed across 5 years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time.

Linking sex differences in corticosterone with individual reproductive behaviour and hatch success in two species of uniparental shorebirds.

PubMed

Edwards, Darryl B; Chin, Eunice H; Burness, Gary; Gilchrist, H Grant; Schulte-Hostedde, Albrecht I

2013-09-01

In birds, corticosterone (CORT) appears to facilitate reproductive activity because baseline and stress-induced CORT levels are elevated in breeding individuals compared with other times of the year. In particular, CORT is lower in the sex providing most of the parental care (i.e., incubation), which could be an important adaptation to tolerate stressors that result in abandoning reproduction. Therefore, one explanation for sex differences in CORT is that lower levels are favoured during the incubation/parental phase of reproduction. Using two species of uniparental shorebird - polyandrous red phalaropes (Phalaropus fulicarius) and polygynous white-rumped sandpipers (Calidris fuscicollis) - we predicted that the incubating sex would have lower baseline and stress-induced CORT, and incubating individuals with lower CORT would more effectively defend nests against a simulated intrusion, would return more quickly afterwards, and would ultimately have higher hatch success. We found that phalaropes followed the predicted pattern: incubating individuals (males) had lower baseline and stress-induced CORT than females but for baseline CORT these differences existed prior to males commencing incubation. Incubating male phalaropes with lower baseline and stress-induced CORT returned to incubate more quickly after a disturbance and there was non-significant tendency for baseline CORT to be lower in successful nests. In sandpipers, we observed no sex differences and no significant relationships between individual CORT levels and nest defence behaviours or hatch success. Our results demonstrate that in phalaropes at least, selection favours lower baseline and stress-induced CORT during the nesting period. These results can explain sex differences in stress-induced levels of CORT, however sex differences in baseline CORT were present prior to incubation. Copyright © 2013 Elsevier Inc. All rights reserved.

Combined Supplementation with Grape Pomace and Omija Fruit Ethanol Extracts Dose-Dependently Improves Body Composition, Plasma Lipid Profiles, Inflammatory Status, and Antioxidant Capacity in Overweight and Obese Subjects.

PubMed

Han, Hye Jin; Jung, Un Ju; Kim, Hye-Jin; Cho, Su-Jung; Kim, Ae Hyang; Han, Youngji; Choi, Myung-Sook

2016-02-01

The aim of this study was to examine the efficacy of combined grape pomace and omija fruit ethanol extracts (GO) on metabolic disorders in overweight or obese subjects. Seventy-six subjects (30-70 years, body mass index ≥23.0 kg/m2) were divided into control (starch, 4 g/day, n = 24), low-GO (low dose GO, grape pomace extract [342.5 mg/day] + omija fruit extract [57.5 mg/day], n = 26), and high-GO (high dose GO, grape pomace extract [685 mg/day] + omija fruit extract [115 mg/day], n = 26) groups. Body composition, nutrient intake, plasma lipid profiles, inflammation, antioxidant capacity, and hepatotoxicity markers were assessed in all subjects at the baseline and 10 weeks after taking the supplements. The body weight and body fat of overweight or obese subjects was not significantly altered in the low-GO and high-GO groups. However, the high-GO supplement significantly decreased the baseline-adjusted final plasma total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-high-density lipoprotein (HDL)-cholesterol levels and increased the baseline-adjusted final plasma apolipoprotein (apo) A-1 level compared with that of the control group. In addition, the high-GO supplement significantly lowered apo B, apo B/apo A-1, lipoprotein a (Lp[a]), atherogenic index, interleukin (IL)-1β, tumor necrosis factor-α, and elevated erythrocyte antioxidant capacity compared with the control group or the baseline levels. The low-GO supplement decreased the plasma IL-1β level and elevated erythrocyte superoxide dismutase activity compared with that at baseline. However, in general, high-GO exerted a greater effect than low-GO. There were no significant differences in activities of plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase between the groups. This study is a preliminary clinical study to verify that GO could be beneficial for amelioration of obesity-related dyslipidemia, inflammation, and oxidative stress without side effect in the overweight or obese subjects.

Acute ST-Elevation Myocardial Infarction, a Unique Complication of Recreational Nitrous Oxide Use.

PubMed

Indraratna, Praveen; Alexopoulos, Chris; Celermajer, David; Alford, Kevin

2017-08-01

A 28-year-old male was admitted to hospital with an acute ST-elevation myocardial infarction. This was in the context of recreational abuse of nitrous oxide. The prevalence of nitrous oxide use in Australia has not been formally quantified, however it is the second most commonly used recreational drug in the United Kingdom. Nitrous oxide has previously been shown to increase serum homocysteine levels. This patient was discovered to have an elevated homocysteine level at baseline, which was further increased after nitrous oxide consumption. Homocysteine has been linked to endothelial dysfunction and coronary atherosclerosis and this case report highlights one of the dangers of recreational abuse of nitrous oxide. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Serial C-reactive protein measurements in patients treated for suspected abdominal tuberculosis.

PubMed

Sharma, Vishal; Mandavdhare, Harshal S; Lamoria, Sandeep; Singh, Harjeet; Kumar, Amit

2018-06-01

Response to treatment is often used as a criterion for the diagnosis of abdominal tuberculosis. To determine utility of serum C reactive protein (CRP) in assessment of response to anti-tubercular therapy (ATT) in abdominal tuberculosis (ATB). We retrospectively analysed the database of patients with suspected ATB (intestinal and/or peritoneal). Response to ATT was assessed using subjective and objective (ulcer healing or ascites resolution) parameters. Serum CRP levels were estimated at baseline and then at 2 months and 6 months of ATT. One hundred and twelve patients were included in the analysis. The mean age was 36.57 ± 15.04 years and 54.46% (61/112) were males. Sixty-six patients (58.92%) had intestinal, 28 (25%) had peritoneal and 18 (16.07%) had both. Eleven patients had a normal CRP at baseline while 101 had elevated levels. The CRP levels declined in 94 patients at 6 months. One patient with increased levels at 2 months had multi-drug resistant TB. Seven patients showed elevated or plateaued CRP levels on follow-up. These patients had underlying Crohn's disease (3 patients), peritoneal carcinomatosis (1), inter-current infection (1), lymphoma (1) and non-healing ulcers (1). Lack of decline in CRP may suggest alternative diagnosis or drug-resistant tuberculosis. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The association between immune activation and manic symptoms in patients with a depressive disorder.

PubMed

Becking, K; Boschloo, L; Vogelzangs, N; Haarman, B C M; Riemersma-van der Lek, R; Penninx, B W J H; Schoevers, R A

2013-10-22

Although recent studies have shown that immunological processes play an important role in the pathophysiology of mood disorders, immune activation may only be present in specific subgroups of patients. Our study aimed to examine whether immune activation was associated with (a) the presence of manic symptoms and (b) the onset of manic symptoms during 2 years of follow-up in depressed patients. Patients with a depressive disorder at baseline (N=957) and healthy controls (N=430) were selected from the Netherlands Study of Depression and Anxiety. Assessments included lifetime manic symptoms at baseline and two-year follow up, as well as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at baseline. Within depressed patients, immune activation was not related to the presence or absence of lifetime manic symptoms at baseline. However, CRP levels were strongly elevated in depressed men who developed manic symptoms compared with those who did not develop manic symptoms over 2 years (P<0.001, Cohen's d=0.89). IL-6 and TNF-α were also higher in depressed men with an onset of manic symptoms, but this association was not significant. However, we found that the onset of manic symptoms was particularly high in men with multiple elevated levels of inflammatory markers. Depressed men who developed manic symptoms during follow-up had increased immunological activity (especially CRP) compared with depressed men who did not develop manic symptoms. Further research should explore whether a treatment approach focusing on inflammatory processes may be more effective in this specific subgroup of depressed patients.

Noninvasive measurement of carboxyhemoglobin levels for adjustment of diffusion capacity measured during pulmonary function testing.

PubMed

Mahoney, Anne M; Stimpson, Claudia L; Scott, Karen L; Hampson, Neil B

2007-12-01

The diffusing capacity of the lungs for carbon monoxide (D(LCO)) is commonly measured during pulmonary function testing (PFT). Although adjustment of the measured D(LCO) for an elevated baseline carboxyhemoglobin level is recommended, carboxyhemoglobin is not routinely measured, which may reduce the accuracy of D(LCO) measurements. We sought to assess the utility of routine carboxyhemoglobin measurement and subsequent D(LCO) correction in patients referred for PFT. We retrospectively reviewed 100 consecutive PFT results, including D(LCO) assessment. We used a pulse CO-oximeter (recently approved by the Food and Drug Administration) to noninvasively measure baseline carboxyhemoglobin (S(pCO)). We used simple descriptive statistics to compare the S(pCO) values. In subjects with elevated S(pCO) (> 2%) we adjusted the percent-of-predicted D(LCO). Interpretation of D(LCO) was categorized according to the American Thoracic Society classification scheme for respiratory impairment. The self-reported smokers had higher average S(pCO) than did self-reported nonsmokers (1.6% vs 3.5%, p < 0.001), although 14% of nonsmokers had an elevated S(pCO) and 26% of smokers had normal S(pCO). When the D(LCO) was corrected for elevated S(pCO), 2 patients moved from a category of moderate impairment to mild impairment. Both were smokers. The noninvasive measurement of carboxyhemoglobin is easy to perform during PFT. When precise measurement of D(LCO) is important, noninvasive measurement of carboxyhemoglobin may be of value. If routine S(pCO) measurement is considered, the highest yield is among current smokers.

Measurement of serum, liver, and brain cytokine induction, thiamine levels, and hepatopathology in rats exposed to a 4-day alcohol binge protocol.

PubMed

Zahr, Natalie M; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

2010-11-01

 In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation. This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho. Ten of 18 wild-type male Wistar rats (~322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ~315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines. There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior cerebellar vermis, cingulate cortex, frontal cortex, hippocampus, hypothalamus, striatum) also failed to identify group effects. A single 4-day bout of binge EtOH exposure alone was insufficient to induce the expression of 7 cytokines in blood, liver, or 6 brain regions of wild-type Wistar rats. Alternative interpretations for elevations in brain Cho in response to a 4-day binge EtOH treatment are therefore necessary and may include induction of cytokines not measured herein or other noninflammatory mechanisms. Copyright © 2010 by the Research Society on Alcoholism.

Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

PubMed Central

Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

2011-01-01

This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

A Psychobiological Perspective on Working Memory Performance at 8 Months of Age

ERIC Educational Resources Information Center

Bell, Martha Ann

2012-01-01

Fifty 8-month-old infants participated in a study of the interrelations among cognition, temperament, and electrophysiology. Better performance on a working memory task (assessed using a looking version of the A-not-B task) was associated with increases in frontal-parietal EEG coherence from baseline to task, as well as elevated levels of…

Adaptation to Altitude as a Vehicle for Experiential Learning of Physiology by University Undergraduates

ERIC Educational Resources Information Center

Weigle, David S.; Buben, Amelia; Burke, Caitlin C.; Carroll, Nels D.; Cook, Brett M.; Davis, Benjamin S.; Dubowitz, Gerald; Fisher, Rian E.; Freeman, Timothy C.; Gibbons, Stephen M.; Hansen, Hale A.; Heys, Kimberly A.; Hopkins, Brittany; Jordan, Brittany L.; McElwain, Katherine L.; Powell, Frank L.; Reinhart, Katherine E.; Robbins, Charles D.; Summers, Cameron C.; Walker, Jennifer D.; Weber, Steven S.; Weinheimer, Caroline J.

2007-01-01

In this article, an experiential learning activity is described in which 19 university undergraduates made experimental observations on each other to explore physiological adaptations to high altitude. Following 2 wk of didactic sessions and baseline data collection at sea level, the group ascended to a research station at 12,500-ft elevation.…

Association of HPA axis hormones with copeptin after psychological stress differs by sex.

PubMed

Spanakis, Elias K; Wand, Gary S; Ji, Nan; Golden, Sherita Hill

2016-01-01

Copeptin levels are elevated in severe medical conditions, an effect that is attributed to elevated arginine vasopressin (AVP) levels in response to physiological stress, resulting in activation of hypothalamus-pituitary-adrenal (HPA) axis. In the current study, we wanted to determine if copeptin is responsive to psychological stress, correlates with cortisol and adrenocorticotropin hormone (ACTH), and if associations differed by sex. In a cross-sectional study that included 100 healthy men (41%) and women (59%) (aged 18-30 years; mean 24.6 ± 3 years), who underwent the Trier Social Stress Test (TSST), we examined the association between percent change (peak-baseline/baseline) in copeptin levels and percent change in log ACTH and cortisol. Three baselines samples were drawn followed by blood sampling at 20, 35, 50, 65 and 85 min after TSST. There was a significant positive association between the percent change in copeptin and the percent change in log-transformed salivary cortisol (β-coefficient=0.95; p=0.02). The association between percent change in copeptin and log-transformed serum cortisol was not statistically significant in the overall population. There was a trend for a non-significant association between percent change in copeptin and percent change in log-transformed ACTH (β-coefficient=1.14; p=0.06). In males, there was a significant positive association between the percent change in copeptin levels and log-transformed salivary (β-coefficient=1.33, p=0.016) and serum cortisol (β-coefficient=0.69, p=0.01), whereas in women there was no statistically significant association. We found a significant positive association between percent change in copeptin and percent change in salivary and serum cortisol among males only. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate.

PubMed

Yokoyama, Keitaro; Fukagawa, Masafumi; Akiba, Takashi; Nakayama, Masaaki; Otoguro, Toshiya; Yamada, Kana; Nagamine, Yasuo; Fishbane, Steven; Hirakata, Hideki

2017-05-01

In hemodialysis patients on ferric citrate hydrate, the increase in ferritin level is mainly due to the administration of the compound. We investigated possible other factors associated with ferritin level and how erythropoietin resistance index and erythropoiesis in those patients were affected. We looked at ferritin-elevating factors using data from a Japanese phase III long-term clinical trial of ferric citrate hydrate. The factors with a strong association with ferritin levels at week 28 were selected by the process of variable selection. In addition, selected factors were analyzed by Mixed Model for Repeated Measurement. Subjects were divided into 3 groups by quantiles (

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

PubMed

Bonds, D E; Craven, T E; Buse, J; Crouse, J R; Cuddihy, R; Elam, M; Ginsberg, H N; Kirchner, K; Marcovina, S; Mychaleckyj, J C; O'Connor, P J; Sperl-Hillen, J-A

2012-06-01

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. ClincalTrials.gov: NCT00000620. The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes.

PubMed

Wu, M-F; Nienhuis, R; Maidment, N; Lam, H A; Siegel, J M

2011-11-07

Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study we have compared the effects of treadmill running, to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level beyond baseline, whereas yard play produces a substantial increase in Hcrt, even though both activities produce comparable increases in heart rate, respiration and body temperature. We conclude that motor and cardiovascular changes are not sufficient to elevate CSF levels of Hcrt and we hypothesize that the emotional aspects of yard play account for the observed increase in Hcrt.

PCDD/Fs and PCBs in seafood species from Moreton Bay, Queensland, Australia.

PubMed

Matthews, V; Päpke, O; Gaus, C

2008-01-01

Previous studies have identified elevated levels of polychlorinated dibenzo-p-dioxins (PCDDs) in sediments and megafauna (dugongs and green turtles) in the marine environment of southeast Queensland, Australia. Little information exists, however, regarding the levels of PCDDs, polychlorinated dibenzofurans (PCDFs) and related polychlorinated biphenyls (PCBs) in seafood from this area. This study aims to establish baseline information on PCDD/F and PCB contamination in a range of seafood species from Moreton Bay and to investigate contaminant variability due to harvesting season, size, habitat location and trophic level. In addition, different seafood extraction methods were tested to evaluate their impact on lipid yields and contaminant concentration. Overall, the median TEQ(DF&PCB) levels in seafood from Moreton Bay were elevated compared to background levels in Australian marine/estuarine and retail fish. However, TEQ(DF&PCB) levels of most seafood analysed were below the respective EU maximum limits. High inter- and intraspecies variability was observed, which could be partially attributed to differences in trophic level, season harvested and habitat location.

The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

PubMed

Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

2017-02-01

In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Avoidance-related EEG asymmetry predicts circulating interleukin-6.

PubMed

Shields, Grant S; Moons, Wesley G

2016-03-01

Recent research has linked avoidance-oriented motivational states to elevated pro-inflammatory cytokine levels. According to one of many theories regarding the association between avoidance and cytokine levels, because the evolutionarily basic avoidance system may be activated when an organism is threatened or overwhelmed, an associated inflammatory response may be adaptive for dealing with potential injury in such threatening situations. To examine this hypothesis, we tested whether the neural correlate of avoidance motivation associates with baseline levels of the circulating pro-inflammatory cytokine interleukin-6 (IL-6). Controlling for covariates, greater resting neural activity in the right frontal cortex relative to the left frontal cortex-the neural correlate of avoidance motivation-was associated with baseline IL-6. These results thus support the hypothesis that the avoidance motivational system may be closely linked to systemic inflammatory activity. (c) 2016 APA, all rights reserved).

Three-year incidence of elevated albuminuria and associated factors in a population-based cohort: The Taichung Community Health Study.

PubMed

Liao, Li-Na; Liu, Chiu-Shong; Li, Chia-Ing; Lin, Wen-Yuan; Lin, Chih-Hsueh; Li, Tsai-Chung; Lin, Cheng-Chieh

2015-06-01

early-stage elevated albuminuria can be effectively detected by a spot urine albumin-to-creatinine ratio (UACR). Elevated albuminuria is a key predictor of diabetic nephropathy, progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD), plus risk of cardiovascular disease (CVD) and mortality. Understanding these detectors may prevent future renal and cardiovascular disease. This study estimates three-year incidence in a representative sample of Taiwanese metropolitan adults to explore predictors. the Taichung Community Health Study (TCHS) is a representative sample of 2359 Chinese adults aged 40 years and over living in a metropolitan city during 2004-2005. In 2007-2009, a total of 1648 (71.3%) individuals participated in follow-up. This study includes only individuals with normal albumin excretion at baseline examination. Three-year incidence and baseline factors linked with elevated albuminuria were evaluated. about 87.0% (n = 1434) of subjects exhibited normal albumin excretion at baseline. Three-year age- and gender-weighted incidence was 4.5% (95% CI: 3.4-5.6%). Multivariate logistic regression showed subjects with elevated waist-to-hip ratio (WHR) (OR: 2.2, 95% CI: 1.2-3.9), abnormal creatinine (OR: 3.7, 95% CI: 1.1-12.6), hyperuricaemia (OR: 1.8, 95% CI: 1.0-3.3) and elevated baseline UACR (OR: 4.0, 95% CI: 1.1-14.3 for UACR of 3.20-6.39 mg/g; OR: 16.7, 95% CI: 5.0-55.5 for UACR of 6.40-29.99 mg/g) were more likely to have elevated albuminuria. this is the first population-based longitudinal study to rate incidence of elevated albuminuria and identify associated factors in a random sample of a Chinese population. Central obesity, renal function, hyperuricaemia and baseline UACR are independent risk factors. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Treatment of lymphatic malformations of head and neck with OK-432 sclerotherapy induce systemic inflammatory response.

PubMed

Närkiö-Mäkelä, Mervi; Mäkelä, Teppo; Saarinen, Pia; Salminen, Päivi; Julkunen, Ilkka; Pitkäranta, Anne

2011-01-01

Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1β, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

Direct-Acting Antiviral Therapy for Chronic HCV Infection Results in Liver Stiffness Regression Over 12 Months Post-treatment.

PubMed

Chan, Justin; Gogela, Neliswa; Zheng, Hui; Lammert, Sara; Ajayi, Tokunbo; Fricker, Zachary; Kim, Arthur Y; Robbins, Gregory K; Chung, Raymond T

2018-02-01

Liver fibrosis stage determines risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. Prior data have shown long-term reversal of liver fibrosis, measured by vibration-controlled transient elastography (VCTE), in patients successfully treated with interferon-based therapies. Our study sought to determine the effect of treatment with modern HCV direct-acting antiviral (DAA) therapy on noninvasive liver fibrosis measurements. A total of 70 patients had VCTE-based liver stiffness measurement (LSM) taken before treatment, directly after treatment completion, and at least 12 months after completion of DAA therapy. Our primary outcome was a >30% improvement in VCTE score at the end of follow-up, relative to baseline. The sustained virologic response rate in our cohort was 95.7%. In our cohort, 34 (48.6%) met the primary outcome. Those who had baseline elevated alanine aminotransferase (OR 3.27; 95% CI 1.13-9.47) and genotype 1 (OR 14.63; 95% CI 1.70-125.83) had higher odds of meeting that outcome, and this remained significant after adjusting for age, baseline body mass index, gender, baseline elevated alkaline phosphatase levels, treatment experience, liver transplant status, smoking, and baseline liver stiffness. Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion.

Red-winged blackbirds (Agelaius phoeniceus) with higher baseline glucocorticoids also invest less in incubation and clutch mass.

PubMed

Schoenle, Laura A; Dudek, Alana M; Moore, Ignacio T; Bonier, Frances

2017-04-01

Glucocorticoid hormones facilitate responses to environmental challenges by mediating diverse physiological and behavioral changes, including resource mobilization and altered reproductive effort. Elevated glucocorticoids might indicate that an individual is facing high levels of environmental challenges and thus, elevated concentrations might be associated with reduced fitness (CORT-fitness hypothesis). Alternatively, the energetic demands of reproduction might be a challenge that requires elevated glucocorticoids to mobilize resources to support reproductive effort, ultimately increasing reproductive investment and fitness (CORT-adaptation hypothesis). Investigations of glucocorticoid-fitness relationships have yielded mixed results. Variation in the direction of this relationship could be caused in part by differences in the contexts in which the relationship was assessed. Incorporating context, such as life history stage, could be key to understanding the role of glucocorticoids in influencing fitness outcomes. We investigated the relationship between corticosterone and reproductive effort and success within a single life history stage: incubation of eggs. In an observational study, we measured baseline corticosterone in incubating female red-winged blackbirds (Agelaius phoeniceus), monitored incubation behavior, and determined hatching success for each nest. Incubating birds with higher baseline corticosterone concentrations had more frequent, shorter incubation bouts and spent less time overall incubating their clutches of eggs than birds with lower corticosterone concentrations. Elevated corticosterone was also associated with lower clutch mass, but neither corticosterone nor incubation effort were correlated with hatching success. Although experimental tests are needed to establish causation, these results suggest that during the incubation period, corticosterone might shift resource investment towards self-maintenance, and away from current reproductive effort. Copyright © 2017 Elsevier Inc. All rights reserved.

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated levels of triglyceride and triglyceride-rich lipoprotein triglyceride induced by a high-carbohydrate diet is associated with polymorphisms of APOA5-1131T>C and APOC3-482C>T in Chinese healthy young adults.

PubMed

Lin, Jia; Fang, Ding Zhi; Du, Juan; Shigdar, Sarah; Xiao, Li Ying; Zhou, Xue Dong; Duan, Wei

2011-01-01

Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort. Copyright © 2011 S. Karger AG, Basel.

Evaluation of inflammation during fixed orthodontic treatment.

PubMed

Bilgic, Fundagul; Akinci Sozer, Ozlem; Ozcan, Oguzhan; Gurpinar, Ahmet Burak; Yilmaz, Hakki; Ay, Yazgi

2016-11-01

The aim of this study was to assess effects of fixed orthodontic therapy on high-sensitivity C-reactive protein (hs-CRP) level, CBC parameters and levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), urea, creatinine, sodium (Na), potassium (K), calcium (Ca), total protein (TP), and albumin (Alb). Blood samples (7ml) were drawn at baseline, on days 1 and 7, and three months after placement of braces in the study group, while only one blood sample was drawn at baseline in the control group. Serum hs-CRP levels were measured by nephelometric method. Friedman two-way variance analysis was used to assess values with skewed distribution obtained at baseline, on days 1 and 7, in the third month. Wilcoxon rank sign test was performed if median values were unequal. During measurement periods, there were significant increases in hs-CRP level, WBC count and neutrophil count while a significant decrease in Na level (p<0.05). K level was significantly decreased on the day 1. No significant differences were detected in other biochemical parameters evaluated. Elevation in serum hs-CRP levels and neutrophil: lymphocyte ratio within first 3 months indicates that a systemic immune response develops against therapy in patients undergoing fixed orthodontic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report.

PubMed

Hippe, Daniel S; Phan, Binh An P; Sun, Jie; Isquith, Daniel A; O'Brien, Kevin D; Crouse, John R; Anderson, Todd; Huston, John; Marcovina, Santica M; Hatsukami, Thomas S; Yuan, Chun; Zhao, Xue-Qiao

2018-03-01

To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P =0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (β=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; P <0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (β=0.33; 95% confidence interval, 0.15-0.52; P <0.001). Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden. © 2018 American Heart Association, Inc.

An interplay between plasticity and parental phenotype determines impacts of ocean acidification on a reef fish.

PubMed

Schunter, Celia; Welch, Megan J; Nilsson, Göran E; Rummer, Jodie L; Munday, Philip L; Ravasi, Timothy

2018-02-01

The impacts of ocean acidification will depend on the ability of marine organisms to tolerate, acclimate and eventually adapt to changes in ocean chemistry. Here, we use a unique transgenerational experiment to determine the molecular response of a coral reef fish to short-term, developmental and transgenerational exposure to elevated CO 2 , and to test how these responses are influenced by variations in tolerance to elevated CO 2 exhibited by the parents. Within-generation responses in gene expression to end-of-century predicted CO 2 levels indicate that a self-amplifying cycle in GABAergic neurotransmission is triggered, explaining previously reported neurological and behavioural impairments. Furthermore, epigenetic regulator genes exhibited a within-generation specific response, but with some divergence due to parental phenotype. Importantly, we find that altered gene expression for the majority of within-generation responses returns to baseline levels following parental exposure to elevated CO 2 conditions. Our results show that both parental variation in tolerance and cross-generation exposure to elevated CO 2 are crucial factors in determining the response of reef fish to changing ocean chemistry.

Preprocedural High-Sensitivity Cardiac Troponin T and Clinical Outcomes in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention.

PubMed

Zanchin, Thomas; Räber, Lorenz; Koskinas, Konstantinos C; Piccolo, Raffaele; Jüni, Peter; Pilgrim, Thomas; Stortecky, Stefan; Khattab, Ahmed A; Wenaweser, Peter; Bloechlinger, Stefan; Moschovitis, Aris; Frenk, Andre; Moro, Christina; Meier, Bernhard; Fiedler, Georg M; Heg, Dik; Windecker, Stephan

2016-06-01

Cardiac troponin detected by new-generation, highly sensitive assays predicts clinical outcomes among patients with stable coronary artery disease (SCAD) treated medically. The prognostic value of baseline high-sensitivity cardiac troponin T (hs-cTnT) elevation in SCAD patients undergoing elective percutaneous coronary interventions is not well established. This study assessed the association of preprocedural levels of hs-cTnT with 1-year clinical outcomes among SCAD patients undergoing percutaneous coronary intervention. Between 2010 and 2014, 6974 consecutive patients were prospectively enrolled in the Bern Percutaneous Coronary Interventions Registry. Among patients with SCAD (n=2029), 527 (26%) had elevated preprocedural hs-cTnT above the upper reference limit of 14 ng/L. The primary end point, mortality within 1 year, occurred in 20 patients (1.4%) with normal hs-cTnT versus 39 patients (7.7%) with elevated baseline hs-cTnT (P<0.001). Patients with elevated hs-cTnT had increased risks of all-cause (hazard ratio 5.73; 95% confidence intervals 3.34-9.83; P<0.001) and cardiac mortality (hazard ratio 4.68; 95% confidence interval 2.12-10.31; P<0.001). Preprocedural hs-TnT elevation remained an independent predictor of 1-year mortality after adjustment for relevant risk factors, including age, sex, and renal failure (adjusted hazard ratio 2.08; 95% confidence interval 1.10-3.92; P=0.024). A graded mortality risk was observed across higher tertiles of elevated preprocedural hs-cTnT, but not among patients with hs-cTnT below the upper reference limit. Preprocedural elevation of hs-cTnT is observed in one fourth of SCAD patients undergoing elective percutaneous coronary intervention. Increased levels of preprocedural hs-cTnT are proportionally related to the risk of death and emerged as independent predictors of all-cause mortality within 1 year. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291. © 2016 American Heart Association, Inc.

Effect of acute intraocular pressure elevation on the minimum rim width in normal, ocular hypertensive and glaucoma eyes.

PubMed

Sharma, Sourabh; Tun, Tin A; Baskaran, Mani; Atalay, Eray; Thakku, Sri Gowtham; Liang, Zhang; Milea, Dan; Strouthidis, Nicholas G; Aung, Tin; Girard, Michael Ja

2018-01-01

To estimate and compare changes in the Bruch's membrane opening-minimum rim width (BMO-MRW) and area in normal, ocular hypertensive and glaucoma eyes following acute elevations in intraocular pressure (IOP). The optic nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and 53 with primary glaucoma) were imaged using Spectral-domain optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and ONH was rescanned with OCT. In each OCT volume, BMO-MRW and area were calculated and at each IOP increment. The baseline MRW was significantly smaller in glaucoma subjects (174.3±54.3 µm) compared with normal (287.4±42.2 µm, p<0.001) and OHT subjects (255.4±45.3 µm, p<0.001). MRW of glaucoma subjects was significantly thinner at the first and second IOP elevations than that at baseline (both p<0.01), but no significant change was noted in normal and OHT subjects. There was no significant change of BMO area at acute IOP elevations from baseline in all diagnoses (all p>0.05). Acute IOP elevation leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma subjects only without changing ONH size. This suggests that the neural and connective tissues at ONH level in glaucoma subjects are more susceptible to acute IOP episodes than OHT or normal controls. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

Fiber intake and plasminogen activator inhibitor-1 in type 2 diabetes: Look AHEAD (Action for Health in Diabetes) Trial findings at baseline and 1 year

USDA-ARS?s Scientific Manuscript database

Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes wit...

Can motivational signs prompt increases in incidental physical activity in an Australian health-care facility?

PubMed

Marshall, A L; Bauman, A E; Patch, C; Wilson, J; Chen, J

2002-12-01

This study aimed to evaluate whether a stair-promoting signed intervention could increase the use of the stairs over the elevator in a health-care facility. A time-series design was conducted over 12 weeks. Data were collected before, during and after displaying a signed intervention during weeks 4-5 and 8-9. Evaluation included anonymous counts recorded by an objective unobtrusive motion-sensing device of people entering the elevator or the stairs. Self-report data on stair use by hospital staff were also collected. Stair use significantly increased after the first intervention phase (P = 0.02), but after the intervention was removed stair use decreased back towards baseline levels. Moreover, stair use did not significantly change after the re-introduction of the intervention. Lastly, stair use decreased below the initial baseline level during the final weeks of evaluation. Furthermore, there was no significant change in self-reported stair use by hospital staff. Therefore, the signed intervention aimed at promoting an increase in incidental physical activity produced small brief effects, which were not maintained. Further research is required to find more effective 'point of choice' interventions to increase incidental physical activity participation with more sustainable impact.

Reproductive Hormones Modify Reception of Species-Typical Communication Signals in a Female Anuran

PubMed Central

Lynch, Kathleen S.; Wilczynski, Walter

2008-01-01

In many vertebrates, the production and reception of species-typical courtship signals occurs when gonadotropin and gonadal hormone levels are elevated. These hormones may modify sensory processing in the signal receiver in a way that enhances behavioral responses to the signal. We examined this possibility in female túngara frogs (Physalaemus pustulosus) by treating them with either gonadotropin (which elevated estradiol) or saline and exposing them to either mate choruses or silence. Expression of an activity-dependent gene, egr-1, was quantified within two sub-nuclei of the auditory midbrain to investigate whether gonadotropin plus chorus exposure induced greater egr-1 induction than either of these stimuli alone. The laminar nucleus (LN), a sub-nucleus of the torus semicircularis that contains steroid receptors, exhibited elevated egr-1 induction in response to chorus exposure and gonadotropin treatment. Further analysis revealed that neither chorus exposure nor gonadotropin treatment alone elevated egr-1 expression in comparison to baseline levels whereas gonadotropin + chorus exposure did. This suggests that mate signals and hormones together produce an additive effect so that together they induce more egr-1 expression than either alone. Our previously published studies of female túngara frogs reveal that (1) gonadotropin-induced estradiol elevations also increase behavioral responses to male signals, and (2) reception of male signals elevates estradiol levels in the female. Here, we report data that reveal a novel mechanism by which males exploit female sensory processing to increase behavioral responses to their courtship signals. PMID:18032889

Alternative complement pathway activation during invasive coronary procedures in acute myocardial infarction and stable angina pectoris.

PubMed

Horváth, Zsófia; Csuka, Dorottya; Vargova, Katarina; Kovács, Andrea; Leé, Sarolta; Varga, Lilian; Préda, István; Tóth Zsámboki, Emese; Prohászka, Zoltán; Kiss, Róbert Gábor

2016-12-01

The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n=24), diagnostic coronary angiography (CA, n=52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6h after elective PCI (baseline: 7.81AU/ml, 6h: 16.09AU/ml, 24h: 4.27AU/ml, p<0.01, n=23) and diagnostic angiography (baseline: 6.13AU/ml, 6h: 12.08AU/ml, 24h: 5.4AU/ml, p<0.01, n=52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r=0.41, r=0.4, r=0.3, p<0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33AU/ml vs. 7.81AU/ml or 6.13AU/ml, p<0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49AU/ml vs. 1.87AU/ml, p=0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.

PubMed

van Capelleveen, Julian C; Bernelot Moens, Sophie J; Yang, Xiaohong; Kastelein, John J P; Wareham, Nicholas J; Zwinderman, Aeilko H; Stroes, Erik S G; Witztum, Joseph L; Hovingh, G Kees; Khaw, Kay-Tee; Boekholdt, S Matthijs; Tsimikas, Sotirios

2017-06-01

Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, ( r =0.39), particle numbers of very-low-density lipoprotein ( r =0.25), intermediate-density lipoprotein ( r =0.23), small dense low-density lipoprotein ( r =0.26), and high-sensitivity C-reactive protein ( r =0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number ( r =-0.11), P <0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein. ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association. © 2017 American Heart Association, Inc.

Assessment of adrenocortical reserve capacity and inflammatory parameters in critically ill dogs.

PubMed

Csöndes, Judit; Fábián, Ibolya; Szabó, Bernadett; Máthé, Ákos; Vajdovich, Péter

2017-12-01

Inflammatory markers and adrenocorticotropic hormone (ACTH) stimulation test results may help us recognise critically ill dogs with poor disease outcome. Systemic inflammatory response syndrome (SIRS) criteria, the fast version of the Acute Patient Physiologic and Laboratory Evaluation Score (APPLE fast ), complete blood count, albumin and C-reactive protein (CRP) levels, baseline and stimulated cortisol levels and Δcortisol value were recorded in 50 client-owned dogs admitted to the Small Animal Hospital of the University of Veterinary Medicine Budapest with various inflammatory or neoplastic conditions. Increasing APPLE fast score was associated with a decreasing chance of survival (P = 0.0420). The Δcortisol value was significantly higher in SIRS dogs than in non-SIRS dogs (mean ± SD Δcortisol SIRS : 342.5 ± 273.96; mean ± SD Δcortisol non-SIRS : 175.3 ± 150.35; P = 0.0443). Elevated baseline or stimulated cortisol levels were associated with a higher chance of non-survival (P = 0.0135 and P = 0.0311, respectively). These data indicate that pathologically higher baseline and stimulated cortisol levels represent an exaggerated stress response in critically ill dogs, which is negatively associated with survival.

Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical Trial.

PubMed

Teodorczyk-Injeyan, Julita A; McGregor, Marion; Triano, John J; Injeyan, Stephen H

2018-01-01

The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects. The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process. Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later. Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant (P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group. The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.

Cortisol levels in response to starting school in children at increased risk for social phobia.

PubMed

Russ, Stephanie J; Herbert, Joe; Cooper, Peter; Gunnar, Megan R; Goodyer, Ian; Croudace, Tim; Murray, Lynne

2012-04-01

Research on depression has identified hyperactivity of the HPA axis as a potential contributory factor to the intergenerational transmission of affective symptoms. This has not yet been examined in the context of social phobia. The current study compared HPA axis activity in response to a universal social stressor (starting school) in children of 2 groups of women: one with social phobia and one with no history of anxiety (comparison group). To determine specificity of effects of maternal social phobia, a third group of children were also examined whose mothers had generalised anxiety disorder (GAD). Children provided salivary cortisol samples in the morning, afternoon and at bedtime across 3 time-blocks surrounding the school start: a month before starting school (baseline), the first week at school (stress response), and the end of the first school term (stress recovery). Child behavioural inhibition at 14 months was assessed to explore the influence of early temperament on later stress responses. All children displayed an elevation in morning and afternoon cortisol from baseline during the first week at school, which remained elevated until the end of the first term. Children in the social phobia group, however, also displayed an equivalent elevation in bedtime cortisol, which was not observed for comparison children or for children of mothers with GAD. Children in the social phobia group who were classified as 'inhibited' at 14 months displayed significantly higher afternoon cortisol levels overall. A persistent stress response to school in the morning and afternoon is typical for all children, but children of mothers with social phobia also display atypical elevations in evening cortisol levels when at school--signalling longer-term disruption of the circadian rhythm in HPA axis activity. This is the first study to report HPA axis disruption in children at increased risk of developing social phobia. Future research should determine whether this represents a pathway for symptom development, taking early temperament into account. Copyright © 2011 Elsevier Ltd. All rights reserved.

Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients.

PubMed

Svetlovska, Daniela; Miskovska, Viera; Cholujova, Dana; Gronesova, Paulina; Cingelova, Silvia; Chovanec, Michal; Sycova-Mila, Zuzana; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Kalavska, Katarina; Usakova, Vanda; Luha, Jan; Ondrus, Dalibor; Spanik, Stanislav; Mardiak, Jozef; Mego, Michal

2017-06-01

Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients. This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling and Analysis of Sea-level Rise Impacts on Salinity in the Lower St. Johns River

NASA Astrophysics Data System (ADS)

Bacopoulos, P.

2015-12-01

There is deliberate attention being paid to studying sea-level rise impacts on the lower St. Johns River, a drowned coastal plain-type estuary with low topographic drive, located in northeastern Florida. One area of attention is salinity in the river, which influences the entire food web, including sea and marsh grasses, juvenile crustaceans and fishes, wading birds and migratory waterfowl, marine mammals and other predator animals. It is expected that elevated ocean levels will increase the salinity of the estuarine waters, leading to deleterious effects on dependent species of the river biology. The objective of the modeling and analysis was: 1) to establish baseline conditions of salinity for the lower St. Johns River; and 2) to examine future conditions of salinity, as impacted by sea-level rise. Establishing baseline conditions entailed validation of the model for present-day salinity in the lower St. Johns River via comparison to available data. Examining future conditions entailed application of the model for sea-level rise scenarios, with comparison to the baseline conditions, for evaluation of sea-level rise impacts on salinity. While the central focus was on the physics of sea-level rise impacts on salinity, some level of salinity-biological assessment was conducted to identify sea-level rise/salinity thresholds, as related to negatively impacting different species of the river biology.

IL-1α and MMP-9 Tear Levels of Patients with Active Ocular Rosacea before and after Treatment with Systemic Azithromycin or Doxycycline.

PubMed

Lam-Franco, Lorena; Perfecto-Avalos, Yocanxochitl; Patiño-Ramírez, Beatriz E; Rodríguez García, Alejandro

2018-06-06

The purpose of this paper was to determine the lacrimal concentration of IL-1α and MMP-9 in patients with active ocular rosacea before and after systemic treatment with azithromycin or doxycycline. After 4 weeks of therapy with azithromycin (500 mg/day, 3 days a week PO) or doxycycline (200 mg/day PO), lacrimal samples were analyzed using an enzyme-linked immunosorbent assay multiplex. There was a significant difference between baseline IL-1α (37.9 pg/mL) and MMP-9 (26.7 ng/mL) in rosacea eyes compared to controls (0.001 pg/mL for IL-1α and 0.2 ng/mL for MMP-9) (p < 0.001). IL-1α decreased from 47.0 pg/mL before azithromycin to 23.5 pg/mL after treatment (p = 0.024), but not after doxycycline therapy. On the contrary, baseline MMP-9 tear levels (10.28 ng/mL) decreased after treatment (8.36 pg/mL) with doxycycline (p = 0.054) but not with azithromycin. There was a strong clinical correlation of higher baseline IL-1α tear levels between patients who responded to doxycycline therapy and those who failed (p = 0.043). Patients unresponsive to azithromycin had significantly higher baseline MMP-9 levels than those with doxycycline (p = 0.040). While IL-1α levels decreased after azithromycin therapy, MMP-9 did so after doxycycline treatment. Baseline cytokine tear levels tend to be markedly elevated in patients with antibiotic failure, suggesting their potential role as therapeutic biomarkers for the disease. © 2018 S. Karger AG, Basel.

Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress.

PubMed

Glaser, R; Pearl, D K; Kiecolt-Glaser, J K; Malarkey, W B

1994-01-01

In this study, we explored the possibility that glucocorticoid hormones, known to increase under stress, might be one component of the mechanism involved in induction of latent Epstein Barr virus (EBV). We obtained blood samples from 45 male medical students during examinations and approximately 3-4 weeks before the examinations (baseline) and measured antibody titers to EBV and plasma cortisol levels. We found reproducible changes in EBV, virus capsid antigen (VCA) antibody titers, with higher antibody titers observed in the examination blood samples consistent with the reactivation of latent virus. However, we found no evidence that day and night plasma cortisol values across the sampling points changed significantly from baseline to examinations. Therefore, academic stress did not elevate cortisol levels, but increases in EBV VCA antibody titers were still observed. The data suggest in these subjects that other neuropeptides or hormones were involved in the induction of latent EBV.

Beta-adrenergic stimulation contributes to maintenance of endothelial barrier functions under baseline conditions.

PubMed

Spindler, Volker; Waschke, Jens

2011-02-01

cAMP signaling within the endothelium is known to reduce paracellular permeability and to protect against loss of barrier functions under various pathological conditions. Because activation of β-adrenergic receptors elevates cellular cAMP, we tested whether β-adrenergic receptor signaling contributes to the maintenance of baseline endothelial barrier properties. We compared hydraulic conductivity of rat postcapillary venules in vivo with resistance measurements and with reorganization of endothelial adherens junctions in cultured microvascular endothelial cells downstream of β-adrenergic receptor-mediated changes of cAMP levels. Inhibition of β-adrenergic receptors by propranolol increased hydraulic conductivity, reduced both cAMP levels and TER of microvascular endothelial cell monolayers and induced fragmentation of VE-cadherin staining. In contrast, activation by epinephrine both increased cAMP levels and TER and resulted in linearized VE-cadherin distribution, however this was not sufficient to block barrier-destabilization by propranolol. Similarly, PDE inhibition did not prevent propranolol-induced TER reduction and VE-cadherin reorganization whereas increased cAMP formation by AC activation enhanced endothelial barrier functions under baseline conditions and under conditions of propranolol treatment. Our results indicate that generation of cAMP mediated by activation of β-adrenergic receptor signaling contributes to the maintenance of endothelial barrier properties under baseline conditions. © 2011 John Wiley & Sons Ltd.

HIV proviral DNA associated with decreased neuropsychological function.

PubMed

Shiramizu, Bruce; Paul, Robert; Williams, Andrew; Shikuma, Cecilia; Watters, Michael; Grove, John; Valcour, Victor

2007-01-01

The authors previously found a strong association between elevated HIV proviral DNA (HIV DNA) and a diagnosis of HIV-1-associated dementia (HAD) vs. normal cognition. It is unclear whether HIV DNA globally affects the diagnosis of HAD or whether the effect is limited to individual neuropsychological deficits. This exploratory study examined baseline HIV DNA and its association with individual neuropsychological deficits. HIV DNA was significantly associated with baseline neuropsychological deficits independent of age, ethnicity, IQ, and plasma HIV-1 RNA levels. However, HIV DNA did not predict future changes in neuropsychological deficits. The data suggest that HIV DNA and neuropsychological deficits may co-vary over time.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

PubMed Central

Brandow, Amanda M.; Wandersee, Nancy J.; Dasgupta, Mahua; Hoffmann, Raymond G.; Hillery, Cheryl A.; Stucky, Cheryl L.; Panepinto, Julie A.

2016-01-01

Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment. PMID:27539682

Effects of anthracycline, cyclophosphamide and taxane chemotherapy on QTc measurements in patients with breast cancer.

PubMed

Veronese, Pedro; Hachul, Denise Tessariol; Scanavacca, Mauricio Ibrahim; Hajjar, Ludhmila Abrahão; Wu, Tan Chen; Sacilotto, Luciana; Veronese, Carolina; Darrieux, Francisco Carlos da Costa

2018-01-01

Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values. In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

A randomized controlled double blind investigation of the effects of Vitamin D dietary supplementation in subjects with atopic dermatitis

PubMed Central

Hata, Tissa R.; Audish, David; Kotol, Paul; Coda, Alvin; Kabigting, Filamer; Miller, Jeremiah; Alexandrescu, Doru; Boguniewicz, Mark; Taylor, Patricia; Aertker, Leela; Kesler, Karen; Hanifin, Jon M.; Leung, Donald Y.M.; Gallo, Richard L.

2013-01-01

Background Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production. Objective To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin. Methods This was a multi-center, placebo controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained. Results At baseline, 20% of AD subjects had serum 25OHD below 20 ng/ml. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13, or EASI scores. Conclusions This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted. PMID:23638978

Short-term effects of a high nitrate diet on nitrate metabolism in healthy individuals.

PubMed

Bondonno, Catherine P; Liu, Alex H; Croft, Kevin D; Ward, Natalie C; Puddey, Ian B; Woodman, Richard J; Hodgson, Jonathan M

2015-03-12

Dietary nitrate, through the enterosalivary nitrate-nitrite-NO pathway, can improve blood pressure and arterial stiffness. How long systemic nitrate and nitrite remain elevated following cessation of high nitrate intake is unknown. In 19 healthy men and women, the time for salivary and plasma nitrate and nitrite to return to baseline after 7 days increased nitrate intake from green leafy vegetables was determined. Salivary and plasma nitrate and nitrite was measured at baseline [D0], end of high nitrate diet [D7], day 9 [+2D], day 14 [+7D] and day 21 [+14D]. Urinary nitrite and nitrate was assessed at D7 and +14D. Increased dietary nitrate for 7 days resulted in a more than fourfold increase in saliva and plasma nitrate and nitrite (p < 0.001) measured at [D7]. At [+2D] plasma nitrite and nitrate had returned to baseline while saliva nitrate and nitrite were more than 1.5 times higher than at baseline levels. By [+7D] all metabolites had returned to baseline levels. The pattern of response was similar between men and women. Urinary nitrate and nitrate was sevenfold higher at D7 compared to +14D. These results suggest that daily ingestion of nitrate may be required to maintain the physiological changes associated with high nitrate intake.

Differential responsiveness to a parenting intervention for mothers in substance abuse treatment.

PubMed

Paris, Ruth; Herriott, Anna; Holt, Melissa; Gould, Karen

2015-12-01

This study examines the relationship between levels of psychological distress in substance-dependent mothers and their differential response to a dyadic parent-child intervention. A sample of 66 mothers who were receiving treatment for substance abuse, as well as a simultaneous parenting intervention, were interviewed pre and post-treatment on measures of psychological distress, adult and child trauma history, parental reflective functioning, and child social-emotional development. Additionally, clinicians provided assessments of the parent-child relationships. As anticipated, trauma histories for mothers and children, children's social emotional development, and parental reflective functioning were associated with aspects of maternal psychological distress. Kruskal-Wallis and subsequent Wilcoxson signed rank tests revealed that women with highest levels of baseline psychological distress showed significant improvements in psychological functioning post-treatment while women with moderately elevated levels of psychological distress did not. Women who were most distressed at baseline showed increased levels of parental reflective functioning post-treatment while women with moderate and lower levels of baseline psychological distress showed improvements on clinician-rated assessments of parent-child relationships. Chi Square analyses showed that parents who endorsed the highest levels of distress at baseline reported that their children's risk status regarding social-emotional development decreased post-treatment. Despite similarities in substance dependence, mothers in this sample had different needs and outcomes in the context of this parenting intervention due to variation in mental health. Given this variation, parenting interventions for substance-dependent mothers need to account for the individual differences in levels of psychological distress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.

PubMed

Toth, Peter P; Catapano, Alberico L; Farnier, Michel; Foody, Joanne; Tomassini, Joanne E; Jensen, Erin; Polis, Adam B; Hanson, Mary E; Musliner, Thomas A; Tershakovec, Andrew M

2016-12-15

Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy. Copyright © 2016 The Authors and Merck Sharp & Dohme Corp. Published by Elsevier Inc. All rights reserved.

Comparison of Acarbose and Metformin on Albumin Excretion in Patients With Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Trial.

PubMed

Pan, Qingrong; Xu, Yuan; Yang, Ning; Gao, Xia; Liu, Jia; Yang, Wenying; Wang, Guang

2016-04-01

Increased urinary albumin excretion in diabetes not only signals nephropathy but also serves as a risk marker for cardiovascular disease. The data of MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) trial demonstrated that acarbose and metformin were similarly efficacious at lowering blood glucose and blood pressure, as well as improving insulin sensitivity in Chinese patients newly diagnosed with type 2 diabetes mellitus. The purpose of this study was to identify the effects of acarbose and metformin therapy on albumin excretion in MARCH study.Baseline urine albumin/creatinine ratio (ACR) of 762 newly diagnosed, drug-naïve patients with type 2 diabetes mellitus was measured. Included patients were randomized to receive either acarbose or metformin and followed for 48 weeks. In addition to change in ACR, the estimated glomerular filtration rates (eGFR) and frequency of metabolic syndrome (MetS) were also assessed.Elevated ACR levels (≥30 mg/g) were present at baseline in 21.9% of all participants. A significant decline in urine ACR was observed in both the acarbose and metformin groups at week 24 and 48 (all P < 0.001). The proportion of patients with elevated ACRs was also reduced in both treatment groups at week 24 and 48 compared with baseline values (all P < 0.05). The change in urine ACR at week 48 was significantly greater in patients prescribed acarbose than in those prescribed metformin (P = 0.01). Both acarbose and metformin significantly decreased the frequency of MetS at week 24 and 48 (both P < 0.05). Neither treatment affected eGFR.In sum, both acarbose and metformin decreased urine ACR levels and reduced the frequency of elevated ACR and MetS in Chinese patients with newly diagnosed type 2 diabetes mellitus without affecting eGFR. After 48 weeks' intervention, acarbose therapy resulted in a greater reduction in urine ACR compared with metformin.

Comparison of Acarbose and Metformin on Albumin Excretion in Patients With Newly Diagnosed Type 2 Diabetes

PubMed Central

Pan, Qingrong; Xu, Yuan; Yang, Ning; Gao, Xia; Liu, Jia; Yang, Wenying; Wang, Guang

2016-01-01

Abstract Increased urinary albumin excretion in diabetes not only signals nephropathy but also serves as a risk marker for cardiovascular disease. The data of MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) trial demonstrated that acarbose and metformin were similarly efficacious at lowering blood glucose and blood pressure, as well as improving insulin sensitivity in Chinese patients newly diagnosed with type 2 diabetes mellitus. The purpose of this study was to identify the effects of acarbose and metformin therapy on albumin excretion in MARCH study. Baseline urine albumin/creatinine ratio (ACR) of 762 newly diagnosed, drug-naïve patients with type 2 diabetes mellitus was measured. Included patients were randomized to receive either acarbose or metformin and followed for 48 weeks. In addition to change in ACR, the estimated glomerular filtration rates (eGFR) and frequency of metabolic syndrome (MetS) were also assessed. Elevated ACR levels (≥30 mg/g) were present at baseline in 21.9% of all participants. A significant decline in urine ACR was observed in both the acarbose and metformin groups at week 24 and 48 (all P < 0.001). The proportion of patients with elevated ACRs was also reduced in both treatment groups at week 24 and 48 compared with baseline values (all P < 0.05). The change in urine ACR at week 48 was significantly greater in patients prescribed acarbose than in those prescribed metformin (P = 0.01). Both acarbose and metformin significantly decreased the frequency of MetS at week 24 and 48 (both P < 0.05). Neither treatment affected eGFR. In sum, both acarbose and metformin decreased urine ACR levels and reduced the frequency of elevated ACR and MetS in Chinese patients with newly diagnosed type 2 diabetes mellitus without affecting eGFR. After 48 weeks’ intervention, acarbose therapy resulted in a greater reduction in urine ACR compared with metformin. PMID:27057866

Examination of moderators of expressive writing in patients with renal cell carcinoma: the role of depression and social support.

PubMed

Milbury, Kathrin; Lopez, Gabriel; Spelman, Amy; Wood, Christopher; Matin, Surena F; Tannir, Nizar M; Jonasch, Eric; Pisters, Louis; Wei, Qi; Cohen, Lorenzo

2017-09-01

To identify groups most likely to benefit from an Expressive Writing (EW) intervention, we examined psychosocial variables as intervention moderators. We hypothesized that EW would be particularly effective for participants with high levels of depressive symptoms and social support at study entry. Patients (n = 277; 60.6% male) with kidney cancer were randomly assigned to either an expressive (EW) or neutral writing (NW) condition. Intervention outcomes included measures of depressive symptoms (CESD), cancer-related symptoms (MDASI), fatigue (BFI), and sleep disturbances (PSQI) assessed at baseline, 1, 4, and 10 months later. Moderators were measured at baseline. As hypothesized, depressive symptoms and social support moderated intervention efficacy. When examining both moderators simultaneously, EW appeared to be most effective in terms of cancer-related symptoms (p < 0.05) and depressive symptoms (p < 0.01) for participants with elevated depressive symptoms who received high levels of social support at baseline relative to their counterparts in the NW condition. Moreover, participants in EW with high levels of social support at baseline reported lower levels sleep disturbances (p = 0.005) than their counterparts in NW. Recognition of baseline depressive symptoms and social support as intervention moderators may lead to improved patient selection for EW interventions, as EW may be particularly beneficial regarding QOL outcomes for patients that have social support available including participants with depressive symptoms. EW may not be beneficial, or potentially even contraindicated, for participants lacking social support. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of vitamin A and vitamin C supplementation on oxidative stress in HIV and HIV-TB co-infection at Lagos University Teaching Hospital (LUTH) Nigeria.

PubMed

Makinde, Oluwamayowa; Rotimi, Kunle; Ikumawoyi, Victor; Adeyemo, Titilope; Olayemi, Sunday

2017-06-01

HIV and TB infections are both associated with elevated oxidative stress parameters. Anti-oxidant supplementation may offer beneficial effects in positively modulating oxidative stress parameters in HIV and HIV-TB infected patients. We investigated the effects of vitamin A and C supplementation on oxidative stress in HIV infected and HIV-TB co-infected subjects. 40 HIV/TB co-infected and 50 HIV mono-infected patients were divided into 2 equal groups. Participants provided demographic information and blood was collected to determine oxidative stress parameters before and after vitamin A (5000 IU) and C (2600 mg) supplementation for 1 month. There was a significantly (p < 0.05) higher level of Malondialdehyde (MDA) at baseline for HIV infected subjects compared with HIV-TB co-infected subjects. There was a significantly (p < 0.05) lower level of MDA and higher level of Catalase (CAT) in subjects administered supplementation compared to subjects without supplementation for the HIV infected group. There was a significantly lower level of Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and higher level of MDA after one month of supplementation compared with baseline levels for HIV/TB co infected subjects. A similar result was also obtained for the HIV mono-infected groups which had a significantly lower level of SOD, MDA and CAT compared to the baseline. There was a significantly lower level of GSH and SOD, and higher level of MDA after supplementation compared with the baseline for HIV/TB co-infected subjects. Comparing the indices at baseline and post no-supplementation in HIV/TB co-infection showed no significant differences in the oxidative stress parameters. HIV/TB co-infection and HIV mono-infection seems to diminish the capacity of the anti-oxidant system to control oxidative stress, however exogenous anti-oxidant supplementation appears not to have beneficial roles in positively modulating the associated oxidative stress.

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

PubMed

Lin, Victor C; Liao, Chun-Hou; Wang, Chung-Cheng; Kuo, Hann-Chorng

2015-09-01

Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients. Copyright © 2013. Published by Elsevier B.V.

Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage.

PubMed

Sato, Shoichiro; Delcourt, Candice; Zhang, Shihong; Arima, Hisatomi; Heeley, Emma; Zheng, Danni; Al-Shahi Salman, Rustam; Stapf, Christian; Tzourio, Christophe; Robinson, Thompson; Lindley, Richard I; Chalmers, John; Anderson, Craig S

2016-01-01

This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. © 2015 S. Karger AG, Basel.

Depressive Symptoms and Inductive Reasoning Performance: Findings from the ACTIVE Reasoning Training Intervention

PubMed Central

Parisi, Jeanine M.; Franchetti, Mary Kathryn; Rebok, George W.; Spira, Adam P.; Carlson, Michelle C.; Willis, Sherry L.; Gross, Alden L.

2015-01-01

Within the context of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, we examined the longitudinal association of baseline depressive symptoms on inductive reasoning performance over a ten-year period between the reasoning training and control conditions (N = 1,375). At baseline, 322 participants (23%) reported elevated depressive symptoms, defined by a score ≥ 9 on the Center for Epidemiological Studies Depression scale (12-item). Differences in baseline depressive status were not associated with immediate post-training gains or with subsequent annual change in reasoning performance, suggesting that the presence of elevated baseline depressive symptoms does not impact the ability to benefit from reasoning training. PMID:25244465

VLBI geodesy - 2 parts-per-billion precision in length determinations for transcontinental baselines

NASA Technical Reports Server (NTRS)

Davis, J. L.; Herring, T. A.; Shapiro, I. I.

1988-01-01

VLBI was to make twenty-two independent measurements, between September 1984 and December 1986, of the length of the 3900-km baseline between the Mojave site in California and the Haystack/Westford site in Massachusetts. These experiments differ from the typical geodetic VLBI experiments in that a large fraction of observations is obtained at elevation angles between 4 and 10 deg. Data from these low elevation angles allow the vertical coordinate of site position, and hence the baseline length, to be estimated with greater precision. For the sixteen experiments processed thus far, the weighted root-mean-square scatter of the estimates of the baseline length is 8 mm.

Effect of an acute bout of aerobic exercise on chemerin levels in obese adults

PubMed Central

Lloyd, Jesse W.; Evans, Kristin A.; Zerfass, Kristy M.; Holmstrup, Michael E.; Kanaley, Jill A.; Keslacy, Stefan

2015-01-01

AIMS Serum chemerin concentrations are elevated in obese individuals and may play a role in type 2 diabetes. Exercise improves insulin sensitivity, which may be related to changes in chemerin. This study explored how an acute bout of aerobic exercise affected chemerin levels in non-diabetic obese adults. METHODS Blood samples from 11 obese adults were obtained during two separate conditions: sedentary (SED) and exercise (EX; 60-65% VO2peak). Samples were drawn at baseline, immediately following exercise and hourly for an additional 2 hours. ANOVA was used to test for differences in chemerin between conditions. RESULTS Unadjusted analysis showed no difference in overall change (baseline to 2 hrs post) in chemerin between conditions. During the 2-hr post-exercise period, chemerin decreased to 12% below baseline, compared to a 2.5% increase above baseline during that time period on the sedentary day (p=0.06, difference in post-to-2hr change between conditions). Controlling for homeostatic model assessment of insulin resistance (HOMA-IR), a significant difference existed between EX and SED in the change in chemerin from baseline to 2-hr post (p=0.02). Stratified analyses showed a consistent exercise-induced decrease in chemerin among non-insulin resistant subjects, while chemerin increased during exercise among insulin resistant subjects, and then decreased post-exercise. CONCLUSION An acute bout of exercise in obese individuals may elicit a drop in chemerin levels during the post-exercise period, and this response may vary based on insulin resistance. PMID:26008676

Cardiovascular and metabolic activity at rest and during psychological and physical challenge in normotensives and subjects with mildly elevated blood pressure.

PubMed

Sims, J; Carroll, D

1990-03-01

Heart rate, systolic and diastolic blood pressure, and respiratory and metabolic activity were recorded prior to and during mental arithmetic and a video game task in 20 young men with mildly elevated casual systolic blood pressures. Twenty-five unambiguously normotensive young men were tested under the same protocol. For pretask baseline physiological activity, group differences emerged for all cardiovascular and metabolic variables; thus the elevated blood pressure group displayed not only higher resting cardiovascular levels than normotensive subjects, but higher levels of metabolic activity too. With regard to change in physiological activity from rest to task, the group with mildly elevated blood pressure showed reliably larger increases in heart rate to the mental arithmetic task than the normotensive subjects. These effects, however, were not paralleled by group differences in metabolic activity increase. Physiological measures were also taken prior to and during graded dynamic exercise. The subsequent calculation of individual heart rate-oxygen consumption exercise regression lines allowed the comparison of actual and predicted heart rates during psychological challenge. The subjects with mildly elevated blood pressure displayed significantly greater discrepancies between actual and predicted heart rate values than normotensives during the psychological tasks in general and mental arithmetic in particular. Group differences in physiological activity during exercise largely reflected the pattern seen at rest. A possible exception here was systolic blood pressure. Not only were systolic blood pressure levels higher throughout the exercise phase for mildly elevated blood pressure subjects, but this group evidenced more of an increase from rest to exercise than the normotensives.

Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team

NASA Technical Reports Server (NTRS)

Robertson, D.; Shannon, J. R.; Biaggioni, I.; Ertl, A. C.; Diedrich, A.; Carson, R.; Furlan, R.; Jacob, G.; Jordan, J.

2000-01-01

Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.

[A prospective follow-up study on the association between serum level of C-reactive protein and risk of digestive system cancers in Chinese women].

PubMed

Wang, G; Cao, L Y; Chen, S H; Xie, S H; Feng, X S; Lyu, Z Y; Guo, L W; Li, F; Su, K; Chang, S; Ren, J S; Dai, M; Li, N; Wu, S L; He, J

2016-11-23

Objective: It has been reported by some prospective studies that C-reactive protein (CRP) is associated with cancer risk. However, the correlation between CRP and digestive system cancers has not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated level of CRP in serum is associated with an increased risk of digestive system cancers in Chinese women. Methods: From the Chinese Kailuan Female Cohort, 19, 437 women were enrolled in this study in July 2006, and all of the subjects were followed up through 2014. At the baseline investigation, the serum levels of high-sensitivity CRP (hsCRP) were tested for all subjects, and demographic information and risk factor data were collected. Multivariable Cox proportional hazards regression model was used to calculate the hazard ratios ( HR ) and 95% confidence intervals (95% CI ) for the baseline levels of hsCRP after adjusting for age, marital status, smoking, drinking, body mass index (BMI), diabetes and physical activity, and risk of digestive system tumors (including colorectal cancer, stomach cancer, pancreas cancer, liver and gallbladder cancer, and other cancers). Results: By Dec 31, 2014, a total of 100 incident cancer cases were observed, including 47 colorectal cancers, 17 stomach cancers, and altogether 29 pancreas, liver and gallbladder cancers. All the subjects investigated were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The 8-year cumulative incidence of digestive system cancers were 405/100 000, 520/100 000 and 787/100 000 in these 3 groups, respectively (Log rank test χ 2 = 8.37, P =0.015). Compared to those with lower hsCRP levels (<1 mg/L), the women with higher hsCRP (>3 mg/L) had a significantly increased risk of pancreas, liver and gallbladder cancers ( HR = 2.70, 95% CI = 1.06-6.91; P trend = 0.036). Conclusions: Elevated levels of hsCRP at baseline may be associated with increased risk of certain digestive system cancers.

Vitamin C treatment reduces elevated C-reactive protein

PubMed Central

Block, Gladys; Jensen, Christopher D.; Dalvi, Tapashi B.; Norkus, Edward P.; Hudes, Mark; Crawford, Patricia B.; Holland, Nina; Fung, Ellen B.; Schumacher, Laurie; Harmatz, Paul

2009-01-01

Plasma C-reactive protein (CRP) is an inflammatory biomarker that predicts cardiovascular disease. We investigated whether vitamins C or E could reduce CRP. Healthy nonsmokers (n=396) were randomized to three groups:1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for two months. Median baseline CRP was low, 0.85 mg/L. No treatment effect was seen when all participants are included. However, significant interaction was found, indicating that treatment effect depends on baseline CRP concentration. Among participants with CRP indicative of elevated cardiovascular risk (≥1.0 mg/L), vitamin C reduced median CRP by 25.3% vs. Placebo (p=0.02), (median reduction in the vitamin C group, 0.25 mg/L, 16.7%). These effects are similar to those of statins. The vitamin E effect was not significant. In summary, treatment with vitamin C but not E significantly reduced CRP among individuals with CRP ≥ 1.0 mg/L. Among the obese, 75% had CRP ≥ 1.0 mg/L. These data extend previous results in smokers, and identify CRP levels susceptible to reductions. Research is needed to determine whether reducing this inflammatory biomarker with vitamin C could reduce diseases associated with obesity. But research on clinical benefits of antioxidants should limit participants to persons with elevations in the target biomarkers. PMID:18952164

Relationships Between Baseline Q Waves, Time From Symptom Onset, and Clinical Outcomes in ST-Segment-Elevation Myocardial Infarction Patients: Insights From the Vital Heart Response Registry.

PubMed

Zheng, Yinggan; Bainey, Kevin R; Tyrrell, Benjamin D; Brass, Neil; Armstrong, Paul W; Welsh, Robert C

2017-11-01

Using a comprehensive ST-segment-elevation myocardial infarction registry, we evaluated the relationships of baseline Q waves, time from symptom onset, and reperfusion strategy with in-hospital clinical outcomes. Consecutive ST-segment-elevation myocardial infarction patients from a defined health region were classified by the presence of baseline Q waves and additionally into primary percutaneous coronary intervention, fibrinolysis, or no reperfusion. ECGs were collected at baseline, after reperfusion, and analyzed for the presence of Q waves using Selvester criteria. Among 2290 ST-segment-elevation myocardial infarction patients, 36.9% had Q waves on their baseline ECG. Patients with Q waves were older (median age, 59 versus 57), were more often male (82.0% versus 75.4%), had higher heart rate (80 versus 72), had higher Global Registry of Acute Coronary Events risk score (129 versus 127), and were with longer time to reperfusion (42 minutes longer). They had higher composite end points (16.3% versus 10.0%), consistent across times from symptom onset to presentation (15.4% versus 9.9% ≤3 hours; 18.5% versus 8.9% >3 to ≤6 hours; 15.9% versus 11.3% >6 hours; Q and no Q, respectively). Baseline Q waves, but not time to reperfusion, were associated with an increased odds of the in-hospital composite end point of death, congestive heart failure, cardiogenic shock, and reinfarction (adjusted odds ratio, 1.65; 95% confidence interval, 1.18-2.30; P =0.003). Type of reperfusion did not modify the association of baseline Q waves and in-hospital outcomes ( P interaction=0.918). The presence of baseline Q waves, rather than time to treatment, was significantly associated with adverse in-hospital events in real-world patients, regardless of reperfusion strategy used. © 2017 American Heart Association, Inc.

Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

PubMed Central

Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

2014-01-01

Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

Hypercortisolism as a potential concern for submariners.

PubMed

Reini, Seth A

2010-12-01

Cortisol is a stress-response hormone that is important for survivability in fight or flight situations. Hypercortisolism is a state of chronically elevated cortisol levels due to a failure to return to, or maintain baseline levels. It is a condition that is often undiagnosed and can aid in the development of many physiological and psychological health problems. Some of the health ailments associated with hypercortisolism include metabolic syndrome, decreases in bone mineral density, and depression. Chronic stress and sleep deprivation are two common causes of hypercortisolism, both areas of concern within the submarine community. This review discusses the etiology of hypercortisolism and the likelihood of submariner vulnerability to the condition along with health problems associated with it. Lastly, strategies to prevent chronic elevation of cortisol and mitigate the potential health risks associated with the condition are covered.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

PubMed

Donnino, Michael W; Andersen, Lars W; Chase, Maureen; Berg, Katherine M; Tidswell, Mark; Giberson, Tyler; Wolfe, Richard; Moskowitz, Ari; Smithline, Howard; Ngo, Long; Cocchi, Michael N

2016-02-01

To determine if intravenous thiamine would reduce lactate in patients with septic shock. Randomized, double-blind, placebo-controlled trial. Two US hospitals. Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.

PubMed

Sokolski, Mateusz; Zymliński, Robert; Biegus, Jan; Siwołowski, Paweł; Nawrocka-Millward, Sylwia; Todd, John; Yerramilli, Malli Rama; Estis, Joel; Jankowska, Ewa Anita; Banasiak, Waldemar; Ponikowski, Piotr

2017-06-01

Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'. In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'. Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

A Tele-Behavioral Health Intervention to Reduce Depression, Anxiety, and Stress and Improve Diabetes Self-Management.

PubMed

Mochari-Greenberger, Heidi; Vue, Lee; Luka, Andi; Peters, Aimee; Pande, Reena L

2016-08-01

Depression is prevalent among individuals with diabetes and associated with suboptimal self-management. Little is known about the feasibility and potential impact of tele-behavioral therapy to improve depressive symptoms and self-management among diabetes patients. This was a retrospective observational study of consecutive graduates enrolled in a national 8-week diabetes behavioral telehealth program between August 1, 2014, and January 31, 2015 (N = 466; mean age 56.8 ± 5.0 years; 56% female). Participant characteristics (demographics, comorbidities) were obtained by standardized questionnaire. Depression, anxiety, and stress symptoms (DASS; validated Depression Anxiety and Stress Scale 21 survey), and glucose self-testing frequency and values (point-of-care monitor) were measured at program start and completion. Changes in DASS severity and glucose self-testing frequency were assessed by chi-square tests. Changes in DASS and blood glucose levels were evaluated by paired t-tests. At baseline, approximately one in three participants had elevated depression (32%), anxiety (33%), or stress (31%) scores. Significant reductions in average DASS, depression (-8.8), anxiety (-6.9), and stress (-9.9), scores were observed at graduation among those with elevated baseline scores (p < 0.0001); most (≥80%) improved to less severe depression, anxiety, or stress categories. Improved glucose self-testing frequency (69% vs. 60% tested ≥once per week; p = 0.0005) and significant reductions in mean morning glucose levels (-12.3 mg/dL; p = 0.0002) were observed from baseline to graduation. Participants with normal versus non-normal depression scores were more likely to have lower (

Lack of Methemoglobin Elevations After Topical Applications of Benzocaine Alone or Benzocaine Plus Tetracaine to the Oral Mucosa.

PubMed

Wang, Steven; Giannakopoulos, Helen; Lowstetter, Jamie; Kaye, Laura; Lee, Catherine; Secreto, Stacey; Ho, Vanessa; Hutcheson, Matthew C; Farrar, John T; Wang, Ping; Doyle, Geraldine; Cooper, Stephen A; Hersh, Elliot V

2017-10-01

This study evaluated changes in methemoglobin and oxygen saturation concentrations after the administration of recommended doses of 14% benzocaine alone or 14% benzocaine combined with 2% tetracaine. American Society of Anesthesiology class 1 and 2 subjects (n = 40) were enrolled in this modified crossover study. Subjects were administered 0.2 mL of 14% benzocaine alone, 0.2 mL of 14% benzocaine plus 2% tetracaine, or 0.4 mL of 14% benzocaine plus 0.2% benzocaine to their cheek mucosa. Venous blood (5 mL) was drawn from the antecubital fossa before and 60 minutes after drug application for methemoglobin analyses. Oxygen saturation was also recorded via pulse oximetry at baseline and every 10 minutes through 60 minutes after drug application. Methemoglobin and oxygen saturation levels did not change from baseline after the administration of benzocaine alone or when combined with tetracaine. Recommended doses of benzocaine or benzocaine combined with tetracaine when applied to the cheek mucosa do not induce even clinically insignificant elevations in methemoglobin levels. Metered dosing, such as that used in this study, can help avoid this overdose phenomena with these drugs. ClinicalTrials.gov identifier: NCT02908620. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Apparatuses and methods of determining if a person operating equipment is experiencing an elevated cognitive load

DOEpatents

Watkins, Michael L.; Keller, Paul Edwin; Amaya, Ivan A.

2015-06-16

A method of, and apparatus for, determining if a person operating equipment is experiencing an elevated cognitive load, wherein the person's use of a device at a first time is monitored so as to set a baseline signature. Then, at a later time, the person's use of the device is monitored to determine the person's performance at the second time, as represented by a performance signature. This performance signature can then be compared against the baseline signature to predict whether the person is experiencing an elevated cognitive load.

[ECS guidelines 2016 - dyslipidaemias].

PubMed

Sinning, D; Landmesser, U

2016-12-01

Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies). In patients with a very high risk for cardiovascular events it is recommended to treat to an LDL cholesterol target of less than 70 mg/dl. Moreover, the new guidelines now additionally recommend a > 50% reduction of LDL cholesterol in patients with very high cardiovascular risk patients and baseline levels between 70 and 135 mg/dl as well as in patients with high cardiovascular risk and baseline LDL cholesterol levels between 100 and 200 mg/dl. Statins are recommended as first-line medicinal treatment and the LDL cholesterol goals given imply the more frequent use of maximum tolerated statin therapy, in particular for patients with very high cardiovascular risk. Treatment with ezetimibe in patients with substantially elevated LDL cholesterol levels despite maximum tolerated statin therapy has now received a stronger recommendation (currently IIa recommendation). The guidelines also now include the potential use of the novel proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and a recent ESC/EAS consensus document provides more detailed information on which patients can be considered for treatment with PCSK9 inhibitors, i. e. in particular patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL cholesterol levels despite maximum tolerated statin and ezetimibe therapy.

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

NASA Technical Reports Server (NTRS)

Stout, M. Shannon; Watenpaugh, Donald E.; Breit, Gregory A.; Hargens, Alan R.

1995-01-01

The cutaneous micro-circulation vasodilates during acute 6 deg. head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. We expected that relative magnitudes of and differences between upper and lower body cutaneous blood flow elevation would be sustained during initial acclimation to simulated microgravity. We measured cutaneous micro-vascular blood flow with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean + SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline throughout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg, baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or humoral effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PubMed

Sayyid, Rashid K; Sayyid, Abdallah K; Klaassen, Zachary; Fadaak, Kamel; Goldberg, Hanan; Chandrasekar, Thenappan; Ahmad, Ardalanejaz; Leao, Ricardo; Perlis, Nathan; Chadwick, Karen; Hamilton, Robert J; Kulkarni, Girish S; Finelli, Antonio; Zlotta, Alexandre R; Fleshner, Neil E

2018-01-01

We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Retrieving improved multi-temporal CryoSat elevations over ice caps and glaciers - a case study of Barnes ice cap

NASA Astrophysics Data System (ADS)

Nilsson, Johan; Burgess, David

2014-05-01

The CryoSat mission was launched in 2010 to observe the Earth's cryosphere. In contrast to previous satellite radar altimeters, this mission is expected to monitor the elevation of small ice caps and glaciers, which according to the IPCC will be the largest contributor to 21st century sea level rise. To date the ESA CryoSat SARiN level-2 (L2) elevation product is not yet fully optimized for use over these types of glaciated regions, as its processed with a more universal algorithm. Thus the aim of this study is to demonstrate that with the use of improved processing CryoSat SARiN data can be used for more accurate topography mapping and elevation change detection for ice caps and glaciers. To demonstrate this, elevations and elevation changes over Barnes ice cap, located on Baffin Island in the Canadian Arctic, have been estimated from available data from the years 2010-2013. ESA's CryoSat level-1b (L1b) SARiN baseline "B" data product was used and processed in-house to estimate surface elevations. The resulting product is referred to as DTU-L2. The processing focused on improving the retracker, reducing phase noise and correcting phase ambiguities. The accuracy of the DTU-L2 and the ESA-L2 product was determined by comparing the measured elevations against NASA's IceBridge Airborne Topographic Mapper (ATM) elevations from May 2011. The resulting difference in accuracy was determined by comparing their associated errors. From the multi-temporal measurements spanning the period 2010-2013, elevation changes where estimated and compared to ICESat derived changes from 2003-2009. The result of the study shows good agreement between the NASA measured ATM elevations and the DTU-L2 data. It also shows that the pattern of elevation change is similar to that derived from ICESat data. The accuracy of the DTU-L2 estimated elevations is on average several factors higher compared to the ESA-L2 elevation product. These preliminary results demonstrates that CryoSat elevation data, using improved processing, can be used for accurate topographic mapping and elevation change detection on ice caps and glaciers. Future work would entail extending this processing to other regions of this type to support these results.

Association of body mass index with amnestic and non-amnestic mild cognitive impairment risk in elderly.

PubMed

Wang, Feng; Zhao, Minghui; Han, Zhaoli; Li, Dai; Zhang, Shishuang; Zhang, Yongqiang; Kong, Xiaodong; Sun, Ning; Zhang, Qiang; Lei, Ping

2017-09-15

Previous studies focused on the relationship between body mass index and cognitive disorder and obtained many conflicting results. This study explored the potential effects of body mass index on the risk of mild cognitive impairment (amnestic and non-amnestic) in the elderly. The study enrolled 240 amnestic mild cognitive impairment patients, 240 non-amnestic mild cognitive impairment patients and 480 normal cognitive function controls. Data on admission and retrospective data at baseline (6 years ago) were collected from their medical records. Cognitive function was evaluated using Mini-Mental State Examination and Montreal Cognitive Assessment. Being underweight, overweight or obese at baseline was associated with an increased risk of amnestic mild cognitive impairment (OR: 2.30, 95%CI: 1.50 ~ 3.52; OR: 1.74, 95%CI: 1.36 ~ 2.20; OR: 1.71, 95%CI: 1.32 ~ 2.22, respectively). Being overweight or obese at baseline was also associated with an increased risk of non-amnestic mild cognitive impairment (OR: 1.51, 95%CI: 1.20 ~ 1.92; OR: 1.52, 95%CI: 1.21 ~ 1.97, respectively). In subjects with normal weights at baseline, an increased or decreased body mass index at follow-up was associated with an elevated risk of amnestic mild cognitive impairment (OR: 1.80, 95%CI: 1.10 ~ 3.05; OR: 3.96, 95%CI: 2.88 ~ 5.49, respectively), but only an increased body mass index was associated with an elevated risk of non-amnestic mild cognitive impairment (OR: 1.71, 95%CI: 1.16 ~ 2.59). Unhealthy body mass index levels at baseline and follow-up might impact the risk of both types of mild cognitive impairment (amnestic and non-amnestic).

Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

PubMed

Nanno, Yoshihide; Toyama, Hirochika; Matsumoto, Ippei; Otani, Kyoko; Asari, Sadaki; Goto, Tadahiro; Ajiki, Tetsuo; Zen, Yoh; Fukumoto, Takumi; Ku, Yonson

The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. Copyright © 2016. Published by Elsevier B.V.

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Tumor type M2 pyruvate kinase expression in advanced breast cancer.

PubMed

Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, P E; Wernecke, K D; Possinger, K

2000-01-01

Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls. Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA). In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly. Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.

Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2.

PubMed

Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Hirakawa, Yoichiro; Wang, Xia; Woodward, Mark; Robinson, Thompson; Stapf, Christian; Parsons, Mark; Lavados, Pablo M; Huang, Yining; Wang, Jiguang; Chalmers, John; Anderson, Craig S

2015-02-03

To investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH). INTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150-220 mm Hg) who were allocated to receive intensive (target SBP <140 mm Hg within 1 hour, with lower limit of 130 mm Hg for treatment cessation) or guideline-recommended (target SBP <180 mm Hg) BP-lowering treatment. Outcome was physical function across all 7 levels of the modified Rankin Scale at 90 days. Analysis of the randomized comparisons showed that intensive BP lowering produced comparable benefits on physical function at 90 days in 5 subgroups defined by baseline SBP of <160, 160-169, 170-179, 180-189, and ≥190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1-24 hours) and acute (2-7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg. Intensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130-139 mm Hg is likely to provide maximum benefit in acute ICH. This study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP. © 2014 American Academy of Neurology.

Elevating Baseline Activation Does Not Facilitate Reading of Unattended Words

NASA Technical Reports Server (NTRS)

Lien, Mei-Ching; Kouchi, Scott; Ruthruff, Eric; Lachter, Joel B.

2009-01-01

Previous studies have disagreed the extent to which people extract meaning from words presented outside the focus of spatial attention. The present study, examined a possible explanation for such discrepancies, inspired by attenuation theory: unattended words can be read more automatically when they have a high baseline level of activation (e.g., due to frequent repetition or due to being expected in a given context). We presented a brief prime word in lowercase, followed by a target word in uppercase. Participants indicated whether the target word belonged to a particular category (e.g., "sport"). When we drew attention to the prime word using a visual cue, the prime produced substantial priming effects on target responses (i.e., faster responses when the prime and target words were identical or from the same category than when they belonged to different categories). When prime words were not attended, however, they produced no priming effects. This finding replicated even when there were only 4 words, each repeated 160 times during the experiment. Even with a very high baseline level of activation, it appears that very little word processing is possible without spatial attention.

Stimulus-dependent changes of extracellular glucose in the rat hippocampus determined by in vivo microdialysis.

PubMed

Rex, A; Bert, B; Fink, H; Voigt, J-P

2009-10-19

Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

L-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study.

PubMed

Florentin, M; Elisaf, M S; Rizos, C V; Nikolaou, V; Bilianou, E; Pitsavos, C; Liberopoulos, E N

2017-01-01

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. L-Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of L-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive L-carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the L-carnitine/simvastatin group [-19.4%, from 52 (20-171) to 42 (15-102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [-6.7%, from 56 (26-108) to 52 (27-93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B and TAG were observed in both groups. Co-administration of L-carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels.

The Effects of Niacin on Inflammation in Patients with Non-ST Elevated Acute Coronary Syndrome

PubMed Central

Karacaglar, Emir; Atar, Ilyas; Altin, Cihan; Yetis, Begum; Cakmak, Abdulkadir; Bayraktar, Nilufer; Coner, Ali; Ozin, Bulent; Muderrisoglu, Haldun

2015-01-01

Background In this study, we aimed to evaluate the effects of niacin on high sensitivity C reactive protein (hs-CRP) and cholesterol levels in non-ST elevated acute coronary syndrome (NSTE-ACS) patients. Methods In this prospective, open label study, 48 NSTE-ACS were randomized to niacin or control group. Patients continued their optimal medical therapy in the control group. In the niacin group patients were assigned to receive extended-release niacin 500 mg/day. Patients were contacted 1 month later to assess compliance and side effects. Blood samples for hs-CRP were obtained upon admittance to the coronary care unit, in the third day and in the first month of the treatment. Fasting blood samples for cholesterol levels were obtained before and 30 days after the treatment. The primary end point of the study was to evaluate changes in hs-CRP, cholesterol levels, short-term cardiovascular events, and the safety of niacin in NSTE-ACS. Results Baseline demographic, clinical and laboratory characteristics were similar between the two groups. Logarithmic transformation of baseline and 3rd day hs-CRP levels were similar between the groups; but 1 month later, logarithmic transformation of hs-CRP level was significantly lower in the niacin group (0.43 ± 0.39 to 0.83 ± 0.91, p = 0.04). HDL-C level was significantly increased in the niacin group during follow-up. Drug related side effects were seen in 7 patients in the niacin group but no patients discontinued niacin. Conclusions Our findings demonstrate that lower dose extended release niacin can be used safely and decreases hs-CRP and lipid parameters successfully in NSTE-ACS patients. PMID:27122858

Short-Term Effects of a High Nitrate Diet on Nitrate Metabolism in Healthy Individuals

PubMed Central

Bondonno, Catherine P.; Liu, Alex H.; Croft, Kevin D.; Ward, Natalie C.; Puddey, Ian B.; Woodman, Richard J.; Hodgson, Jonathan M.

2015-01-01

Dietary nitrate, through the enterosalivary nitrate-nitrite-NO pathway, can improve blood pressure and arterial stiffness. How long systemic nitrate and nitrite remain elevated following cessation of high nitrate intake is unknown. In 19 healthy men and women, the time for salivary and plasma nitrate and nitrite to return to baseline after 7 days increased nitrate intake from green leafy vegetables was determined. Salivary and plasma nitrate and nitrite was measured at baseline [D0], end of high nitrate diet [D7], day 9 [+2D], day 14 [+7D] and day 21 [+14D]. Urinary nitrite and nitrate was assessed at D7 and +14D. Increased dietary nitrate for 7 days resulted in a more than fourfold increase in saliva and plasma nitrate and nitrite (p < 0.001) measured at [D7]. At [+2D] plasma nitrite and nitrate had returned to baseline while saliva nitrate and nitrite were more than 1.5 times higher than at baseline levels. By [+7D] all metabolites had returned to baseline levels. The pattern of response was similar between men and women. Urinary nitrate and nitrate was sevenfold higher at D7 compared to +14D. These results suggest that daily ingestion of nitrate may be required to maintain the physiological changes associated with high nitrate intake. PMID:25774606

Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

PubMed

Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

2014-02-01

Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulse oximetry in the evaluation of peripheral vascular disease.

PubMed

Jawahar, D; Rachamalla, H R; Rafalowski, A; Ilkhani, R; Bharathan, T; Anandarao, N

1997-08-01

The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD) was investigated. In addition, the value of elevating the limb to improve the sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse oximetry reading in the toes were obtained in 40 young, healthy volunteers and in 40 randomly selected patients referred to the vascular investigation laboratory over a period of two months. All 40 healthy volunteers had normal pulse oximetry readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry readings were either normal or not detected at all. Since there was no gradation in decrease in the pulse oximetry reading with severity of disease or with elevation of the patient's lower extremity, an absent or no reading was considered as an abnormal result from the test. The frequency of abnormal pulse oximetry readings increased significantly in groups with abnormal ankle-brachial pressure index (ABPI) and also varied significantly with elevation of the patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9), pulse oximetry readings were normal in all. However, in patients with moderate PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry readings and 16% had an abnormal reading at baseline level (flat). An additional 12% of the lower limbs in this group had an abnormal reading on elevation of the limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients' lower limbs had an abnormal reading at baseline and an additional 23% had an abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse oximetry was not a sensitive test for detecting early PVD.

Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

PubMed

Almasi, Bettina; Béziers, Paul; Roulin, Alexandre; Jenni, Lukas

2015-09-01

Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits.

Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.

PubMed

Cheong, June-Won; Kim, Hyeoung-Joon; Lee, Kyoo-Hyung; Yoon, Sung-Soo; Lee, Jae Hoon; Park, Hee-Sook; Kim, Ho Young; Shim, Hyeok; Seong, Chu-Myung; Kim, Chul Soo; Chung, Jooseop; Hyun, Myung Soo; Jo, Deog-Yeon; Jung, Chul Won; Sohn, Sang Kyun; Yoon, Hwi-Joong; Kim, Byung Soo; Joo, Young-Don; Park, Chi-Young; Min, Yoo Hong

2014-06-01

Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented. © 2013 AABB.

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

PubMed Central

Doleschall, Márton; Szabó, Julianna Anna; Pázmándi, Júlia; Szilágyi, Ágnes; Koncz, Klára; Farkas, Henriette; Tóth, Miklós; Igaz, Péter; Gláz, Edit; Prohászka, Zoltán; Korbonits, Márta; Rácz, Károly; Patócs, Attila

2014-01-01

Purpose Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels. Methods The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available. Results The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects. Conclusions The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution. PMID:25210767

The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study.

PubMed

Wang, Haoyu; Liu, Aihua; Zhou, Yingying; Xiao, Yue; Yan, Yumeng; Zhao, Tong; Gong, Xun; Pang, Tianxiao; Fan, Chenling; Zhao, Jiajun; Teng, Weiping; Shan, Zhongyan; Lai, Yaxin

2017-09-01

Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.

Levels of fecal corticosterone in sandhill cranes during a human-led migration.

PubMed

Hartup, Barry K; Olsen, Glenn H; Czekala, Nancy M; Paul-Murphy, Joanne; Langenberg, Julia A

2004-04-01

Fourteen captive-reared greater sandhill cranes (Grus canadensis tabida) were conditioned to follow ultralight aircraft to promote migration between Wisconsin and Florida (USA) after release. Fecal samples were collected throughout the training period in Wisconsin and during a l977-km human-led migration to Florida to determine fecal corticosterone (FC) concentrations by radioimmunnoassay. The mean (+/-SE) FC concentration during the training period was 109.5 +/- 7.5 ng/g and was representative of baseline levels recorded previously from sandhill cranes. Fecal corticosterone concentrations increased in early migration compared to concentrations I mo prior to departure (P < 0.01) but were not different from baseline concentrations at tile end of the 6-wk migration period. The variability of FC concentrations in individual samples was greater throughout the migration than the training period. Increases in FC during migration were modest and generally consistent with normal corticosterone elevations observed in migrating birds.

Autotransfusion from experimental hemothorax: levels of coagulation factors.

PubMed

Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

1987-03-01

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

Association of Post-Saline Load Plasma Aldosterone Levels With Left Ventricular Hypertrophy in Primary Hypertension.

PubMed

Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A

2016-03-01

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.

PubMed

Hoffman, Robert W; Merrill, Joan T; Alarcón-Riquelme, Marta M E; Petri, Michelle; Dow, Ernst R; Nantz, Eric; Nisenbaum, Laura K; Schroeder, Krista M; Komocsar, Wendy J; Perumal, Narayanan B; Linnik, Matthew D; Airey, David C; Liu, Yushi; Rocha, Guilherme V; Higgs, Richard E

2017-03-01

To characterize baseline gene expression and pharmacodynamically induced changes in whole blood gene expression in 1,760 systemic lupus erythematosus (SLE) patients from 2 phase III, 52-week, randomized, placebo-controlled, double-blind studies in which patients were treated with the BAFF-blocking IgG4 monoclonal antibody tabalumab. Patient samples were obtained from SLE patients from the ILLUMINATE-1 and ILLUMINATE-2 studies, and control samples were obtained from healthy donors. Blood was collected in Tempus tubes at baseline, week 16, and week 52. RNA was analyzed using Affymetrix Human Transcriptome Array 2.0 and NanoString. At baseline, expression of the interferon (IFN) response gene was elevated in patients compared with controls, with 75% of patients being positive for this IFN response gene signature. There was, however, substantial heterogeneity of IFN response gene expression and complex relationships among gene networks. The IFN response gene signature was a predictor of time to disease flare, independent of anti-double-stranded DNA (anti-dsDNA) antibody and C3 and C4 levels, and overall disease activity. Pharmacodynamically induced changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin genes, and were consistent with other pharmacodynamic changes including anti-dsDNA antibody, C3, and immunoglobulin levels. SLE patients demonstrated increased expression of an IFN response gene signature (75% of patients had an elevated IFN response gene signature) at baseline in ILLUMINATE-1 and ILLUMINATE-2. Substantial heterogeneity of gene expression was detected among individual patients and in gene networks. The IFN response gene signature was an independent risk factor for future disease flares. Pharmacodynamic changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab. © 2016, American College of Rheumatology.

Unsupportive parenting moderates the effects of family psychosocial intervention on metabolic syndrome in African American youth.

PubMed

Chen, E; Miller, G E; Yu, T; Brody, G H

2018-04-01

Family relationships have been linked to obesity and related disorders in youth, but few studies have provided causal evidence of this association. This study tested the impact of a family psychosocial intervention on components of metabolic syndrome-a condition driven largely by abdominal obesity-in African American youth. In particular, the study tested whether effects were strongest among those who started at highest risk, that is, with high levels of unsupportive parenting at baseline. Randomized clinical trial of a community sample of 391 African American youth (mean age=11.2 years) conducted in 2001-2002, with follow-up metabolic syndrome assessment in 2014-2015. Participants were assigned either to receive a weekly family intervention or to a control group. The primary study outcome was the number of components of metabolic syndrome that were clinically elevated at age 25, including central adiposity, blood pressure, triglycerides, glucose and low high-density lipoproteins. Unsupportive parenting was measured by questionnaires at baseline. Significant interaction effects were found between group assignment and baseline unsupportive parenting on counts of metabolic syndrome components in youth (beta=-0.17, P=0.03). Among those who started with higher levels of unsupportive parenting at age 11, participation in the family intervention reduced the number of clinically elevated components of the metabolic syndrome at age 25 relative to the control group. No such effect was seen among those who started with good parenting. Mediation analyses suggested that changes in the psychosocial targets of the parenting intervention partially accounted for the effects amongst those high in unsupportive parenting at baseline (effect size=-0.350, s.e.=0.178). These findings suggest that efforts to improve family relationships may be able to ameliorate the detrimental effects that harsh and unsupportive parenting have on obesity-related outcomes such as metabolic syndrome in youth.

Unsupportive Parenting Moderates the Effects of Family Psychosocial Intervention on Metabolic Syndrome in African American Youth

PubMed Central

Chen, Edith; Miller, Greg; Yu, Tianyi; Brody, Gene H.

2017-01-01

Background/Objective Family relationships have been linked to obesity and related disorders in youth, but few studies have provided causal evidence of this association. This study tested the impact of a family psychosocial intervention on components of metabolic syndrome – a condition driven largely by abdominal obesity - in African American youth. In particular, the study tested whether effects were strongest among those who started at highest risk, that is, with high levels of unsupportive parenting at baseline. Subjects/Methods Randomized clinical trial of a community sample of 391 African American youth (mean age=11.2 years) conducted in 2001–2002, with follow-up metabolic syndrome assessment in 2014–2015. Participants were assigned either to receive a weekly family intervention or to a control group. The primary study outcome was the number of components of metabolic syndrome that were clinically elevated at age 25, including central adiposity, blood pressure, triglycerides, glucose, and low high-density lipoproteins. Unsupportive parenting was measured by questionnaires at baseline. Results Significant interaction effects were found between group assignment and baseline unsupportive parenting on counts of metabolic syndrome components in youth (beta=−.17, p=.03). Among those who started with higher levels of unsupportive parenting at age 11, participation in the family intervention reduced the number of clinically elevated components of the metabolic syndrome at age 25 relative to the control group. No such effect was seen among those who started with good parenting. Mediation analyses suggested that changes in the psychosocial targets of the parenting intervention partially accounted for the effects amongst those high in unsupportive parenting at baseline (effect size=−.350, se=.178). Conclusions These findings suggest that efforts to improve family relationships may be able to ameliorate the detrimental effects that harsh and unsupportive parenting have on obesity-related outcomes such as metabolic syndrome in youth. PMID:28984843

Divergence of seafloor elevation and sea level rise in coral reef ecosystems

USGS Publications Warehouse

Yates, Kimberly K.; Zawada, David G.; Smiley, Nathan A.; Tiling-Range, Ginger

2017-01-01

Coral reefs serve as natural barriers that protect adjacent shorelines from coastal hazards such as storms, waves, and erosion. Projections indicate global degradation of coral reefs due to anthropogenic impacts and climate change will cause a transition to net erosion by mid-century. Here, we provide a comprehensive assessment of the combined effect of all of the processes affecting seafloor accretion and erosion by measuring changes in seafloor elevation and volume for five coral reef ecosystems in the Atlantic, Pacific, and Caribbean over the last several decades. Regional-scale mean elevation and volume losses were observed at all five study sites and in 77 % of the 60 individual habitats that we examined across all study sites. Mean seafloor elevation losses for whole coral reef ecosystems in our study ranged from −0.09 to −0.8 m, corresponding to net volume losses ranging from 3.4  ×  106 to 80.5  ×  106 m3 for all study sites. Erosion of both coral-dominated substrate and non-coral substrate suggests that the current rate of carbonate production is no longer sufficient to support net accretion of coral reefs or adjacent habitats. We show that regional-scale loss of seafloor elevation and volume has accelerated the rate of relative sea level rise in these regions. Current water depths have increased to levels not predicted until near the year 2100, placing these ecosystems and nearby communities at elevated and accelerating risk to coastal hazards. Our results set a new baseline for projecting future impacts to coastal communities resulting from degradation of coral reef systems and associated losses of natural and socioeconomic resources.

Divergence of seafloor elevation and sea level rise in coral reef ecosystems

NASA Astrophysics Data System (ADS)

Yates, Kimberly K.; Zawada, David G.; Smiley, Nathan A.; Tiling-Range, Ginger

2017-04-01

Coral reefs serve as natural barriers that protect adjacent shorelines from coastal hazards such as storms, waves, and erosion. Projections indicate global degradation of coral reefs due to anthropogenic impacts and climate change will cause a transition to net erosion by mid-century. Here, we provide a comprehensive assessment of the combined effect of all of the processes affecting seafloor accretion and erosion by measuring changes in seafloor elevation and volume for five coral reef ecosystems in the Atlantic, Pacific, and Caribbean over the last several decades. Regional-scale mean elevation and volume losses were observed at all five study sites and in 77 % of the 60 individual habitats that we examined across all study sites. Mean seafloor elevation losses for whole coral reef ecosystems in our study ranged from -0.09 to -0.8 m, corresponding to net volume losses ranging from 3.4 × 106 to 80.5 × 106 m3 for all study sites. Erosion of both coral-dominated substrate and non-coral substrate suggests that the current rate of carbonate production is no longer sufficient to support net accretion of coral reefs or adjacent habitats. We show that regional-scale loss of seafloor elevation and volume has accelerated the rate of relative sea level rise in these regions. Current water depths have increased to levels not predicted until near the year 2100, placing these ecosystems and nearby communities at elevated and accelerating risk to coastal hazards. Our results set a new baseline for projecting future impacts to coastal communities resulting from degradation of coral reef systems and associated losses of natural and socioeconomic resources.

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

PubMed

van den Brand, Jan A J G; Mutsaers, Henricus A M; van Zuilen, Arjan D; Blankestijn, Peter J; van den Broek, Petra H; Russel, Frans G M; Masereeuw, Rosalinde; Wetzels, Jack F M

2016-01-01

To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease.

PubMed

Seydelmann, Nora; Liu, Dan; Krämer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; Störk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

2016-05-31

High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; P<0.001) and slightly elevated hs-TNT (baseline, 44.7 [30.1-65.3] ng/L; follow-up, 49.1 [27.6-69.5] ng/L; P=0.116) during follow-up. Left ventricular wall thickness and EF of patients with elevated hs-TNT were decreased during follow-up, indicating potential cardiomyopathy progression. hs-TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

MOLA-Based Landing Site Characterization

NASA Technical Reports Server (NTRS)

Duxbury, T. C.; Ivanov, A. B.

2001-01-01

The Mars Global Surveyor (MGS) Mars Orbiter Laser Altimeter (MOLA) data provide the basis for site characterization and selection never before possible. The basic MOLA information includes absolute radii, elevation and 1 micrometer albedo with derived datasets including digital image models (DIM's illuminated elevation data), slopes maps and slope statistics and small scale surface roughness maps and statistics. These quantities are useful in downsizing potential sites from descent engineering constraints and landing/roving hazard and mobility assessments. Slope baselines at the few hundred meter level and surface roughness at the 10 meter level are possible. Additionally, the MOLA-derived Mars surface offers the possibility to precisely register and map project other instrument datasets (images, ultraviolet, infrared, radar, etc.) taken at different resolution, viewing and lighting geometry, building multiple layers of an information cube for site characterization and selection. Examples of direct MOLA data, data derived from MOLA and other instruments data registered to MOLA arc given for the Hematite area.

The HBV DNA cutoff value for discriminating patients with HBeAgnegative chronic hepatitis B from inactive carriers.

PubMed

Kim, Eun Sun; Seo, Yeon Seok; Keum, Bora; Kim, Ji Hoon; A, Hyonggin; Yim, Hyung Joon; Kim, Yong Sik; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Um, Soon Ho; Duck Kim, Chang; Ryu, Ho Sang

2011-05-01

Patients with HBeAg-negative chronic hepatitis B (CHB) has a significantly different prognosis than inactive carriers; there is however, no reliable strategy for accurately differentiating these two disease conditions. To determine a strategy for discriminating patients with HBeAg-negative CHB from inactive carriers. Consecutive inactive carriers (i.e. HBeAg-negativity, anti-HBe-positivity, normal ALT levels, and HBV DNA < 2000 IU/mL) were enrolled. HBV reactivation was defined as the elevation of the HBV DNA level to ≥ 2000 IU/mL. Patients were classified into true inactive carriers when their HBV DNA levels remained at < 2000 IU/mL or false inactive carriers when their HBV DNA levels increased to ≥ 2000 IU/mL during the first year. The Mean ± SD age of 208 inactive carriers (140 males) was 47.7 ± 12.6 years. The Mean ± SD serum ALT and HBV DNA levels were 22.8 ± 8.6 IU/L and 360 ± 482 IU/mL, respectively. HBV reactivation developed in 41 (19.7%) patients during the first year. Baseline HBV DNA and ALT levels differed significantly between true inactive and false inactive carriers. The AUROCs of the baseline ALT and HBV DNA levels for predicting a false inactive carrier were 0.609 and 0.831, respectively. HBV reactivation developed more often in patients with a baseline HBV DNA level of ≥ 200 IU/mL than in those with a baseline HBV DNA level of < 200 IU/mL during a Mean ± SD follow-up of 622 ± 199 days. The HBV DNA level was useful for discriminating patients with HBeAg-negative CHB from true inactive carriers. The follow-up strategies applied to inactive carriers need to vary with their HBV DNA levels.

Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery.

PubMed

Modan-Moses, D; Ehrlich, S; Kanety, H; Dagan, O; Pariente, C; Esrahi, N; Lotan, D; Vishne, T; Barzilay, Z; Paret, G

2001-12-01

Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters. Investigative study. University-affiliated tertiary care hospital. Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use. The leptin levels in group 1 decreased during CPB to 51% of baseline (p <.001), then gradually increased, reaching 120% of baseline levels at 12-18 hrs postoperatively (p <.001), returning to baseline levels at 24 hrs (p <.01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p =.002) and showed a tendency to return to baseline thereafter. All group 1 patients' cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18-24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = -2.8, p <.01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p <.05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course. CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.

Variation in testosterone and corticosterone in amphibians and reptiles: relationships with latitude, elevation, and breeding season length.

PubMed

Eikenaar, Cas; Husak, Jerry; Escallón, Camilo; Moore, Ignacio T

2012-11-01

Latitudinal variation in life-history traits has been the focus of numerous investigations, but underlying hormonal mechanisms have received much less attention. Steroid hormones play a central role in vertebrate reproduction and may be associated with life-history trade-offs. Consequently, circulating concentrations of these hormones vary tremendously across vertebrates, yet interspecific geographic variation in male hormone concentrations has been studied in detail only in birds. We here report on such variation in amphibians and reptiles, confirming patterns observed in birds. Using phylogenetic comparative analyses, we found that in amphibians, but not in reptiles, testosterone and baseline corticosterone were positively related to latitude. Baseline corticosterone was negatively related to elevation in amphibians but not in reptiles. For both groups, testosterone concentrations were negatively related to breeding-season length. In addition, testosterone concentrations were positively correlated with baseline corticosterone in both groups. Our findings may best be explained by the hypothesis that shorter breeding seasons increase male-male competition, which may favor increased testosterone concentrations that modulate secondary sexual traits. Elevated energetic demands resulting from greater reproductive intensity may require higher baseline corticosterone. Thus, the positive relationship between testosterone and corticosterone in both groups suggests an energetic demand for testosterone-regulated behavior that is met with increased baseline glucocorticoid concentrations.

Moderators of two indicated cognitive-behavioral depression prevention approaches for adolescents in a school-based effectiveness trial.

PubMed

Brière, Frédéric N; Rohde, Paul; Shaw, Heather; Stice, Eric

2014-02-01

Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program (CB group) and CB bibliotherapy, relative to an educational brochure control condition and to one another, in a school-based effectiveness randomized controlled prevention trial. 378 adolescents (M age = 15.5, 68% female) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest, posttest, and 6-month follow-up. We tested the moderating effect of three individual (baseline depressive symptoms, negative attributional style, substance use), three environmental (negative life events, parental support, peer support), and two sociodemographic (sex, age) characteristics. Baseline depressive symptoms interacted with condition and time. Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest (but not 6-month follow-up) relative to the control condition, but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy. Specifically, CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated, but not average or low baseline symptoms. We found no interaction effect for other putative moderators. Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline. The fact that no study variable moderated the effects of CB group, which had a significant main effect in reducing depressive symptoms relative to the control condition, suggests that this indicated prevention intervention is effective for a wide range of adolescents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Moderators of two Indicated Cognitive-Behavioral Depression Prevention Approaches for Adolescents in a School-Based Effectiveness Trial

PubMed Central

Brière, Frédéric N.; Rohde, Paul; Shaw, Heather; Stice, Eric

2014-01-01

Objective Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program (CB group) and CB bibliotherapy, relative to an educational brochure control condition and to one another, in a school-based effectiveness randomized controlled prevention trial. Method 378 adolescents (M age = 15.5, 68% female) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest, posttest, and 6-month follow-up. We tested the moderating effect of three individual (Baseline Depressive Symptoms, Negative Attributional Style, Substance Use), three environmental (Negative Life Events, Parental Support, Peer Support), and two sociodemographic (Sex, Age) characteristics. Results Baseline Depressive Symptoms interacted with Condition and Time. Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest (but not 6-month follow-up) relative to the control condition, but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy. Specifically, CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated, but not average or low baseline symptoms. We found no interaction effect for other putative moderators. Conclusions Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline. The fact that no study variable moderated the effects of CB group, which had a significant main effect in reducing depressive symptoms relative to the control condition, suggests that this indicated prevention intervention is effective for a wide range of adolescents. PMID:24418653

Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma.

PubMed

Noah, Terry L; Tudor, Gail E; Ivins, Sally S; Murphy, Paula C; Peden, David B; Henderson, Frederick W

2006-02-01

Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium. To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline. We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls. In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients. Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.

Combination therapy with clomiphene citrate and anastrozole is a safe and effective alternative for hypoandrogenic subfertile men.

PubMed

Alder, Nathan J; Keihani, Sorena; Stoddard, Gregory J; Myers, Jeremy B; Hotaling, James M

2018-06-06

To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow-ups. Treatment side effects were recorded; prostatic-specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t-test and Wilcoxon's signed-rank test. A total of 51 men were included, with a mean age of 35.4 ± 7.4 years and a mean body mass index of 35.0 ± 8.0 kg/m 2 . After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Acetylcholine release in the mesocorticolimbic dopamine system during cocaine seeking: conditioned and unconditioned contributions to reward and motivation.

PubMed

You, Zhi-Bing; Wang, Bin; Zitzman, Dawnya; Wise, Roy A

2008-09-03

Microdialysis was used to assess the contribution to cocaine seeking of cholinergic input to the mesocorticolimbic dopamine system in ventral tegmental area (VTA). VTA acetylcholine (ACh) was elevated in animals lever pressing for intravenous cocaine and in cocaine-experienced and cocaine-naive animals passively receiving similar "yoked" injections. In cocaine-trained animals, the elevations comprised an initial (first hour) peak to approximately 160% of baseline and a subsequent plateau of 140% of baseline for the rest of the cocaine intake period. In cocaine-naive animals, yoked cocaine injections raised ACh levels to the 140% plateau but did not cause the initial 160% peak. In cocaine-trained animals that received unexpected saline (extinction conditions) rather than the expected cocaine, the initial peak was seen but the subsequent plateau was absent. VTA ACh levels played a causal role and were not just a correlate of cocaine seeking. Blocking muscarinic input to the VTA increased cocaine intake; the increase in intake offset the decrease in cholinergic input, resulting in the same VTA dopamine levels as were seen in the absence of the ACh antagonists. Increased VTA ACh levels (resulting from 10 microM VTA neostigmine infusion) increased VTA dopamine levels and reinstated cocaine seeking in cocaine-trained animals that had undergone extinction; these effects were strongly attenuated by local infusion of a muscarinic antagonist and weakly attenuated by a nicotinic antagonist. These findings identify two cholinergic responses to cocaine self-administration, an unconditioned response to cocaine itself and a conditioned response triggered by cocaine-predictive cues, and confirm that these cholinergic responses contribute to the control of cocaine seeking.

Effects of acute temperature change, confinement and housing on plasma corticosterone in water snakes, Nerodia sipedon (Colubridae: Natricinae).

PubMed

Sykes, Kyle Lea; Klukowski, Matthew

2009-03-01

Body temperature affects many aspects of reptilian behavior and physiology, but its effect on hormonal secretion has been little studied, especially in snakes. Major objectives of this study were to determine if acute changes in body temperature during confinement influenced plasma corticosterone levels and if initial body temperatures upon capture in the field were related to baseline corticosterone levels in water snakes (Nerodia sipedon). Water snakes were bled upon capture in the field and after one hour of confinement in a cooled, control, or heated incubator. Since little is known about the potential metabolic changes in response to stress in reptiles, plasma triglyceride levels were also measured. Upon completion of the field study, snakes were housed for 5-8 days without food to determine the effect of chronic stress on both corticosterone and triglyceride levels. Plasma corticosterone concentrations were measured using enzyme-linked immunosorbant assay (ELISA) and plasma triglycerides were determined enzymatically. In the field, experimental alterations of body temperature during confinement had no effect on corticosterone levels. Similarly, there was no correlation between initial body temperature and baseline plasma corticosterone concentrations. However, post-confinement corticosterone levels were approximately three-times greater in females than males. Plasma triglyceride levels were not affected by temperature treatment, confinement, or sex. Compared to field values, both baseline and post-confinement corticosterone levels were elevated after the chronic stress of short-term laboratory housing but triglyceride levels decreased. Overall, these results indicate that sex but not body temperature has a major influence on the adrenocortical stress response in Nerodia sipedon.

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

PubMed Central

Borges, Álvaro H.; O’Connor, Jemma L.; Phillips, Andrew N.; Baker, Jason V.; Vjecha, Michael J.; Losso, Marcelo H.; Klinker, Hartwig; Lopardo, Gustavo; Williams, Ian; Lundgren, Jens D.

2014-01-01

Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. PMID:24626096

Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

PubMed Central

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Fà, Mauro; Gessa, Gian Luigi

2005-01-01

Background Previous studies by our group suggest that extracellular dopamine (DA) and noradrenaline (NA) may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC). This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC), occipital cortex (Occ), and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM) markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT) blocker desipramine (DMI, 100 μM), multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant release of DA and NA in the mPFC and Occ. The different time-course of LC-induced elevation of DA and NA suggests that their co-release may be differentially controlled. PMID:15865626

Mood state sub-types in adults who stutter: A prospective study.

PubMed

Tran, Yvonne; Blumgart, Elaine; Craig, Ashley

2018-06-01

Many adults who stutter have elevated negative mood states like anxiety and depressive mood. Little is known about how mood states change over time. The purpose of this study was to determine the trajectories or sub-types of mood states in adults who stutter over a 6 month period, and establish factors that contribute to these sub-types. Participants included 129 adults who stutter who completed an assessment regimen at baseline, including a measure of mood states (Symptom Checklist-90-Revised). Three mood states were assessed (interpersonal sensitivity or IS, depressive mood and anxiety) once a month over 6 months. Latent class growth mixture modeling was used to establish trajectories of change in these mood states over time. Logistic regression was then used to determine factors assessed at baseline that contribute to the IS trajectories. Three-class trajectory models were accepted as the best fit for IS, depressive mood and anxiety mood sub-types. Stable and normal mood state sub-types were found, incorporating around 60% of participants. Up to 40% belonged to sub-types comprising elevated levels of negative mood states. The logistic regression was conducted only with the IS domain, and revealed four factors that significantly contributed to IS mood sub-types. Those with low perceived control, low vitality, elevated social fears and being female were more likely to belong to elevated IS classes. This research revealed mood sub-types in adults who stutter, providing direction for the treatment of stuttering. Clarification of how much stuttering influences mood sub-types versus pre-existing mood is required. Copyright © 2017 Elsevier Inc. All rights reserved.

Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO.

PubMed

Kapil, Vikas; Milsom, Alexandra B; Okorie, Michael; Maleki-Toyserkani, Sheiva; Akram, Farihah; Rehman, Farkhanda; Arghandawi, Shah; Pearl, Vanessa; Benjamin, Nigel; Loukogeorgakis, Stavros; Macallister, Raymond; Hobbs, Adrian J; Webb, Andrew J; Ahluwalia, Amrita

2010-08-01

Ingestion of dietary (inorganic) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation. In addition, nitrite is a potent vasodilator in humans, an effect thought to underlie the blood pressure-lowering effects of dietary nitrate (in the form of beetroot juice) ingestion. Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain. Using a randomized crossover study design, we show that nitrate supplementation (KNO(3) capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO(3) (1488 mg of nitrate) versus 24 mmol of KCl [n=20]) or vegetable intake (250 mL of beetroot juice [5.5 mmol nitrate] versus 250 mL of water [n=9]) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers. In addition, post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration, whereby blood pressure is decreased in male volunteers, with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers. Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation. In addition, our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women.

Transcapillary fluid shifts in head and neck tissues during and after simulated microgravity

NASA Technical Reports Server (NTRS)

Parazynski, S. E.; Hargens, Alan R.; Tucker, B.; Aratow, M.; Styf, J.; Crenshaw, A.

1991-01-01

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.2 +/- 5 mm Hg pre-HDT to 33.9 +/- 1.7 mm Hg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values, despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr. These results indicate that facial edema resulting from HDT is primarily caused by elevated capillary pressures and decreased plasma colloid osmotic pressures. Elevation of cephalic capillary pressures sustained for 4 hr after HDT suggests that there is a compensatory vasodilation to maintain microvascular perfusion. The negativity of interstitial fluid pressures above heart level also has implications for the maintenance of tissue fluid balance in upright posture.

Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats.

PubMed

Jain, Sushil K; Croad, Jennifer L; Velusamy, Thirunavukkarasu; Rains, Justin L; Bull, Rebeca

2010-09-01

Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 microg Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats.

A study of the prostate, androgens and sexual activity of male rats

PubMed Central

Hernandez, Maria Elena; Soto-Cid, Abraham; Aranda-Abreu, Gonzalo E; Díaz, Rosaura; Rojas, Fausto; Garcia, Luis I; Toledo, Rebeca; Manzo, Jorge

2007-01-01

Background The prostate is a sexual gland that produces important substances for the potency of sperm to fertilize eggs within the female reproductive tract, and is under complex endocrine control. Taking advantage of the peculiar behavioral pattern of copulating male rats, we developed experimental paradigms to determine the influence of sexual behavior on the level of serum testosterone, prostate androgen receptors, and mRNA for androgen receptors in male rats displaying up to four consecutive ejaculations. Methods The effect of four consecutive ejaculations was investigated by determining levels of (i) testosterone in serum by solid phase RIA, (ii) androgen receptors at the ventral prostate with Western Blots, and (iii) androgen receptors-mRNA with RT-PCR. Data were analyzed with a one-way ANOVA followed by a post hoc application of Dunnett's test if required. Results The constant execution of sexual behavior did not produce any change in the weight of the ventral prostate. Serum testosterone increased after the second ejaculation, and remained elevated even after four ejaculations. The androgen receptor at the ventral prostate was higher after the first to third ejaculations, but returned suddenly to baseline levels after the fourth ejaculation. The level of mRNA increased after the first ejaculation, continued to increase after the second, and reached the highest peak after the third ejaculation; however, it returned suddenly to baseline levels after the fourth ejaculation. Conclusion Four consecutive ejaculations by sexually experienced male rats had important effects on the physiological responses of the ventral prostate. Fast responses were induced as a result of sexual behavior that involved an increase and decrease in androgen receptors after one and four ejaculations, respectively. However, a progressive response was observed in the elevation of mRNA for androgen receptors, which also showed a fast decrease after four ejaculations. All of these changes with the prostate gland occurred in the presence of a sustained elevation of testosterone in the serum that started after two ejaculations. A consideration of these fast-induced changes suggests that the nerve supply plays a key role in prostate physiology during the sexual behavior of male rats. PMID:17367532

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects

PubMed Central

Gosmanov, Aidar R.; Smiley, Dawn D.; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. PMID:22483976

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

PubMed

Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

2014-10-15

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women.

PubMed

Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

2015-08-01

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus.

PubMed

Shlomai, Amir; Kariv, Revital; Leshno, Moshe; Beth-or, Anat; Sheinberg, Bracha; Halpern, Zamir

2010-10-01

Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Fluoride bioavailability in saliva and plaque

PubMed Central

2012-01-01

Background Different fluoride formulations may have different effects on caries prevention. It was the aim of this clinical study to assess the fluoride content, provided by NaF compared to amine fluoride, in saliva and plaque. Methods Eight trained volunteers brushed their teeth in the morning for 3 minutes with either NaF or amine fluoride, and saliva and 3-day-plaque-regrowth was collected at 5 time intervals during 6 hours after tooth brushing. The amount of collected saliva and plaque was measured, and the fluoride content was analysed using a fluoride sensitive electrode. All subjects repeated all study cycles 5 times, and 3 cycles per subject underwent statistical analysis using the Wilcoxon-Mann-Whitney test. Results Immediately after brushing the fluoride concentration in saliva increased rapidly and dropped to the baseline level after 360 minutes. No difference was found between NaF and amine fluoride. All plaque fluoride levels were elevated after 30 minutes until 120 minutes after tooth brushing, and decreasing after 360 minutes to baseline. According to the highly individual profile of fluoride in saliva and plaque, both levels of bioavailability correlated for the first 30 minutes, and the fluoride content of saliva and plaque was back to baseline after 6 hours. Conclusions Fluoride levels in saliva and plaque are interindividually highly variable. However, no significant difference in bioavailability between NaF and amine fluoride, in saliva, or in plaque was found. PMID:22230722

The platelet-poor plasma 5-HT response to carbohydrate rich meal administration in adult autistic patients compared with normal controls.

PubMed

Vered, Yaffa; Golubchik, Pavel; Mozes, Tamar; Strous, Rael; Nechmad, Allon; Mester, Roberto; Weizman, Abraham; Spivak, Baruch

2003-07-01

There are cumulative data indicating involvement of the 5-HT system in autistic disorder. Most studies examining 5-HT function have focused on whole blood 5-HT content. The carbohydrate-rich meal test (CRMT) is a dietary manipulation that could significantly influence platelet-poor plasma (PPP) 5-HT levels and reflect the responsiveness of the serotonergic system in 'free' plasma. In this study, CRMT was used as an indicator of 5-HT responsivity in drug-free adults with autistic disorder (n = 7), compared with normal controls (n = 10). The PPP 5-HT levels were measured at baseline and during 3 h after administration of the CRMT. A significant elevation in PPP 5-HT levels in adult autistic patients was reached 60 min after meal administration (p < 0.03 vs control and p = 0.05 vs baseline) and a significant decrease was noted after 120 min (p < 0.01 vs baseline). In contrast to the biphasic response of the autistic patients, normal controls exhibited a gradual linear increase of PPP 5-HT levels. Our results indicate that in adult autistic patients, the pattern of PPP 5-HT responsivity to a dietary challenge of CRMT is dysregulated compared with normal controls and provide further support for the role of 5-HT in autism. Copyright 2003 John Wiley & Sons, Ltd.

The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.

PubMed

Cansu, Ali; Yesilkaya, Ediz; Serdaroglu, Ayse; Camurdan, Orhun; Hirfanoglu, Tugba Luleci; Karaoglu, Abdulbaki; Bideci, Aysun; Cinaz, Peyami

2012-01-01

This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.

Longitudinal Study of Intestinal Symptoms and Fecal Continence in Patients With Conformal Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geinitz, Hans, E-mail: hans.geinitz@lrz.tu-muenchen.d; Thamm, Reinhard; Keller, Monika

2011-04-01

Purpose: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. Methods and Materials: A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. Results: The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecationmore » pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for {<=}1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. Conclusion: Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.« less

Effects of a 7-day military training exercise on inflammatory biomarkers, serum hepcidin, and iron status.

PubMed

McClung, James P; Martini, Svein; Murphy, Nancy E; Montain, Scott J; Margolis, Lee M; Thrane, Ingjerd; Spitz, Marissa G; Blatny, Janet-Martha; Young, Andrew J; Gundersen, Yngvar; Pasiakos, Stefan M

2013-11-04

Hepcidin, a peptide that is released into the blood in response to inflammation, prevents cellular iron export and results in declines in iron status. Elevated serum and urinary levels of hepcidin have been observed in athletes following exercise, and declines in iron status have been reported following prolonged periods of training. The objective of this observational study was to characterize the effects of an occupational task, military training, on iron status, inflammation, and serum hepcidin. Volunteers (n = 21 males) included Norwegian Soldiers participating in a 7-day winter training exercise that culminated in a 3-day, 54 km ski march. Fasted blood samples were collected at baseline, on day 4 (PRE, prior to the ski march), and again on day 7 (POST, following the ski march). Samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), interleukin-6 (IL-6), and serum hepcidin. Military training affected inflammation and serum hepcidin levels, as IL-6 and hepcidin concentrations increased (P < 0.05) from the baseline to POST (mean ± SD, 9.1 ± 4.9 vs. 14.5 ± 8.4 pg/mL and 6.5 ± 3.5 vs. 10.2 ± 6.9 ng/mL, respectively). Iron status was not affected by the training exercise, as sTfR levels did not change over the course of the 7-day study. Military training resulted in significant elevations in IL-6 and serum hepcidin. Future studies should strive to identify the role of hepcidin in the adaptive response to exercise, as well as countermeasures for the prevention of chronic or repeated elevations in serum hepcidin due to exercise or sustained occupational tasks which may result in longer term decrements in iron status.

Dissociation of muscle sympathetic nerve activity and leg vascular resistance in humans

NASA Technical Reports Server (NTRS)

Shoemaker, J. K.; Herr, M. D.; Sinoway, L. I.

2000-01-01

We examined the hypothesis that the increase in inactive leg vascular resistance during forearm metaboreflex activation is dissociated from muscle sympathetic nerve activity (MSNA). MSNA (microneurography), femoral artery mean blood velocity (FAMBV, Doppler), mean arterial pressure (MAP), and heart rate (HR) were assessed during fatiguing static handgrip exercise (SHG, 2 min) followed by posthandgrip ischemia (PHI, 2 min). Whereas both MAP and MSNA increase during SHG, the transition from SHG to PHI is characterized by a transient reduction in MAP but sustained elevation in MSNA, facilitating separation of these factors in vivo. Femoral artery vascular resistance (FAVR) was calculated (MAP/MBV). MSNA increased by 59 +/- 20% above baseline during SHG (P < 0.05) and was 58 +/- 18 and 78 +/- 18% above baseline at 10 and 20 s of PHI, respectively (P < 0.05 vs. baseline). Compared with baseline, FAVR increased 51 +/- 22% during SHG (P < 0.0001) but returned to baseline levels during the first 30 s of PHI, reflecting the changes in MAP (P < 0.005) and not MSNA. It was concluded that control of leg muscle vascular resistance is sensitive to changes in arterial pressure and can be dissociated from sympathetic factors.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

PubMed

Bernhard, Felix P; Heinzel, Sebastian; Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

PubMed Central

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels.

PubMed

Lin, C; Andersen, J R; Våge, V; Rajalahti, T; Mjøs, S A; Kvalheim, O M

2016-08-01

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients' own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid. © 2016 World Obesity.

Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.

PubMed

Hussein, Ayman A; Bartz, Traci M; Gottdiener, John S; Sotoodehnia, Nona; Heckbert, Susan R; Lloyd-Jones, Donald; Kizer, Jorge R; Christenson, Robert; Wazni, Oussama; deFilippi, Christopher

2015-05-01

Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset. The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF). In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses. Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF. The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

PubMed Central

Chen, Der-Yuan; Chen, Hsin-Hua; Hsieh, Chia-Wei; Yeh, Yea-Wen; Lan, Joung-Liang

2016-01-01

QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas. PMID:27861525

Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome.

PubMed

Lunde, Sigrid; Kristoffersen, Einar K; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

2016-01-01

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6-9.5 g/L, IgA 1.8-1.5 g/L, and IgM 0.97-0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B-cell regulatory effects on T-cell or NK-cell subsets are not the main mechanisms for the observed improvements in ME/CFS symptoms observed in the two previous trials. The modest increase in serum BAFF levels at baseline may indicate an activated B-lymphocyte system in a subgroup of ME/CFS patients.

Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome

PubMed Central

Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

2016-01-01

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B-cell regulatory effects on T-cell or NK-cell subsets are not the main mechanisms for the observed improvements in ME/CFS symptoms observed in the two previous trials. The modest increase in serum BAFF levels at baseline may indicate an activated B-lymphocyte system in a subgroup of ME/CFS patients. PMID:27536947

Mastocytosis and insect venom allergy.

PubMed

Bonadonna, Patrizia; Zanotti, Roberta; Müller, Ulrich

2010-08-01

To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 microg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.

A blended wing body airplane with a close-coupled, tilting tail

NASA Astrophysics Data System (ADS)

Nasir, R. E. M.; Mazlan, N. S. C.; Ali, Z. M.; Wisnoe, W.; Kuntjoro, W.

2016-10-01

This paper highlights a novel approach to stabilizing and controlling pitch and yaw motion via a set of horizontal tail that can act as elevator and rudder. The tail is incorporated into a new design of blended wing body (BWB) aircraft, known as Baseline-V, located just aft of the trailing edge of its inboard wing. The proposed close-coupled tail is equipped with elevators that deflect in unison, and can tilt - an unusual means of tilting where if starboard side is tilted downward at k degree, and then the portside must be tilted upward at k degree too. A wind tunnel experiment is conducted to investigate aerodynamics and static stability of Baseline-V BWB aircraft. The model is being tested at actual flight speed of 15 m/s (54 km/h) with varying angle of attack for five elevator angle cases at zero tilt angle and varying sideslip angle for four tilt angle cases at one fixed elevator angle. The result shows that the aircraft's highest lift-to-drag ratio is 32. It is also found that Baseline-V is statically stable in pitch and yaw but has no clear indication in terms of roll stability.

A precise vertical network: Establishing new orthometric heights with static surveys in Florida tidal marshes

USGS Publications Warehouse

Raabe, E.A.; Stumpf, R.P.; Marth, N.J.; Shrestha, R.L.

1996-01-01

Elevation differences on the order of 10 cm within Florida's marsh system influence major variations in tidal flooding and in the associated plant communities. This low elevation gradient combined with sea level fluctuation of 5-to-10 cm over decadel and longer periods can generate significant alteration and erosion of marsh habitats along the Gulf Coast. Knowledge of precise and accurate elevations in the marsh is critical to the efficient monitoring and management of these habitats. Global positioning system (GPS) technology was employed to establish six new orthometric heights along the Gulf Coast from which kinematic surveys into the marsh interior are conducted. The vertical accuracy achieved using GPS technology was evaluated using two networks with 16 vertical and nine horizontal NGS published high accuracy positions. New positions were occupied near St. Marks National Wildlife Refuge and along the coastline of Levy County and Citrus County. Static surveys were conducted using four Ashtech dual frequency P-code receivers for 45-minute sessions and a data logging rate of 10 seconds. Network vector lengths ranged from 4 to 64 km and, including redundant baselines, totaled over 100 vectors. Analysis includes use of the GEOID93 model with a least squares network adjustment and reference to the National Geodetic Reference System (NGRS). The static surveys show high internal consistency and the desired centimeter-level accuracy is achieved for the local network. Uncertainties for the newly established vertical positions range from 0.8 cm to 1.8 cm at the 95% confidence level. These new positions provide sufficient vertical accuracy to achieve the project objectives of tying marsh surface elevations to long-term water level gauges recording sea level fluctuations along the coast.

Angiopoietin-like protein 6 in patients with obesity, type 2 diabetes mellitus, and anorexia nervosa: The influence of very low-calorie diet, bariatric surgery, and partial realimentation.

PubMed

Cinkajzlova, Anna; Lacinova, Zdenka; Klouckova, Jana; Kavalkova, Petra; Trachta, Pavel; Kosak, Mikulas; Haluzikova, Denisa; Papezova, Hana; Mraz, Milos; Haluzík, Martin

2017-02-01

Angiopoietin-like protein 6 (ANGPTL6) is a circulating protein with a potential role in energy homeostasis. The aim of the study was to explore the changes in ANGPTL6 levels in patients with obesity (Body mass index, BMI > 40 kg/m 2 ) with and without type 2 diabetes mellitus (T2DM) undergoing dietary intervention (very low calorie diet - VLCD) and in a subgroup of T2DM patients after bariatric surgery. Additionally, we examined changes in ANGPTL6 in anorexia nervosa (AN) patients at baseline and after partial realimentation. We also explored the changes in ANGPTL6 mRNA expression in subcutaneous adipose tissue (SAT) of obese subjects. The study included 23 non-diabetic obese patients, 40 obese patients with T2DM (27 underwent VLCD and 13 underwent bariatric surgery), 22 patients with AN, and 37 healthy control subjects. ANGPTL6 levels of AN patients were increased relative to the control group (68.6 ± 9.9 ng/ml) and decreased from 110.2 ± 13.3 to 73.6 ± 7.1 ng/ml (p = 0.004) after partial realimentation. Baseline ANGPTL6 levels in patients with obesity and T2DM did not differ from the control group. VLCD decreased ANGPTL6 levels only in obese patients with T2DM. Bariatric surgery induced a transient elevation of ANGPTL6 levels with a subsequent decrease to baseline levels. ANGPTL6 mRNA expression transiently increased after bariatric surgery and returned to baseline levels after 12 months. Collectively, our data suggest that serum ANGPTL6 levels and ANGPTL6 mRNA expression in SAT are affected by metabolic disorders and their treatment but do not appear to directly reflect nutritional status.

High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

PubMed

Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

2016-04-01

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.

PubMed

Corlier, Fabian; Hafzalla, George; Faskowitz, Joshua; Kuller, Lewis H; Becker, James T; Lopez, Oscar L; Thompson, Paul M; Braskie, Meredith N

2018-05-15

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline. Copyright © 2018 Elsevier Inc. All rights reserved.

Fiber Intake and PAI-1 in type 2 diabetes: Look AHEAD Trial Findings at Baseline and Year 1

PubMed Central

Belalcazar, L. Maria; Anderson, Andrea M.; Lang, Wei; Schwenke, Dawn C.; Haffner, Steven M.; Yatsuya, Hiroshi; Rushing, Julia; Vitolins, Mara Z.; Reeves, Rebecca; Pi-Sunyer, F. Xavier; Tracy, Russell P.; Ballantyne, Christie M.

2014-01-01

Plasminogen Activator Inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes (T2DM) and may contribute, independently of traditional factors, to increased cardiovascular disease (CVD) risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1, before and during an intensive lifestyle intervention for weight loss (ILI) in 1,701 Look AHEAD participants with dietary, fitness and PAI-1 data at baseline and 1-year. Look AHEAD was a randomized CVD trial in 5,145 overweight/obese subjects with T2DM, comparing ILI (goal of ≥7% reduction in baseline weight) with a control arm of diabetes support and education (DSE). ILI participants were encouraged to consume vegetables, fruits and grain products low in sugar and fat. At baseline, median fiber intake was 17.9 g/d. Each 8.3 g/day higher fiber intake was associated with a 9.2% lower PAI-1 level (p=0.008); this association persisted after weight and fitness adjustments (p=0.03). Higher baseline intake of fruit (p=0.019) and high-fiber grain and cereal (p=0.029) were related to lower PAI-1 levels. Although successful in improving weight and physical fitness at 1-year, ILI in Look AHEAD resulted in small increases in fiber intake (4.1g/day, compared with -2.35 g/day with DSE), which were not related to PAI-1 change (p=0.34). Only 31.3% of ILI participants (39.8% of women; 19.1% of men) met daily fiber intake recommendations. Increasing fiber intake in overweight/obese individuals with diabetes interested in weight loss is challenging. Future studies evaluating changes in fiber consumption during weight loss interventions are warranted. PMID:25131348

Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials.

PubMed

Petri, Michelle A; van Vollenhoven, Ronald F; Buyon, Jill; Levy, Roger A; Navarra, Sandra V; Cervera, Ricard; Zhong, Z John; Freimuth, William W

2013-08-01

To identify predictors of moderate-to-severe systemic lupus erythematosus (SLE) flare in 562 patients treated with standard therapy alone in phase III belimumab trials, and to evaluate the impact of standard therapies on preventing flares. Post hoc analysis assessed baseline demographics, disease activity, and biomarkers in patients with and those without flare at treatment weeks 24 and 52. Severe flare was defined by the modified SLE Flare Index (SFI) and the development of any new British Isles Lupus Assessment Group (BILAG) A domain score. Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores. Baseline characteristics associated with a ≥10% absolute difference or a ≥50% increase in flare rates were considered predictive. Frequencies of flares over 52 weeks according to the SFI, any new BILAG A domain score, and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7%, 23.1%, and 32.0%, respectively. Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI); anti-double-stranded DNA (anti-dsDNA) positivity; proteinuria (≥0.5 gm/24 hours); BILAG renal, vasculitic, and hematologic scores; elevated C-reactive protein levels; and B lymphocyte stimulator (BLyS) levels ≥2 ng/ml. Independent predictors by multivariate analysis at week 52 were SELENA-SLEDAI and/or BILAG renal involvement and anti-dsDNA ≥200 IU/ml (on all 3 indices); SELENA-SLEDAI and/or BILAG neurologic and vasculitic involvement (on 2 indices: any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores); BLyS levels ≥2 ng/ml (on 2 indices: the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores); and low C3 level (on the SFI). Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk. Patients who were receiving standard SLE therapy and had renal, neurologic, or vasculitic involvement, elevated anti-dsDNA or BLyS levels, or low C3 had increased risk of clinically meaningful flare over 1 year. Hydroxychloroquine use was not predictive. Copyright © 2013 by the American College of Rheumatology.

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT.

PubMed

Zhi, Zhongwei; Cepurna, William; Johnson, Elaine; Jayaram, Hari; Morrison, John; Wang, Ruikang K

2015-09-01

To determine if retinal capillary filling is preserved in the face of acutely elevated intraocular pressure (IOP) in anesthetized rats, despite a reduction in total retinal blood flow (RBF), using optical microangiography/optical coherence tomography (OMAG/OCT). OMAG provided the capability of depth-resolved imaging of the retinal microvasculature down to the capillary level. Doppler OCT was applied to measure the total RBF using an enface integration approach. The microvascular pattern, capillary density, and total RBF were monitored in vivo as the IOP was increased from 10 to 100mmHg in 10mmHg intervals and returned back to 10mmHg. In animals with mean arterial pressure (MAP) of 102±4mmHg (n=10), when IOP was increased from 0 to 100mmHg, the capillary density remained at or above 80% of baseline for the IOP up to 60mmHg [or ocular perfusion pressure (OPP) at 40mmHg]. This was then decreased, achieving 60% of baseline at IOP 70mmHg and OPP of 30mmHg. Total RBF was unaffected by moderate increases in IOP up to 30mmHg, beyond which total RBF decreased linearly, reaching 50% of baseline at IOP 60mmHg and OPP 40mmHg. Both capillary density and total RBF were totally extinguished at 100mmHg, but fully recovered when IOP returned to baseline. By comparison, a separate group of animals with lower MAP (mean=75±6mmHg, n=7) demonstrated comparable decreases in both capillary filling and total RBF at IOPs that were 20mmHg lower than in the initial group. Both were totally extinguished at 80mmHg, but fully recovered when IOP returned to baseline. Relationships of both parameters to OPP were unchanged. Retinal capillary filling and total RBF responses to IOP elevation can be monitored non-invasively by OMAG/OCT and both are influenced by OPP. Retinal capillary filling was relatively preserved down to a perfusion pressure of 40mmHg, despite a linear reduction in total RBF. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of topical benzocaine and lignocaine on upper airway reflex sensitivity.

PubMed

Raphael, J H; Stanley, G D; Langton, J A

1996-02-01

We studied the degree and duration of effect on upper airway reflex sensitivity of oral benzocaine lozenges, nebulised lignocaine and lignocaine sprayed onto the vocal cords under direct vision, using low concentrations of ammonia as a stimulus to upper airway receptors. Ten minutes after the administration of oral benzocaine 20 mg the threshold response of the upper airway to ammonia (NH3TR) had risen significantly from baseline mean (SEM) of 680 (95) to 975 (109) ppm of ammonia with a return to baseline values after 25 min (n = 8, p < 0.05, repeated measures of ANOVA; p < 0.001, t-test). A direct spray of lignocaine 100 mg onto the vocal cords resulted in a significant elevation in NH3TR from a baseline mean (SEM) of 665 (81) to a maximum of 1600 (88) ppm of ammonia with a significant elevation in the threshold persisting for 100 min (n = 7, p < 0.001, repeated measures of ANOVA; p < 0.05, t-test). The application of 4% nebulised lignocaine 4 ml significantly increased NH3TR from a baseline mean (SEM) of 770 (56) to a maximum of 1190 (63) ppm of ammonia with a significant elevation in the threshold persisting for 30 min (n = 8, p < 0.001, repeated measures of ANOVA; p < 0.05, t-test). The maximum elevations in NH3TR with the two methods of lignocaine delivery were significantly different (p < 0.01, 2-way ANOVA).

Serum A-FABP is increased and closely associated with elevated NT-proBNP levels in type 2 diabetic patients treated with rosiglitazone.

PubMed

Zhou, Mi; Bao, Yuqian; Lu, Junxi; Zhou, Jian; Jia, Weiping

2011-01-01

Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment. A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007). Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.

Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH.

PubMed

van der Velde, A Rogier; Gullestad, Lars; Ueland, Thor; Aukrust, Pål; Guo, Yu; Adourian, Aram; Muntendam, Pieter; van Veldhuisen, Dirk J; de Boer, Rudolf A

2013-03-01

In several cross-sectional analyses, circulating baseline levels of galectin-3, a protein involved in myocardial fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with heart failure (HF). The importance and clinical use of repeated measurements of galectin-3 have not yet been reported. Plasma galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324). Patient results were analyzed by categorical and percentage changes in galectin-3 level. A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients. Increasing galectin-3 levels over time, from a low to high galectin-3 category, were associated with significantly more HF hospitalization and mortality compared with stable or decreasing galectin-3 levels (hazard ratio in CORONA, 1.60; 95% confidence interval, 1.13-2.25; P=0.007; hazard ratio in COACH, 2.38; 95% confidence interval, 1.02-5.55; P=0.046). In addition, patients whose galectin-3 increased by >15% between measurements had a 50% higher relative hazard of adverse event than those whose galectin-3 stayed within ±15% of the baseline value, independent of age, sex, diabetes mellitus, left ventricular ejection fraction, renal function, medication (β-blocker, angiotensin converting enzyme inhibitor, and angiotensin receptor blocker), and N-terminal probrain natriuretic peptide (hazard ratio in CORONA, 1.50; 95% confidence interval, 1.17-1.92; P=0.001). The impact of changing galectin-3 levels on other secondary end points was comparable. In 2 large cohorts of patients with chronic and acute decompensated HF, repeated measurements of galectin-3 level provided important and significant prognostic value in identifying patients with HF at elevated risk for subsequent HF morbidity and mortality.

Depressive symptoms and inductive reasoning performance: findings from the ACTIVE reasoning training intervention.

PubMed

Parisi, Jeanine M; Franchetti, Mary Kathryn; Rebok, George W; Spira, Adam P; Carlson, Michelle C; Willis, Sherry L; Gross, Alden L

2014-12-01

Within the context of the Advanced Cognitive Training for Independent and Vital Elderly study (ACTIVE; Ball et al., 2002; Jobe et al., 2001; Willis et al., 2006), we examined the longitudinal association of baseline depressive symptoms on inductive reasoning performance over a 10-year period between the reasoning training and control conditions (N = 1,375). At baseline, 322 participants (23%) reported elevated depressive symptoms, defined by a score ≥9 on the 12-item version of the Center for Epidemiological Studies Depression Scale (CES-D; Mirowsky & Ross, 2003; Radloff, 1977). Differences in baseline depressive status were not associated with immediate posttraining gains or with subsequent annual change in reasoning performance, suggesting that the presence of elevated baseline depressive symptoms does not impact the ability to benefit from reasoning training. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

PubMed Central

Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

2016-01-01

Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

Investigation of PAH Biomarkers in the Urine of Workers Exposed to Hot Asphalt

PubMed Central

Sobus, Jon R.; Mcclean, Michael D.; Herrick, Robert F.; Waidyanatha, Suramya; Onyemauwa, Frank; Kupper, Lawrence L.; Rappaport, Stephen M.

2009-01-01

Airborne emissions from hot asphalt contain mixtures of polycyclic aromatic hydrocarbons (PAHs), including several carcinogens. We investigated urinary biomarkers of three PAHs, namely naphthalene (Nap), phenanthrene (Phe), and pyrene (Pyr) in 20 road-paving workers exposed to hot asphalt and in 6 road milling workers who were not using hot asphalt (reference group). Our analysis included baseline urine samples as well as postshift, bedtime, and morning samples collected over three consecutive days. We measured unmetabolized Nap (U-Nap) and Phe (U-Phe) as well as the monohydroxylated metabolites of Nap (OH-Nap), Phe (OH-Phe), and Pyr (OH-Pyr) in each urine sample. In baseline samples, no significant differences in biomarker levels were observed between pavers and millers, suggesting similar background exposures. In postshift, bedtime, and morning urine samples, the high pairwise correlations observed between levels of all biomarkers suggest common exposure sources. Among pavers, levels of all biomarkers were significantly elevated in postshift samples, indicating rapid uptake and elimination of PAHs following exposure to hot asphalt (biomarker levels were not elevated among millers). Results from linear mixed-effects models of levels of U-Nap, U-Phe, OH-Phe, and OH-Pyr across pavers showed significant effects of work assignments with roller operators having lower biomarker levels than the other workers. However, no work-related effect was observed for levels of OH-Nap, apparently due to the influence of cigarette smoking. Biological half-lives, estimated from regression coefficients for time among pavers, were 8 h for U-Phe, 10 h for U-Nap, 13 h for OH-Phe and OH-Pyr, and 26 h for OH-Nap. These results support the use of U-Nap, U-Phe, OH-Phe, and OH-Pyr, but probably not OH-Nap, as short-term biomarkers of exposure to PAHs emanating from hot asphalt. PMID:19602500

Longitudinal relationship between diabetes-specific emotional distress and follow-up HbA1c in adults with Type 1 diabetes mellitus

PubMed Central

Strandberg, R B; Graue, M; Wentzel-Larsen, T; Peyrot, M; Thordarson, H B; Rokne, B

2015-01-01

Aim To examine whether diabetes-specific emotional distress was related to follow-up glycaemic control in adults with Type 1 diabetes mellitus. Methods Adults with Type 1 diabetes mellitus completed the Diabetes Distress Scale and reported sociodemographic information when attending a clinical consultation at a university endocrinology unit. Blood samples to determine baseline HbA1c were taken during consultations. All respondents’ HbA1c measurements registered from January 2009 to December 2011 were collected from medical records. The relationship between baseline diabetes-specific emotional distress and HbA1c was examined with linear mixed-effects models in 175 patients with complete data. Results After controlling for confounders, baseline diabetes-specific emotional distress and glycaemic control were significantly associated (fixed-effect coefficient 0.40, P < 0.001) and the regimen-related distress subscale had the strongest association with glycaemic control (fixed-effect coefficient 0.47, P < 0.001). The two-item measure of diabetes-specific distress had a weaker but still significant association with glycaemic control (fixed-effect coefficient 0.31, P < 0.001). None of these relationships was significant after adjusting for the baseline HbA1c. Conclusions People with elevated baseline diabetes-specific emotional distress are at risk of prolonged suboptimum glycaemic control; therefore, elevated diabetes-specific emotional distress, especially regimen-related distress, might be an important marker for prolonged suboptimum glycaemic control, and might indicate a need for special attention regarding patient self-management. What’s new? In adults with Type 1 diabetes, elevated baseline diabetes-specific emotional distress is associated with worse glycaemic control over a 1–3-year period and regimen-related distress had the strongest association with subsequent glycaemic control. Baseline diabetes-specific emotional distress is associated with the stable component of glycaemic control and does not account for within-individual change in glycaemic control over 1–3 years. Elevated diabetes-specific emotional distress may be an important marker for risk of prolonged suboptimum glycaemic control. PMID:25865313

Water temperature, streamflow, and ground-water elevation in and adjacent to the Russian river between Hopland and Guerneville, California from 1998-2002

USGS Publications Warehouse

Cox, Marisa H.; Hatch, Christine

2003-01-01

Temperature, water level elevation, stage height, and river discharge data for this report were collected in and adjacent to the Russian River from Hopland to Guerneville, CA over a four-year period from 1998 to 2002 to establish baselines for long-term water quality, water supply and habitat. Data files presented in this report were collected by the USGS and the Sonoma County Water Agency's Engineering Resource and Planning, and Natural Resource Divisions. Temperature data were collected in single-channel submersible microloggers or temperature data were collected simultaneously with water-elevation data in dual-channel down-hole data loggers. Stream stage and streamflow data were collected at USGS stream gaging stations located near Hopland, Healdsburg, and Guerneville over a 130 km reach of the Russian River. During the period of record stream flow ranged from 3 to 1458 m3/s. Stream temperature ranged from 8 to 29 oC while groundwater temperature ranged from 10 to 38 oC. Stream stage varied 5 m seasonly, while ground-water level varied 19 m over the same time scale.

Identifying potential barriers to physical activity adherence: anxiety sensitivity and body mass as predictors of fear during exercise.

PubMed

Smits, Jasper A J; Tart, Candyce D; Presnell, Katherine; Rosenfield, David; Otto, Michael W

2010-01-01

A growing body of work suggests that obese adults are less likely to adhere to exercise than normal-weight adults because they experience greater levels of discomfort and distress during exercise sessions. The present study introduces and provides a preliminary test of the hypothesis that the distress experienced during exercise among persons with elevated body mass index is particularly high among those who fear somatic arousal (i.e. elevated anxiety sensitivity [AS]). Young adults were randomly assigned to complete 20 min of treadmill exercise (at 70% of their age-adjusted predicted maximum heart rate) or 20 min of rest. Body mass, AS, and negative affect were measured at baseline, and fear was measured at 4-min intervals during the experimental phase. Consistent with the authors' hypothesis, there was a significant Exercise x BMI x ASI interaction (sr(2) = .08), suggesting that the greatest fear levels during exercise were observed among participants with high body mass, but only if they also had elevated AS. These findings offer a new approach for identifying specific vulnerable individuals and have clear clinical implications, given that the amplification factor of AS can be modified with clinical intervention.

Personality disorders and perceived stress in Major Depressive Disorder

PubMed Central

Candrian, Michele; Schwartz, Faye; Farabaugh, Amy; Perlis, Roy H.; Ehlert, Ulrike; Fava, Maurizio

2008-01-01

The investigation of comorbidity between major depressive disorder (MDD) and personality disorders (PDs) has attracted considerable interest. Whereas some studies found that the presence of PDs has adverse effects on the course and treatment of MDD, others have failed to demonstrate this link. These inconsistent findings suggest that specific PD comorbidity might affect the course of MDD by modulating factors that increase the overall risk of depression, including an elevated tendency to perceive stress. To investigate whether the presence of a specific PD cluster was associated with elevated levels of stress appraisal, we administered the Perceived Stress Scale (PSS) before and after treatment to 227 MDD outpatients enrolled in an 8-week open-label treatment with fluoxetine. Following treatment, multiple linear regression analyses revealed that the presence of Cluster A, but not Cluster B or C, was associated with higher levels of perceived stress, even after adjusting for baseline depression severity and PSS scores, as well as various sociodemographic variables. The presence of Cluster A PD comorbidity was uniquely associated with elevated stress appraisal after antidepressant treatment, raising the possibility that stress exacerbation might be an important factor linked to poor treatment outcome in MDD subjects with Cluster A pathology. PMID:18573540

Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

PubMed Central

Bang, Hyun Seok; Seo, Dae Yun; Chung, Yong Min; Oh, Kyoung-Mo; Park, Jung Jun; Arturo, Figueroa; Jeong, Seung-Hun; Kim, Nari

2014-01-01

Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37±5.14 years; body mass index=27.13±2.16 kg/m2) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT. PMID:25352765

Future Coastal Population Growth and Exposure to Sea-Level Rise and Coastal Flooding - A Global Assessment

PubMed Central

Neumann, Barbara; Vafeidis, Athanasios T.; Zimmermann, Juliane; Nicholls, Robert J.

2015-01-01

Coastal zones are exposed to a range of coastal hazards including sea-level rise with its related effects. At the same time, they are more densely populated than the hinterland and exhibit higher rates of population growth and urbanisation. As this trend is expected to continue into the future, we investigate how coastal populations will be affected by such impacts at global and regional scales by the years 2030 and 2060. Starting from baseline population estimates for the year 2000, we assess future population change in the low-elevation coastal zone and trends in exposure to 100-year coastal floods based on four different sea-level and socio-economic scenarios. Our method accounts for differential growth of coastal areas against the land-locked hinterland and for trends of urbanisation and expansive urban growth, as currently observed, but does not explicitly consider possible displacement or out-migration due to factors such as sea-level rise. We combine spatially explicit estimates of the baseline population with demographic data in order to derive scenario-driven projections of coastal population development. Our scenarios show that the number of people living in the low-elevation coastal zone, as well as the number of people exposed to flooding from 1-in-100 year storm surge events, is highest in Asia. China, India, Bangladesh, Indonesia and Viet Nam are estimated to have the highest total coastal population exposure in the baseline year and this ranking is expected to remain largely unchanged in the future. However, Africa is expected to experience the highest rates of population growth and urbanisation in the coastal zone, particularly in Egypt and sub-Saharan countries in Western and Eastern Africa. The results highlight countries and regions with a high degree of exposure to coastal flooding and help identifying regions where policies and adaptive planning for building resilient coastal communities are not only desirable but essential. Furthermore, we identify needs for further research and scope for improvement in this kind of scenario-based exposure analysis. PMID:25760037

Future coastal population growth and exposure to sea-level rise and coastal flooding--a global assessment.

PubMed

Neumann, Barbara; Vafeidis, Athanasios T; Zimmermann, Juliane; Nicholls, Robert J

2015-01-01

Coastal zones are exposed to a range of coastal hazards including sea-level rise with its related effects. At the same time, they are more densely populated than the hinterland and exhibit higher rates of population growth and urbanisation. As this trend is expected to continue into the future, we investigate how coastal populations will be affected by such impacts at global and regional scales by the years 2030 and 2060. Starting from baseline population estimates for the year 2000, we assess future population change in the low-elevation coastal zone and trends in exposure to 100-year coastal floods based on four different sea-level and socio-economic scenarios. Our method accounts for differential growth of coastal areas against the land-locked hinterland and for trends of urbanisation and expansive urban growth, as currently observed, but does not explicitly consider possible displacement or out-migration due to factors such as sea-level rise. We combine spatially explicit estimates of the baseline population with demographic data in order to derive scenario-driven projections of coastal population development. Our scenarios show that the number of people living in the low-elevation coastal zone, as well as the number of people exposed to flooding from 1-in-100 year storm surge events, is highest in Asia. China, India, Bangladesh, Indonesia and Viet Nam are estimated to have the highest total coastal population exposure in the baseline year and this ranking is expected to remain largely unchanged in the future. However, Africa is expected to experience the highest rates of population growth and urbanisation in the coastal zone, particularly in Egypt and sub-Saharan countries in Western and Eastern Africa. The results highlight countries and regions with a high degree of exposure to coastal flooding and help identifying regions where policies and adaptive planning for building resilient coastal communities are not only desirable but essential. Furthermore, we identify needs for further research and scope for improvement in this kind of scenario-based exposure analysis.

Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10-year prospective study.

PubMed

Tsukagawa, Eri; Adachi, Hisashi; Hirai, Yuji; Enomoto, Mika; Fukami, Ako; Ogata, Kinuka; Kasahara, Akiko; Yokoi, Kanako; Imaizumi, Tsutomu

2013-07-01

Hepatocyte growth factor (HGF) receptors form a hybrid complex with insulin receptors in the liver of mice, which lead to robust signalling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship between HGF and the development of insulin resistance (IR) in a general population without IR at baseline. A total of 1492 subjects received health examinations. After excluding subjects with diabetes and/or IR (n = 402) at baseline, the remaining subjects (n = 1090) were followed-up 10 years later. Complete data sets were available from 716 subjects for prospective analysis. Logistic regression was performed to determine factors associated with the development of IR after 10 years. In subjects without diabetes at baseline, serum HGF levels were higher (0·26 ± 0·10 ng/ml, n = 259) in subjects with IR than without it (0·22 ± 0·09 ng/ml, n = 1090). After deleting subjects who developed liver disease during follow-up, 188 were found to have developed IR at 10 years after the original screening. HGF (P < 0·05), age (P < 0·001), homoeostasis model assessment index (P < 0·001), HDL-c (P < 0·05; inversely) and hypertensive medication (P < 0·05) were significantly associated with the development of IR by multivariate stepwise logistic regression analysis. A significant (P < 0·05) relative risk [1·75 (95%CI: 1·01-3·12)] for the development of IR was observed in the highest (≥0·30 ng/ml) vs the lowest categories (<0·15 ng/ml) of HGF after adjustments for confounders. Our 10-year prospective study suggests that elevated serum HGF levels were significantly associated with the development of IR. © 2012 John Wiley & Sons Ltd.

Adaptive selection of diurnal minimum variation: a statistical strategy to obtain representative atmospheric CO2 data and its application to European elevated mountain stations

NASA Astrophysics Data System (ADS)

Yuan, Ye; Ries, Ludwig; Petermeier, Hannes; Steinbacher, Martin; Gómez-Peláez, Angel J.; Leuenberger, Markus C.; Schumacher, Marcus; Trickl, Thomas; Couret, Cedric; Meinhardt, Frank; Menzel, Annette

2018-03-01

Critical data selection is essential for determining representative baseline levels of atmospheric trace gases even at remote measurement sites. Different data selection techniques have been used around the world, which could potentially lead to reduced compatibility when comparing data from different stations. This paper presents a novel statistical data selection method named adaptive diurnal minimum variation selection (ADVS) based on CO2 diurnal patterns typically occurring at elevated mountain stations. Its capability and applicability were studied on records of atmospheric CO2 observations at six Global Atmosphere Watch stations in Europe, namely, Zugspitze-Schneefernerhaus (Germany), Sonnblick (Austria), Jungfraujoch (Switzerland), Izaña (Spain), Schauinsland (Germany), and Hohenpeissenberg (Germany). Three other frequently applied statistical data selection methods were included for comparison. Among the studied methods, our ADVS method resulted in a lower fraction of data selected as a baseline with lower maxima during winter and higher minima during summer in the selected data. The measured time series were analyzed for long-term trends and seasonality by a seasonal-trend decomposition technique. In contrast to unselected data, mean annual growth rates of all selected datasets were not significantly different among the sites, except for the data recorded at Schauinsland. However, clear differences were found in the annual amplitudes as well as the seasonal time structure. Based on a pairwise analysis of correlations between stations on the seasonal-trend decomposed components by statistical data selection, we conclude that the baseline identified by the ADVS method is a better representation of lower free tropospheric (LFT) conditions than baselines identified by the other methods.

Temporal dynamics of the HPA axis linked to exploratory behavior in a wild European songbird (Parus major).

PubMed

Baugh, Alexander T; Davidson, Sarah C; Hau, Michaela; van Oers, Kees

2017-09-01

Variation in the reactivity of the endocrine stress axis is thought to underlie aspects of persistent individual differences in behavior (i.e. animal personality). Previous studies, however, have focused largely on estimating baseline or peak levels of glucocorticoids (CORT), often in captive animals. In contrast, the temporal dynamics of the HPA axis-how quickly it turns on and off, for example-may better indicate how an individual copes with stressors. Moreover, these HPA components might be correlated, thereby representing endocrine suites. Using wild-caught great tits (Parus major) we tested birds for exploratory behavior using a standardized novel environment assay that serves as a validated proxy for personality. We then re-captured a subset of these birds (n=85) and characterized four components of HPA physiology: baseline, endogenous stress response, a dexamethasone (DEX) challenge to estimate the strength of negative feedback, and an adrenocorticotropic hormone (ACTH) challenge to estimate adrenal capacity. We predicted that these four HPA responses would be positively correlated and that less exploratory birds would have a more rapid onset of the stress response (a CORT elevation during the baseline bleed) and weaker negative feedback (higher CORT after DEX). We found support for the first two predictions but not the third. All four components were positively correlated with each other and less exploratory birds exhibited an elevation in CORT during the baseline bleed (<3min from capture). Less exploratory birds, however, did not exhibit weaker negative feedback following the DEX challenge, but did exhibit weaker adrenal capacity. Together, our findings provide partial support for the hypothesis that the temporal reactivity of the HPA axis is linked with consistent individual differences in behavior, with more cautious (slower exploring) individuals exhibiting a faster CORT response. Copyright © 2017 Elsevier Inc. All rights reserved.

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

NASA Technical Reports Server (NTRS)

Stout, M. Shannon; Watenpaugh, Donald E.; Breit, Gregory A.; Hargens, Alan R.

1995-01-01

The cutaneous microcirculation vasodilates during acute 6 degree head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. Cutaneous microvascular blood flow was measured with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean +/- SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline througout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or hurmonal effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity.

Influence of Exogenous β-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion.

PubMed

James, Shaun; Kjerulf Greer, Beau

2018-06-28

This study investigates the effect of a supplementary ketone, β-hydroxybutyrate (BHB), on walking economy and ratings of perceived exertion in apparently healthy individuals. In a repeated-measures, crossover design, ten non-aerobically trained participants (three males; seven females) performed two stages of a duration-modified Bruce treadmill protocol. Participants blindly consumed either 1 ounce of an exogenous BHB solution (KETO) or a noncaloric placebo (CON) 30 minutes prior to exercise testing. Blood ketone and glucose concentrations were measured prior to supplementation (baseline), immediately before exercise, and after exercise. Oxygen consumption (VO 2 ), respiratory exchange ratio (RER), energy expenditure (EE), and rating of perceived exertion (RPE) were recorded during the last two minutes of each stage. Blood BHB concentrations were significantly elevated at the pre-exercise and postexercise time points as compared to the CON condition (p < .001), and blood glucose was significantly elevated postexercise in both conditions as compared to baseline levels (p < .001). No significant between-trial differences (p > .05) were found for VO 2 , RER, EE, or RPE. The intervention of this study did not produce evidence of an ergogenic benefit from BHB supplementation in a healthy subject pool.

Groundwater age for identification of baseline groundwater quality and impacts of land-use intensification - The National Groundwater Monitoring Programme of New Zealand

NASA Astrophysics Data System (ADS)

Morgenstern, Uwe; Daughney, Christopher J.

2012-08-01

SummaryWe identified natural baseline groundwater quality and impacts caused by land use intensification by relating groundwater chemistry with water age. Tritium, the most direct tracer for groundwater dating, including the time of water passage through the unsaturated zone, was overwhelmed over the recent decades by contamination from bomb-tritium from nuclear weapons testing in the early 1960s. In the Southern Hemisphere, this situation has changed now with the fading of the bomb-tritium, and tritium has become a tool for accurate groundwater dating. Tritium dating will become efficient also in the Northern Hemisphere over the next decade. Plotting hydrochemistry and field parameters versus groundwater age allowed us to identify those parameters that have increasing concentrations with age and are therefore from geological sources. These indicators for natural groundwater evolution are: Na, HCO3, SiO2, F, PO4, the redox-sensitive elements and compounds Fe, Mn, NH4, CH4, and pH and conductivity. In young groundwater that was recharged after the intensification of agriculture, nitrate, sulphate, CFC-11 and CFC-12, and pesticides are the most representative indicators for the impact of land-use intensification on groundwater quality, with 66% of the sites showing such an impact. Elevated concentrations of nitrate in oxic groundwater allowed us to reconstruct the timing and magnitude of the impact of land-use intensification on groundwater which in New Zealand occurred in two stages. Old pristine groundwater reflects the natural baseline quality. A transition to slightly elevated concentration due to low-intensity land-use was observed in groundwater recharged since around 1880. A sharp increase in nitrate and other agrochemicals due to high-intensity agriculture was observed in groundwater recharged since 1955. The threshold concentrations that distinguish natural baseline quality water from low-intensity land-use water, and low-intensity from high intensity land-use water, are 0.25 and 2.5 mg/L NO3-N, respectively. The change in groundwater quality from pristine baseline to low-intensity impact around 1880 coincides with the start of the meat export industry. The change in groundwater quality from low to high intensity landuse impact around 1955 coincides with the start of industrialised agriculture. No elevated levels of phosphate, a main compound in agricultural fertilisers and, together with nitrogen, a trigger of algae blooms in lakes, were found in young groundwater. This implies that fertiliser phosphate from non-point sources is still retained in the soil and has not yet reached the saturated groundwater systems. The source of elevated PO4, observed only in old groundwater, is therefore due purely to natural geochemical factors.

Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise.

PubMed

Tékus, Éva; Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta

2017-02-01

The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p < 0.05), as well as baseline and the highest value of post-exercise AGP (p < 0.05). Relationships were found between GSN levels and other indirect EIMD markers (between all GSN levels at post-exercise and CK activity at 6 h, p < 0.05; GSNMIN and muscle soreness at post-exercise, p < 0.04), GSN and AGP; however, actin did not correlate at any time points with GSN. Actin, GSN, AGP and CK responses after eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury.

Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise

PubMed Central

Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta

2017-01-01

Abstract The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p < 0.05), as well as baseline and the highest value of post-exercise AGP (p < 0.05). Relationships were found between GSN levels and other indirect EIMD markers (between all GSN levels at post-exercise and CK activity at 6 h, p < 0.05; GSNMIN and muscle soreness at post-exercise, p < 0.04), GSN and AGP; however, actin did not correlate at any time points with GSN. Actin, GSN, AGP and CK responses after eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury. PMID:28469748

Personal Genomic Testing for Cancer Risk: Results From the Impact of Personal Genomics Study.

PubMed

Gray, Stacy W; Gollust, Sarah E; Carere, Deanna Alexis; Chen, Clara A; Cronin, Angel; Kalia, Sarah S; Rana, Huma Q; Ruffin, Mack T; Wang, Catharine; Roberts, J Scott; Green, Robert C

2017-02-20

Purpose Significant concerns exist regarding the potential for unwarranted behavior changes and the overuse of health care resources in response to direct-to-consumer personal genomic testing (PGT). However, little is known about customers' behaviors after PGT. Methods Longitudinal surveys were given to new customers of 23andMe (Mountain View, CA) and Pathway Genomics (San Diego, CA). Survey data were linked to individual-level PGT results through a secure data transfer process. Results Of the 1,042 customers who completed baseline and 6-month surveys (response rate, 71.2%), 762 had complete cancer-related data and were analyzed. Most customers reported that learning about their genetic risk of cancers was a motivation for testing (colorectal, 88%; prostate, 95%; breast, 94%). No customers tested positive for pathogenic mutations in highly penetrant cancer susceptibility genes. A minority of individuals received elevated single nucleotide polymorphism-based PGT cancer risk estimates (colorectal, 24%; prostate, 24%; breast, 12%). At 6 months, customers who received elevated PGT cancer risk estimates were not significantly more likely to change their diet, exercise, or advanced planning behaviors or engage in cancer screening, compared with individuals at average or reduced risk. Men who received elevated PGT prostate cancer risk estimates changed their vitamin and supplement use more than those at average or reduced risk (22% v 7.6%, respectively; adjusted odds ratio, 3.41; 95% CI, 1.44 to 8.18). Predictors of 6-month behavior include baseline behavior (exercise, vitamin or supplement use, and screening), worse health status (diet and vitamin or supplement use), and older age (advanced planning, screening). Conclusion Most adults receiving elevated direct-to-consumer PGT single nucleotide polymorphism-based cancer risk estimates did not significantly change their diet, exercise, advanced care planning, or cancer screening behaviors.

Personal Genomic Testing for Cancer Risk: Results From the Impact of Personal Genomics Study

PubMed Central

Gollust, Sarah E.; Carere, Deanna Alexis; Chen, Clara A.; Cronin, Angel; Kalia, Sarah S.; Rana, Huma Q.; Ruffin, Mack T.; Wang, Catharine; Roberts, J. Scott; Green, Robert C.

2017-01-01

Purpose Significant concerns exist regarding the potential for unwarranted behavior changes and the overuse of health care resources in response to direct-to-consumer personal genomic testing (PGT). However, little is known about customers’ behaviors after PGT. Methods Longitudinal surveys were given to new customers of 23andMe (Mountain View, CA) and Pathway Genomics (San Diego, CA). Survey data were linked to individual-level PGT results through a secure data transfer process. Results Of the 1,042 customers who completed baseline and 6-month surveys (response rate, 71.2%), 762 had complete cancer-related data and were analyzed. Most customers reported that learning about their genetic risk of cancers was a motivation for testing (colorectal, 88%; prostate, 95%; breast, 94%). No customers tested positive for pathogenic mutations in highly penetrant cancer susceptibility genes. A minority of individuals received elevated single nucleotide polymorphism-based PGT cancer risk estimates (colorectal, 24%; prostate, 24%; breast, 12%). At 6 months, customers who received elevated PGT cancer risk estimates were not significantly more likely to change their diet, exercise, or advanced planning behaviors or engage in cancer screening, compared with individuals at average or reduced risk. Men who received elevated PGT prostate cancer risk estimates changed their vitamin and supplement use more than those at average or reduced risk (22% v 7.6%, respectively; adjusted odds ratio, 3.41; 95% CI, 1.44 to 8.18). Predictors of 6-month behavior include baseline behavior (exercise, vitamin or supplement use, and screening), worse health status (diet and vitamin or supplement use), and older age (advanced planning, screening). Conclusion Most adults receiving elevated direct-to-consumer PGT single nucleotide polymorphism-based cancer risk estimates did not significantly change their diet, exercise, advanced care planning, or cancer screening behaviors. PMID:27937091

In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects.

PubMed

Eshima, Hiroaki; Poole, David C; Kano, Yutaka

2015-07-15

In Type 1 diabetes, skeletal muscle resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is impaired following muscle contractions. It is unclear to what degree this behavior is contingent upon fiber type and muscle oxygenation conditions. We tested the hypotheses that: 1) the rise in resting [Ca(2+)]i evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast-twitch (type II) muscle following contraction; and 2) these elevated [Ca(2+)]i levels would relate to derangement of microvascular partial pressure of oxygen (PmvO2 ) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca(2+) imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA increased fatigability in EDL (P < 0.05) but not SOL. In recovery, SOL [Ca(2+)]i either returned to its resting baseline within 150 s (CONT 1.00 ± 0.02 at 600 s) or was not elevated in recovery at all (DIA 1.03 ± 0.02 at 600 s, P > 0.05). In recovery, EDL CONT [Ca(2+)]i also decreased to values not different from baseline (1.06 ± 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca(2+)]i remained elevated for the entire recovery period (i.e., 1.23 ± 0.03 at 600 s, P < 0.05). The inability of [Ca(2+)]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca(2+)-ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30-40%, P < 0.05). However, Pmv(O2) recovery kinetics were markedly slowed in EDL such that mean Pmv(O2) was substantially depressed (CONT 27.9 ± 2.0 vs. DIA 18.4 ± 2.0 Torr, P < 0.05), and this behavior was associated with the elevated [Ca(2+)]i. In contrast, this was not the case for SOL (P > 0.05) in that neither [Ca(2+)]i nor Pmv(O2) were deranged in recovery with DIA. In conclusion, recovery of [Ca(2+)]i homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced Pmv(O2) pressures. Copyright © 2015 the American Physiological Society.

Soluble Mediators and Clinical Features Discern Risk of Transitioning to Classified Disease in Relatives of Systemic Lupus Erythematosus Patients

PubMed Central

Munroe, Melissa E.; Young, Kendra A.; Kamen, Diane L.; Guthridge, Joel M.; Niewold, Timothy B.; Costenbader, Karen H.; Weisman, Michael H.; Ishimori, Mariko L.; Wallace, Daniel J.; Gilkeson, Gary S.; Karp, David R.; Harley, John B.; Norris, Jill M.; James, Judith A.

2016-01-01

Objective Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential to curtail irreversible inflammatory damage. The objective of this study was to identify factors associated with transition to classified disease that inform SLE risk. Methods Previously identified lupus patient blood relatives with < 4 American College of Rheumatology SLE classification criteria at baseline (n=409) were enrolled in this follow-up study. Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEE) were applied to identify factors anticipating disease transition. Results Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time=6.4 years). Relatives who transitioned displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (p<0.0001) at baseline than non-transitioned relatives. Importantly, they also had elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS), stem cell factor (SCF), and interferon-associated chemokines (p≤0.02), with concurrent decreases in levels of regulatory mediators, tumor growth factor (TGF)-β and interleukin (IL)-10 (p≤0.03). GEE revealed that baseline SLE-CSQ or ACR scores and plasma levels of SCF and TGF-β (p≤0.03), but not autoantibodies, were significant and independent predictors of SLE transition. Conclusions Altered levels of soluble mediators anticipate transition to classified disease in lupus relatives. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials. PMID:27863174

NT-proBNP and Heart Failure Risk Among Individuals With and Without Obesity: The ARIC Study

PubMed Central

Ndumele, Chiadi E.; Matsushita, Kunihiro; Sang, Yingying; Lazo, Mariana; Agarwal, Sunil K.; Nambi, Vijay; Deswal, Anita; Blumenthal, Roger S.; Ballantyne, Christie M.; Coresh, Josef; Selvin, Elizabeth

2016-01-01

Background Obesity is a risk factor for heart failure (HF), but is associated with lower N-terminal of pro-Brain Natriuretic Peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. Methods and Results We followed 12,230 ARIC participants free of prior HF at baseline (visit 2, 1990–1992) with BMI ≥18.5 kg/m2. We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1,861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r = −0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall and even among those with severe obesity (BMI ≥35 kg/m2; improvement in c-statistic +0.032 [95% CI 0.011–0.053]). However, given higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP 100 to < 200 pg/ml, the average 10-year HF risk was <5% among normal weight individuals but >10% if severely obese. Conclusions Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information regarding the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population. PMID:26746175

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.

PubMed

Walters, H M; Pan, N; Lehman, T J A; Adams, A; Kalliolias, G D; Zhu, Y S; Santiago, F; Nguyen, J; Sitaras, L; Cunningham-Rundles, S; Walsh, T J; Toussi, S S

2016-06-01

The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects. © 2016 British Society for Immunology.

Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: a 4 year retrospective longitudinal study.

PubMed

Jung, Chang Hee; Lee, Min Jung; Kang, Yu Mi; Hwang, Jenie Yoonoo; Jang, Jung Eun; Leem, Jaechan; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

2014-01-01

Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men. This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method. During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30-2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48-0.99, P for trend = 0.041). The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects. © 2013.

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

PubMed

Simsek, Gönül; Karter, Yesari; Aydin, Seval; Uzun, Hafize

2003-12-31

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.

Resistance management strategies in malaria vector mosquito control. Baseline data for a large-scale field trial against Anopheles albimanus in Mexico.

PubMed

Penilla, R P; Rodríguez, A D; Hemingway, J; Torres, J L; Arredondo-Jiménez, J I; Rodríguez, M H

1998-07-01

A high level of DDT resistance and low levels of resistance to organophosphorus, carbamate and pyrethroid insecticides were detected by discriminating dose assays in field populations of Anopheles albimanus in Chiapas, southern Mexico, prior to a large-scale resistance management project described by Hemingway et al. (1997). Biochemical assays showed that the DDT resistance was caused by elevated levels of glutathione S-transferase (GST) activity leading to increased rates of metabolism of DDT to DDE. The numbers of individuals with elevated GST and DDT resistance were well correlated, suggesting that this is the only major DDT resistance mechanism in this population. The carbamate resistance in this population is conferred by an altered acetylcholinesterase (AChE)-based resistance mechanism. The level of resistance observed in the bioassays correlates with the frequency of individuals homozygous for the altered AChE allele. This suggests that the level of resistance conferred by this mechanism in its heterozygous state is below the level of detection by the WHO carbamate discriminating dosage bioassay. The low levels of organophosphate (OP) and pyrethroid resistance could be conferred by either the elevated esterase or monooxygenase enzymes. The esterases were elevated only with the substrate pNPA, and are unlikely to be causing broad spectrum OP resistance. The altered AChE mechanism may also be contributing to the OP but not the pyrethroid resistance. Significant differences in resistance gene frequencies were obtained from the F1 mosquitoes resulting from adults obtained by different collection methods. This may be caused by different insecticide selection pressures on the insects immediately prior to collection, or may be an indication that the indoor- and outdoor-resting A. albimanus collections are not from a randomly mating single population. The underlying genetic variability of the populations is currently being investigated by molecular methods.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.

PubMed

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J; Zetterberg, Henrik; Price, Richard W; Gisslén, Magnus; Spudich, Serena

2017-04-01

We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

PubMed Central

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J.; Zetterberg, Henrik; Price, Richard W.; Gisslén, Magnus

2017-01-01

Abstract Background. We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods. The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. Results. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = −0.352 and P < .001 at baseline and r = −0.387 and P = .008 longitudinally) but not with neuropsychological performance. Conclusion. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. PMID:28368497

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

Cardiovascular Risk Factors in Severely Obese Adolescents

PubMed Central

Michalsky, Marc P.; Inge, Thomas H.; Simmons, Mark; Jenkins, Todd M.; Buncher, Ralph; Helmrath, Michael; Brandt, Mary L.; Harmon, Carroll M.; Courcoulas, Anita; Chen, Michael; Horlick, Mary; Daniels, Stephen R.; Urbina, Elaine M.

2015-01-01

IMPORTANCE Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. OBJECTIVE To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children’s Hospital in Columbus, Ohio; Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio; Texas Children’s Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children’s Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. MAIN OUTCOMES AND MEASURES This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. RESULTS The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit increase in body mass index (P < .01). Dyslipidemia (adjusted relative risk = 1.60 [95% CI, 1.26–2.03]; P < .01) and elevated blood pressure (adjusted relative risk = 1.48 [95% CI, 1.16–1.89]; P < .01) were more likely in adolescent boys compared with adolescent girls. White individuals were at greater risk of having elevated triglyceride levels (adjusted relative risk = 1.76 [95% CI, 1.14–2.72]; P = .01) but were less likely to have impaired fasting glucose levels (adjusted relative risk = 0.58 [95% CI, 0.38–0.89]; P = .01). CONCLUSIONS AND RELEVANCE Numerous CVD risk factors are apparent in adolescents undergoing weight-loss surgery. Increasing body mass index and male sex increase the relative risk of specific CVD risk factors. These data suggest that even among severely obese adolescents, recognition and treatment of CVD risk factors is important to help limit further progression of disease. PMID:25730293

Cardiovascular Risk Factors in Severely Obese Adolescents: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Study.

PubMed

Michalsky, Marc P; Inge, Thomas H; Simmons, Mark; Jenkins, Todd M; Buncher, Ralph; Helmrath, Michael; Brandt, Mary L; Harmon, Carroll M; Courcoulas, Anita; Chen, Michael; Horlick, Mary; Daniels, Stephen R; Urbina, Elaine M

2015-05-01

Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children's Hospital in Columbus, Ohio; Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio; Texas Children's Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children's Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit increase in body mass index (P < .01). Dyslipidemia (adjusted relative risk = 1.60 [95% CI, 1.26-2.03]; P < .01) and elevated blood pressure (adjusted relative risk = 1.48 [95% CI, 1.16-1.89]; P < .01) were more likely in adolescent boys compared with adolescent girls. White individuals were at greater risk of having elevated triglyceride levels (adjusted relative risk = 1.76 [95% CI, 1.14-2.72]; P = .01) but were less likely to have impaired fasting glucose levels (adjusted relative risk = 0.58 [95% CI, 0.38-0.89]; P = .01). Numerous CVD risk factors are apparent in adolescents undergoing weight-loss surgery. Increasing body mass index and male sex increase the relative risk of specific CVD risk factors. These data suggest that even among severely obese adolescents, recognition and treatment of CVD risk factors is important to help limit further progression of disease.

Fluctuations in Nucleus Accumbens Extracellular Glutamate and Glucose during Motivated Glucose-drinking Behavior: Dissecting the Neurochemistry of Reward

PubMed Central

Wakabayashi, Ken T.; Myal, Stephanie E.; Kiyatkin, Eugene A.

2015-01-01

While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain’s excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery due to neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. PMID:25393775

Association between anxiety and depression in patients with acute coronary syndromes due to financial crisis.

PubMed

Lampropoulos, Kostandinos; Kavvouras, Charalampos; Megalou, Aikaterini; Tsikouri, Pinelopi; Kafkala, Chrysanthi; Derka, Dimitra; Bonou, Maria; Barbetseas, John

2016-01-01

The effect of anxiety and depression on patients with acute coronary syndromes (ACS) warrants investigation, especially during periods of economic crisis. To investigate the relation between anxiety and depression in patients presenting with ACS due to financial crisis and to investigate whether these two entities could predict long-term cardiovascular mortality. Anxiety and depression symptoms were assessed in 350 patients (210 men) presenting with ACS, with 70 (20%) patients showing elevated scores (Hellenic Heart Failure Protocol). Over a mean follow-up of 48 months there were 36 (10%) cardiovascular deaths. Cox proportional hazards models adjusted for other prognostic factors (including age, sex, marital status, creatinine levels, left ventricular ejection fraction, heart failure, atrial fibrillation, previous hospitalisation, and baseline medications) showed that elevated anxiety and depression scores significantly predicted cardiovascular mortality (primary outcome) and all-cause mortality. Elevated anxiety and depression symptoms are related to cardiovascular mortality due probably to financial crisis, even after adjustment for other prognostic indicators in patients with ACS, who received optimised medical treatment.

Dexamethasone and perioperative blood glucose in patients undergoing total joint arthroplasty: A retrospective study.

PubMed

Nurok, Michael; Cheng, Jennifer; Romeo, Giulio R; Vecino, Stephanie M; Fields, Kara G; YaDeau, Jacques T

2017-02-01

Perioperative dexamethasone is commonly used to prevent nausea. It can also increase blood glucose levels, and recent concern about its blood glucose-elevating effect in humans has been raised. This study aimed to demonstrate relationships between dexamethasone administration and elevated perioperative blood glucose in patients undergoing total joint arthroplasty. Retrospective study. Academic, orthopedic hospital. A total of 625 patients (18-99years) who underwent total hip or total knee arthroplasty with an ASA ≤3 were included in the study. Patients who received dexamethasone perioperatively were compared to those who did not receive dexamethasone. The primary outcome, which was any postoperative glucose >200mg/dl, was compared between groups using multiple logistic regression. Demographic information, intraoperative information, incidence of postoperative nausea and vomiting, white blood cell count, medication use, and length of stay were also collected. Perioperative dexamethasone (median [1st quartile, 3rd quartile] dose=4 [4, 8] mg) was administered to 76% of patients. Only 5.6% (95% CI: 3.8-7.5) of patients had postoperative glucose levels >200mg/dl. After covariate adjustment, there was no evidence of a difference in odds of experiencing postoperative glucose levels >200mg/dl (odds ratio [95% CI]: 0.76 [0.28-2.07]; P=0.594) and maximum glucose levels (P=0.518) between groups. Dexamethasone-treated patients had greater changes in white blood cell count between baseline and postoperative days 0-1. There was no evidence of a difference in wound healing and length of stay between groups. There was no evidence of an association between perioperative dexamethasone administration and the odds of having postoperative glucose levels >200mg/dl or higher maximum glucose levels. However, these findings may not be generalizable to patients having different baseline characteristics or procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Iodinated contrast media can induce long-lasting oxidative stress in hemodialysis patients.

PubMed

Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel; Yoon, Soo Young

2013-11-01

Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients.

Stress and selective attention: the interplay of mood, cortisol levels, and emotional information processing.

PubMed

Ellenbogen, Mark A; Schwartzman, Alex E; Stewart, Jane; Walker, Claire-Dominique

2002-11-01

The effects of a stressful challenge on the processing of emotional words were examined in college students. Stress induction was achieved using a competitive computer task, where the individual either repeatedly lost or won against a confederate. Mood, attention, and cortisol were recorded during the study. There were four findings: (1) Participants in the negative stressor condition were faster to shift attention away from negative words than positive or neutral words; (2) attentional shifts away from negative words were associated with stress-induced mood lowering; (3) participants in the negative stress condition with elevated scores on the Beck Depression Inventory were slow to disengage attention from all stimuli; and (4) elevated depression scores were associated with lower cortisol change from baseline during the experimental phase, and with higher cortisol levels during the recovery phase. These findings point to information-processing strategies as a means to regulate emotion, and to atypical features of cognitive and adrenocortical function that may serve as putative risk markers of depression.

Moderators of the Intervention Effects for a Dissonance-Based Eating Disorder Prevention Program; Results from an Amalgam of Three Randomized Trials

PubMed Central

Müller, Sina; Stice, Eric

2013-01-01

Objective To investigate factors hypothesized to moderate the effects of a dissonance-based eating disorder prevention program, including initial elevations in thin-ideal internalization, body dissatisfaction, eating disorder symptoms, and older participant age. Method Adolescent female high school and college students with body image concerns (N = 977; M age = 18.6) were randomized to a dissonance-based thin-ideal internalization reduction program or an assessment-only control condition in three prevention trials. Results The intervention produced (a) significantly stronger reductions in thin-ideal internalization for participants with initial elevations in thin-ideal internalization and a threshold/subthreshold DSM-5 eating disorder at baseline, (b) significantly greater reductions in eating disorder symptoms for participants with versus without a DSM-5 eating disorder at baseline, and (c) significantly stronger reductions in body dissatisfaction for late adolescence/young adulthood versus mid-adolescent participants. Baseline body dissatisfaction did not moderate the intervention effects. Conclusion Overall, intervention effects tended to be amplified for individuals with initial elevations in risk factors and a DSM-5 eating disorder at baseline. Results suggest that this prevention program is effective for a broad range of individuals, but is somewhat more beneficial for the subgroups identified in the moderation analyses. PMID:23337181

Thyroid Function among Breastfed Children with Chronically Excessive Iodine Intakes

PubMed Central

Aakre, Inger; Strand, Tor A.; Bjøro, Trine; Norheim, Ingrid; Barikmo, Ingrid; Ares, Susana; Alcorta, Marta Duque; Henjum, Sigrun

2016-01-01

Iodine excess may impair thyroid function and trigger adverse health consequences for children. This study aims to describe iodine status among breastfed infants with high iodine exposure in the Saharawi refugee camps Algeria, and further assess thyroid function and iodine status among the children three years later. In 2010, a cross-sectional study among 111 breastfed children aged 0–6 months was performed (baseline study). In 2013, a second cross-sectional study (follow-up study) was conducted among 289 children; 213 newly selected and 76 children retrieved from baseline. Urinary iodine concentration (UIC) and breast milk iodine concentration (BMIC) were measured at baseline. UIC, thyroid hormones and serum thyroglobulin (Tg) were measured at follow-up. At baseline and follow-up, 88% and 72% had excessive iodine intakes (UIC ≥ 300 µg/L), respectively. At follow-up, 24% had a thyroid hormone disturbance and/or elevated serum Tg, including 9% with subclinical hypothyroidism (SCH), 4% with elevated fT3 and 14% with elevated Tg. Children with SCH had poorer linear growth and were more likely to be underweight than the children without SCH. Excessive iodine intakes and thyroid disturbances were common among children below four years of age in our study. Further, SCH seemed to be associated with poor growth and weight. PMID:27367720

Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

PubMed Central

Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

2013-01-01

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

Local and systemic inflammatory responses to experimentally induced gingivitis.

PubMed

Leishman, Shaneen J; Seymour, Gregory J; Ford, Pauline J

2013-01-01

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study.

PubMed

Chen, Li-Ping; Dai, Hai-Yang; Dai, Zhuo-Zhi; Xu, Chong-Tao; Wu, Ren-Hua

2014-05-01

We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Foliar concentrations of volunteer willows growing on polluted sediment-derived sites versus sites with baseline contamination levels.

PubMed

Vandecasteele, Bart; Quataert, Paul; De Vos, Bruno; Tack, Filip M G; Muys, Bart

2004-04-01

Many alluvial soils along navigable waterways are affected by disposal of dredged sediments or overbank sedimentation and contain metal concentrations that are elevated compared to baseline levels. Uptake patterns for metals and other elements by several volunteer Salix species growing on these sites were determined during a growing season in field plots and compared with the same species growing on soils with baseline contamination levels. For Cd and Zn, foliar concentrations were clearly higher on dredged sediment landfills. Uptake patterns differed significantly between species. A high uptake of Mn and low uptake of Cu, K and S in S. cinerea was attributed to wetland soil chemistry. Site effects on metal uptake were evaluated in more detail for Salix cinerea and S. alba growing on different sediment-derived sites under field conditions. Foliar Cd concentrations were higher in S. cinerea than in S. alba. This appeared to be a genetic feature not influenced by soil chemical properties, as it was observed both on clean sites and polluted sediment-derived sites. For S. cinerea, soil chemistry was reflected in foliar concentrations, while foliar Cd concentrations and bioavailability were found to be independent of the thickness of the polluted horizon. Dredged sediment landfills and freshwater tidal marshes with comparable Cd soil pollution had significantly different foliar Cd concentrations.

C-Peptide, Baseline and Postprandial Insulin Resistance after a Carbohydrate-Rich Test Meal - Evidence for an Increased Insulin Clearance in PCOS Patients?

PubMed

Stassek, J; Erdmann, J; Ohnolz, F; Berg, F D; Kiechle, M; Seifert-Klauss, V

2017-01-01

Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study ( L ifestyle I ntervention for Patients with Polycystic Ovary Syndrome [ PCOS ]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p < 0.001) so was C-peptide (p < 0.025). Conclusions In the present study we have shown for the first time that, after consumption of a standardised test meal, PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients.

Predictors of early infection in cerebral ischemic stroke.

PubMed

Ashour, Wmr; Al-Anwar, A D; Kamel, A E; Aidaros, M A

2016-01-01

Infection is the most common complication of stroke. To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the independent predictors of PSI.

Predictors of early infection in cerebral ischemic stroke

PubMed Central

Ashour, WMR; Al-Anwar, AD; Kamel, AE; Aidaros, MA

2016-01-01

Background: Infection is the most common complication of stroke. Aim: To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. Subjects: The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. Methods: All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. Results: SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Conclusion: Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the independent predictors of PSI. PMID:27453748

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

PubMed Central

Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

2014-01-01

Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

Prognostic Implications of Single-Sample Confirmatory Testing for Undiagnosed Diabetes: A Prospective Cohort Study.

PubMed

Selvin, Elizabeth; Wang, Dan; Matsushita, Kunihiro; Grams, Morgan E; Coresh, Josef

2018-06-19

Current clinical definitions of diabetes require repeated blood work to confirm elevated levels of glucose or hemoglobin A1c (HbA1c) to reduce the possibility of a false-positive diagnosis. Whether 2 different tests from a single blood sample provide adequate confirmation is uncertain. To examine the prognostic performance of a single-sample confirmatory definition of undiagnosed diabetes. Prospective cohort study. The ARIC (Atherosclerosis Risk in Communities) study. 13 346 ARIC participants (12 268 without diagnosed diabetes) with 25 years of follow-up for incident diabetes, cardiovascular outcomes, kidney disease, and mortality. Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and HbA1c (≥6.5%) from a single blood sample. Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes. Lack of repeated measurements of fasting glucose and HbA1c. A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population. National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.

National study of the role of recent illicit substance use on the relationship between depressive symptoms and sexual risk behavior among child welfare-involved adolescents.

PubMed

Traube, Dorian; Holloway, Ian; Zhang, Jinjin

2013-07-01

The present study examined the association between early-adolescent depressive symptoms and lifetime sexual risk behavior and whether that association was moderated by recent illicit substance use among adolescents reported for maltreatment. Data came from Waves 1 (baseline) and 4 (36-month follow-up) of the National Survey of Child and Adolescent Well-Being, a national probability study of youths undergoing investigation for abuse or neglect (n = 861). Multivariate logistic regression was used to explore main effects and moderation models among baseline depressive symptoms, lifetime sexual risk behavior, and recent illicit substance use. Baseline depressive symptoms and recent illicit drug use played little role in predicting ever having intercourse, age at first intercourse, or pregnancy. Recent use of illicit substances moderated the relationship between early-adolescent depressive symptoms and condom use behavior (odds ratio = 0.85, p < .001) such that individuals who were more depressed at baseline and who used illicit drugs within the last 30 days were less likely to have often/always used condoms. Conversely, individuals with higher levels of depressive symptoms at baseline who had not engaged in illicit substance use in the last 30 days were more likely to often use condoms during sexual activity. Results suggest that among adolescents reported for maltreatment, use of illicit substances may moderate the relationship between elevated levels of depressive symptoms during early adolescence and condom use as children age thorough adolescence. Interventions for child welfare-engaged youths should focus on prevention and treatment of depression and substance use.

Mindfulness-based yoga intervention for women with depression.

PubMed

Schuver, Katie J; Lewis, Beth A

2016-06-01

The purpose of this study was to examine the efficacy of a 12-week mindfulness-based yoga intervention on depressive symptoms and rumination among depressed women. Prospective, randomized, controlled 12 week intervention pilot study. Depressive symptoms were assessed at baseline, post-intervention (12 weeks), and one-month follow-up. Women with a history of diagnosed depression and currently depressed were randomized to a mindfulness-based yoga condition or a walking control. The mindfulness-based yoga intervention consisted of a home-based yoga asana, pranayama and meditation practice with mindfulness education sessions delivered over the telephone. The walking control condition consisted of home-based walking sessions and health education sessions delivered over the phone. The Beck Depression Inventory (BDI) and Ruminative Responses Scale (RRS). Both groups reported decreases in depressive symptoms from baseline to post-intervention, f(1,33)=34.83, p<0.001, and from baseline to one-month follow-up, f(1,33)=37.01, p<0.001. After controlling for baseline, there were no significant between group differences on depression scores at post-intervention and the one-month follow-up assessment. The mindfulness-based yoga condition reported significantly lower levels of rumination than the control condition at post-intervention, after controlling for baseline levels of rumination, f(1,31)=6.23, p<0.01. These findings suggest that mindfulness-based yoga may provide tools to manage ruminative thoughts among women with elevated depressive symptoms. Future studies, with larger samples are needed to address the effect of yoga on depression and further explore the impact on rumination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of 10-year C-reactive protein trajectories with markers of healthy aging: findings from the English Longitudinal Study of Ageing.

PubMed

Lassale, Camille; Batty, G David; Steptoe, Andrew; Cadar, Dorina; Akbaraly, Tasnime N; Kivimäki, Mika; Zaninotto, Paola

2018-02-15

Elevated systematic inflammation is a hallmark of aging, but the association of long-term inflammation trajectories with subsequent aging phenotypes has been little examined. We assessed inflammatory marker C-reactive protein (CRP) repeatedly over time and examined whether long-term changes predicted aging outcomes. A total of 2,437 men and women aged 47-87 years at baseline (1998-2001) who were participants in the English Longitudinal Study of Ageing had CRP measured on two or three occasions between 1998 and 2009. Inflammation trajectories were computed using latent-class growth mixture modelling and were related to aging outcomes measured in 2012/2013: physical functioning, cardiometabolic, respiratory, mental health, and a composite "healthy aging" outcome. Four CRP trajectories were identified: 'stable-low' (71% of the sample) with baseline mean 1.33mg/L remaining <3mg/L; 'medium-to-high' (14%) with baseline 2.7mg/L rising to 5.3mg/L; 'high-to-medium' (10%) with baseline 6.6mg/L decreasing to 2.4mg/L; 'stable-high' (5%) with levels from 5.7 to 7.5mg/L. Relative to the stable-low trajectory, individuals in the medium-to-high had a higher risk of limitations in basic activities of daily living (ADL, Odds Ratio; 95% Confidence Interval: 2.09; 1.51,2.88), instrumental ADL (1.62; 1.15,2.30), impaired balance (1.59; 1.20,2.11) and walking speed (1.61; 1.15,2.24), arthritis (1.55; 1.16,2.06), hypertension (1.57; 1.21,2.04), obesity (1.95; 1.36,2.80), poor respiratory function (1.84; 1.36,2.50), and depression (1.55; 1.13,2.12). A lower odds of healthy aging was observed in people in the medium-to-high (0.57; 0.40,0.79) and stable-high (0.50; 0.27,0.91) trajectories. Older people who displayed an elevation in CRP levels over a decade experienced an increased risk of adverse aging outcomes.

Self-Compassion as a Prospective Predictor of PTSD Symptom Severity Among Trauma-Exposed U.S. Iraq and Afghanistan War Veterans

PubMed Central

Hiraoka, Regina; Meyer, Eric C.; Kimbrel, Nathan A.; DeBeer, Bryann B.; Gulliver, Suzy Bird; Morissette, Sandra B.

2016-01-01

U. S. combat veterans of the Iraq and Afghanistan wars have elevated rates of posttraumatic stress disorder (PTSD) compared to the general population. Self-compassion, characterized by self-kindness, a sense of common humanity when faced with suffering, and mindful awareness of suffering, is a potentially modifiable factor implicated in the development and maintenance of PTSD. We examined the concurrent and prospective relationship between self-compassion and PTSD symptom severity after accounting for level of combat exposure and baseline PTSD severity. Participants at baseline assessment were 115 Iraq and Afghanistan war veterans exposed to 1 or more traumatic events during deployment (n = 101 at follow-up). PTSD symptoms were assessed using the Clinician Administered PTSD Scale for DSM-IV at baseline and 12 months. Self-compassion and combat exposure were assessed at baseline via self-report. Self-compassion was associated with baseline PTSD symptoms after accounting for combat exposure (β = −.59; p < .001; ΔR2 = .34; f2 = .67; large effect) and predicted 12-month PTSD symptom severity after accounting for combat exposure and baseline PTSD severity (β = −.24; p = .008; ΔR2 = .03; f2 = .08; small effect). Findings suggest that interventions that increase self-compassion may be beneficial for treating chronic PTSD symptoms among some Iraq and Afghanistan war veterans. PMID:25808565

Carbon dioxide induced plasticity of branchial acid-base pathways in an estuarine teleost

PubMed Central

Allmon, Elizabeth B.; Esbaugh, Andrew J.

2017-01-01

Anthropogenic CO2 is expected to drive ocean pCO2 above 1,000 μatm by 2100 – inducing respiratory acidosis in fish that must be corrected through branchial ion transport. This study examined the time course and plasticity of branchial metabolic compensation in response to varying levels of CO2 in an estuarine fish, the red drum, which regularly encounters elevated CO2 and may therefore have intrinsic resilience. Under control conditions fish exhibited net base excretion; however, CO2 exposure resulted in a dose dependent increase in acid excretion during the initial 2 h. This returned to baseline levels during the second 2 h interval for exposures up to 5,000 μatm, but remained elevated for exposures above 15,000 μatm. Plasticity was assessed via gene expression in three CO2 treatments: environmentally realistic 1,000 and 6,000 μatm exposures, and a proof-of-principle 30,000 μatm exposure. Few differences were observed at 1,000 or 6,000 μatm; however, 30,000 μatm stimulated widespread up-regulation. Translocation of V-type ATPase after 1 h of exposure to 30,000 μatm was also assessed; however, no evidence of translocation was found. These results indicate that red drum can quickly compensate to environmentally relevant acid-base disturbances using baseline cellular machinery, yet are capable of plasticity in response to extreme acid-base challenges. PMID:28378831

Carbon dioxide induced plasticity of branchial acid-base pathways in an estuarine teleost

NASA Astrophysics Data System (ADS)

Allmon, Elizabeth B.; Esbaugh, Andrew J.

2017-04-01

Anthropogenic CO2 is expected to drive ocean pCO2 above 1,000 μatm by 2100 - inducing respiratory acidosis in fish that must be corrected through branchial ion transport. This study examined the time course and plasticity of branchial metabolic compensation in response to varying levels of CO2 in an estuarine fish, the red drum, which regularly encounters elevated CO2 and may therefore have intrinsic resilience. Under control conditions fish exhibited net base excretion; however, CO2 exposure resulted in a dose dependent increase in acid excretion during the initial 2 h. This returned to baseline levels during the second 2 h interval for exposures up to 5,000 μatm, but remained elevated for exposures above 15,000 μatm. Plasticity was assessed via gene expression in three CO2 treatments: environmentally realistic 1,000 and 6,000 μatm exposures, and a proof-of-principle 30,000 μatm exposure. Few differences were observed at 1,000 or 6,000 μatm however, 30,000 μatm stimulated widespread up-regulation. Translocation of V-type ATPase after 1 h of exposure to 30,000 μatm was also assessed; however, no evidence of translocation was found. These results indicate that red drum can quickly compensate to environmentally relevant acid-base disturbances using baseline cellular machinery, yet are capable of plasticity in response to extreme acid-base challenges.

The effect of increased intra-abdominal pressure on orbital subarachnoid space width and intraocular pressure.

PubMed

Liu, Su-Meng; Wang, Ning-Li; Zuo, Zhen-Tao; Chen, Wei-Wei; Yang, Di-Ya; Li, Zhen; Cao, Yi-Wen

2018-02-01

In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can relieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22-30 years (12 females and 3 males), at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg (1 mmHg = 0.133 kPa), then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ± 0.1 mm (range: 0.77-1.05 mm), 0.77 ± 0.11 mm (range: 0.60-0.94 mm), 0.70 ± 0.08 mm (range: 0.62-0.80 mm), and 0.68 ± 0.08 mm (range: 0.57-0.77 mm) at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased intra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-ONRC-14004947).

Can urine dipstick predict an elevated serum creatinine?

PubMed

Shah, Kaushal; Kilian, Barbara; Hsieh, Wei-Jen; Kyrillou, Emily; Hedge, Vishal; Newman, David H

2010-06-01

Chart review studies have suggested that point-of-care urine dipstick testing may accurately predict an elevation in serum creatinine (Cr). We aimed to prospectively evaluate the test characteristics of proteinuria/hematuria in predicting elevated serum Cr. A prospective, observational study was conducted between March 2007 and June 2008 at 2 affiliated, urban hospitals with an annual emergency department census of 150,000. Patients undergoing laboratory urinalysis, point-of-care urine dipstick, and a serum chemistry panel were enrolled. Trained research assistants collected data on consecutive patients 18 hours per day using preformatted data forms and entry into an anonymized Access (Microsoft, Seattle, Wash) database. Demographic baseline variables including age, sex, chief complaint, vital signs, and source of sample (catheter vs "clean catch") were also collected. An elevated Cr level was defined as greater than 1.3 based on the laboratory reference range. Standard statistical methods were used to calculate diagnostic test operating characteristics of proteinuria or hematuria as a predictor of elevated serum Cr. Five thousand four hundred sixteen subjects were enrolled with 28.3% male and a mean age of 50.2 years. Elevated serum Cr greater than 1.3 mg/dL was found in 13.9% (755/5416) of subjects. The sensitivity of either proteinuria or hematuria for elevated Cr was 82.5% (95% confidence interval [CI], 80%-85%) and specificity was 34.4% (95% CI, 33%-36%). Positive predictive value was 16.9% (95% CI, 16%-18%) and negative predictive value was 92.4% (95% CI, 91-94%). The likelihood ratio for a positive test was 1.3 (95% CI, 1.1-1.5), and the likelihood ratio for a negative test was 0.5 (95% CI, 0.3-0.8). Although negative predictive value was high, the presence of proteinuria/hematuria was only moderately predictive of elevated serum Cr level. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women.

PubMed

Lovallo, William R; Farag, Noha H; Vincent, Andrea S; Thomas, Terrie L; Wilson, Michael F

2006-03-01

Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Preclinical High-Dose Acetaminophen With N-Acetylcysteine Rescue Enhances the Efficacy of Cisplatin Chemotherapy in Atypical Teratoid Rhabdoid Tumors

PubMed Central

Neuwelt, Alexander J.; Nguyen, Tam; Wu, Y. Jeffrey; Donson, Andrew M.; Vibhakar, Rajeev; Venkatamaran, Sujatha; Amani, Vladimir; Neuwelt, Edward A.; Rapkin, Louis B.; Foreman, Nicholas K.

2016-01-01

Background Atypical teratoid rhabdoid tumors (AT-RT) are pediatric tumors of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) with high dose acetaminophen (AAP), may improve therapeutic efficacy in AT-RT in vitro. Procedure BT16 (cisplatin-resistant) and BT12 (cisplatin-sensitive) AT-RT cell lines were treated with combinations of AAP, cisplatin, and the anti-oxidant N-acetylcysteine (NAC). Cell viability, GSH and peroxide concentrations, mitochondrial damage, and apoptosis were evaluated in vitro. Results AAP enhanced cisplatin cytotoxicity in cisplatin-resistant BT16 cells but not cisplatin-sensitive BT12 cells. Baseline GSH levels were elevated in BT16 cells compared to BT12 cells, and AAP decreased GSH to a greater magnitude in BT16 cells than BT12 cells. Unlike BT12 cells, BT16 cells did not have elevated peroxide levels upon treatment with cisplatin alone, but did have elevated levels when treated with AAP + cisplatin. Both cell lines had markedly increased mitochondrial injury when treated with AAP + cisplatin relative to either drug treatment alone. The enhanced toxic effects were partially reversed with concurrent administration of NAC. Conclusions Our results suggest that AAP could be used as a chemo-enhancement agent to potentiate cisplatin chemotherapeutic efficacy particularly in cisplatin-resistant AT-RT tumors with high GSH levels in clinical settings. PMID:23956023

High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

PubMed

Qi, Weiwei; Yang, Chuan; Dai, Zhiyu; Che, Di; Feng, Juan; Mao, Yuling; Cheng, Rui; Wang, Zhongxiao; He, Xuemin; Zhou, Ti; Gu, Xiaoqiong; Yan, Li; Yang, Xia; Ma, Jian-Xing; Gao, Guoquan

2015-04-01

Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/β-catenin signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Assessing human metal accumulations in an urban superfund site.

PubMed

Hailer, M Katie; Peck, Christopher P; Calhoun, Michael W; West, Robert F; James, Kyle J; Siciliano, Steven D

2017-09-01

Butte, Montana is part of the largest superfund site in the continental United States. Open-pit mining continues in close proximity to Butte's urban population. This study seeks to establish baseline metal concentrations in the hair and blood of individuals living in Butte, MT and possible routes of exposure. Volunteers from Butte (n=116) and Bozeman (n=86) were recruited to submit hair and blood samples and asked to complete a lifestyle survey. Elemental analysis of hair and blood samples was performed by ICP-MS. Three air monitors were stationed in Butte to collect particulate and filters were analyzed by ICP-MS. Soil samples from the yards of Butte volunteers were quantified by ICP-MS. Hair analysis revealed concentrations of Al, As, Cd, Cu, Mn, Mo, and U to be statistically elevated in Butte's population. Blood analysis revealed that the concentration of As was also statistically elevated in the Butte population. Multiple regression analysis was performed for the elements As, Cu, and Mn for hair and blood samples. Soil samples revealed detectable levels of As, Pb, Cu, Mn, and Cd, with As and Cu levels being higher than expected in some of the samples. Air sampling revealed consistently elevated As and Mn levels in the larger particulate sampled as compared to average U.S. ambient air data. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparing effects of carbohydrate (CHO) blockers and trivalent chromium on CHO-induced insulin resistance and elevated blood pressure in rats.

PubMed

Preuss, Harry G; Echard, Bobby; Bagchi, Debasis; Perricone, Nicholas V

2013-01-01

In Sprague-Dawley rats (SD), we compared two categories of natural dietary supplements that influence carbohydrate (CHO) metabolism via different basic mechanisms to ameliorate insulin resistance (IR) and elevated blood pressure (BP) associated with heavy sugar/starch consumption. Two dietary supplements (bean extract and l-arabinose) are often referred to as carb blockers (CBs), because they slow the gastrointestinal absorption of CHO. Trivalent chromium (CR) falls into a group of so-called insulin sensitizers, because its major effect is to enhance peripheral insulin sensitivity. We divided 48 mature male SD into 4 groups of 12. The first group received powdered baseline diet alone (Con). The remaining 3 SD groups (groups 2-4) ingested regular rat chow containing 20% w/w sucrose and 20% w/w rice starch. The second group received only this CHO-enriched chow. To the high-CHO diets of the remaining two groups, either CB to slow CHO absorption (CHO + CB) (group 3) or an insulin sensitizer, trivalent CR (CHO + CR; group 4), was added. Compared to Con group 1, adding high CHO content to the diet of group 2 significantly increased circulating glucose levels and systolic BP (SBP). Addition of CB or CR to the feed of groups 3 and 4 overcame the perturbations that occurred with high CHO challenge in group 2; that is, they lowered circulating glucose concentrations to Con levels, enhanced response to exogenous insulin, and overcame the gradual elevation of SBP. Compared to group 2, the two treatment groups (3 and 4) also showed decreased renin-angiotensin system activity, decreased serum angiotensin-converting enzyme activity, and enhanced nitric oxide activity. Our data indicate that high doses of CB and CR, despite their different mechanisms of action, can completely overcome CHO-induced IR and BP elevations. The data further suggest that CB and CR affect only the changes brought on by heavy CHO ingestion, because IR and SBP in groups 3 and 4 mirrored Con values (group 1), never producing values lower than baseline. Earlier use of CB and CR in the life cycle appears more effective in overcoming CHO-induced perturbations than later use.

Is there any relationship between coronary artery disease and postprandial triglyceride levels?

PubMed

Atar, Inci Aslı; Atar, Ilyas; Aydınalp, Alp; Ertan, Cağatay; Bozbaş, Hüseyin; Ozin, Bülent; Yıldırır, Aylin; Müderrisoğlu, Haldun

2011-05-01

We aimed to evaluate the relationship between postprandial triglyceride (PPTG) levels and coronary artery disease (CAD). A total of 80 patients were included in this prospective cohort study. Oral lipid loading was used in order to measure PPTG levels. In the fasting state and after the high fat breakfast, triglyceride levels were measured by enzymatic methods at 2nd, 4th, 6th and 8th hours. We made subgroup analysis to show the effects of lipid loading on triglyceride levels in patients with and without fasting hypertriglyceridemia. We evaluated triglyceride levels and changes of triglyceride levels in percentages after lipid loading using a general linear model for repeated measures. Sample size analysis was performed. Baseline clinical, demographic and laboratory characteristics of both groups were similar. The peak triglyceride levels were seen at the 4th hour in both groups. Triglyceride levels were significantly increased after lipid-rich-breakfast loading compared to baseline levels in both groups (p<0.001) but these changes were not significant (p=0.279). In patients with elevated fasting triglyceride levels, the area under the plasma triglyceride concentration curve was significantly larger in CAD group than control group (334±103 vs. 233±58 mg/dl, p=0.02). Our data show that in patients who have a high fasting triglyceride level, high levels of PPTG may be related to CAD, however high PPTG levels are not related to CAD in patients with normal fasting levels of triglyceride.

Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis

PubMed Central

Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano

2017-01-01

Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs –7.31 [6.23]; P = .04). Conclusions and Relevance These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001. PMID:28384752

[Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China].

PubMed

Shi, Jun; Chang, Hong; Zhang, Li; Shao, Yinqi; Nie, Neng; Zhang, Jing; Huang, Jinbo; Zhang, Li; Tang, Xudong; Quan, Richeng; Zheng, Chunmei; Xiao, Haiyan; Hu, Dengming; Hu, Lingyan; Liu, Feng; Zhou, Yongming; Zheng, Yizhou; Zhang, Fengkui

2016-01-01

To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload. A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload. All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period. AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

PubMed

Anderson, George M; Scahill, Lawrence; McCracken, James T; McDougle, Christopher J; Aman, Michael G; Tierney, Elaine; Arnold, L Eugene; Martin, Andrés; Katsovich, Liliya; Posey, David J; Shah, Bhavik; Vitiello, Benedetto

2007-02-15

The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p < .0001). Prolactin levels were also significantly increased at 6 months (32.4 +/- 17.8 ng/ml; N = 43, p < .0001) and at 22 months (N = 30, 25.3 +/- 15.6 ng/ml, p < .0001). Prolactin levels were not associated with adverse effects and DRD2 alleles (Taq1A, -141C Ins/Del, C957T) did not significantly influence baseline levels or risperidone-induced increases in prolactin. Risperidone treatment was associated with two- to four-fold mean increases in serum prolactin in children with autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.

Fecal corticoid monitoring in whooping cranes (Grus americana) undergoing reintroduction

USGS Publications Warehouse

Hartup, Barry K.; Olsen, Glenn H.; Czekala, Nancy M.

2005-01-01

We used radioimmunoassay to determine fecal corticoid concentrations and assess potential stress in 10 endangered whooping cranes (Grus americana) undergoing reintroduction to the wild. Fecal samples were collected shortly after hatching at a captive facility in Maryland, during field training in Wisconsin, and throughout a human-led migration to Florida. After a 14-day decline following hatching, fecal corticoid concentrations stabilized at baseline levels for the duration of the captive period, despite exposure to potentially stressful stimuli. Shipment of the cranes to the field training site was correlated with an eight- to 34-fold increase in fecal corticoid concentrations, which returned to baseline levels within 1 week. Increases were positively correlated with age but not body weight at the time of shipping. Fecal corticoid concentrations during the training period increased slightly and exhibited greater variation than levels observed at the captive facility, but were well within expected norms based on previous studies. Fecal corticoid concentrations increased twofold following premigration physical examinations and placement of radiotransmitters, and persisted for up to 4 days before they returned to baseline levels. Though fecal corticoid concentrations and variation during the migration period were similar to training levels, there was an overall decline in fecal corticoid concentrations during the artificial migration. Acute stressors, such as capture, restraint, and severe storms, were associated with stress responses by the cranes that varied in accordance with lasting physical or psychological stimuli. The overall reintroduction process of costume-rearing, ultralight aircraft habituation, training, and artificial migration was not associated with elevations in fecal corticoid concentrations suggestive of chronic stress.

The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

PubMed

Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Pacheco-Moisés, Fermín Paul; Román-Pintos, Luis Miguel; Miranda-Díaz, Alejandra Guillermina

2016-07-01

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan.

PubMed

Kuwabara, Masanari; Borghi, Claudio; Cicero, Arrigo F G; Hisatome, Ichiro; Niwa, Koichiro; Ohno, Minoru; Johnson, Richard J; Lanaspa, Miguel A

2018-06-15

High serum uric acid (SUA) is associated with the dyslipidemia, but whether hyperuricemia predicts an increase in serum low-density lipoprotein (LDL) cholesterol is unknown. This study is to evaluate whether an elevated SUA predicts the development of high LDL cholesterol as well as hypertriglyceridemia. This is a retrospective 5-year cohort study of 6476 healthy Japanese adults (age, 45.7 ± 10.1 years; 2.243 men) who underwent health examinations at 2004 and were reevaluated in 2009 at St. Luke's International Hospital, Tokyo, Japan. Subjects were included if at their baseline examination they did not have hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, or if they were on medication for hyperuricemia and/or gout. The analysis was adjusted for age, body mass index (BMI), smoking and drinking habits, baseline estimated glomerular filtration rate (eGFR), baseline SUA and SUA change over the 5 years. High baseline SUA was an independent risk for developing high LDL cholesterol both in men (OR: 1.159 per 1 mg/dL increase, 95% CI:1.009-1.331) and women (OR: 1.215, 95% CI:1.061-1.390). Other risk factors included a higher baseline LDL cholesterol, higher BMI, and higher baseline eGFR (the latter two in women only). Increased SUA over 5 years were also independent risks for developing high LDL cholesterol and hypertriglyceridemia, but not for low high-density lipoprotein (HDL) cholesterol. This is the first study to report that an elevated SUA increases the risk for developing high LDL cholesterol, as well as hypertriglyceridemia. This may shed light into the role of SUA in cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

PubMed

Froud, Tatiana; Venkat, Shree R; Barbery, Katuzka J; Gunjan, Arora; Narayanan, Govindarajan

2015-09-01

Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. Copyright © 2015. Published by Elsevier Inc.

Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

PubMed

Humbert, M; Segal, E S; Kiely, D G; Carlsen, J; Schwierin, B; Hoeper, M M

2007-08-01

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.

Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.

PubMed

Wetherell, Mark A; Montgomery, Catharine

2014-04-01

Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

Clinical Significance of Postvoid Residual Volume in Older Ambulatory Women

PubMed Central

Huang, Alison J.; Brown, Jeanette S.; Boyko, Edward J.; Moore, Elya E.; Scholes, Delia; Walter, Louise C.; Lin, Feng; Vittinghoff, Eric; Fihn, Stephan D.

2013-01-01

Objectives To examine the prevalence, natural history, and clinical significance of elevations in postvoid residual (PVR) volume in ambulatory older women Design Prospective cohort study Setting Group health plan in Washington state Participants 987 ambulatory women aged 55 to 75 years Measurements PVR was measured by bladder ultrasonography at baseline, 1 year, and 2 years. Participants completed questionnaires about urinary symptoms and provided urine samples for microbiologic evaluation. Results Of the 987 participants, 79% had a PVR <50 mL, 10% had a PVR of 50–99 mL, 6% had a PVR of 100–199 mL, and 5% had a PVR ≥200 mL at baseline. Of women with a PVR <50, 66% reported at least one urinary symptom at baseline. Of women with a PVR ≥200 mL, 27% reported no significant symptoms at baseline. In adjusted analyses using data from all study visits, women with a PVR ≥100 mL were more likely to report urinating >8 times during the day (OR=1.42, CI=1.07–1.87), and women with a PVR ≥200 mL were more likely to report weekly urgency incontinence (OR=1.50, CI=1.03–2.18), versus those with a PVR <50 mL. Elevated PVR was not associated with increased risk of stress incontinence, nocturnal frequency, or urinary tract infection in adjusted analyses. Forty-six percent of those with a PVR ≥200 mL and 63% of those with a PVR of 100–199 mL at baseline had a PVR <50 mL at 2 years. Conclusion Over 10% of ambulatory older women may have a PVR ≥100 mL associated with increased risk of some urinary symptoms, but many with elevated PVR are asymptomatic, and elevations in PVR frequently resolve within 2 years. Symptom-guided management of urinary symptoms may be more appropriate than PVR-guided management in this population. PMID:21806559

Crisis occurrence and resolution in patients with severe and persistent mental illness: the contribution of suicidality.

PubMed

Links, Paul S; Eynan, Rahel; Ball, Jeffrey S; Barr, Aiala; Rourke, Sean

2005-01-01

Assertive community treatment appears to have limited impact on the risk of suicide in persons with severe and persistent mental illness (SPMI). This exploratory prospective study attempts to understand this observation by studying the contribution of suicidality to the occurrence of crisis events in patients with SPMI. Specifically, an observer-rated measure of the need for hospitalization, the Crisis Triage Rating Scale, was completed at baseline, crisis occurrence, and resolution to determine how much the level of suicidality contributed to the deemed level of crisis. Second, observer-ratings of suicidal ideation, the Modified Scale for Suicide Ideation, and psychopathology and suicidality, Brief Psychiatric Rating Scale, were measured at baseline, crisis occurrence, and resolution. A self-report measure of distress, the Symptom Distress Scale, was completed at baseline, crisis occurrence, and resolution. Finally, the patients' crisis experiences were recorded qualitatively to compare with quantitative measures of suicidality. Almost 40% of the subjects experienced crisis events and more than a quarter of these events were judged to be severe enough to warrant the need for hospitalization. Our findings suggest that elevation of psychiatric symptoms is a major contributor to the crisis occurrences of individuals with SPMI; although the risk of suicide may have to be conceived as somewhat separate from crisis occurrence.

Viral blips during suppressive antiretroviral treatment are associated with high baseline HIV-1 RNA levels.

PubMed

Sörstedt, Erik; Nilsson, Staffan; Blaxhult, Anders; Gisslén, Magnus; Flamholc, Leo; Sönnerborg, Anders; Yilmaz, Aylin

2016-06-21

Many HIV-1-infected patients on suppressive antiretroviral therapy (ART) have transiently elevated HIV RNA levels. The clinical significance of these viral blips is uncertain. We have determined the incidence of blips and investigated important associations in the Swedish HIV-cohort. HIV-1-infected ART naïve adults who commenced ART 2007-2013 were retrospectively included. Viral blips were defined as a transient viral load between 50 and 500 copies/mL Subjects not suppressed after six months on ART were excluded. Viral blips were found in 76/735 included subjects (10.3 %) and in 90/4449 samples (2.0 %). Median blip viral load was 76 copies/mL (range 56-138). Median follow-up time was 170 weeks (range 97-240). Baseline viral load was higher in subjects with viral blips (median log10 4.85 copies/mL) compared with subjects without blips (median log10 4.55 copies/mL) (p < 0.01). There was a significant association between viral blips and risk for subsequent virological failure (p < 0.001). The Swedish national HIV-cohort has a low incidence of viral blips (10 %). Blips were associated with high baseline viral load and an increased risk of subsequent virological failure.

Serum C-reactive protein and white blood cell count in morbidly obese surgical patients.

PubMed

Chen, Sheng-Bin; Lee, Yi-Chih; Ser, Kong-Han; Chen, Jung-Chien; Chen, Shu Chung; Hsieh, Hsing-Fang; Lee, Wei-Jei

2009-04-01

Obesity has been widely recognized as a chronic inflammatory condition and associated with elevated inflammatory indicators including C-reactive protein (CRP) and white blood cell count (WBC). Recent studies have shown elevated CRP or WBC is a significant risk factor for cardiac events and stroke but the clinical significance of CRP and WBC has not been clearly studied in morbidly obese patients. This study is aimed at the clinical significance of WBC and CRP in morbidly obese patients and the change after bariatric surgery. The study was a prospectively controlled clinical study. From December 1, 2001 to January 31, 2006, of 640 (442 females and 198 males) consecutive morbid obese patients enrolled in a surgically supervised weight loss program with at least 1 year's follow-up were examined. Of the patients, 476 (74.4%) had elevated CRP and 100 (15.6%) had elevated WBC at preoperative study. CRP and WBC were significantly related and both increased with increasing body mass index (BMI). CRP is also increased with increasing waist, glucose level, hemoglobin, albumin, Ca, insulin, C-peptide, and metabolic syndrome while WBC is increased with metabolic syndrome but decreased with increasing age. Multivariate analysis confirmed fasting glucose level and hemoglobin are independent predictors of the elevation of CRP while age is the only independent predictor for elevated WBC. Both WBC and CRP levels decreased rapidly after obesity surgery. These improvements resulted in a 69.8% reduction of CRP and 26.4% reduction of WBC 1 year after surgery. Although individuals who underwent laparoscopic gastric bypass lost significantly more weight (36.8 +/- 11.7 kg vs. 17.3 +/- 10.8 kg; p = 0.000) and achieved a lower BMI (27.8 +/- 4.6 vs. 35.0 +/- 5.5; p = 0.000) than individuals who underwent laparoscopic gastric banding, there was no difference in the resolution of elevated CRP 1 year after surgery (95.9% vs. 84.5%; p = 0.169) and WBC (99.4% vs. 98.3%; p = 0.323). Both baseline WBC and CRP are elevated in morbid obese patients but CRP has a better clinical significance. Significant weight reduction 1 year after surgery markedly reduced CRP and WBC with a resolution rate of 93.9% and 98.2% separately. Obesity surgery performed by laparoscopic surgery is recommended for obese patients with elevated CRP or WBC.

Association of Risk of Suicide Attempts With Methylphenidate Treatment.

PubMed

Man, Kenneth K C; Coghill, David; Chan, Esther W; Lau, Wallis C Y; Hollis, Chris; Liddle, Elizabeth; Banaschewski, Tobias; McCarthy, Suzanne; Neubert, Antje; Sayal, Kapil; Ip, Patrick; Schuemie, Martijn J; Sturkenboom, Miriam C J M; Sonuga-Barke, Edmund; Buitelaar, Jan; Carucci, Sara; Zuddas, Alessandro; Kovshoff, Hanna; Garas, Peter; Nagy, Peter; Inglis, Sarah K; Konrad, Kerstin; Häge, Alexander; Rosenthal, Eric; Wong, Ian C K

2017-10-01

Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear. To investigate the association between methylphenidate and the risk of suicide attempts. A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients. Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods. Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35). The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXIX. Elevation of erythrocyte sedimentation rate is associated with disease activity and damage accrual.

PubMed

Vilá, Luis M; Alarcón, Graciela S; McGwin, Gerald; Bastian, Holly M; Fessler, Barri J; Reveille, John D

2005-11-01

To determine if different categories of erythrocyte sedimentation rate (ESR) elevation are associated with disease activity and/or damage in systemic lupus erythematosus (SLE). We studied 2317 study visits in 553 SLE patients (> or = 4 American College of Rheumatology criteria, < or = 5 years' disease duration at enrollment) from a multiethnic (Hispanic, African American, and Caucasian) longitudinal study of outcome. A study visit was done every 6 months for the first year and annually thereafter. Erythrocyte sedimentation rate (ESR) was measured using the Westergren method; results were expressed in 4 categories: < 25 (normal), 25-50 (mild elevation), 51-75 (moderate elevation), and > 75 (marked elevation) mm/h. Anti-dsDNA antibodies were measured at enrollment with the Crithidia luciliae assay. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM) and the Physician's Global Assessment (PGA). Because ESR is one of the measures evaluated in the SLAM, it was excluded from the total SLAM score. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics damage index (SDI). The relationship between the SLAM (total and PGA) and SDI scores (at baseline and for all visits) and anti-dsDNA antibodies (at enrollment) with ESR was examined by univariable and generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered in all regression models. The cohort consisted of 89.7% women with mean age 36.8 (SD 12.6) years and disease duration 4.6 (SD 3.2) years. GEE analyses showed that increasing levels of ESR and anti-dsDNA antibody positivity were independently associated with SLAM and PGA scores, at enrollment and for all visits. Overall, the associations of ESR with SLAM and PGA scores were stronger than for the presence of anti-dsDNA antibodies. At baseline, there was no relationship of ESR elevation or anti-dsDNA positivity with SDI scores. However, when all visits were studied, moderate and marked elevations of ESR were independently associated with SDI scores. Mild, moderate, and marked ESR elevations are strongly associated with disease activity in SLE. Moderate and marked ESR elevations are also associated with damage accrual. These associations are stronger than those for the presence of anti-dsDNA antibodies. Our data suggest that ESR could be used to assess disease activity and predict organ/system damage in a relatively rapid and inexpensive manner in SLE.

Kidney Injury Associated with Telavancin Dosing Regimen in an Animal Model

PubMed Central

Ledesma, Kimberly R.; Bowers, Dana R.; Zhou, Jian; Truong, Luan D.

2015-01-01

The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted. PMID:25712358

Evaluating physiological stress in Sumatran tigers (Panthera tigris ssp. sumatrae) managed in Australian zoos.

PubMed

Parnell, Tempe; Narayan, Edward J; Magrath, Michael J L; Roe, Sheila; Clark, Giles; Nicolson, Vere; Martin-Vegue, Patrick; Mucci, Al; Hero, Jean-Marc

2014-01-01

Glucocorticoid quantification using non-invasive methods provides a powerful tool for assessing the health and welfare of wildlife in zoo-based programmes. In this study, we provide baseline data on faecal-based glucocorticoid (cortisol) monitoring of Sumatran tigers (Panthera tigris ssp. sumatrae) managed at the Melbourne Zoo in Victoria, Australia. We sampled five tigers daily for 60 days. Faecal cortisol metabolites (FCMs) in tiger faecal extracts were quantified using enzyme immunoassays that were successfully validated using parallelism and accuracy recovery checks. Two female tigers had significantly higher mean FCM levels than the two males and another female, suggesting that females may have higher FCM levels. A significant elevation was noted in the FCM levels for one female 2 days after she was darted and anaesthetized; however, the FCM levels returned to baseline levels within 3 days after the event. Comparative analysis of FCM levels of tigers sampled at Melbourne Zoo with tigers sampled earlier at two other Australian Zoos (Dreamworld Themepark and Australia Zoo) showed that FCM levels varied between zoos. Differences in the enclosure characteristics, timing of sampling, size and composition of groupings and training procedures could all contribute to this variation. Overall, we recommend the use of non-invasive sampling for the assessment of adrenocortical activity of felids managed in zoos in Australia and internationally in order to improve the welfare of these charismatic big cats.

Evaluating physiological stress in Sumatran tigers (Panthera tigris ssp. sumatrae) managed in Australian zoos

PubMed Central

Parnell, Tempe; Narayan, Edward J.; Magrath, Michael J. L.; Roe, Sheila; Clark, Giles; Nicolson, Vere; Martin-Vegue, Patrick; Mucci, Al; Hero, Jean-Marc

2014-01-01

Glucocorticoid quantification using non-invasive methods provides a powerful tool for assessing the health and welfare of wildlife in zoo-based programmes. In this study, we provide baseline data on faecal-based glucocorticoid (cortisol) monitoring of Sumatran tigers (Panthera tigris ssp. sumatrae) managed at the Melbourne Zoo in Victoria, Australia. We sampled five tigers daily for 60 days. Faecal cortisol metabolites (FCMs) in tiger faecal extracts were quantified using enzyme immunoassays that were successfully validated using parallelism and accuracy recovery checks. Two female tigers had significantly higher mean FCM levels than the two males and another female, suggesting that females may have higher FCM levels. A significant elevation was noted in the FCM levels for one female 2 days after she was darted and anaesthetized; however, the FCM levels returned to baseline levels within 3 days after the event. Comparative analysis of FCM levels of tigers sampled at Melbourne Zoo with tigers sampled earlier at two other Australian Zoos (Dreamworld Themepark and Australia Zoo) showed that FCM levels varied between zoos. Differences in the enclosure characteristics, timing of sampling, size and composition of groupings and training procedures could all contribute to this variation. Overall, we recommend the use of non-invasive sampling for the assessment of adrenocortical activity of felids managed in zoos in Australia and internationally in order to improve the welfare of these charismatic big cats. PMID:27293659

Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes

PubMed Central

Zanchi, Davide; Viallon, Magalie; Le Goff, Caroline; Millet, Grégoire P.; Giardini, Guido; Croisille, Pierre; Haller, Sven

2017-01-01

Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport. PMID:28105018

Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes.

PubMed

Zanchi, Davide; Viallon, Magalie; Le Goff, Caroline; Millet, Grégoire P; Giardini, Guido; Croisille, Pierre; Haller, Sven

2016-01-01

Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods: This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results: The whole brain ADC significantly increased from baseline to arrival ( p = 0.005) and then significantly decreased at recovery ( p = 0.005) to lower values than at baseline ( p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality ( p = 0.01), cholesterol ( p = 0.009), c-reactive protein ( p = 0.04), sodium ( p = 0.01), and chloride ( p = 0.002) plasma level variations. Conclusions: These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport.

Favorable Cardiovascular Health, Compression of Morbidity, and Healthcare Costs: Forty-Year Follow-Up of the CHA Study (Chicago Heart Association Detection Project in Industry).

PubMed

Allen, Norrina B; Zhao, Lihui; Liu, Lei; Daviglus, Martha; Liu, Kiang; Fries, James; Shih, Ya-Chen Tina; Garside, Daniel; Vu, Thanh-Huyen; Stamler, Jeremiah; Lloyd-Jones, Donald M

2017-05-02

We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual's all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up. We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health ( P <0.001) during Medicare eligibility. Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages. © 2017 American Heart Association, Inc.

The effects of alcohol on plasma lipid mediators of inflammation resolution in patients with Type 2 diabetes mellitus.

PubMed

Barden, Anne; Shinde, Sujata; Phillips, Michael; Beilin, Lawrence; Mas, Emilie; Hodgson, Jonathan M; Puddey, Ian; Mori, Trevor A

2018-06-01

Type 2 diabetes mellitus is characterized by peripheral insulin resistance and low-grade systemic inflammation. Inflammation resolution is recognised as an important process driven by specialised pro-resolving mediators of inflammation (SPMs) and has the potential to moderate chronic inflammation. Alcohol has the potential to affect synthesis of SPMs by altering key enzymes involved in SPM synthesis and may influence ongoing inflammation associated with Type 2 diabetes mellitus. (i) To examine the effects of alcohol consumed as red wine on plasma SPM in men and women with Type 2 diabetes in a randomised controlled trial and (ii) compare baseline plasma SPM levels in the same patients with those of healthy volunteers. Twenty-four patients with Type 2 diabetes mellitus were randomized to a three-period crossover study with men drinking red wine 300 ml/day (∼31 g alcohol/day) and women drinking red wine 230 ml/day (∼24 g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. The SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins (Rv) (RvE1-RvE3), 17-hydroxydocosahexaenoic acid (17-HDHA), and D-series resolvins (RvD1, 17R-RvD1, RvD2, RvD5), 14-hydroxydocosahexaenoic acid (14-HDHA) and Maresin 1 were measured at the end of each period. A baseline comparison of plasma SPM, hs CRP, lipids and glucose was made with healthy volunteers. Red wine did not differentially affect any of the SPM measured when compared with DRW or water. Baseline levels of the hs-CRP and the SPM 18-HEPE, 17-HDHA, RvD1 and 17R-RvD1 in patients with Type 2 diabetes mellitus were all significantly elevated compared with healthy controls and remained so after adjusting for age and gender. Moderate alcohol consumption as red wine does not alter plasma SPM in patients with Type 2 diabetes mellitus. The elevation of SPM levels compared with healthy volunteers may be a homeostatic response to counter ongoing inflammation. Copyright © 2018 Elsevier Ltd. All rights reserved.

HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity.

PubMed

Gurrin, Lyle C; Bertalli, Nadine A; Dalton, Gregory W; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Nicoll, Amanda J; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Lawrie W; Allen, Katrina J

2009-07-01

The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 microg/L for compound heterozygotes and from 35 to 64 microg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

PubMed

McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A

2013-02-01

What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

PubMed

Leite-Moreira, A F; Correia-Pinto, J; Gillebert, T C

1999-08-01

Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

NASA Technical Reports Server (NTRS)

Spatz, J. M.; Fields, E. E.; Yu, E. W.; Divieti, Pajevic P.; Bouxsein, M. L.; Sibonga, M. L.; Zwart, S. R.; Smith, S. M.

2011-01-01

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin associated with decreased serum PTH and elevated bone resorption markers in otherwise healthy men subjected to long-term immobilization.

Experimental Study of Vane Heat Transfer and Aerodynamics at Elevated Levels of Turbulence

NASA Technical Reports Server (NTRS)

Ames, Forrest E.

1994-01-01

A four vane subsonic cascade was used to investigate how free stream turbulence influences pressure surface heat transfer. A simulated combustor turbulence generator was built to generate high level (13 percent) large scale (Lu approximately 44 percent inlet span) turbulence. The mock combustor was also moved upstream to generate a moderate level (8.3 percent) of turbulence for comparison to smaller scale grid generated turbulence (7.8 percent). The high level combustor turbulence caused an average pressure surface heat transfer augmentation of 56 percent above the low turbulence baseline. The smaller scale grid turbulence produced the next greatest effect on heat transfer and demonstrated the importance of scale on heat transfer augmentation. In general, the heat transfer scaling parameter U(sub infinity) TU(sub infinity) LU(sub infinity)(exp -1/3) was found to hold for the turbulence. Heat transfer augmentation was also found to scale approximately on Re(sub ex)(exp 1/3) at constant turbulence conditions. Some evidence of turbulence intensification in terms of elevated dissipation rates was found along the pressure surface outside the boundary layer. However, based on the level of dissipation and the resulting heat transfer augmentation, the amplification of turbulence has only a moderate effect on pressure surface heat transfer. The flow field turbulence does drive turbulent production within the boundary layer which in turn causes the high levels of heat transfer augmentation. Unlike heat transfer, the flow field straining was found to have a significant effect on turbulence isotropy. On examination of the one dimensional spectra for u' and v', the effect to isotropy was largely limited to lower wavenumber spectra. The higher wavenumber spectra showed little or no change. The high level large scale turbulence was found to have a strong influence on wake development. The free stream turbulence significantly enhanced mixing resulting in broader and shallower wakes than the baseline case. High levels of flow field turbulence were found to correlate with a significant increase in total pressure loss in the core of the flow. Documenting the wake growth and characteristics provides boundary conditions for the downstream rotor.

Incidence, Risk Factors, and Timing of Elevated Intraocular Pressure After Intravitreal Triamcinolone Acetonide Injection for Macular Edema Secondary to Retinal Vein Occlusion: SCORE Study Report 15.

PubMed

Aref, Ahmad A; Scott, Ingrid U; Oden, Neal L; Ip, Michael S; Blodi, Barbara A; VanVeldhuisen, Paul C

2015-09-01

The Standard of Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study showed that intravitreal triamcinolone acetonide (IVTA) is effective at reducing macular edema and improving visual acuity in participants with retinal vein occlusion. Secondary analysis of the incidence, risk factors, and timing of intraocular pressure (IOP) elevation occurring after IVTA provides guidance for clinical decision making and management of patients treated with IVTA. To investigate the incidence, risk factors, and time course of IOP elevation in participants in the SCORE Study. Secondary analysis conducted from August through December 2014 of a prospective, randomized clinical trial featuring an evaluable population conducted at 75 clinical sites. Six hundred eighty-two patients with macular edema secondary to retinal vein occlusion were enrolled in the study. The SCORE Study enrollment period ran from November 4, 2004, to February 29, 2008, with participant follow-up ending February 28, 2009. Study participants were randomized to standard of care, 1 mg of IVTA, or 4 mg of IVTA therapy and followed up for a mean (SD) of 24.7 (10.3) months. Intraocular pressure elevation greater than 10 mm Hg from baseline. Kaplan-Meier incidences of IOP elevation greater than 10 mm Hg from baseline at 36 months were 0.02 (95% CI, 0.01-0.06), 0.09 (95% CI, 0.05-0.14), and 0.45 (95% CI, 0.38-0.53) in the standard of care, 1-mg IVTA, and 4-mg IVTA groups, respectively. The rates of IOP-related events were higher for the 4-mg IVTA group compared with the other groups (P ≤ .001 for main outcome measure). Younger age, 4-mg IVTA vs 1-mg IVTA treatment, and higher baseline IOP were found to confer greater risk for IOP-related events (P < .05 for all). The median number of days from time of first injection to IOP elevation greater than 10 mm Hg from baseline was 34.0 and 52.5 days in participants treated with 1-mg and 4-mg IVTA, respectively. Intravitreal triamcinolone acetonide injection therapy, in particular the 4-mg dose, is associated with an increased risk for IOP elevation. The risk factors for an IOP-related event include higher treatment dose, younger age, and higher baseline IOP. Intraocular pressure-related events may take several months from the time of first IVTA injection to occur. Clinicians should be mindful of these risk factors when assessing the risks and benefits of IVTA therapy and also of the need for long-term follow-up of participants at risk for this complication. clinicaltrials.gov Identifier: NCT00105027.

NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease.

PubMed

Svensson, M; Gorst-Rasmussen, A; Schmidt, E B; Jorgensen, K A; Christensen, J H

2009-04-01

Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p < 0.0001). In spite of generally elevated levels of NT-pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD.

Externalizing symptoms moderate associations among interpersonal skills, parenting, and depressive symptoms in adolescents seeking mental health treatment.

PubMed

Rodriguez, Erin M; Donenberg, Geri R; Emerson, Erin; Wilson, Helen W; Javdani, Shabnam

2015-04-01

Adolescents' interpersonal skills are associated with fewer teen depressive symptoms and more positive parenting, but little is known about how teens' externalizing problems moderate these relationships. This study examines links among teens' interpersonal skills, parenting, and withdrawn-depressed symptoms in adolescents seeking outpatient psychiatric treatment with elevated or non-elevated externalizing problems. Adolescents (N = 346; 42 % female; 61 % African-American) ages 12-19 years old (M = 14.9; SD = 1.8) and parents completed assessments at baseline and 6 months. At baseline parents and teens reported on teen withdrawn-depressed and externalizing symptoms, and were observed interacting to assess teen interpersonal skills. At 6 months adolescents reported on parenting, and parents and teens reported on teen withdrawn-depressed symptoms. Structural equation modeling tested two models (one with teen reported symptoms and one with parent reported symptoms). Model fit was better for youth with elevated externalizing problems regardless of reporter. For youth with elevated externalizing problems, baseline teen positive interpersonal skills were not directly associated with 6-month withdrawn-depressed symptoms, but more positive parenting was associated with fewer withdrawn-depressed symptoms. In the teen report model, more positive teen interpersonal skills were associated with more positive parenting, and there was a trend for parenting to indirectly account for the relationship between interpersonal skills and withdrawn-depressed symptoms. The findings extend research on the role of externalizing problems in teens' depression risk. Interventions for depression that target interpersonal skills may be particularly effective in youth with elevated externalizing problems.

Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure.

PubMed

Lenk, Karsten; Erbs, Sandra; Höllriegel, Robert; Beck, Ephraim; Linke, Axel; Gielen, Stephan; Winkler, Sven Möbius; Sandri, Marcus; Hambrecht, Rainer; Schuler, Gerhard; Adams, Volker

2012-06-01

In chronic heart failure (CHF), cardiac cachexia is often associated with the terminal stage of this disease. In animal studies it has been demonstrated that myostatin, a key regulator of skeletal muscle mass, is elevated in advanced stages of this syndrome. The aim of the present study was to investigate the expression of myostatin in patients with late stage CHF (NYHA IIIb) in comparison to healthy subjects. Furthermore the effects of physical exercise on myostatin were analyzed. Twenty-four patients were either randomized to a sedentary control group (CHF-S) or exercise training (CHF-E). At baseline and after 12 weeks mRNA and myostatin protein in the peripheral skeletal muscle as well as myostatin serum concentration were measured. Furthermore 12 age-matched healthy men were compared to all patients at baseline (HC). CHF patients showed a two-fold increase of myostatin mRNA (p = 0.05) and a 1.7-fold (p = 0.01) augmentation of protein content in skeletal muscle compared to healthy subjects. In late-stage CHF, exercise training led to a 36% reduction of the mRNA and a 23% decrease of the myostatin protein compared to baseline. The serum concentration of myostatin revealed no significant alteration between the groups. In the skeletal muscle, myostatin increases significantly in the course of CHF. The observed effects of a significant reduction of myostatin in skeletal muscle after 12 weeks of exercise training demonstrate the reversibility of molecular changes that might be able to halt the devastating process of muscle wasting in chronic heart failure.

Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells.

PubMed

Liu, Ji; Lu, Wennan; Guha, Sonia; Baltazar, Gabriel C; Coffey, Erin E; Laties, Alan M; Rubenstein, Ronald C; Reenstra, William W; Mitchell, Claire H

2012-07-15

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAMP reacidified alkalinized lysosomes in retinal pigmented epithelial (RPE) cells. As the influx of anions to electrically balance proton accumulation may enhance lysosomal acidification, the contribution of the cAMP-activated anion channel CFTR to lysosomal reacidification was probed. The antagonist CFTR(inh)-172 had little effect on baseline levels of lysosomal pH in cultured human RPE cells but substantially reduced the reacidification of compromised lysosomes by cAMP. Likewise, CFTR activators had a bigger impact on cells whose lysosomes had been alkalinized. Knockdown of CFTR with small interfering RNA had a larger effect on alkalinized lysosomes than on baseline levels. Inhibition of CFTR in isolated lysosomes altered pH. While CFTR and Lamp1 were colocalized, treatment with cAMP did not increase targeting of CFTR to the lysosome. The inhibition of CFTR slowed lysosomal degradation of photoreceptor outer segments while activation of CFTR enhanced their clearance from compromised lysosomes. Activation of CFTR acidified RPE lysosomes from the ABCA4(-/-) mouse model of recessive Stargardt's disease, whose lysosomes are considerably alkalinized. In summary, CFTR contributes more to reducing lysosomal pH from alkalinized levels than to maintaining baseline pH. Treatment to activate CFTR may thus be of benefit in disorders of accumulation associated with lysosomal alkalinization.

High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

PubMed Central

Ishikawa, Koji; Nagai, Takashi; Sakamoto, Keizo; Ohara, Kenji; Eguro, Takeshi; Ito, Hiroshi; Toyoshima, Yoichi; Kokaze, Akatsuki; Toyone, Tomoaki; Inagaki, Katsunori

2016-01-01

Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium. PMID:27980413

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Dicker, David T; Joude, Jamal; Allen, Joshua E; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel E; Li, Guangfu; Staveley-O'Carroll, Kevin F; El-Deiry, Wafik S

2015-01-01

Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition.

PubMed

Chaturvedi, N; Fuller, J H; Pokras, F; Rottiers, R; Papazoglou, N; Aiello, L P

2001-04-01

To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF. Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated. No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0--27.9) pg/ml in those without retinopathy, 12.9 (6.0--38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1--33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER. Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.

Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells

PubMed Central

Liu, Ji; Lu, Wennan; Guha, Sonia; Baltazar, Gabriel C.; Coffey, Erin E.; Laties, Alan M.; Rubenstein, Ronald C.; Reenstra, William W.

2012-01-01

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAMP reacidified alkalinized lysosomes in retinal pigmented epithelial (RPE) cells. As the influx of anions to electrically balance proton accumulation may enhance lysosomal acidification, the contribution of the cAMP-activated anion channel CFTR to lysosomal reacidification was probed. The antagonist CFTRinh-172 had little effect on baseline levels of lysosomal pH in cultured human RPE cells but substantially reduced the reacidification of compromised lysosomes by cAMP. Likewise, CFTR activators had a bigger impact on cells whose lysosomes had been alkalinized. Knockdown of CFTR with small interfering RNA had a larger effect on alkalinized lysosomes than on baseline levels. Inhibition of CFTR in isolated lysosomes altered pH. While CFTR and Lamp1 were colocalized, treatment with cAMP did not increase targeting of CFTR to the lysosome. The inhibition of CFTR slowed lysosomal degradation of photoreceptor outer segments while activation of CFTR enhanced their clearance from compromised lysosomes. Activation of CFTR acidified RPE lysosomes from the ABCA4−/− mouse model of recessive Stargardt's disease, whose lysosomes are considerably alkalinized. In summary, CFTR contributes more to reducing lysosomal pH from alkalinized levels than to maintaining baseline pH. Treatment to activate CFTR may thus be of benefit in disorders of accumulation associated with lysosomal alkalinization. PMID:22572847

Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose-drinking behavior: dissecting the neurochemistry of reward.

PubMed

Wakabayashi, Ken T; Myal, Stephanie E; Kiyatkin, Eugene A

2015-02-01

While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

PubMed

Zheng, Tian; Liu, Linsheng; Shi, Jian; Yu, Xiaoyi; Xiao, Wenjing; Sun, Runbing; Zhou, Yahong; Aa, Jiye; Wang, Guangji

2014-07-01

Although the stimulating and psychotropic effects of methamphetamine (METH) on the nervous system are well documented, the impact of METH abuse on biological metabolism and the turnover of peripheral transmitters are poorly understood. Metabolomics has the potential to reveal the effect of METH abuse on systemic metabolism and potential markers suggesting the underlying mechanism of toxicity. In this study, male Sprague Dawley rats were intraperitoneally injected with METH at escalating doses of mg kg(-1) for 5 consecutive days and then were withdrawn for 2 days. The metabolites in the serum and urine were profiled and the systemic effects of METH on metabolic pathways were evaluated. Multivariate statistical analysis showed that METH caused distinct deviations, whereas the withdrawal of METH restored the metabolic patterns towards baseline. METH administration elevated energy metabolism, which was manifested by the distinct depletion of branched-chain amino acids, accelerated tricarboxylic-acid cycle and lipid metabolism, reduced serum glycerol-3-phosphate, and elevated serum and urinary 3-hydroxybutyrate and urinary glycerol. In addition to the increased serum levels of the excitatory amino acids glutamate and aspartate (the inhibitory neurotransmitters in the brain), a marked decline in serum alanine and glycine after METH treatment suggested the activation and decreased inhibition of the nervous system and hence elevated nervous activity. Withdrawal of METH for 2 days efficiently restored all but a few metabolites to baseline, including serum creatinine, citrate, 2-ketoglutarate, and urinary lactate. Therefore, these metabolites are potential markers of METH use, and they may be used to facilitate the diagnosis of METH abuse.

A new pure ω-3 eicosapentaenoic acid ethyl ester (AMR101) for the management of hypertriglyceridemia: the MARINE trial.

PubMed

Jacobson, Terry A

2012-06-01

ω-3 fatty acids reduce triglyceride (TG) levels, but corresponding increases in low-density lipoprotein cholesterol (LDL-C) levels may compromise achievement of lipid goals in patients with elevated cardiovascular risk. AMR101 is an investigational agent containing ≥96% of pure icosapent ethyl (the ethyl ester of eicosapentaenoic acid). The Phase III Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study with an Open-Label Extension (MARINE) investigated the efficacy and safety of AMR101 in 229 patients with very high TG levels (≥500 mg/dl). AMR101 4 g/day significantly reduced median placebo-adjusted TG levels from baseline by 33.1% (p < 0.0001), and AMR101 2 g/day reduced TG levels by 19.7% (p = 0.0051). Changes in LDL-C were minimal and nonsignificant. AMR101 may offer substantial TG lowering without increases in LDL-C levels.

Evaluation of current tropospheric mapping functions by Deep Space Network very long baseline interferometry

NASA Technical Reports Server (NTRS)

Sovers, O. J.; Lanyi, G. E.

1994-01-01

To compare the validity of current algorithms that map zenith tropospheric delay to arbitrary elevation angles, 10 different tropospheric mapping functions are used to analyze the current data base of Deep Space Network Mark 3 intercontinental very long baseline interferometric (VLBI) data. This analysis serves as a stringent test because of the high proportion of low-elevation observations necessitated by the extremely long baselines. Postfit delay and delay-rate residuals are examined, as well as the scatter of baseline lengths about the time-linear model that characterizes tectonic motion. Among the functions that utilize surface meteorological data as input parameters, the Lanyi 1984 mapping shows the best performance both for residuals and baselines, through the 1985 Davis function is statistically nearly identical. The next best performance is shown by the recent function of Niell, which is based on an examination of global atmospheric characteristics as a function of season and uses no weather data at the time of the measurements. The Niell function shows a slight improvement in residuals relative to Lanyi, but also an increase in baseline scatter that is significant for the California-Spain baseline. Two variants of the Chao mapping function, as well as the Chao tables used with the interpolation algorithm employed in the Orbit Determination Program software, show substandard behavior for both VLBI residuals and baseline scatter. The length of the California-Australia baseline (10,600 km) in the VLBI solution can vary by as much as 5 to 10 cm for the 10 mapping functions.

Predicting success in an online parenting intervention: the role of child, parent, and family factors.

PubMed

Dittman, Cassandra K; Farruggia, Susan P; Palmer, Melanie L; Sanders, Matthew R; Keown, Louise J

2014-04-01

The present study involved an examination of the extent to which a wide range of child, parent, family, and program-related factors predicted child behavior and parenting outcomes after participation in an 8-session online version of the Triple P-Positive Parenting Program. Participants were mothers and fathers of 97 children aged between 3 and 8 years displaying elevated levels of disruptive behavior problems. For both mothers and fathers, poorer child behavior outcomes at postintervention were predicted by the number of sessions of the intervention completed by the family. For mothers, postintervention child behavior was also predicted by the quality of the mother-child relationship at baseline; for fathers, baseline child behavior severity was an additional predictor. Mothers' postintervention ineffective parenting was predicted by session completion and preintervention levels of ineffective parenting, whereas the only predictor of fathers' ineffective parenting at postintervention was preintervention levels of ineffective parenting. Socioeconomic risk, parental adjustment, and father participation in the intervention were not significant predictors of mother- or father-reported treatment outcomes. The implications of the findings for the provision of online parenting support are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Impact of a Traditional Dietary Supplement with Coconut Milk and Soya Milk on the Lipid Profile in Normal Free Living Subjects

PubMed Central

Ekanayaka, R. A. I.; Ekanayaka, N. K.; Perera, B.; De Silva, P. G. S. M.

2013-01-01

Background. The effects of coconut fat and soya fat on serum lipids are controversial. This study was designed to investigate the lipid effects of coconut milk and soya milk supplementation on the lipid profile of free living healthy subjects. Methods. Sixty (60) healthy volunteers aged 18–57 years were given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by a 2-week washout period, subsequent to which they received isoenergetic soya milk porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels decreased with CMP and reached statistical significance in the total study population and in the >130 baseline LDL group. The HDL (high density lipoprotein) levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We conclude that coconut fat in the form of CM does not cause a detrimental effect on the lipid profile in the general population and in fact is beneficial due to the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose baseline LDL levels are elevated. PMID:24282632

Risk factors associated with the development of overt nephropathy in type 2 diabetes patients: A 12 years observational study

PubMed Central

Viswanathan, Vijay; Tilak, Priyanka; Kumpatla, Satyavani

2012-01-01

Background & objectives: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease in developing countries. Early detection and risk reduction measures can prevent DN. The aim of the study was to determine the risk factors for the development of proteinuria over a period of 12 years of follow up in normoalbuminuric type 2 diabetes patients attending a specialized centre. Methods: Of the 2630 type 2 diabetes subjects newly registered in 1996, 152 (M:F;92:60) normoalbuminuric subjects had baseline and subsequent measurements of anthropometric, haemodynamic and biochemical details spanning 12 years. The subjects were divided into 2 groups based on the renal status during follow up visits. Group 1 (non-progressors) had persistent normoalbuminuria and group 2 (progressors) had persistent proteinuria. Presence of other diabetic complications during follow up and details on antidiabetic and antihypertensive agents were noted. Results: During median follow up of 11 years in subjects with normal renal function at baseline, 44.1 per cent developed proteinuria at follow up. Glucose levels, HbA1c, systolic blood pressure (SBP), triglycerides, and urea levels were significantly higher at baseline among progressors than non-progressors. Progressors had a longer duration of diabetes and significant fall in estimated glomerular filtration rate (eGFR) levels at follow up. In Cox's regression analysis, baseline age, duration of diabetes, baseline HbA1c and mean values of HbA1c, triglycerides, SBP and presence of retinopathy showed significant association with the development of macroalbuminuria. Interpretation & conclusions: Type 2 diabetes patients with uncontrolled diabetes and increase in blood pressure are at high risk of developing nephropathy. Age, long duration of diabetes, elevated BP, poor glycaemic control and presence of retinopathy were significantly associated with the progression of diabetic nephropathy. PMID:22885263

Determinants and trajectory of phobic anxiety in patients living with an implantable cardioverter defibrillator.

PubMed

Cho, En-Young Nicole; von Känel, Roland; Marten-Mittag, Birgit; Ronel, Joram; Kolb, Christof; Baumert, Jens; Ladwig, Karl-Heinz

2012-05-01

The implantable cardioverter defibrillator (ICD) is the gold standard therapy to prevent life-threatening arrhythmias. Phobic anxiety predicts ventricular arrhythmia in coronary heart disease patients, but little is known about phobic anxiety in ICD patients. This study aimed to identify determinants and the course of phobic anxiety in ICD patients. 140 outpatients living with an ICD (mean age 56±14 years, 66% men). Phobic anxiety was assessed with the Symptom Checklist-90 Revised at a mean of 27±21 months (range 3-109) post-ICD placement (baseline) and after an average follow-up of 41±18 months (range 10-82). Multivariate linear regression models considered sociodemographic factors, clinical variables and psychological scales as potential determinants of phobic anxiety scores. ICD patients reported more than 10-fold higher levels of phobic anxiety than a previous representative population survey (2.6±3.4 vs 0.2±0.4). Greater age (p=0.003), previous shock experience (p=0.007), depressed mood (p<0.001) and hypochondriasis (p=0.005) were associated with higher phobic anxiety scores at baseline. Multimorbidity (p=0.030) and higher baseline phobic anxiety (p<0.001) determined greater phobic anxiety at follow-up. Younger age (p=0.029) and an elevated number of non-cardiac diseases (p=0.019) were both associated with an increase in phobic anxiety scores from baseline to follow-up. More patients had high phobic anxiety levels (score >4) at follow-up compared with baseline (31% vs 24%; p=0.048). Phobic anxiety was comparably high and persisted over time in ICD patients. Modifiable determinants of phobic anxiety were identified, which may inform tailored interventions to improve ICD patients' distress and perhaps also prognosis.

Volunteering predicts health among those who value others: two national studies.

PubMed

Poulin, Michael J

2014-02-01

The purpose of these studies was to examine the role of positive views of other people in predicting stress-buffering effects of volunteering on mortality and psychological distress. In Study 1, stressful life events, volunteering, and hostile cynicism assessed in a baseline Detroit-area survey (N = 846) predicted survival over a 5-year period, adjusting for relevant covariates. In Study 2, stressful life events, volunteering, and world benevolence beliefs assessed in a baseline national survey (N = 1,157) predicted psychological distress over a 1-year period, adjusting for distress at baseline. In Study 1, a Cox proportional hazard model indicated that for individuals low in cynicism, stress predicted mortality at low levels of volunteering but not at high levels of volunteering. This effect was not present among those high in cynicism. In Study 2, multiple regression analysis revealed that among individuals high in world benevolence beliefs, stress predicted elevated distress at low levels of volunteering but not at high levels of volunteering. This effect was absent for those lower in world benevolence beliefs. Consistent with prior research on helping behavior, these studies indicate that helping behavior can buffer the effects of stress on health. However, the results of these studies indicate that stress-buffering effects of volunteering are limited to individuals with positive views of other people. Not all individuals may benefit from volunteering, and health-promotion efforts seeking to draw on health benefits of helping behavior may need to target their approach accordingly. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Effect of canagliflozin on circulating active GLP-1 levels in patients with type 2 diabetes: a randomized trial.

PubMed

Takebayashi, Kohzo; Hara, Kenji; Terasawa, Tomoko; Naruse, Rika; Suetsugu, Mariko; Tsuchiya, Takafumi; Inukai, Toshihiko

2017-09-30

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity

PubMed Central

Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2015-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18–30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. PMID:26316585

Moderating effects of parental well-being on parenting efficacy outcomes by intervention delivery model of the early risers conduct problems prevention program.

PubMed

Piehler, Timothy F; Lee, Susanne S; Bloomquist, Michael L; August, Gerald J

2014-10-01

Parent-focused preventive interventions for youth conduct problems are efficacious when offered in different models of delivery (e.g., individual in-home, group center-based). However, we know little about the characteristics of parents associated with a positive response to a particular model of delivery. We randomly assigned the parents of an ethnically diverse sample of kindergarten through second grade students (n = 246) displaying elevated levels of aggression to parent-focused program delivery models emphasizing receiving services in a community center largely with groups (Center; n = 121) or receiving services via an individualized in-home strategy (Outreach; n = 125). In both delivery models, parents received parent skills training and goal setting/case management/referrals over an average of 16 months. Structural equation modeling revealed a significant interaction between parental well-being at baseline and intervention delivery model in predicting parenting efficacy at year 2, while controlling for baseline levels of parenting efficacy. Within the Outreach model, parents with lower levels of well-being as reported at baseline appeared to show greater improvements in parenting efficacy than parents with higher levels of well-being. Within the Center model, parental well-being did not predict parenting efficacy outcomes. The strong response of low well-being parents within the Outreach model suggests that this may be the preferred model for these parents. These findings provide support for further investigation into tailoring delivery model of parent-focused preventive interventions using parental well-being in order to improve parenting outcomes.

Moderating Effects of Parental Well-Being on Parenting Efficacy Outcomes by Intervention Delivery Model of the Early Risers Conduct Problems Prevention Program

PubMed Central

Piehler, Timothy F.; Lee, Susanne S.; Bloomquist, Michael L.; August, Gerald J.

2014-01-01

Parent-focused preventive interventions for youth conduct problems are efficacious when offered in different models of delivery (e.g., individual in-home, group center-based). However, we know little about the characteristics of parents associated with a positive response to a particular model of delivery. We randomly assigned the parents of an ethnically diverse sample of kindergarten through second grade students (n = 246) displaying elevated levels of aggression to parent-focused program delivery models emphasizing receiving services in a community center largely with groups (Center; n = 121) or receiving services via an individualized in-home strategy (Outreach; n = 125). In both delivery models, parents received parent skills training and goal setting/case management/referrals over an average of 16 months. Structural equation modeling revealed a significant interaction between parental well-being at baseline and intervention delivery model in predicting parenting efficacy at year two, while controlling for baseline levels of parenting efficacy. Within the Outreach model, parents with lower levels of well-being as reported at baseline appeared to show greater improvements in parenting efficacy than parents with higher levels of well-being. Within the Center model, parental well-being did not predict parenting efficacy outcomes. The strong response of low well-being parents within the Outreach model suggests that this may be the preferred model for these parents. These findings provide support for further investigation into tailoring delivery model of parent-focused preventive interventions using parental well-being in order to improve parenting outcomes. PMID:25037843

Impact of volcanic aerosols on stratospheric ozone recovery

NASA Astrophysics Data System (ADS)

Naik, Vaishali; Horowitz, Larry W.; Daniel Schwarzkopf, M.; Lin, Meiyun

2017-09-01

We use transient GFDL-CM3 chemistry-climate model simulations over the 2006-2100 period to show how the influence of volcanic aerosols on the extent and timing of ozone recovery varies with (a) future greenhouse gas scenarios (Representative Concentration Pathway (RCP)4.5 and RCP8.5) and (b) halogen loading. Current understanding is that elevated volcanic aerosols reduce ozone under high halogen loading but increase ozone under low halogen loading when the chemistry is more NOx dominated. With extremely low aerosol loadings (designated here as "background"), global stratospheric ozone burden is simulated to return to 1980 levels around 2050 in the RCP8.5 scenario but remains below 1980 levels throughout the 21st century in the RCP4.5 scenario. In contrast, with elevated volcanic aerosols, ozone column recovers more quickly to 1980 levels, with recovery dates ranging from the mid-2040s in RCP8.5 to the mid-2050s to early 2070s in RCP4.5. The ozone response in both future emission scenarios increases with enhanced volcanic aerosols. By 2100, the 1980 baseline-adjusted global stratospheric ozone column is projected to be 20-40% greater in RCP8.5 and 110-200% greater in RCP4.5 with elevated volcanic aerosols compared to simulations with the extremely low background aerosols. The weaker ozone enhancement at 2100 in RCP8.5 than in RCP4.5 in response to elevated volcanic aerosols is due to a factor of 2.5 greater methane in RCP8.5 compared with RCP4.5. Our results demonstrate the substantial uncertainties in stratospheric ozone projections and expected recovery dates induced by volcanic aerosol perturbations that need to be considered in future model ozone projections.

High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy.

PubMed

Mondy, Kristin E; Gottdiener, John; Overton, E Turner; Henry, Keith; Bush, Tim; Conley, Lois; Hammer, John; Carpenter, Charles C; Kojic, Erna; Patel, Pragna; Brooks, John T

2011-02-01

in the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/μL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. in this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

Depression Symptom Trajectories and Associated Risk Factors among Adolescents in Chile

PubMed Central

Stapinski, Lexine A.; Montgomery, Alan A.; Heron, Jon; Jerrim, John; Vignoles, Anna; Araya, Ricardo

2013-01-01

Adolescence is a key period for studying the development of depression, with studies in Europe and North America showing a pattern of elevated risk that begins in early adolescence and continues to increase as adolescents age. Few studies have examined the course of adolescent depression and associated risk factors in low and middle-income countries. This longitudinal cohort study examined depression symptom trajectories and risk factors in a sample of socio-economically disadvantaged adolescents in Chile (n = 2,508). Data were collected over an 18-month period as part of a clinical trial for secondary students aged 12 to 18 (median age 14). Clinical levels of depression were prevalent in this sample at baseline (35% for girls and 28% for boys); yet latent growth models of symptom trajectories revealed a pattern of decreasing symptoms over time. There was evidence of an anxiety-depression developmental pathway for girls, with elevated anxiety levels initially predicting poorer depression outcomes later on. Poor problem-solving skills were associated with initial depression levels but did not predict the course of depressive symptoms. Critically, the declining symptom trajectories raise important methodological issues regarding the effects of repeated assessment in longitudinal studies. PMID:24147131

Depression symptom trajectories and associated risk factors among adolescents in Chile.

PubMed

Stapinski, Lexine A; Montgomery, Alan A; Heron, Jon; Jerrim, John; Vignoles, Anna; Araya, Ricardo

2013-01-01

Adolescence is a key period for studying the development of depression, with studies in Europe and North America showing a pattern of elevated risk that begins in early adolescence and continues to increase as adolescents age. Few studies have examined the course of adolescent depression and associated risk factors in low and middle-income countries. This longitudinal cohort study examined depression symptom trajectories and risk factors in a sample of socio-economically disadvantaged adolescents in Chile (n = 2,508). Data were collected over an 18-month period as part of a clinical trial for secondary students aged 12 to 18 (median age 14). Clinical levels of depression were prevalent in this sample at baseline (35% for girls and 28% for boys); yet latent growth models of symptom trajectories revealed a pattern of decreasing symptoms over time. There was evidence of an anxiety-depression developmental pathway for girls, with elevated anxiety levels initially predicting poorer depression outcomes later on. Poor problem-solving skills were associated with initial depression levels but did not predict the course of depressive symptoms. Critically, the declining symptom trajectories raise important methodological issues regarding the effects of repeated assessment in longitudinal studies.

Evaluation of a group cognitive-behavioral depression prevention program for young adolescents: a randomized effectiveness trial.

PubMed

Gillham, Jane E; Reivich, Karen J; Brunwasser, Steven M; Freres, Derek R; Chajon, Norma D; Kash-Macdonald, V Megan; Chaplin, Tara M; Abenavoli, Rachel M; Matlin, Samantha L; Gallop, Robert J; Seligman, Martin E P

2012-01-01

Depression is a common psychological problem in adolescence. Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth. Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors (as opposed to research team staff). We evaluated the effectiveness of the Penn Resiliency Program for adolescents (PRP-A), a school-based group intervention that targets cognitive behavioral risk factors for depression. We randomly assigned 408 middle school students (ages 10-15) to one of three conditions: PRP-A, PRP-AP (in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component), or a school-as-usual control. Adolescents completed measures of depression and anxiety symptoms, cognitive style, and coping at baseline, immediately after the intervention, and at 6-month follow-up. PRP-A reduced depression symptoms relative to the school as usual control. Baseline levels of hopelessness moderated intervention effects. Among participants with average and high levels of hopelessness, PRP (A and AP) significantly improved depression symptoms, anxiety symptoms, hopelessness, and active coping relative to control. Among participants with low baseline hopelessness, we found no intervention effects. PRP-AP was not more effective than PRP-A alone. We found no intervention effects on clinical levels of depression or anxiety. These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors. These interventions may be most helpful to students with elevated hopelessness.

Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression.

PubMed

Hung, Yi-Yung

2018-06-13

Changes in the brain's inflammatory status can lead to psychopathological responses, especially depression. Using animal models, recent studies have revealed that this pathology is due, in part, to innate immune responses of monocytes. We focus on the involvement of Toll-like receptors (TLRs) and expression of genes encoding their negative regulators, SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2, and TNFAIP3, in CD14+ monocytes from 34 patients with major depressive disorder (MDD) and 33 healthy controls before and after treatment with antidepressants. We also seek to investigate their association with depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17). mRNA expression of all TLRs, except TLR3 and -5, was significantly higher in monocytes from patients with MDD than in those from controls. Conversely, the "brakes" in TLR signaling, including TOLLIP, MyD88s, NOD2, and TNFAIP3, were downregulated. In clinical findings, the remission group showed higher baseline TLR4 and lower baseline IRAK3 mRNA levels but only baseline elevated SOCS1 mRNA levels, which were inversely correlated with HAMD-17 scores, predicting worsened outcome in MDD patients. In addition, TNFAIP3 mRNA levels were increased by antidepressant treatment. Collectively, our findings suggest a role for dysregulation of TLR signaling in monocytes in MDD and identify a balancing effect of antidepressants on this dysregulation. © 2018 S. Karger AG, Basel.

Atmospheric gradients from very long baseline interferometry observations

NASA Technical Reports Server (NTRS)

Macmillan, D. S.

1995-01-01

Azimuthal asymmetries in the atmospheric refractive index can lead to errors in estimated vertical and horizontal station coordinates. Daily average gradient effects can be as large as 50 mm of delay at a 7 deg elevation. To model gradients, the constrained estimation of gradient paramters was added to the standard VLBI solution procedure. Here the analysis of two sets of data is summarized: the set of all geodetic VLBI experiments from 1990-1993 and a series of 12 state-of-the-art R&D experiments run on consecutive days in January 1994. In both cases, when the gradient parameters are estimated, the overall fit of the geodetic solution is improved at greater than the 99% confidence level. Repeatabilities of baseline lengths ranging up to 11,000 km are improved by 1 to 8 mm in a root-sum-square sense. This varies from about 20% to 40% of the total baseline length scatter without gradient modeling for the 1990-1993 series and 40% to 50% for the January series. Gradients estimated independently for each day as a piecewise linear function are mostly continuous from day to day within their formal uncertainties.

Cyclical secretion of prorenin during the menstrual cycle: synchronization with luteinizing hormone and progesterone.

PubMed Central

Sealey, J E; Atlas, S A; Glorioso, N; Manapat, H; Laragh, J H

1985-01-01

Plasma prorenin, a high molecular weight precursor form of renin, (renin, EC 3.4.23.15; old number, EC 3.4.99.19), was measured three times weekly in normal young women during the menstrual cycle and was related to changes in luteinizing hormone, estradiol, and progesterone. In all subjects a stable baseline level of prorenin occurred during the follicular phase. Then, simultaneously or soon after the luteinizing hormone peak, plasma prorenin consistently increased about 2-fold. Baseline prorenin ranged from 18 to 40 ng per ml per hr, and peak prorenin ranged from 35 to 65 ng per ml per hr. The maximum increase in prorenin averaged 80%. Prorenin remained elevated during the mid-luteal phase of the menstrual cycle and returned to baseline during the late-luteal phase in coordination with the decrease in progesterone. The changes in prorenin were not synchronized with changes in active renin which was significantly increased only during the mid-luteal phase. These findings suggest that prorenin may be involved in reproductive physiology. PMID:3909151

A randomized trial of the effect of dust control on children's blood lead levels.

PubMed

Lanphear, B P; Winter, N L; Apetz, L; Eberly, S; Weitzman, M

1996-07-01

Dust control is recommended as one of the cornerstones of controlling childhood lead exposure; however, the effectiveness of dust control has not been demonstrated for children who have low to mild elevations in blood lead (ie, less than 25 micrograms/dL). The objective of this study was to determine whether dust control, as performed by families, had an effect on children's blood lead levels and dust lead levels in children's homes. Randomized, controlled trial. Community-based trial in Rochester, NY. One hundred four children, 12 to 31 months of age at baseline. Families and children were randomized to one of two groups. Families of children in the intervention group received cleaning supplies, information about cleaning areas that are often contaminated with lead, and a cleaning demonstration. Families in the control group received only a brochure about lead poisoning prevention. Baseline measurements of lead in blood, house dust, soil, water, and paint were taken from both groups. Seven months after enrollment, a second blood lead assay was obtained, and lead levels in household dust were measured. The main outcome measures were change in blood lead levels and dust lead levels by treatment group. The median blood lead level of children enrolled in the study was 6.7 micrograms/dL (range, 1.7 to 30.6 micrograms/dL). There was no significant difference in the change of children's blood lead levels or dust lead levels by treatment group. The median change in blood lead levels among children in the intervention group was -0.05 micrograms/dL compared with -0.60 micrograms/dL among those in the control group. There also was no significant difference in the change of dust lead by group assignment, although there was a trend toward a significant difference in the percentage of change in dust lead levels on noncarpeted floors, which was greater among houses in the intervention group. These data suggest that an intervention that consists only of providing cleaning supplies and a brief description of dust control is not effective at reducing blood lead levels among urban children with low to mild elevations in blood lead levels at a 7-month follow-up.

Mercury concentrations and distribution in soil, water, mine waste leachates, and air in and around mercury mines in the Big Bend region, Texas, USA.

PubMed

Gray, John E; Theodorakos, Peter M; Fey, David L; Krabbenhoft, David P

2015-02-01

Samples of soil, water, mine waste leachates, soil gas, and air were collected from areas mined for mercury (Hg) and baseline sites in the Big Bend area, Texas, to evaluate potential Hg contamination in the region. Soil samples collected within 300 m of an inactive Hg mine contained elevated Hg concentrations (3.8-11 µg/g), which were considerably higher than Hg in soil collected from baseline sites (0.03-0.05 µg/g) distal (as much as 24 km) from mines. Only three soil samples collected within 300 m of the mine exceeded the probable effect concentration for Hg of 1.06 µg/g, above which harmful effects are likely to be observed in sediment-dwelling organisms. Concentrations of Hg in mine water runoff (7.9-14 ng/L) were generally higher than those found in springs and wells (0.05-3.1 ng/L), baseline streams (1.1-9.7 ng/L), and sources of drinking water (0.63-9.1 ng/L) collected in the Big Bend region. Concentrations of Hg in all water samples collected in this study were considerably below the 2,000 ng/L drinking water Hg guideline and the 770 ng/L guideline recommended by the U.S. Environmental Protection Agency (USEPA) to protect aquatic wildlife from chronic effects of Hg. Concentrations of Hg in water leachates obtained from leaching of mine wastes varied widely from <0.001 to 760 µg of Hg in leachate/g of sample leached, but only one leachate exceeded the USEPA Hg industrial soil screening level of 31 µg/g. Concentrations of Hg in soil gas collected at mined sites (690-82,000 ng/m(3)) were highly elevated compared to soil gas collected from baseline sites (1.2-77 ng/m(3)). However, air collected from mined areas at a height of 2 m above the ground surface contained concentrations of Hg (4.9-64 ng/m(3)) that were considerably lower than Hg in soil gas from the mined areas. Although concentrations of Hg emitted from mine-contaminated soils and mine wastes were elevated, persistent wind in southwest Texas disperses Hg in the air within a few meters of the ground surface.

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes.

PubMed

Crimi, Gabriele; Somaschini, Alberto; Cattaneo, Marco; Angiolillo, Dominick J; Piscione, Federico; Palmerini, Tullio; De Servi, Stefano

2018-05-01

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the β coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p < 0.001] at baseline and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.

Airborne culturable fungi in naturally ventilated primary school environments in a subtropical climate

NASA Astrophysics Data System (ADS)

Salonen, Heidi; Duchaine, Caroline; Mazaheri, Mandana; Clifford, Sam; Morawska, Lidia

2015-04-01

There is currently a lack of reference values for indoor air fungal concentrations to allow for the interpretation of measurement results in subtropical school settings. Analysis of the results of this work established that, in the majority of properly maintained subtropical school buildings, without any major affecting events such as floods or visible mould or moisture contamination, indoor culturable fungi levels were driven by outdoor concentration. The results also allowed us to benchmark the "baseline range" concentrations for total culturable fungi, Penicillium spp., Cladosporium spp. and Aspergillus spp. in such school settings. The measured concentration of total culturable fungi and three individual fungal genera were estimated using Bayesian hierarchical modelling. Pooling of these estimates provided a predictive distribution for concentrations at an unobserved school. The results indicated that "baseline" indoor concentration levels for indoor total fungi, Penicillium spp., Cladosporium spp. and Aspergillus spp. in such school settings were generally ≤1450, ≤680, ≤480 and ≤90 cfu/m3, respectively, and elevated levels would indicate mould damage in building structures. The indoor/outdoor ratio for most classrooms had 95% credible intervals containing 1, indicating that fungi concentrations are generally the same indoors and outdoors at each school. Bayesian fixed effects regression modelling showed that increasing both temperature and humidity resulted in higher levels of fungi concentration.

Self-Compassion as a prospective predictor of PTSD symptom severity among trauma-exposed U.S. Iraq and Afghanistan war veterans.

PubMed

Hiraoka, Regina; Meyer, Eric C; Kimbrel, Nathan A; DeBeer, Bryann B; Gulliver, Suzy Bird; Morissette, Sandra B

2015-04-01

U.S. combat veterans of the Iraq and Afghanistan wars have elevated rates of posttraumatic stress disorder (PTSD) compared to the general population. Self-compassion, characterized by self-kindness, a sense of common humanity when faced with suffering, and mindful awareness of suffering, is a potentially modifiable factor implicated in the development and maintenance of PTSD. We examined the concurrent and prospective relationship between self-compassion and PTSD symptom severity after accounting for level of combat exposure and baseline PTSD severity in 115 Iraq and Afghanistan war veterans exposed to 1 or more traumatic events during deployment. PTSD symptoms were assessed using the Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) at baseline and 12 months (n =101). Self-compassion and combat exposure were assessed at baseline via self-report. Self-compassion was associated with baseline PTSD symptoms after accounting for combat exposure (β = -.59; p < .001; ΔR(2) = .34; f(2) = .67; large effect) and predicted 12-month PTSD symptom severity after accounting for combat exposure and baseline PTSD severity (β = -.24; p = .008; ΔR(2) = .03; f(2) = .08; small effect). Findings suggest that interventions that increase self-compassion may be beneficial for treating chronic PTSD symptoms among some Iraq and Afghanistan war veterans. Copyright © 2015 Wiley Periodicals, Inc., A Wiley Company.

Ovarian cancer-related hypophosphatemic osteomalacia--a case report.

PubMed

Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao; Tsai, Keh-Sung

2014-12-01

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. We investigated a 57-year-old woman with progressive low back pain. Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

Effect of intramuscular cholecalciferol megadose in children with nutritional rickets.

PubMed

Bothra, Meenakshi; Gupta, Nandita; Jain, Vandana

2016-06-01

The treatment practices for vitamin D deficiency rickets are highly variable. Though a single intramuscular (IM) megadose of vitamin D is economical, and ensures good compliance, it poses the risk of hypervitaminosis D. This observational study was conducted to assess the duration of effect and safety of single IM megadose of cholecalciferol in the treatment of vitamin D deficiency rickets. Children younger than 14 years with rickets were enrolled. Baseline investigations included radiograph of wrists and estimation of serum calcium, phosphate, alkaline phosphatase (ALP), 25(OH) vitamin D and parathormone (PTH) levels. All children received a single IM megadose of vitamin D3. Biochemical parameters were re-evaluated at 1.5, 3 and 6 months after the megadose and the values were compared to the baseline. We enrolled 21 children, out of which nine remained under active follow-up till 6 months. Radiological evidence of rickets was present in all 21 children, 14 had hypocalcemia at the time of presentation. After IM cholecalciferol megadose, median 25 hydroxy vitamin D [25(OH)D] level remained significantly more than the baseline till 6 months after the megadose. At 1.5 months after the vitamin D megadose, three (30%) of the children were found to develop toxic levels of vitamin D (>150 ng/mL), although none had hypercalcemia or any clinical manifestation of vitamin D toxicity. At 3 months and 6 months after the megadose, 25(OH)D levels remained in the sufficient range (20-100 ng/mL) in seven out of the eight children who came for follow-up. A single IM megadose of vitamin D may be effective in significantly increasing the 25(OH)D levels for at least 6 months in children with rickets, but elevation of 25(OH)D to toxic range raises concern regarding its safety.

Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies

PubMed Central

Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.

2016-01-01

Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755

Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies.

PubMed

Baker, Peter R; Nanduri, Priyaanka; Gottlieb, Peter A; Yu, Liping; Klingensmith, Georgeanna J; Eisenbarth, George S; Barker, Jennifer M

2012-05-01

Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Compared with nonprogressors, in the time period 2 months-2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11-22 pM, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months-2 years preceding the onset of AD. © 2012 Blackwell Publishing Ltd.

Evidence for metaboreceptor stimulation of sweating in normothermic and heat-stressed humans

NASA Technical Reports Server (NTRS)

Shibasaki, M.; Kondo, N.; Crandall, C. G.

2001-01-01

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents.

PubMed

Ohlsson, Bodil; Roth, Bodil; Larsson, Ewa; Höglund, Peter

2017-04-01

Calprotectin is a marker of inflammation and zonulin is a marker of intestinal permeability. Diets with lower carbohydrate content and higher contents of fat, fiber and protein, e.g., Okinawan-based diet, are considered to reduce inflammation and intestinal permeability. The aim of the present study was to evaluate calprotectin and zonulin levels in serum and feces after intervention with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2 diabetes, mean age 57.5±8.2 years, BMI 29.9±4.1 kg/m 2 , were served the diet during 12 weeks, and were followed for another 16 weeks. Anthropometric and metabolic parameters were registered. Fasting levels of calprotectin and zonulin in serum and feces, and hormones in plasma, were measured by Luminex or ELISA before study start and after 12 and 28 weeks. Calprotectin in serum tended to be increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28 weeks (P=0.014). In contrast to baseline, there was a correlation between calprotectin and zonulin in serum and feces after dietary intervention (P=0.025 vs. P=0.079). Energy percentage of protein in breakfast correlated with serum calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059). Calprotectin in serum tended to be elevated, and zonulin in serum and feces are elevated after introduction of an Okinawan-based Nordic diet. These biomarkers correlate with energy percentage of protein.

Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

PubMed Central

Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun

2016-01-01

Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01). A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity. PMID:27240398

Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

PubMed

Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun

2016-05-26

Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01). A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

When heart goes “BOOM” to fast. Heart rate greater than 80 as mortality predictor in acute myocardial infarction

PubMed Central

Davidovic, Goran; Iric-Cupic, Violeta; Milanov, Srdjan; Dimitijevic, Aleksandra; Petrovic-Janicijevic, Mirjana

2013-01-01

Many prospective studies established association between high heart rate and increased cardiovascular morbidity and mortality, independently of other risk factors. Heart rate over 80 beats per minute more often leads to atherosclerotic plaque disruption, the main step in developing acute coronary syndrome. Purpose was to investigate the incidence of higher heart rate levels in patients with anterior wall acute myocardial infarction with ST-segment elevation and the influence of heart rate on mortality. Research included 140 patients with anterior wall acute myocardial infarction with ST-segment elevation treated in Coronary Unit, Clinical Center Kragujevac in the period from January 2001-June 2006. Heart rate was calculated as the mean value of baseline and heart rate in the first 30 minutes after admission. Other risk factors were also followed to determine their connection with elevated heart rate. Results showed that the majority of patients survived (over 70%). In a total number of patients, more than 75% had a heart rate levels greater than 80 beats per minute. There was a significant difference in heart rate on addmision between survivors and patients who died, with a greater levels in patients with fatal outcome. Both, univariate and multivariate regression analysis singled out heart rate greater than 80 beats per minute as independent mortality predictor in these patients. Heart rate greater than 80 beats per minute is a major, independent risk factor for morbidity and important predictor of mortality in patients with acute myocardial infarction. PMID:23991346

Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: An 8.5-year prospective case-control study.

PubMed

Jansen, Rasmus Bo; Christensen, Tomas Møller; Bülow, Jens; Rørdam, Lene; Holstein, Per E; Jørgensen, Niklas Rye; Svendsen, Ole Lander

2018-02-01

Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism. An 8.5-year follow-up case-control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005-2007, who were followed up in 2015 with DXA scans and blood samples. 21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302). We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD. Copyright © 2017 Elsevier Inc. All rights reserved.

Baseline aquatic contamination and endocrine status in a resident fish of Biscayne National Park

USGS Publications Warehouse

Bargar, Timothy A.; Whelan, Kevin R.T.; Alvarez, David; Echols, Kathy R.; Peterman, Paul H.

2017-01-01

Surface water, sediment, and fish from Biscayne Bay, coastal wetlands adjacent to the Bay, and canals discharging into the Bay were sampled for determination of baseline contamination in Biscayne National Park. While the number of contaminants detected in canal waters was greater during the wet season than the dry season, no seasonal difference was evident for Biscayne Bay or coastal wetland waters. Estrogen equivalency (as 17β-estradiol equivalents), as predicted by the Yeast Estrogen Screen, for extracts of passive water samplers deployed in canals and wetlands was elevated during the wet relative to the dry season. Generally, contamination in water, sediments, and fish was greater in the canals than in Biscayne Bay and the wetlands. Guideline levels for sediment contaminant were exceeded most frequently in canals relative to the coastal wetlands and the Bay. Further investigation is necessary to better understand the impact of contaminants in Biscayne National Park.

The effects of signage and the physical environment on stair usage.

PubMed

Bungum, Tim; Meacham, Mindy; Truax, Nicole

2007-07-01

Physical activity (PA) is a health behavior that most Americans do not participate in at recommended levels. We sought to increase PA by use of motivational signs in selected buildings. Because physical environments are known to influence PA, the relationship of building characteristics and stair usage was also assessed. One pre- and two post-intervention observations were conducted. The proportion of those using the stairs increased from baseline to the second data collection, (chi2 = 39.31, p < 0.01) and baseline to a final data collection (chi2 = 10.1, p < 0.01). Built environment factors, including steps to the next higher floor and the number of floors in the building were consistent predictors of stair use. With signs positioned, the visibility of the stairs while standing in front of elevators became a significant predictor of stair usage. Motivational signs and characteristics of built environments are associated with increased stair usage.

Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

1992-01-01

In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

PubMed

Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

2015-07-01

Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Matrix metalloproteinases and their tissue inhibitor after reperfused ST-elevation myocardial infarction treated with doxycycline. Insights from the TIPTOP trial.

PubMed

Cerisano, Giampaolo; Buonamici, Piergiovanni; Gori, Anna Maria; Valenti, Renato; Sciagrà, Roberto; Giusti, Betti; Sereni, Alice; Raspanti, Silvia; Colonna, Paolo; Gensini, Gian Franco; Abbate, Rosanna; Schulz, Richard; Antoniucci, David

2015-10-15

The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart. In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

How Configuration Management (CM) Can Help Project Teams To Innovate and Communicate

NASA Technical Reports Server (NTRS)

Cioletti, Louis

2009-01-01

Traditionally, CM is relegated to a support role in project management activities. CM s traditional functions of identification, change control, status accounting, and audits/verification are still necessary and play a vital role. However, this presentation proposes CM s role in a new and innovative manner that will significantly improve communication throughout the organization and, in turn, augment the project s success. CM s new role is elevated to the project management level, above the engineering or sub-project level in the Work Breakdown Structure (WBS), where it can more effectively accommodate changes, reduce corrective actions, and ensure that requirements are clear, concise, and valid, and that results conform to the requirements. By elevating CM s role in project management and orchestrating new measures, a new communication will emerge that will improve information integrity, structured baselines, interchangeability/traceability, metrics, conformance to standards, and standardize the best practices in the organization. Overall project performance (schedule, quality, and cost) can be no better than the ability to communicate requirements which, in turn, is no better than the CM process to communicate project decisions and the correct requirements.

Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

PubMed Central

Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel

2013-01-01

Purpose Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. Materials and Methods We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. Results In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Conclusion Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients. PMID:24142649

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

Baseline and stress-induced levels of corticosterone in male and female Afrotropical and European temperate stonechats during breeding.

PubMed

Apfelbeck, Beate; Helm, Barbara; Illera, Juan Carlos; Mortega, Kim G; Smiddy, Patrick; Evans, Neil P

2017-05-22

Latitudinal variation in avian life histories falls along a slow-fast pace of life continuum: tropical species produce small clutches, but have a high survival probability, while in temperate species the opposite pattern is found. This study investigated whether differential investment into reproduction and survival of tropical and temperate species is paralleled by differences in the secretion of the vertebrate hormone corticosterone (CORT). Depending on circulating concentrations, CORT can both act as a metabolic (low to medium levels) and a stress hormone (high levels) and, thereby, influence reproductive decisions. Baseline and stress-induced CORT was measured across sequential stages of the breeding season in males and females of closely related taxa of stonechats (Saxicola spp) from a wide distribution area. We compared stonechats from 13 sites, representing Canary Islands, European temperate and East African tropical areas. Stonechats are highly seasonal breeders at all these sites, but vary between tropical and temperate regions with regard to reproductive investment and presumably also survival. In accordance with life-history theory, during parental stages, post-capture (baseline) CORT was overall lower in tropical than in temperate stonechats. However, during mating stages, tropical males had elevated post-capture (baseline) CORT concentrations, which did not differ from those of temperate males. Female and male mates of a pair showed correlated levels of post-capture CORT when sampled after simulated territorial intrusions. In contrast to the hypothesis that species with low reproduction and high annual survival should be more risk-sensitive, tropical stonechats had lower stress-induced CORT concentrations than temperate stonechats. We also found relatively high post-capture (baseline) and stress-induced CORT concentrations, in slow-paced Canary Islands stonechats. Our data support and refine the view that baseline CORT facilitates energetically demanding activities in males and females and reflects investment into reproduction. Low parental workload was associated with lower post-capture (baseline) CORT as expected for a slow pace of life in tropical species. On a finer resolution, however, this tropical-temperate contrast did not generally hold. Post-capture (baseline) CORT was higher during mating stages in particular in tropical males, possibly to support the energetic needs of mate-guarding. Counter to predictions based on life history theory, our data do not confirm the hypothesis that long-lived tropical populations have higher stress-induced CORT concentrations than short-lived temperate populations. Instead, in the predator-rich tropical environments of African stonechats, a dampened stress response during parental stages may increase survival probabilities of young. Overall our data further support an association between life history and baseline CORT, but challenge the role of stress-induced CORT as a mediator of tropical-temperate variation in life history.

Diversity reception of COMSTAR SHF beacons with the Tampa triad, 1978 - 1981

NASA Technical Reports Server (NTRS)

Davidson, D.; Tang, D. D.

1982-01-01

The results of 19 GHz downlink rain attenuation diversity measurements in Tampa over a 29 month period (1978-1980), and the results of a 20 GHz diversity study during the summer of 1981, using the remaining COMSTAR beacon are presented. At 19 GHz, site separations of 11, 16, and 20 km were used, with reception at high elevation angle (about 57 deg). At 29 GHz, only the 16 km baseline was employed, with elevation angle about 32 deg. Almost identical long term performance of the two longer baselines indicates that for separations above about 15 km diversity improvement was not sensitive to baseline length or direction. Diversity improvement at 29 GHz with the 16 km baseline was similar to that predicted by scaling the 19 GHz results of the previous seasons. Also discussed are the type of attenuation distributions and typical fade durations to be found under persistent convective conditions. For rain climates like Tampa's, site diversity in some form will be required for high reliability SHF satellite links. The diversity data may be helpful in designing schemes for resource sharing among numbers of links.

Elevated temperatures are associated with stress in rooftop-nesting Common Nighthawk (Chordeiles minor) chicks.

PubMed

Newberry, Gretchen N; Swanson, David L

2018-01-01

Grasslands and riparian forests in southeastern South Dakota have been greatly reduced since historical times, primarily due to conversion to row-crop agriculture. Common Nighthawk ( Chordeiles minor ) nesting habitat includes grasslands, open woodlands and urban rooftops, but nesting sites in southeastern South Dakota are confined to rooftops, as natural nesting habitat is limited. Nighthawks nesting on exposed rooftop habitats may encounter thermal conditions that increase operative temperatures relative to vegetated land cover types. Mean humidity has increased and mean wind speed and cloud cover have decreased during the nighthawk breeding season from 1948 to 2016 in southeastern South Dakota. These changes might contribute to increasing operative temperatures at exposed rooftop nest sites and this could influence chick condition. We studied nest micro-climate and the plasma stress response for 24 rooftop-nesting nighthawk chicks from 17 nests during 2015 and 2016. High humidity prior to blood collection reduced both baseline and stress-induced plasma corticosterone (CORT). In contrast, high maximum temperatures during the day before sampling increased stress-induced CORT. The magnitude of the chick stress response was significantly negatively related to maximum wind speed for the week prior to CORT measurement. Other weather and micro-climate variables were not significant effectors of CORT metrics. Most chicks had low baseline CORT and were able to mount a stress response, but a subset of chicks ( n = 4) showed elevated baseline CORT and a negative association between the magnitude of stress response and ambient temperature. For this subset, mean ambient temperature for the day before sampling was significantly higher (2.3°C) than for chicks with typical baseline CORT levels. These data suggest that regional climate change trends could affect the ability of nighthawk chicks to mount a stress response, which, in turn, might influence the susceptibility of nighthawk chicks to climate change in the Northern Prairie region.

Increased Femoral Head Offset is Associated With Elevated Metal Ions in Asymptomatic Patients With Metal-on-Polyethylene Total Hip Arthroplasty.

PubMed

Martin, John R; Camp, Christopher L; Wyles, Cody C; Taunton, Michael J; Trousdale, Robert T; Lewallen, David G

2016-12-01

Predisposing factors for trunnionosis and elevated metal ion levels in metal-on-polyethylene (MOP) total hip arthroplasty (THA) are currently unknown. This retrospective cohort study enrolled 80 consecutive patients (43 males) with an asymptomatic MOP THA at 2- to 5-year follow-up and no other metal implants. Serum cobalt (Co) and chromium (Cr) levels were collected at the time of enrollment, and retrospective review was performed regarding demographic, implant, and surgical characteristics. Mean age at the time of surgery was 65.7 years (range 35.6-85.9 years), and mean postoperative follow-up was 28.7 months (range 24.4-58.9 months). Femoral head offset was the only evaluated factor shown to increase serum Co ion levels above baseline within the cohort. Mean difference in Co level for high and low offset implants was 0.58 ppb (95% confidence interval [CI] = 0.05-1.11 ppb; P = .03). Mean difference in Cr level for high and low offset implants was 0.19 ppb (95% CI = -0.23 to 0.60 ppb; P = .37). Mean difference in Co level for small and large femoral heads was 0.20 ppb (95% CI = -0.41 to 0.81 ppb; P = .59). Mean difference in Cr level for small and large femoral heads was 0.28 ppb (95% CI = -0.18 to 0.74 ppb; P = .06). Age, gender, Harris Hip Score, and implant duration were not associated with changes in metal ion levels. Femoral head offset appears to be an important source of elevated metal ion levels in MOP THA. Further studies will be needed to understand if increasing femoral head offset is associated with subsequent adverse local tissue reactions. Copyright © 2016 Elsevier Inc. All rights reserved.

N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ndumele, Chiadi E; Matsushita, Kunihiro; Sang, Yingying; Lazo, Mariana; Agarwal, Sunil K; Nambi, Vijay; Deswal, Anita; Blumenthal, Roger S; Ballantyne, Christie M; Coresh, Josef; Selvin, Elizabeth

2016-02-16

Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese. Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population. © 2016 American Heart Association, Inc.

Elevated corticosterone in the dorsal hindbrain increases plasma norepinephrine and neuropeptide Y, and recruits a vasopressin response to stress

PubMed Central

Daubert, Daisy L.; Looney, Benjamin M.; Clifton, Rebekah R.; Cho, Jake N.

2014-01-01

Repeated stress and chronically elevated glucocorticoids cause exaggerated cardiovascular responses to novel stress, elevations in baseline blood pressure, and increased risk for cardiovascular disease. We hypothesized that elevated corticosterone (Cort) within the dorsal hindbrain (DHB) would: 1) enhance arterial pressure and neuroendocrine responses to novel and repeated restraint stress, 2) increase c-Fos expression in regions of the brain involved in sympathetic stimulation during stress, and 3) recruit a vasopressin-mediated blood pressure response to acute stress. Small pellets made of 10% Cort were implanted on the surface of the DHB in male Sprague-Dawley rats. Blood pressure was measured by radiotelemetry. Cort concentration was increased in the DHB in Cort-treated compared with Sham-treated rats (60 ± 15 vs. 14 ± 2 ng Cort/g of tissue, P < 0.05). DHB Cort significantly increased the integrated arterial pressure response to 60 min of restraint stress on days 6, 13, and 14 following pellet implantation (e.g., 731 ± 170 vs. 1,204 ± 68 mmHg/60 min in Sham- vs. Cort-treated rats, day 6, P < 0.05). Cort also increased baseline blood pressure by day 15 (99 ± 2 vs. 108 ± 3 mmHg for Sham- vs. Cort-treated rats, P < 0.05) and elevated baseline plasma norepinephrine and neuropeptide Y concentrations. Cort significantly enhanced stress-induced c-Fos expression in vasopressin-expressing neurons in the paraventricular nucleus of the hypothalamus, and blockade of peripheral vasopressin V1 receptors attenuated the effect of DHB Cort to enhance the blood pressure response to restraint. These data indicate that glucocorticoids act within the DHB to produce some of the adverse cardiovascular consequences of chronic stress, in part, by a peripheral vasopressin-dependent mechanism. PMID:24829502

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery.

PubMed

Smith, K J; MacLeod, D; Willie, C K; Lewis, N C S; Hoiland, R L; Ikeda, K; Tymko, M M; Donnelly, J; Day, T A; MacLeod, N; Lucas, S J E; Ainslie, P N

2014-12-15

We examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CDO2) in excess of that required by an increasing cerebral metabolic rate of oxygen ( CM RO2); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20-60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained CDO2 and elevated absolute CM RO2 at HA compared with SL, the relative increase in CM RO2 was similar during 20-80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain CDO2. Despite adequate CDO2 at HA the brain appears to increase non-oxidative metabolism during exercise and recovery. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery

PubMed Central

Smith, K J; MacLeod, D; Willie, C K; Lewis, N C S; Hoiland, R L; Ikeda, K; Tymko, M M; Donnelly, J; Day, T A; MacLeod, N; Lucas, S J E; Ainslie, P N

2014-01-01

We examined the hypotheses that: (1) during incremental exercise and recovery following 4–6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery () in excess of that required by an increasing cerebral metabolic rate of oxygen (); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial–jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20–60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained and elevated absolute at HA compared with SL, the relative increase in was similar during 20–80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain . Despite adequate at HA the brain appears to increase non-oxidative metabolism during exercise and recovery. PMID:25362150

Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

PubMed

Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

Constitutive Activity among Orphan Class-A G Protein Coupled Receptors

PubMed Central

Martin, Adam L.; Steurer, Michael A.; Aronstam, Robert S.

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention. PMID:26384023

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women.

PubMed

Gray, Dona L; O'Brien, Kevin D; D'Alessio, David A; Brehm, Bonnie J; Deeg, Mark A

2008-04-01

Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor high-density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating GPI-PLD levels. The objective of the study was to determine the effect of weight loss and changes in insulin sensitivity on plasma GPI-PLD levels. Forty-two nondiabetic obese women were included in the study, which involved a 3-month dietary intervention randomizing patients to a low-fat or a low-carbohydrate diet. The study's main outcome measures were plasma GPI-PLD levels and insulin sensitivity as estimated by the homeostasis model assessment. The very low carbohydrate diet group lost more weight after 3 months (-7.6 +/- 3.2 vs -4.2 +/- 3.5 kg, P < .01), although the decrease in insulin resistance was similar between groups. Weight loss with either diet did not alter plasma GPI-PLD levels. However, baseline GPI-PLD levels correlated with the change in insulin sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity correlated with the change in insulin sensitivity in response to the low-carbohydrate diet. Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity.

Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite.

PubMed

Bruno, R; Arnold, C; Jacobson, L; Winick, M; Wynder, E

1983-07-01

Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels. This paper reports such a positive response to a nonpharmacologic, behavioral education program at the worksite. Employees at the New York Telephone Company corporate headquarters were assigned randomly to treatment and control groups. Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours. It comprised a multiple-treatment approach--food behavior change techniques combined with nutrition education, physical activity planning, and self-management skills. The treatment group showed substantial change compared with the control group at the program's completion. Those treated displayed a significant 6.4% reduction in total serum cholesterol (266 mg% average at baseline) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels. A significant increase in nutrition knowledge and moderate weight loss were also documented for this group. The magnitudes of a participant's baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels. Over the same period, decreases in high-density lipoprotein levels and no changes in serum cholesterol, weight, and nutrition knowledge were observed for the control group. Overall, participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight. Directions for future study are suggested.

Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes.

PubMed

Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Hollmann, Charleen; Crystal, Ronald G

2018-05-14

Little is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes. Ten never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of "Blu" brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals. Two hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine. This study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking. ClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

Elevated cardiac troponin T is associated with higher mortality and amputation rates in patients with peripheral arterial disease.

PubMed

Linnemann, Birgit; Sutter, Thilo; Herrmann, Eva; Sixt, Sebastian; Rastan, Aljoscha; Schwarzwaelder, Uwe; Noory, Elias; Buergelin, Karlheinz; Beschorner, Ulrich; Zeller, Thomas

2014-04-22

The aim of the present study was to evaluate whether elevated cardiac troponin T (cTnT) was independently associated with an increased all-cause mortality or risk of cardiovascular events and amputation among patients with peripheral arterial disease (PAD). PAD patients often have impaired renal function, and the blood concentration of cardiac troponin often increases with declining glomerular filtration rate. The cohort consisted of 1,041 consecutive PAD patients (653 males, 388 females, age 70.7 ± 10.8 years, Rutherford stages 2 to 5) undergoing endovascular peripheral revascularization. At baseline, measurable cTnT levels (≥0.01 ng/ml) were detected in 21.3% of individuals. Compared with patients who had undetectable cTnT levels, those with cTnT levels ≥0.01 ng/ml had higher rates for mortality (31.7% vs. 3.9%, respectively; p < 0.001), myocardial infarction (4.1% vs. 1.1%, respectively; p = 0.003), and amputation (10.1% vs. 2.4%, respectively; p < 0.001) during a 1-year follow-up. In adjusted Cox regression models, cTnT levels ≥0.01 ng/ml were associated with increased total mortality (hazard ratio [HR]: 8.14; 95% confidence interval [CI]: 3.77 to 17.6; p < 0.001) and amputation rates (HR: 3.71; 95% CI: 1.33 to 10.3; p = 0.012). cTnT is frequently elevated in PAD patients and is associated with higher event rates in terms of total mortality and amputation. Even small cTnT elevations predict a markedly increased risk that is independent of an impaired renal function. (Troponin T as Risk Stratification Tool in Patients With Peripheral Arterial Occlusive Disease; NCT01087385). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Kidney Disease End Points in a Pooled Analysis of Individual Patient-Level Data From a Large Clinical Trials Program of the Dipeptidyl Peptidase 4 Inhibitor Linagliptin in Type 2 Diabetes.

PubMed

Cooper, Mark E; Perkovic, Vlado; McGill, Janet B; Groop, Per-Henrik; Wanner, Christoph; Rosenstock, Julio; Hehnke, Uwe; Woerle, Hans-Juergen; von Eynatten, Maximilian

2015-09-01

Although assessment of cardiovascular safety is mandated by regulatory agencies for the development of new drugs to treat type 2 diabetes, evaluation of their renal safety has been relatively neglected. Individual patient-level data pooled analysis of 13 phase 2 or 3 randomized, double-blind, placebo-controlled, clinical trials of the dipeptidyl peptidase 4 inhibitor linagliptin. Participants who participated in any of 13 randomized clinical trials and fulfilled predefined inclusion/exclusion criteria, such as being drug-naive (hemoglobin A1c, 7.0%-11.0% [53-97 mmol/mol]) or being on background glucose-lowering therapy (hemoglobin A1c, 6.5%-10.5% [48-91 mmol/mol]). Of 5,466 consenting individuals with inadequately controlled type 2 diabetes, 3,505 received linagliptin, 5mg/d, and 1,961 received placebo. The primary kidney disease outcome was defined as first occurrence during the study of 6 predefined safety end points: new onset of moderate elevation of albuminuria (urinary albumin-creatinine ratio [ACR] >30 mg/g with baseline values ≤ 30 mg/g), new onset of severe elevation of albuminuria (ACR > 300 mg/g with baseline values ≤ 300 mg/g), reduction in kidney function (serum creatinine increase to ≥250 μmol/L from a baseline value <250 μmol/L), halving of estimated glomerular filtration rate (loss of baseline eGFR >50%), acute renal failure (ascertained from diagnostic codes), or death from any cause. Albuminuria was assessed using ACR. GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Cumulative exposure (person-years) was 1,751 for linagliptin and 1,055 for placebo. The primary composite outcome occurred in 448 (12.8%) and 306 (15.6%) participants in the linagliptin and placebo groups, respectively. Linagliptin treatment significantly reduced the hazard of kidney disease events by 16% compared with placebo (HR, 0.84; 95% CI, 0.72-0.97; P=0.02). Retrospective and hypothesis-generating study involving short- to midterm clinical trials. Linagliptin was not associated with increased kidney disease risk in patients with type 2 diabetes. The potential of this drug to improve kidney disease outcomes warrants further investigation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco.

PubMed

Lorkiewicz, Pawel; Riggs, Daniel W; Keith, Rachel J; Conklin, Daniel J; Xie, Zhengzhi; Sutaria, Saurin; Lynch, Blake; Srivastava, Sanjay; Bhatnagar, Aruni

2018-06-02

Cigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products. We recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids. Urinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users. Smoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites. This study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of most VOCs, with the exception of xylene, N,N-dimethylformamide, and acrylonitrile, whose metabolite levels were higher in the urine of e-cigarette users than nontobacco users. Absence of anatabine in the urine of e-cigarette users suggests that measuring urinary levels of this alkaloid may be useful in distinguishing between users of e-cigarettes and combustible cigarettes. However, these results have to be validated in a larger cohortcomprised of users of e-cigarettes of multiple brands.

Different Effects of Oral Contraceptive and Dydrogesterone Treatment on Oxidative Stress Levels in Premenopausal Women.

PubMed

Chen, Jui-Tung; Kotani, Kazuhiko

2018-02-01

The aim of the study was to observe the changes in blood oxidative stress levels by oral contraceptive (OC) and/or dydrogesterone (DG) treatment. A retrospective cohort of 27 premenopausal women with primary dysmenorrhea consisted of the OC treatment group (N = 17) and the DG treatment group (N = 10) by choice of the initial treatment. The OC group included two subgroups: patients with continuous OC treatment (treated for at least 15 months, N = 10) and patients with discontinuous OC treatment (switched to DG treatment after approximately 6 months of initial OC treatment: N = 7). The DG group had 15 months of continuous DG treatment. Blood parameters, including diacron-reactive oxygen metabolites (d-ROMs: an oxidative stress marker), were measured. The d-ROMs level was elevated in the OC group 3 months after initial treatment (mean: from 321 (at baseline) to 512 Carratelli Units (Carr U); P < 0.01), while such changes were not observed in the DG group. The d-ROMs level was reduced in the discontinuous OC subgroup 15 months after initial treatment (from 508 (3 months after initial treatment) to 372 Carr U; P < 0.01), while such changes were not observed in the continuous OC subgroup. The DG group displayed unchanged the d-ROMs level. Replacing OC with DG can attenuate oxidative stress as elevated by OC, thereby alleviating the possible vascular risks with OC treatment.

Relation between amniotic fluid infection or cytokine levels and hearing screen failure in infants at 32 wk gestation or less.

PubMed

Jung, Eun Young; Choi, Byung Yoon; Rhee, Jihye; Park, Jaehong; Cho, Soo-Hyun; Park, Kyo Hoon

2017-02-01

To determine whether the presence of intra-amniotic infection and elevated proinflammatory cytokine levels in amniotic fluid (AF) are associated with failure in the newborn hearing screen (NHS) test in very preterm neonates. This is a retrospective cohort study of 112 premature singleton neonates born to women with preterm labor or preterm premature rupture of membranes at ≤32 wk. AF obtained through amniocentesis was cultured, and interleukin-6 (IL-6) and IL-8 levels were determined. Fourteen (12.5%) neonates failed the NHS test. The prevalence of a positive AF culture was 40% (45/112). Multiple logistic regression analyses indicated that intra-amniotic infection was significantly associated with failure in the NHS test after adjusting for baseline covariates such as maternal white blood cell count (WBC) and periventricular leukomalacia. However, the IL-6 and IL-8 levels in AF were not significantly associated with hearing screen failure. Moreover, neither gestational age at birth nor birth weight was associated with NHS failure. The presence of intra-amniotic infection, but not elevated levels of AF IL-6 and IL-8, may contribute to the risk for failure in the NHS test in very preterm neonates. This finding suggests that intra-amniotic infection in utero might contribute to the development of congenital sensorineural hearing loss.

Effects of arm elevation on radial artery pressure: a new method to distinguish hypovolemic shock and septic shock from hypotension.

PubMed

Xie, Zhiyi; Zhang, Zhenyu; Xu, Yuan; Zhou, Hua; Wu, Sheng; Wang, Zhong

2018-06-01

In this prospective observational study, we investigated the variability in radial artery invasive blood pressure associated with arm elevation in patients with different hemodynamic types. We carried out a prospective observational study using data from 73 general anesthesia hepatobiliary postoperative adult patients admitted to an ICU over a 1-year period. A standard procedure was used for the arm elevation test. The value of invasive radial arterial pressure was recorded at baseline, and 30 and 60 s after the arm had been raised from 0° to 90°. We compared the blood pressure before versus after arm elevation, and between hemodynamically stable, hypovolemic shock, and septic shock patient groups. In all 73 patients, systolic arterial pressure (SAP) decreased, diastolic arterial pressure (DAP) increased, and pulse pressure (PP) decreased at 30 and 60 s after arm elevation (P<0.01), but the mean arterial pressure (MAP) was unchanged (P>0.05). On comparing 30 and 60 s, there was no significant difference in SAP, DAP, PP, or MAP (P>0.05). In 40 hemodynamically stable patients, SAP and PP decreased, and DAP and MAP increased significantly at 30 and 60 s after arm elevation compared with baseline (P<0.01). In 16 hypovolemic patients, SAP, DAP, and MAP increased significantly compared with baseline at 30 and 60 s (P<0.01), but PP was unchanged (P>0.05). In 17 patients with septic shock, SAP, PP, and MAP decreased significantly versus baseline at 30 and 60 s (P<0.01), but DAP was unchanged (P>0.05). Comparison of the absolute value of pressure change of septic shock patients at 30 s after raising the arm showed that SAP, DAP, and MAP changes were significantly lower compared with those in hypovolemic shock and hemodynamically stable patients (P<0.01). The areas under the receiver operator characteristic curve for predicting septic shock was 0.930 [95% confidence interval (CI): 0.867-0.992, P< 0.001] for change value at 30 s after arm elevation of SAP. The best cut-off point for the SAP change value was -5 mmHg or less, with a sensitivity of 94.12%, a specificity of 80.36%, a positive likelihood ratio of 4.79 (95% CI: 2.8-8.2), and a negative likelihood ratio of 0.073 (95% CI: 0.01-0.5). Our study shows that hypovolemic shock and septic shock patients have significantly different radial artery invasive blood pressure changes in an arm elevation test, which could be applied as a new method to distinguish hypovolemic shock and septic shock from hypotension.

Rail commuting duration and passenger stress.

PubMed

Evans, Gary W; Wener, Richard E

2006-05-01

Over 100 million Americans commute to work every weekday. Little is known, however, about how this aspect of work, which may indeed be the most stressful aspect of the job for some, affects human health and well-being. The authors studied a sample of 208 male and female suburban rail commuters who took the train to Manhattan, New York. The greater the duration of the commute, the larger the magnitude of salivary cortisol elevations in reference to resting baseline levels, the less the commuter's persistence on a task at the end of the commute, and the greater the levels of perceived stress. These effects were not moderated by gender. Commuting stress is an important and largely overlooked aspect of environmental health. 2006 APA, all rights reserved

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

GABAergic control of neostriatal dopamine D2 receptor binding and behaviors in the rat.

PubMed

Nikolaus, Susanne; Beu, Markus; de Souza Silva, Maria Angelica; Huston, Joseph P; Antke, Christina; Müller, Hans-Wilhelm; Hautzel, Hubertus

2017-02-01

The present study assessed the influence of the GABA A receptor agonist muscimol and the GABA A receptor antagonist bicuculline on neostriatal dopamine D 2 receptor binding in relation to motor and exploratory behaviors in the rat. D 2 receptor binding was measured in baseline and after challenge with either 1mg/kg muscimol or 1mg/kg bicuculline. In additional rats, D 2 receptor binding was measured after injection of saline. After treatment with muscimol, bicuculline and saline, motor and exploratory behaviors were assessed for 30min in an open field prior to administration of [ 123 I]S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide ([ 123 I]IBZM). For baseline and challenges, striatal equilibrium ratios (V 3 ″) were computed as estimation of the binding potential. Muscimol but not bicuculline reduced D 2 receptor binding relative to baseline and to saline. Travelled distance, duration of rearing and frequency of rearing and of head-shoulder motility were lower after muscimol compared to saline. In contrast, duration of rearing and grooming and frequency of rearing, head-shoulder motility and grooming were elevated after bicuculline relative to saline. Moreover, bicuculline decreased duration of sitting and head-shoulder motility. The muscimol-induced decrease of motor/exploratory behaviors can be related to an elevation of striatal dopamine levels. In contrast, bicuculline is likely to elicit a decline of synaptic dopamine, which, however, is compensated by the time of D 2 receptor imaging studies. The results indicate direct GABAergic control over D 2 receptor binding in the neostriatum in relation to behavioral action, and, thus, complement earlier pharmacological studies. Copyright © 2016. Published by Elsevier Inc.

Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum

NASA Technical Reports Server (NTRS)

Farber, S. A.; Kischka, U.; Marshall, D. L.; Wurtman, R. J.

1993-01-01

We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration, 20 Hz and 200 microA, ACh release increased to 357 +/- 30% (P < 0.01) of baseline and was blocked by the addition of tetrodotoxin (TTX). Pulse durations of 2.0 ms or greater were required to increase DA release. Unlike ACh release, DA release showed no frequency dependence above 5 Hz. The maximal evoked releases of ACh and DA were 556 +/- 94% (P < 0.01) and 254 +/- 38% (P < 0.05) of baseline, respectively. Peripheral administration of choline (Ch) chloride (30-120 mg/kg) to anesthetized animals caused dose-related (r = 0.994, P < 0.01) increases in ACh release; basal release rose from 117 +/- 7% to 141 +/- 5% of initial baseline levels (P < 0.05) and electrically evoked ACh release rose from 386 +/- 38% to 600 +/- 34% (P < 0.01) in rats given 120 mg/kg. However, Ch failed to affect basal or evoked DA release although neostigmine (10 microM) significantly elevated basal DA release (from 36.7 fmol/10 min to 71.5 fmol/10 min; P < 0.05). In awake animals, Ch (120 mg/kg) also elevated both basal (from 106 +/- 7% to 154 +/- 17%; P < 0.05) and electrically evoked (from 146 +/- 13 to 262 +/- 16%; P < 0.01) ACh release.(ABSTRACT TRUNCATED AT 250 WORDS).

[Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status].

PubMed

López-Alarcón, Mardia; Chávez-Negrete, Adolfo; Montalvo-Velarde, Irene; Maldonado-Hernández, Jorge; Vital-Reyes, Víctor Saúl

2011-01-01

Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.

The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.

PubMed

Joeyen-Waldorf, Jennifer; Edgar, Nicole; Sibille, Etienne

2009-08-25

Mood disorders are influenced by genetic make-up and differentially affect men and women. The s/l promoter polymorphism in the serotonin transporter (SERT) gene moderates both trait emotion and the vulnerability to develop depressive states in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated emotionality phenotype. We now report that the SERT-KO phenotype is maintained throughout late-adulthood, and that female KO mice develop a larger emotionality phenotype with increasing age. Thus, to test the hypothesis that these findings reflected a putative sexual dimorphism in SERT-mediated modulation of emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral changes. In males, the elevated SERT-KO emotion-related behavior converged with other groups after UCMS. Conversely, female SERT-KO displayed a normal non-stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed variable and intermediate phenotypes in both experiments. Thus, consistent results across different biological modalities (age, stress) revealed a high contribution of SERT genotype for baseline "trait" emotionality in males, and low contribution for females. In contrast, age-correlated and stress-induced behavioral changes resulted in a high SERT genotype-mediated behavioral variance in females, but low in males. This suggests that high emotionality states associated with low SERT were differentially achieved in males (high baseline/trait) compared to females (increased vulnerability to develop high emotionality). This sex-by-SERT double dissociation provides a framework to investigate molecular substrates of emotionality regulation in concert with serotonin function and may contribute to the sexually dimorphic features of mood disorders.

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries.

PubMed

Rosenfield, Robert L; Wroblewski, Kristen; Padmanabhan, Vasantha; Littlejohn, Elizabeth; Mortensen, Monica; Ehrmann, David A

2012-07-01

To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Prospective case-control study. General clinical research center. Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries

PubMed Central

Rosenfield, Robert L.; Wroblewski, Kristen; Padmanabhan, Vasantha; Littlejohn, Elizabeth; Mortensen, Monica; Ehrmann, David A.

2013-01-01

Objective To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Design Prospective case-control study. Setting General clinical research center. Participant(s) Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Intervention(s) Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Main Outcome Measure(s) Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. Result(s) AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. Conclusion(s) AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool. PMID:22541936

Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome

PubMed Central

Plée, Julie; Le Jan, Sébastien; Giustiniani, Jérôme; Barbe, Coralie; Joly, Pascal; Bedane, Christophe; Vabres, Pierre; Truchetet, François; Aubin, François; Antonicelli, Frank; Bernard, Philippe

2015-01-01

Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment. PMID:26656739

Metacognitive deficits predict future levels of negative symptoms in schizophrenia controlling for neurocognition, affect recognition, and self-expectation of goal attainment.

PubMed

Lysaker, Paul H; Kukla, Marina; Dubreucq, Julien; Gumley, Andrew; McLeod, Hamish; Vohs, Jenifer L; Buck, Kelly D; Minor, Kyle S; Luther, Lauren; Leonhardt, Bethany L; Belanger, Elizabeth A; Popolo, Raffaele; Dimaggio, Giancarlo

2015-10-01

The recalcitrance of negative symptoms in the face of pharmacologic treatment has spurred interest in understanding the psychological factors that contribute to their formation and persistence. Accordingly, this study investigated whether deficits in metacognition, or the ability to form integrated ideas about oneself, others, and the world, prospectively predicted levels of negative symptoms independent of deficits in neurocognition, affect recognition and defeatist beliefs. Participants were 53 adults with a schizophrenia spectrum disorder. Prior to entry into a rehabilitation program, all participants completed concurrent assessments of metacognition with the Metacognitive Assessment Scale-Abbreviated, negative symptoms with the Positive and Negative Syndrome Scale, neurocognition with the MATRICS battery, affect recognition with the Bell Lysaker Emotion Recognition Task, and one form of defeatist beliefs with the Recovery Assessment Scale. Negative symptoms were then reassessed one week, 9weeks, and 17weeks after entry into the program. A mixed effects regression model revealed that after controlling for baseline negative symptoms, a general index of neurocognition, defeatist beliefs and capacity for affect recognition, lower levels of metacognition predicted higher levels of negative symptoms across all subsequent time points. Poorer metacognition was able to predict later levels of elevated negative symptoms even after controlling for initial levels of negative symptoms. Results may suggest that metacognitive deficits are a risk factor for elevated levels of negative symptoms in the future. Clinical implications are also discussed. Published by Elsevier B.V.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives.

PubMed

Sun, Wu-Ping; Li, Da; Lun, Yong-Zhi; Gong, Xiao-Jie; Sun, Shen-Xia; Guo, Ming; Jing, Li-Xin; Zhang, Li-Bin; Xiao, Fu-Cheng; Zhou, Shi-Sheng

2012-02-01

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N(1)-methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N(1)-methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamide-loading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

Heavy metals in wild rice from northern Wisconsin

USGS Publications Warehouse

Bennett, J.P.; Chiriboga, E.; Coleman, J.; Waller, D.M.

2000-01-01

Wild rice grain samples from various parts of the world have been found to have elevated concentrations of heavy metals, raising concern for potential effects on human health. It was hypothesized that wild rice from north-central Wisconsin could potentially have elevated concentrations of some heavy metals because of possible exposure to these elements from the atmosphere or from water and sediments. In addition, no studies of heavy metals in wild rice from Wisconsin had been performed, and a baseline study was needed for future comparisons. Wild rice plants were collected from four areas in Bayfield, Forest, Langlade, Oneida, Sawyer and Wood Counties in September, 1997 and 1998 and divided into four plant parts for elemental analyses: roots, stems, leaves and seeds. A total of 194 samples from 51 plants were analyzed across the localities, with an average of 49 samples per part depending on the element. Samples were cleaned of soil, wet digested, and analyzed by ICP for Ag, As, Cd, Cr, Cu, Hg, Mg, Pb, Se and Zn. Roots contained the highest concentrations of Ag, As, Cd, Cr, Hg, Pb, and Se. Copper was highest in both roots and seeds, while Zn was highest just in seeds. Magnesium was highest in leaves. Seed baseline ranges for the 10 elements were established using the 95% confidence intervals of the medians. Wild rice plants from northern Wisconsin had normal levels of the nutritional elements Cu, Mg and Zn in the seeds. Silver, Cd, Hg, Cr, and Se were very low in concentration or within normal limits for food plants. Arsenic and Pb, however, were elevated and could pose a problem for human health. The pathway for As, Hg and Pb to the plants could be atmospheric.

Brain-derived neurotrophic factor modulates angiotensin signaling in the hypothalamus to increase blood pressure in rats

PubMed Central

Backes, Iara; McCowan, Michael L.; Hayward, Linda F.; Scheuer, Deborah A.

2015-01-01

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli including stress and hyperosmolarity. However, it is unclear whether BDNF in the PVN contributes to increases in blood pressure (BP). We tested the hypothesis that increased BDNF levels within the PVN would elevate baseline BP and heart rate (HR) and cardiovascular stress responses by altering central angiotensin signaling. BP was recorded using radiotelemetry in male Sprague-Dawley rats after bilateral PVN injections of adeno-associated viral vectors expressing green fluorescent protein (GFP) or myc epitope-tagged BDNF fusion protein. Cardiovascular responses to acute stress were evaluated 3 to 4 wk after injections. Additional GFP and BDNF-treated animals were equipped with osmotic pumps for intracerebroventricular infusion of saline or the angiotensin type-1 receptor (AT1R) inhibitor losartan (15 μg·0.5 μl−1·h−1). BDNF treatment significantly increased baseline BP (121 ± 3 mmHg vs. 99 ± 2 mmHg in GFP), HR (394 ± 9 beats/min vs. 314 ± 4 beats/min in GFP), and sympathetic tone indicated by HR- and BP-variability analysis and adrenomedullary tyrosine hydroxylase protein expression. In contrast, body weight and BP elevations to acute stressors decreased. BDNF upregulated AT1R mRNA by ∼80% and downregulated Mas receptor mRNA by ∼50% in the PVN, and losartan infusion partially inhibited weight loss and increases in BP and HR in BDNF-treated animals without any effect in GFP rats. Our results demonstrate that BDNF overexpression in the PVN results in sympathoexcitation, BP and HR elevations, and weight loss that are mediated, at least in part, by modulating angiotensin signaling in the PVN. PMID:25576628

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications.

PubMed

Gentry, Chris A; Nguyen, Ann T

2013-12-01

Adverse events associated with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) for outpatient infections, particularly those likely caused by community-acquired methicillin-resistant Staphylococcus aureus, have not been adequately characterized. Describe hyperkalemia and acute renal injury associated with high-dose TMP-SMX. An electronic medical record database retrospective study was conducted of outpatients receiving high-dose or low-dose TMP-SMX, comparing the incidences of hyperkalemia and acute renal injury. Of 6162 patients, more developed hyperkalemia (3.06% vs 1.05%, P < .0001) or acute renal injury (1.99% vs 0.700%, P = .0001) in the high-dose TMP-SMX group. Variables independently associated with hyperkalemia included age >58 years (odds ratio [OR] = 3.44; 95% CI = 1.86-7.0; P < .0001), concomitant receipt of an NSAID (OR = 1.71; 95% CI = 1.02-2.79; P = .044) or an ACE inhibitor (OR = 3.27; 95% CI = 2.06-5.14; P < .0001), high-dose TMP-SMX prescribed (OR = 2.92; 95% CI = 1.85-4.60; P < .0001), and baseline elevated serum creatinine (OR = 45.1; 95% CI = 21.7-93.2; P < .0001). Variables independently associated with acute renal injury included concomitant receipt of an ACE inhibitor (OR = 2.36; 95% CI = 1.01-5.24; P = .048) or a potassium supplement (OR = 4.10; 95% CI = 1.45-10.1; P = .010), high-dose TMP-SMX prescribed (OR = 3.70; 95% CI = 1.70-8.12; P = .0012), and baseline elevated serum creatinine (OR = 2110; 95% CI = 724-7980; P < .0001). Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose TMP-SMX.

Ocean warming and acidification modulate energy budget and gill ion regulatory mechanisms in Atlantic cod (Gadus morhua).

PubMed

Kreiss, C M; Michael, K; Lucassen, M; Jutfelt, F; Motyka, R; Dupont, S; Pörtner, H-O

2015-10-01

Ocean warming and acidification are threatening marine ecosystems. In marine animals, acidification is thought to enhance ion regulatory costs and thereby baseline energy demand, while elevated temperature also increases baseline metabolic rate. Here we investigated standard metabolic rates (SMR) and plasma parameters of Atlantic cod (Gadus morhua) after 3-4 weeks of exposure to ambient and future PCO2 levels (550, 1200 and 2200 µatm) and at two temperatures (10, 18 °C). In vivo branchial ion regulatory costs were studied in isolated, perfused gill preparations. Animals reared at 18 °C responded to increasing CO2 by elevating SMR, in contrast to specimens at 10 °C. Isolated gills at 10 °C and elevated PCO2 (≥1200 µatm) displayed increased soft tissue mass, in parallel to increased gill oxygen demand, indicating an increased fraction of gill in whole animal energy budget. Altered gill size was not found at 18 °C, where a shift in the use of ion regulation mechanisms occurred towards enhanced Na(+)/H(+)-exchange and HCO3 (-) transport at high PCO2 (2200 µatm), paralleled by higher Na(+)/K(+)-ATPase activities. This shift did not affect total gill energy consumption leaving whole animal energy budget unaffected. Higher Na(+)/K(+)-ATPase activities in the warmth might have compensated for enhanced branchial permeability and led to reduced plasma Na(+) and/or Cl(-) concentrations and slightly lowered osmolalities seen at 18 °C and 550 or 2200 µatm PCO2 in vivo. Overall, the gill as a key ion regulation organ seems to be highly effective in supporting the resilience of cod to effects of ocean warming and acidification.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction.

PubMed

Chrastina, Adrian; Pokreisz, Peter; Schnitzer, Jan E

2014-01-15

We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 ± 6 ng/ml, n = 4, P < 0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 ± 3% of the left ventricle at day 1 with a decrease to 20 ± 3% at day 40 (n = 6 for each group, P < 0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n = 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions.

The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure.

PubMed

Ahmad, Tariq; Fiuzat, Mona; Mark, Daniel B; Neely, Ben; Neely, Megan; Kraus, William E; Kitzman, Dalane W; Whellan, David J; Donahue, Mark; Zannad, Faiez; Piña, Ileana L; Adams, Kirkwood; O'Connor, Christopher M; Felker, G Michael

2014-02-01

Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear. Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP (P = .10), hs-CRP (P = .80), or detectable cTnT levels (P = .83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 (P < .001) at 3 months and decreased risk of hospitalizations or mortality (P ≤ .04), even after adjustment for a comprehensive set of known predictors. Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events. © 2014.

Baseline blood Pb levels of black-necked stilts on the upper Texas coast

USGS Publications Warehouse

Riecke, Thomas V.; Conway, Warren C.; Haukos, David A.; Moon, Jena A.; Comer, Christopher E.

2015-01-01

There are no known biological requirements for lead (Pb), and elevated Pb levels in birds can cause a variety of sub-lethal effects and mortality. Historic and current levels of Pb in mottled ducks (Anas fulvigula) suggest that environmental sources of Pb remain available on the upper Texas coast. Because of potential risks of Pb exposure among coexisting marsh birds, black-necked stilt (Himantopus mexicanus) blood Pb concentrations were measured during the breeding season. Almost 80 % (n = 120) of 152 sampled stilts exceeded the background threshold (>20 μg/dL) for Pb exposure. However, blood Pb concentrations did not vary by age or gender, and toxic or potentially lethal concentrations were rare (<5 %). Consistent, low-level blood Pb concentrations of black-necked stilts in this study suggest the presence of readily bioavailable sources of Pb, although potential impacts on local stilt populations remain unclear.

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events.

PubMed

Addison, Christina L; Bouganim, Nathaniel; Hilton, John; Vandermeer, Lisa; Dent, Susan; Amir, Eitan; Hopkins, Sean; Kuchuk, Iryna; Segal, Roanne; Song, Xinni; Gertler, Stan; Mazzarello, Sasha; Dranitsaris, George; Ooi, Daylily; Pond, Gregory; Clemons, Mark

2014-04-01

The optimal frequency of intravenous (IV) bisphosphonate administration is unclear. We thus performed a study evaluating the effects of switching from 3-4 to 12 weekly therapy in patients with biochemically defined low-risk bone metastases. Patients with serum C-telopeptide (CTx) levels ≤600 ng/L after ≥3 months of 3-4 weekly IV pamidronate were switched to 12 weekly therapy for 48 weeks. Primary endpoint was the proportion of patients maintaining CTx levels in the lower-risk range. All endpoints (serum CTx and bone-specific alkaline phosphatase (BSAP), skeletal-related events (SREs) and self-reported pain) were measured at baseline, 6, 12, 24, 36 and 48 weeks. Treatment failure was defined as biochemical failure (CTx > 600 ng/L) or a SRE. Exploratory biomarkers including; serum TGF-β, activin-A, bone sialoprotein (BSP), procollagen type 1 N-terminal propeptide and urinary N-telopeptide (NTx) were assessed at baseline as predictors for failure to complete treatment. Seventy-one patients accrued and 43 (61 %) completed 48 weeks of de-escalated therapy. Reasons for failure to complete treatment included; biochemical failure (CTx > 600 ng/L) (n = 10, 14.1 %), on-study SRE (n = 9, 12.7 %), disease progression (n = 7, 9.9 % including death from disease [n = 1, 1.4 %]) or patient choice (n = 2, 2.8 %). Elevated baseline levels of CTx, BSAP, NTx and BSP were associated with treatment failure. The majority of patients in this biochemically defined low-risk population could switch from 3-4 weekly to 12 weekly bisphosphonate therapy with no effect on CTx levels or SREs during the 48 week study. Larger trials are required to assess the roles of biomarkers as predictors of adequacy of de-escalated therapy.

Loneliness, Social Integration and Consumption of Sugar-Containing Beverages: Testing the Social Baseline Theory

PubMed Central

Henriksen, Roger Ekeberg; Torsheim, Torbjørn; Thuen, Frode

2014-01-01

Objective Social Baseline Theory (SBT) proposes that close relationships aid in metabolic resource management and that individuals without significant relationships may experience more demands on their own neural metabolic resources on a daily basis when solving problems, remaining vigilant against potential threats and regulating emotional responses. This study tests a hypothesised consequence derived from SBT: relative social isolation leads to increased levels of sugar intake. Methods Based on cross-sectional, self-reported data from the Norwegian Mother and Child Cohort Study (N = 90 084), information on social integration and the consumption of both sugar-sweetened and artificially sweetened sodas and juices was obtained from a large number of women in early pregnancy. Multiple regression analyses were conducted to assess whether loneliness, marital status, relationship satisfaction, advice from others than partner, and cohesion at work is associated with consumption of sodas and juices. Results Perceived loneliness was associated with elevated intake of all sugary beverages, while relationship satisfaction was negatively associated with all sugary beverages. Being married or cohabitating, having supportive friends, and having a sense of togetherness at work were associated with lower intake of two out of three sugar-containing beverages. These associations were significant, even after controlling for factors such as body mass index, weight related self-image, depression, physical activity, educational level, age and income. In comparison, a statistically significant relationship emerged between relationship satisfaction and artificially sweetened cola. No other predictor variables were significantly associated with any type of artificially sweetened beverage. Conclusions This study indicates that loneliness and social integration influence the level of consumption of sugary beverages. The results support the hypothesis derived from the Social Baseline Theory that relative social isolation leads to increased levels of sugar intake. PMID:25105408

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

PubMed

Huang, Chun-Jung; Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2016-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18-30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. © 2015 by the Society for Experimental Biology and Medicine.

Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

PubMed

Li, Ge; Mayer, Cynthia L; Morelli, Daniel; Millard, Steven P; Raskind, Wendy H; Petrie, Eric C; Cherrier, Monique; Fagan, Anne M; Raskind, Murray A; Peskind, Elaine R

2017-09-19

To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42 , total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status. Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42 , total tau, and p-tau 181 , respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 ( p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.

A Longitudinal Investigation of Predictors of the Association Between Age 3 and Age 6 Behavioural Inhibition

PubMed Central

Johnson, Victoria C.; Olino, Thomas M.; Klein, Daniel N.; Dyson, Margaret W.; Bufferd, Sara J.; Durbin, C. Emily; Dougherty, Lea R.; Hayden, Elizabeth P.

2016-01-01

Children who exhibit elevated levels of the temperament trait behavioural inhibition (BI) across time may be at greatest risk for anxiety. However, little research has investigated the influence of other temperamental traits, particularly positive emotionality (PE), on the continuity of BI in childhood, nor whether parental overprotection influences associations between early and later child BI. To explore whether PE and overprotection shape associations between early and later BI, this longitudinal study of three-year-olds (N = 446) followed up at age 6 included tasks tapping child temperament, and parental overprotection was assessed via interview ratings and parent-report. Lower levels of child PE and higher levels of caregiver overprotection at baseline predicted stronger associations between laboratory-assessed BI at ages 3 and 6. Findings elucidate influences shaping the developmental continuity of BI. PMID:27765998

A Longitudinal Investigation of Predictors of the Association Between Age 3 and Age 6 Behavioural Inhibition.

PubMed

Johnson, Victoria C; Olino, Thomas M; Klein, Daniel N; Dyson, Margaret W; Bufferd, Sara J; Durbin, C Emily; Dougherty, Lea R; Hayden, Elizabeth P

2016-08-01

Children who exhibit elevated levels of the temperament trait behavioural inhibition (BI) across time may be at greatest risk for anxiety. However, little research has investigated the influence of other temperamental traits, particularly positive emotionality (PE), on the continuity of BI in childhood, nor whether parental overprotection influences associations between early and later child BI. To explore whether PE and overprotection shape associations between early and later BI, this longitudinal study of three-year-olds ( N = 446) followed up at age 6 included tasks tapping child temperament, and parental overprotection was assessed via interview ratings and parent-report. Lower levels of child PE and higher levels of caregiver overprotection at baseline predicted stronger associations between laboratory-assessed BI at ages 3 and 6. Findings elucidate influences shaping the developmental continuity of BI.

Evaluating integration of inland bathymetry in the U.S. Geological Survey 3D Elevation Program, 2014

USGS Publications Warehouse

Miller-Corbett, Cynthia

2016-09-01

Inland bathymetry survey collections, survey data types, features, sources, availability, and the effort required to integrate inland bathymetric data into the U.S. Geological Survey 3D Elevation Program are assessed to help determine the feasibility of integrating three-dimensional water feature elevation data into The National Map. Available data from wading, acoustic, light detection and ranging, and combined technique surveys are provided by the U.S. Geological Survey, National Oceanic and Atmospheric Administration, U.S. Army Corps of Engineers, and other sources. Inland bathymetric data accessed through Web-hosted resources or contacts provide useful baseline parameters for evaluating survey types and techniques used for collection and processing, and serve as a basis for comparing survey methods and the quality of results. Historically, boat-mounted acoustic surveys have provided most inland bathymetry data. Light detection and ranging techniques that are beneficial in areas hard to reach by boat, that can collect dense data in shallow water to provide comprehensive coverage, and that can be cost effective for surveying large areas with good water clarity are becoming more common; however, optimal conditions and techniques for collecting and processing light detection and ranging inland bathymetry surveys are not yet well defined.Assessment of site condition parameters important for understanding inland bathymetry survey issues and results, and an evaluation of existing inland bathymetry survey coverage are proposed as steps to develop criteria for implementing a useful and successful inland bathymetry survey plan in the 3D Elevation Program. These survey parameters would also serve as input for an inland bathymetry survey data baseline. Integration and interpolation techniques are important factors to consider in developing a robust plan; however, available survey data are usually in a triangulated irregular network format or other format compatible with the 3D Elevation Program so that data can be integrated with a minimal level of effort. Geomorphic site conditions are known to affect the success and accuracy of light detection and ranging and other bathymetric surveys, and a baseline that includes geomorphic data is recommended to help in evaluation of limitations imposed by geomorphology for surveys completed in the variable physiographic provinces across the United States. The geographic distribution for existing surveys identifies regions where inland bathymetry data have been collected and, conversely, where little or no survey data seem to be available to provide hydrologic and hydraulic information. This distribution, in conjunction with local to regional data needs to characterize and monitor river and lake resources, provides another important set of criteria to propose and guide acquisition of new bathymetry data for the 3D Elevation Program. An initial evaluation of needs can be based on the importance of water resources that provide primary water supplies for communities, agriculture, energy, and ecological systems; the importance of flood plain analyses; and projected population growth across the United States.

Elevated lipoprotein(a) levels predict cardiovascular disease in type 2 diabetes mellitus: a 10-year prospective cohort study.

PubMed

Lim, Tae-Seok; Yun, Jae-Seung; Cha, Seon-Ah; Song, Ki-Ho; Yoo, Ki-Dong; Ahn, Yu-Bae; Park, Yong-Moon; Ko, Seung-Hyun

2016-11-01

Elevated lipoprotein(a) (Lp[a]) level is known to be a risk factor for cardiovascular disease (CVD). However, the data that has been reported on the association between the Lp(a) level and CVD in type 2 diabetes has been limited and incoherent. The aim of this study was to investigate the relationship between the Lp(a) concentration and new onset CVD in type 2 diabetes. From March 2003 to December 2004, patients with type 2 diabetes without a prior history of CVD were consecutively enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. Cox proportional hazards models were used to identify the associations between the Lp(a) and CVD after adjusting for confounding variables. Of the 1,183 patients who were enrolled, 833 participants were evaluated with a median follow-up time of 11.1 years. A total of 202 participants were diagnosed with CVD (24.2%). The median Lp(a) level for 1st and 4th quartile group was 5.4 (3.5 to 7.1) and 55.7 mg/dL (43.1 to 75.3). Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin and angiotensin converting enzyme inhibitors/angiotensin receptor blockers at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with serum Lp(a) level (hazard ratio, 1.92; 95% confidence interval [CI], 1.26 to 2.92; p < 0.001, comparing the 4th vs. 1st quartile of Lp[a]). Elevated Lp(a) level was an independent predictable risk factor for CVD in type 2 diabetes. Other cardiovascular risk factors should be treated more intensively in type 2 diabetic patients with high Lp(a) levels.

The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.

PubMed

Tutuncu, Levent; Ergur, Ali Rustu; Mungen, Ercument; Gun, Ismet; Ertekin, Aktug; Yergok, Yusuf Ziya

2005-03-01

An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.

Evaluation of a group cognitive-behavioral depression prevention program for young adolescents: A randomized effectiveness trial

PubMed Central

Gillham, Jane E.; Reivich, Karen J.; Brunwasser, Steven M.; Freres, Derek R.; Chajon, Norma D.; Megan Kash-MacDonald, V.; Chaplin, Tara M.; Abenavoli, Rachel M.; Matlin, Samantha L.; Gallop, Robert J.; Seligman, Martin E.P.

2015-01-01

Objective Depression is a common psychological problem in adolescence. Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth. Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors (as opposed to research team staff). Method We evaluated the effectiveness of the Penn Resiliency Program for adolescents (PRP-A), a school-based group intervention that targets cognitive behavioral risk factors for depression. We randomly assigned 408 middle school students (ages 10-15) to one of three conditions: PRP-A, PRP-AP (in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component), or a school-as-usual control. Adolescents completed measures of depression and anxiety symptoms, cognitive style, and coping at baseline, immediately after the intervention, and at 6-month follow-up. Results PRP-A reduced depression symptoms relative to the school as usual control. Baseline levels of hopelessness moderated intervention effects. Among participants with average and high levels of hopelessness, PRP (A and AP) significantly improved depression symptoms, anxiety symptoms, hopelessness, and active coping relative to control. Among participants with low baseline hopelessness, we found no intervention effects. PRP-AP was not more effective than PRP-A alone. We found no intervention effects on clinical levels of depression or anxiety. Conclusion These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors. These interventions may be most helpful to students with elevated hopelessness. PMID:22889296

Peripheral blood microRNA and VEGFA mRNA changes following electroconvulsive therapy: implications for psychotic depression.

PubMed

Kolshus, E; Ryan, K M; Blackshields, G; Smyth, P; Sheils, O; McLoughlin, D M

2017-12-01

MicroRNAs are short, non-coding molecules that regulate gene expression. Here, we investigate the role of microRNAs in depression and electroconvulsive therapy (ECT). We performed three studies: a deep sequencing discovery-phase study of miRNA changes in whole blood following ECT (n = 16), followed by a validation study in a separate cohort of patients pre-/post-ECT (n = 37) and matched healthy controls (n = 34). Changes in an experimentally validated gene target (VEGFA) were then analysed in patients pre-/post-ECT (n = 97) and in matched healthy controls (n = 53). In the discovery-phase study, we found no statistically significant differences in miRNA expression from baseline to end of treatment in the group as a whole, but post hoc analysis indicated a difference in patients with psychotic depression (n = 3). In a follow-up validation study, patients with psychotic depression (n = 7) had elevated baseline levels of miR-126-3p (t = 3.015, P = 0.006) and miR-106a-5p (t = 2.598, P = 0.025) compared to healthy controls. Following ECT, these differences disappeared. Baseline VEGFA levels were significantly higher in depressed patients compared to healthy controls (F(1,144) = 27.688, P = <0.001). Following ECT, there was a significant change in VEGFA levels in the psychotic group only (t = 2.915, P = 0.010). Molecular differences (miRNA and VEGFA) may exist between psychotic and non-psychotic depression treated with ECT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of fundus autofluorescence with photopic and scotopic fine matrix mapping in patients with retinitis pigmentosa: 4- to 8-year follow-up.

PubMed

Robson, Anthony G; Lenassi, Eva; Saihan, Zubin; Luong, Vy A; Fitzke, Fred W; Holder, Graham E; Webster, Andrew R

2012-09-14

To assess the significance and evolution of parafoveal rings of high-density fundus autofluorescence (AF) in 12 patients with retinitis pigmentosa (RP). Twelve patients with autosomal recessive RP or Usher syndrome type 2 were ascertained who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better at baseline. Photopic and scotopic fine matrix mapping (FMM) were performed to test sensitivity across the macula. AF imaging and FMM were repeated after 4 to 8 years and optical coherence tomography (OCT) performed. The size of the AF ring reduced over time and disappeared in one subject. Photopic thresholds were normal over the fovea; thresholds were elevated by 0.6 log units over the ring and by 1.2 log units external to the ring at baseline and differed by less than 0.1 log unit at follow-up. Mild photopic losses close to the internal edge of the ring were detected at baseline or follow-up in all. Mean scotopic thresholds over parafoveal areas within the ring were markedly elevated in 8 of 10 at baseline and were severely elevated in 9 of 11 at follow-up. The eccentricity of the inner edge of the AF ring corresponded closely with the lateral extent of the inner segment ellipsoid band in the OCT image. Ring constriction was largely coincident with progressive centripetal photopic threshold elevation led by worsening of rod photoreceptor function. The rate of constriction differed across patients, and a ring may reach a critical minimum before disappearing, at which stage central visual loss occurs. The structural and functional changes associated with rings of increased autofluorescence confirm that they provide an objective index of macular involvement and may aid the management of RP patients and the monitoring of future treatment efficacy.

Anterior Cingulate Glutamate Is Reduced by Acamprosate Treatment in Patients With Alcohol Dependence.

PubMed

Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D

2016-12-01

Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.

Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration

PubMed Central

Bhattacharyya, Sudeepa; Pence, Lisa; Beger, Richard; Chaudhuri, Shubhra; McCullough, Sandra; Yan, Ke; Simpson, Pippa; Hennings, Leah; Hinson, Jack; James, Laura

2013-01-01

High doses of acetaminophen (APAP) result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI) to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP) or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT) levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA) expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS) model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines. PMID:24958141

A phase II, randomized, controlled trial of S-adenosylmethionine in reducing serum alpha-fetoprotein (AFP) in patients with hepatitis C cirrhosis and elevated AFP

PubMed Central

Morgan, Timothy R.; Osann, Kathryn; Bottiglieri, Teodoro; Pimstone, Neville; Hoefs, John C.; Hu, Ke-Qin; Hassanein, Tarek; Boyer, Thomas D.; Kong, Lorene; Chen, Wen-Pin; Richmond, Ellen; Gonzalez, Rachel; Rodriguez, Luz M.; Meyskens, Frank L.

2015-01-01

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC while administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum AFP level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 grams/day, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. 110 subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury, or markers of oxidative stress or antioxidant potential. PMID:26130251

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

PubMed Central

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421.

PubMed

Lara, Primo N; Ely, Benjamin; Quinn, David I; Mack, Philip C; Tangen, Catherine; Gertz, Erik; Twardowski, Przemyslaw W; Goldkorn, Amir; Hussain, Maha; Vogelzang, Nicholas J; Thompson, Ian M; Van Loan, Marta D

2014-04-01

Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration-resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value of bone biomarkers in sera from CRPC patients treated on a placebo-controlled phase III trial of docetaxel with or without the bone targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were fit for overall survival. Models were fit with main effects for marker levels and with/without terms for marker-treatment interaction, adjusted for clinical variables, to assess the prognostic and predictive value of atrasentan. Analysis was adjusted for multiple comparisons. Two-sided P values were calculated using the Wald test. Sera from 778 patients were analyzed. Elevated baseline levels of each of the markers were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy were also associated with subsequent poor survival (P < .001). Patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005). Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.

PubMed

Hook, Julie N; Giordani, Bruno; Schteingart, David E; Guire, Kenneth; Giles, Jodie; Ryan, Kelley; Gebarski, Stephen S; Langenecker, Scott A; Starkman, Monica N

2007-01-01

Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment.

Preoperative Statin Therapy in Cardiac Surgery Is More Effective in Patients Who Display Preoperative Activation of the Inflammatory System

PubMed Central

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass. PMID:23466655

Preoperative statin therapy in cardiac surgery is more effective in patients who display preoperative activation of the inflammatory system.

PubMed

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass.

Lipoprotein-associated phospholipase A2 mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

PubMed

Ryu, Sung Kee; Hutten, Barbara A; Vissers, Maud N; Wiegman, Albert; Kastelein, John J P; Tsimikas, Sotirios

2011-01-01

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor of cardiovascular disease and a target of treatment. Lp-PLA(2) levels in children have not been previously reported. The effect of statin therapy on Lp-PLA(2) mass and activity in children with familial hypercholesterolemia (FH) is also not known. Lp-PLA(2) mass and activity levels were measured at baseline and after 2 years in 178 children with FH randomized to pravastatin or placebo and in 78 unaffected and untreated siblings. At the end of the randomized period, all FH children were then placed on pravastatin for an additional 2 years, and Lp-PLA(2) mass and activity levels were correlated with changes in carotid intima-media thickness during 4 years of follow-up. Baseline levels of Lp-PLA(2) mass and activity were significantly greater in children with FH compared with unaffected siblings (mass: 240.3 ± 41.6 vs 222.1 ± 36.5 ng/mL, P = .002; activity: 205.7 ± 41.6 vs 124.3±23.0 nmol/min/mL, P < .0001). In the randomized FH cohort, after 2 years treatment, Lp-PLA(2) mass (217.8 ± 35.0 vs 231.5 ± 34.8 ng/mL, P = .001) and activity (178.8 ± 37.3 vs 206.2 ± 33.5 nmol/min/mL, P < .0001) were significantly reduced by pravastatin compared with placebo. Change in Lp-PLA(2) activity was related to change in low-density lipoprotein cholesterol (pravastatin: r = 0.53, P < .0001, placebo: r = 0.23, P < .001) but change in Lp-PLA(2) mass was not related to change in low-density lipoprotein cholesterol. Baseline levels of Lp-PLA(2) mass and activity were not significantly associated with carotid intima-media thickness at baseline or at 4 years. Lp-PLA(2) mass and activity are significantly elevated in children with heterozygous FH compared with unaffected siblings and are significantly reduced by pravastatin therapy. Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

PubMed Central

Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

2014-01-01

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

Effects of dietary sesame seeds on plasma tocopherol levels.

PubMed

Cooney, R V; Custer, L J; Okinaka, L; Franke, A A

2001-01-01

The tocopherols, the major vitamers of vitamin E, are believed to play a role in the prevention of human aging-related diseases such as cancer and heart disease, yet little is known concerning determinants of their plasma concentrations. Evidence from animal studies suggests that the dietary source of gamma-tocopherol can significantly affect plasma levels of this tocopherol as well as its functional vitamin E activity. To determine whether plasma levels of tocopherols in humans are similarly altered, a study was undertaken in which subjects (n = 9) were fed muffins containing equivalent amounts of gamma-tocopherol from sesame seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of gamma-tocopherol per day over a three-day period from sesame seeds, but not from walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1% increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p = 0.01). No significant changes in baseline or postintervention plasma levels of cholesterol, triglycerides, or carotenoids were seen for any of the intervention groups. All subjects consuming sesame seed-containing muffins had detectable levels of the sesame lignan sesamolin in their plasma. Consumption of moderate amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol and alter plasma tocopherol ratios in humans and is consistent with the effects of dietary sesame seeds observed in rats leading to elevated plasma gamma-tocopherol and enhanced vitamin E bioactivity.

Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

PubMed

Denardo, Scott J; Vock, David M; Schmalfuss, Carsten M; Young, Gregory D; Tcheng, James E; O'Connor, Christopher M

2016-07-01

Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern. © 2016 American Heart Association, Inc.

Serum Neutrophil Gelatinase B-associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Marker for Mucosal Healing in Patients with Crohn's Disease.

PubMed

de Bruyn, Magali; Arijs, Ingrid; De Hertogh, Gert; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Séverine; Opdenakker, Ghislain

2015-12-01

Although costly and uncomfortable for the patient, the current standard to assess mucosal healing in Crohn's disease [CD] patients is endoscopy. The aim of this study was to evaluate NGAL-MMP-9 as surrogate marker for mucosal healing in CD patients. Serum NGAL-MMP-9 levels were determined with sandwich enzyme-linked immunosorbent assay before and up to 5 years after first infliximab infusion in 108 active CD patients [median age at first infliximab 36 years, 57% female] and 43 healthy controls [HC, median age 27 years, 60% female]. Serum samples were matched to the time of endoscopy and complete endoscopic healing was defined as absence of ulcerations. Histological healing was defined as absence of epithelial damage [D'Haens score]. At baseline, median [interquartile range] NGAL-MMP-9 levels were significantly higher in active CD patients vs HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p < 0.001). After treatment, NGAL-MMP-9 levels significantly decreased in completely healed CD patients [n = 38] (84.5 [36.7-138.4] to 23.4 [7.4-42.5] ng/ml; p < 0.001) and--to a lesser extent--in non-healed CD patients [n = 36] (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p = 0.001). Receiver operating characteristic analysis defined a NGAL-MMP-9 cut-off level of 45 ng/ml corresponding to complete endoscopic healing (area under the curve [AUC] = 0.79, 82% sensitivity, 65% specificity) and histological healing [AUC = 0.72, 79% sensitivity, 53% specificity]. At baseline, C-reactive protein [CRP] was not elevated in 33% of active CD patients, whereas 53% of these patients did have elevated NGAL-MMP-9 levels. In the search for surrogate markers to assess mucosal healing in inflammatory bowel disease, NGAL-MMP-9 supplements and outperforms CRP in both ulcerative colitis and CD patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Step It UP: a multicomponent intervention to increase stair use in a university residence building.

PubMed

Howie, Erin Kaye; Young, Deborah Rohm

2011-01-01

Examine the effects of a multicomponent intervention on stair usage. Nonrandomized controlled intervention. Two multistory university dormitories. Total of 5711 direct observations of university dormitory residents. The 2-week "Step It UP" intervention used poster prompts and fun/competitive challenges with incentives to encourage residents to take the stairs instead of the elevators. Ascending stair and elevator use was directly observed and coded for gender at high traffic times in intervention and control dormitories for 14 nonconsecutive hours over 1 week each at baseline, midintervention, and 1 week postintervention. The proportions of ascending stair and elevator users were compared using χ(2) analyses. Baseline stair use was equal between intervention and control dormitories (24.9% and 27.8%, respectively; χ(2)[1, N  =  1849]  =  .08; p  =  .77). Stair use significantly increased from baseline in the intervention dormitory to 33.24% (χ(2)[1, N  =  2192]  =  18.44; p < .001) compared with no change in the control. Stair use returned to baseline in the intervention dormitory at postintervention (25.4%; χ(2)[1, N  =  2297]  =  .08; p  =  .78). There were no significant differences between genders. This multicomponent, short-duration intervention significantly increased stair usage in a university dormitory relative to the control but was unable to sustain the increase when prompts were removed. Campaigns to sustain stair use are needed. Formative assessment is required to determine what combinations of components may yield the most cost-effective approach for future interventions.

Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil

PubMed Central

2010-01-01

Background Poor control of blood pressure leads to hypertension which is a major risk factor for development of cardiovascular disease. The present study aimed to explore possible mechanisms of elevation in blood pressure following consumption of heated vegetable oil. Methods Forty-two male Sprague-Dawley rats were equally divided into six groups: Group I (control) - normal rat chow, Group II - fresh soy oil, Group III - soy oil heated once, Group IV - soy oil heated twice, Group V - soy oil heated five times, Group VI - soy oil heated ten times. Blood pressure was measured at the baseline level and at a monthly interval for six months. Plasma nitric oxide, heme oxygenase and angiotensin-converting enzyme levels were measured prior to treatment, at month-three and month-six later. At the end of treatment, the rats were sacrificed and thoracic aortas were taken for measurement of vascular reactivity. Results Blood pressure increased significantly (p < 0.01) in the repeatedly heated oil groups compared to the control and fresh soy oil groups. Consumption of diet containing repeatedly heated oil resulted higher plasma angiotensin-converting enzyme level and lower nitric oxide content and heme oxygenase concentration. Reheated soy oil groups exhibited attenuated relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Conclusion As a result of consumption of repeatedly heated soy oil, an elevation in blood pressure was observed which may be due to the quantitative changes in endothelium dependent and independent factors including enzymes directly involved in the regulation of blood pressure. PMID:20573259

Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.

PubMed

Kátai, Emese; Pál, József; Poór, Viktor Soma; Purewal, Rupeena; Miseta, Attila; Nagy, Tamás

2016-12-01

O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H 2 O 2 for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H 2 O 2 -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Waist circumference and the metabolic syndrome predict the development of elevated albuminuria in non-diabetic subjects: the DESIR Study.

PubMed

Bonnet, Fabrice; Marre, Michel; Halimi, Jean-Michel; Stengel, Bénédicte; Lange, Céline; Laville, Martine; Tichet, Jean; Balkau, Beverley

2006-06-01

Metabolic determinants of microalbuminuria remain poorly understood in non-diabetic individuals and particularly in women. We investigated in both sexes whether an elevated waist circumference (WC) or the presence of the metabolic syndrome (MetS) predict the development of elevated albuminuria at 6 years. We studied 2738 subjects from the DESIR cohort without microalbuminuria or diabetes at baseline and who were followed up for 6 years. At 6 years, 254 individuals [9.3%; 95% confidence interval (CI) 8.2-10.4%] had developed elevated albuminuria (> or = 20 mg/l), which was significantly and positively associated with WC and blood pressure, but not with fasting glucose, lipids or body mass index in either sex. In both sexes, subjects with a high WC or with MetS at baseline were more likely to develop elevated albuminuria at 6 years compared with those with a normal WC or absence of MetS. In multivariate logistic analysis, WC as a continuous variable or a WC of 94 cm or greater for men and a WC greater than 88 cm for women were predictive of the development of elevated albuminuria, after adjusting for age, hypertension, the use of angiotensin-converting enzyme inhibitors, fibrinogen and glycaemia. MetS was a risk factor for elevated albuminuria in men (odds ratio 1.87; 95% CI 1.25-2.81), with differences according to the MetS definition. Abdominal adiposity is related to the development of elevated albuminuria in both sexes, suggesting that the measurement of WC may improve the identification of non-diabetic individuals at risk of developing microalbuminuria and emphasizing the interest of screening for albuminuria among those with MetS.

Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

USGS Publications Warehouse

Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel N.; Mulcahy, D.M.; Rizzolo, D.J.

2008-01-01

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.

Responding for a conditioned reinforcer or unconditioned sensory reinforcer in mice: interactions with environmental enrichment, social isolation, and monoamine reuptake inhibitors.

PubMed

Browne, Caleb J; Fletcher, Paul J; Zeeb, Fiona D

2016-03-01

Environmental factors influence the etiology of many psychiatric disorders. Likewise, environmental factors can alter processes central to motivation. Therefore, motivational deficits present in many disorders may be influenced by early life environmental conditions. We examined whether housing animals in different environmental conditions influenced the ability of sensory stimuli to acquire incentive value and whether elevated monoamine activity altered responsing for these stimuli. Isolation-housed (IH), pair-housed (PH), and environmentally enriched (EE) male C57BL/6N mice were examined in tests of responding for a conditioned reinforcer (CRf) or an unconditioned sensory reinforcer (USRf). The CRf was previously paired with saccharin delivery through Pavlovian conditioning, while the USRf was not conditioned with a reward. Following baseline tests of responding for the CRf or USRf, the effects of elevated monoamine activity were examined. At baseline, PH and EE mice responded similarly for the CRf or USRf. IH mice responded more for the CRf but exhibited slower acquisition of responding for the USRf. Administration of citalopram, a serotonin transporter blocker, or atomoxetine, a norepinephrine transporter blocker, decreased responding for the CRf and USRf in all groups. The dopamine transporter blocker GBR 12909 generally increased responding for the CRf and USRf, but further analysis revealed enhanced responding for both reinforcers only in EE mice. Baseline incentive motivation is strongly influenced by the social component of housing conditions. Furthermore, environmental enrichment increased the sensitivity to elevated dopamine activity, while acute elevations in serotonin and norepinephrine inhibit incentive motivation irrespective of housing condition.

Effects of enzyme-treated asparagus extract on heat shock protein 70, stress indices, and sleep in healthy adult men.

PubMed

Ito, Tomohiro; Goto, Kazunori; Takanari, Jun; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Tanaka, Aiko; Nishihira, Jun

2014-01-01

Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time.

RelA Mutant Enterococcus faecium with Multiantibiotic Tolerance Arising in an Immunocompromised Host.

PubMed

Honsa, Erin S; Cooper, Vaughn S; Mhaissen, Mohammed N; Frank, Matthew; Shaker, Jessica; Iverson, Amy; Rubnitz, Jeffrey; Hayden, Randall T; Lee, Richard E; Rock, Charles O; Tuomanen, Elaine I; Wolf, Joshua; Rosch, Jason W

2017-01-03

Serious bacterial infections in immunocompromised patients require highly effective antibacterial therapy for cure, and thus, this setting may reveal novel mechanisms by which bacteria circumvent antibiotics in the absence of immune pressure. Here, an infant with leukemia developed vancomycin-resistant Enterococcus faecium (VRE) bacteremia that persisted for 26 days despite appropriate antibiotic therapy. Sequencing of 22 consecutive VRE isolates identified the emergence of a single missense mutation (L152F) in relA, which constitutively activated the stringent response, resulting in elevated baseline levels of the alarmone guanosine tetraphosphate (ppGpp). Although the mutant remained susceptible to both linezolid and daptomycin in clinical MIC testing and during planktonic growth, it demonstrated tolerance to high doses of both antibiotics when growing in a biofilm. This biofilm-specific gain in resistance was reflected in the broad shift in transcript levels caused by the mutation. Only an experimental biofilm-targeting ClpP-activating antibiotic was able to kill the mutant strain in an established biofilm. The relA mutation was associated with a fitness trade-off, forming smaller and less-well-populated biofilms on biological surfaces. We conclude that clinically relevant relA mutations can emerge during prolonged VRE infection, causing baseline activation of the stringent response, subsequent antibiotic tolerance, and delayed eradication in an immunocompromised state. The increasing prevalence of antibiotic-resistant bacterial pathogens is a major challenge currently facing the medical community. Such pathogens are of particular importance in immunocompromised patients as these individuals may favor emergence of novel resistance determinants due to lack of innate immune defenses and intensive antibiotic exposure. During the course of chemotherapy, a patient developed prolonged bacteremia with vancomycin-resistant Enterococcus faecium that failed to clear despite multiple front-line antibiotics. The consecutive bloodstream isolates were sequenced, and a single missense mutation identified in the relA gene, the mediator of the stringent response. Strains harboring the mutation had elevated baseline levels of the alarmone and displayed heightened resistance to the bactericidal activity of multiple antibiotics, particularly in a biofilm. Using a new class of compounds that modulate ClpP activity, the biofilms were successfully eradicated. These data represent the first clinical emergence of mutations in the stringent response in vancomycin-resistant entereococci. Copyright © 2017 Honsa et al.

Evidence for Neuroinflammatory and Microglial Changes in the Cerebral Response to Sleep Loss

PubMed Central

Wisor, Jonathan P.; Schmidt, Michelle A.; Clegern, William C.

2011-01-01

Study Objectives: Sleep loss has pro-inflammatory effects, but the roles of specific cell populations in mediating these effects have not been delineated. We assessed the modulation of the electroencephalographic and molecular responses to sleep deprivation (S-DEP) by minocycline, a compound that attenuates microglial activation occurring in association with neuroinflammatory events. Design: Laboratory rodents were subjected to assessment of sleep and wake in baseline and sleep deprived conditions. Participants: Adult male CD-1 mice (30-35 g) subjected to telemetric electroencephalography. Interventions: Minocycline was administered daily. Mice were subjected to baseline data collection on the first day of minocycline administration and, on subsequent days, 2 S-DEP sessions, 1 and 3 h in duration, followed by recovery sleep. Following EEG studies, mice were euthanized either at the end of a 3 h S-DEP or as time-of day controls for sampling of brain messenger RNAs. Gene expression was measured by real-time polymerase chain reaction. Measurements and Results: Minocycline-treated mice exhibited a reduction in time spent asleep, relative to saline-treated mice, in the 3-h interval immediately after administration. S-DEP resulted in an increase in EEG slow wave activity relative to baseline in saline-treated mice. This response to S-DEP was abolished in animals subjected to chronic minocycline administration. S-DEP suppressed the expression of the microglial-specific transcript cd11b and the neuroinflammation marker peripheral benzodiazepine receptor, in the brain at the mRNA level. Minocycline attenuated the elevation of c-fos expression by S-DEP. Brain levels of pro-inflammatory cytokine mRNAs interleukin-1β (il-1β), interleukin-6 (il-6), and tumor necrosis factor-α (tnfα) were unaffected by S-DEP, but were elevated in minocycline-treated mice relative to saline-treated mice. Conclusions: The anti-neuroinflammatory agent minocycline prevents either the buildup or expression of sleep need in rodents. The molecular mechanism underlying this effect is not known, but it is not mediated by suppression of il-1β, il-6, and tnfα at the transcript level. Citation: Wisor JP; Schmidt MA; Clegern WC. Evidence for neuroinflammatory and microglial changes in the cerebral response to sleep loss. SLEEP 2011;34(3):261-272. PMID:21358843

PubMed Central

Stassek, J.; Erdmann, J.; Ohnolz, F.; Berg, F. D.; Kiechle, M.; Seifert-Klauss, V.

2017-01-01

Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p < 0.001) so was C-peptide (p < 0.025). Conclusions In the present study we have shown for the first time that, after consumption of a standardised test meal, PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients. PMID:28190890

Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle.

PubMed

Cobley, James N; Sakellariou, George K; Murray, Scott; Waldron, Sarah; Gregson, Warren; Burniston, Jatin G; Morton, James P; Iwanejko, Lesley A; Close, Graeme L

2013-07-12

The aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout. PARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status. Collectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people.

Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

PubMed

Luo, T David; Alton, Timothy B; Apel, Peter J; Cai, Jiaozhong; Barnwell, Jonathan C; Sonntag, William E; Smith, Thomas L; Li, Zhongyu

2016-10-01

Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016. © 2016 Wiley Periodicals, Inc.

Developmental pathways to depressive symptoms in adolescence: A multi-wave prospective study of negative emotionality, stressors, and anxiety

PubMed Central

Barrocas, Andrea L.; Hankin, Benjamin L.

2014-01-01

This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N=350, 6th–10th graders). The primary hypothesized model was that baseline NE leads to increased stressors, which results in increases in anxious arousal, which culminates with elevated depressive symptoms. An alternate model hypothesized that baseline NE leads to increased anxious arousal, which results in increases in stressors, and this culminates in elevated depressive symptoms. Youth completed self-report measures of NE, stressors, anxious arousal, and depressive symptoms at four time-points. Path analysis supported the primary model and showed that the mediating influence of stressors and anxious arousal explained 78% of the association between NE and prospective elevations in depressive symptoms. The alternate model was not supported. Neither gender nor age were moderators. PMID:21249517

Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.

PubMed

Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

2015-03-01

Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.

High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study.

PubMed

Otsuka, Hiromasa; Yanai, Mitsuru; Kobayashi, Hiroki; Haketa, Akira; Hara, Motohiko; Sugama, Kaoru; Kato, Kimitoshi; Soma, Masayoshi

2017-10-19

Serum adiponectin levels are associated with frailty and cardiovascular diseases. Longitudinal changes in adiponectin levels might enhance our understanding of age-related conditions and diseases. This prospective observational study aimed to: (1) elucidate age-related changes in high-molecular-weight (HMW) adiponectin levels; and (2) identify variables predictive of elevated HMW adiponectin levels and the association with well-known adiponectin single-nucleotide polymorphisms (SNPs) in healthy, elderly Japanese participants. Healthy elderly volunteers (n = 196; 55 men and 141 women; median age 72.0 years; range 69.0-75.0 years) underwent anthropometric and physical function measurements, as well as laboratory tests at baseline and the 5-year follow-up. HMW adiponectin levels were significantly higher in women than in men (8.4, 5.3-11.9 vs. 5.7, 3.1-9.0 μg/mL; p < 0.001) at baseline and decreased significantly at follow-up in women (7.7, 4.8-11.2 μg/mL; p < 0.001), but not in men. In the multiple regression analysis, high-density lipoprotein cholesterol levels and body weight were independent predictors of HMW adiponectin levels. The rate of change in HMW adiponectin levels was inversely correlated with the rates of change in body weight, body mass index, and knee leg extension strengths, and positively correlated with rates of change in high-density lipoprotein cholesterol and one-leg standing time. There were no significant differences in HMW adiponectin levels among SNPs. Decreasing HMW adiponectin levels might lead to an increased risk of cardiovascular diseases in elderly women. HMW adiponectin levels significantly decreased over a 5-year period in community-dwelling elderly Japanese women.

Impact of hyperglycemia in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: the HORIZONS-AMI trial.

PubMed

Planer, David; Witzenbichler, Bernhard; Guagliumi, Giulio; Peruga, Jan Z; Brodie, Bruce R; Xu, Ke; Fahy, Martin; Mehran, Roxana; Stone, Gregg W

2013-09-10

Few studies have examined the association between hyperglycemia and adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). We therefore evaluated the prognostic utility of admission hyperglycemia in the HORIZONS-AMI trial. Admission glucose levels were available in 3405 of 3602 (94.5%) enrolled patients, of which 566 patients (16.6%) were known to have diabetes. Outcomes were assessed at 30 days and 3 years, stratified by baseline glucose level and diabetes status. Median [IQR] admission glucose level in the entire study cohort was 138.0 [115.4, 171.0] mg/dl. Multivariable adjusted 30-day mortality was significantly increased in all patients with admission glucose in the highest glucose tertile vs. the lower two-thirds (HR [95%CI]=3.53 [1.89, 6.60], p<0.0001); in patients with diabetes (4.40 [2.04, 9.50], p=0.0002); and in patients without diabetes (3.33 [1.16, 9.55], p=0.03). By ROC analysis, the best cut-off values for 30-day mortality were 169 mg/dl for all patients (AUC=0.76), 149 mg/dl for patients without diabetes (AUC=0.77), and 231 mg/dl for patients with diabetes (AUC=0.69). Baseline hyperglycemia was also an independent predictor of 3-year mortality in all patients (HR [95%CI]=1.93 [1.35, 2.76], P=0.0003), patients with diabetes (2.65 [1.28, 5.47], P=0.008), and patients without diabetes (1.58 [1.05, 2.36], P=0.03). In patients with STEMI undergoing primary PCI, admission hyperglycemia is an independent predictor of early and late mortality in both patients with and without known diabetes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

An altered peripheral IL6 response in major depressive disorder.

PubMed

Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

2016-05-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

An altered peripheral IL6 response in major depressive disorder

PubMed Central

Money, Kelli M.; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A.; Shelton, Richard C.; Mirnics, Karoly

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of antidepressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated proinflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. PMID:26804030

Longer Work/Rest Intervals During High-Intensity Interval Training (HIIT) Lead to Elevated Levels of miR-222 and miR-29c

PubMed Central

Schmitz, Boris; Rolfes, Florian; Schelleckes, Katrin; Mewes, Mirja; Thorwesten, Lothar; Krüger, Michael; Klose, Andreas; Brand, Stefan-Martin

2018-01-01

Aim: MicroRNA-222 (miR-222) and miR-29c have been identified as important modulators of cardiac growth and may protect against pathological cardiac remodeling. miR-222 and -29c may thus serve as functional biomarkers for exercise-induced cardiac adaptations. This investigation compared the effect of two workload-matched high-intensity interval training (HIIT) protocols with different recovery periods on miR-222 and -29c levels. Methods: Sixty-three moderately trained females and males (22.0 ± 1.7 years) fulfilled the eligibility criteria and were randomized into two HIIT groups using sex and exercise capacity. During a controlled 4-week intervention (two sessions/week) a 4 × 30 HIIT group performed 4 × 30 s runs (all-out, 30 s active recovery) and a 8 × 15 HIIT group performed 8 × 15 s runs (all-out, 15 s active recovery). miR-222 and -29c as well as transforming growth factor-beta1 (TGF-beta1) mRNA levels were determined during high-intensity running as well as aerobic exercise using capillary blood from earlobes. Performance parameters were assessed using an incremental continuous running test (ICRT) protocol with blood lactate diagnostic and heart rate (HR) monitoring to determine HR recovery and power output at individual anaerobic threshold (IAT). Results: At baseline, acute exercise miR-222 and -29c levels were increased only in the 4 × 30 HIIT group (both p < 0.01, pre- vs. post-exercise). After the intervention, acute exercise miR-222 levels were still increased in the 4 × 30 HIIT group (p < 0.01, pre- vs. post-exercise) while in the 8 × 15 HIIT group again no acute effect was observed. However, both HIIT interventions resulted in elevated resting miR-222 and -29c levels (all p < 0.001, pre- vs. post-intervention). Neither of the two miRNAs were elevated at any ICRT speed level at baseline nor follow-up. While HR recovery was improved by >24% in both HIIT groups (both p ≤ 0.0002) speed at IAT was improved by 3.6% only in the 4 × 30 HIIT group (p < 0.0132). Correlation analysis suggested an association between both miRNAs and TGF-beta1 mRNA (all p ≤ 0.006, r ≥ 0.74) as well as change in speed at IAT and change in miR-222 levels (p = 0.024, r = 0.46). Conclusions: HIIT can induce increased circulating levels of cardiac growth-associated miR-222 and -29c. miR-222 and miR-29c could be useful markers to monitor HIIT response in general and to identify optimal work/rest combinations. PMID:29719514

Longer Work/Rest Intervals During High-Intensity Interval Training (HIIT) Lead to Elevated Levels of miR-222 and miR-29c.

PubMed

Schmitz, Boris; Rolfes, Florian; Schelleckes, Katrin; Mewes, Mirja; Thorwesten, Lothar; Krüger, Michael; Klose, Andreas; Brand, Stefan-Martin

2018-01-01

Aim: MicroRNA-222 (miR-222) and miR-29c have been identified as important modulators of cardiac growth and may protect against pathological cardiac remodeling. miR-222 and -29c may thus serve as functional biomarkers for exercise-induced cardiac adaptations. This investigation compared the effect of two workload-matched high-intensity interval training (HIIT) protocols with different recovery periods on miR-222 and -29c levels. Methods: Sixty-three moderately trained females and males (22.0 ± 1.7 years) fulfilled the eligibility criteria and were randomized into two HIIT groups using sex and exercise capacity. During a controlled 4-week intervention (two sessions/week) a 4 × 30 HIIT group performed 4 × 30 s runs (all-out, 30 s active recovery) and a 8 × 15 HIIT group performed 8 × 15 s runs (all-out, 15 s active recovery). miR-222 and -29c as well as transforming growth factor-beta1 (TGF-beta1) mRNA levels were determined during high-intensity running as well as aerobic exercise using capillary blood from earlobes. Performance parameters were assessed using an incremental continuous running test (ICRT) protocol with blood lactate diagnostic and heart rate (HR) monitoring to determine HR recovery and power output at individual anaerobic threshold (IAT). Results: At baseline, acute exercise miR-222 and -29c levels were increased only in the 4 × 30 HIIT group (both p < 0.01, pre- vs. post-exercise). After the intervention, acute exercise miR-222 levels were still increased in the 4 × 30 HIIT group ( p < 0.01, pre- vs. post-exercise) while in the 8 × 15 HIIT group again no acute effect was observed. However, both HIIT interventions resulted in elevated resting miR-222 and -29c levels (all p < 0.001, pre- vs. post-intervention). Neither of the two miRNAs were elevated at any ICRT speed level at baseline nor follow-up. While HR recovery was improved by >24% in both HIIT groups (both p ≤ 0.0002) speed at IAT was improved by 3.6% only in the 4 × 30 HIIT group ( p < 0.0132). Correlation analysis suggested an association between both miRNAs and TGF-beta1 mRNA (all p ≤ 0.006, r ≥ 0.74) as well as change in speed at IAT and change in miR-222 levels ( p = 0.024, r = 0.46). Conclusions: HIIT can induce increased circulating levels of cardiac growth-associated miR-222 and -29c. miR-222 and miR-29c could be useful markers to monitor HIIT response in general and to identify optimal work/rest combinations.

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study.

PubMed

Younis, Arwa; Eskenazi, Dana; Goldkorn, Ronen; Leor, Jonathan; Naftali-Shani, Nili; Fisman, Enrique Z; Tenenbaum, Alexander; Goldenberg, Ilan; Klempfner, Robert

2017-05-22

Patients with type 2 diabetes present with an accelerated atherosclerotic process. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors (gliptins) have anti-inflammatory and anti-atherosclerotic effects, yet clinical data are scarcely available. A prospective, randomized, open-label study was performed in 60 patients with coronary artery disease (CAD) and type 2 diabetes, who participated in a cardiac rehabilitation program. After a washout period of 3 weeks, patients were randomized in a 2:1 ratio to receive combined vildagliptin/metformin therapy (intervention group: n = 40) vs. metformin alone (control group: n = 20) for a total of 12 weeks. Blinded assessment of interleukin-1ß (IL-1ß, the primary endpoint), hemoglobin A1c (HbA1c), and high sensitivity C reactive protein (hsCRP), were performed at baseline and after 12 weeks. Mean age of study patients was 67 ± 9 years, 75% were males, and baseline HbA1c and inflammatory markers levels were similar between the two groups. At 12 weeks of follow up, levels of IL-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß among the control group, which was not observed in the intervention group (49 vs. 4%, respectively; p < 0.001). The hsCRP was lowered by 60% in the vildagliptin/metformin group vs. 23% in the metformin group (p < 0.01). Moreover, a significant relative reduction of the HbA1c was seen in the intervention group (7% reduction, p < 0.03). The addition of vildagliptin to metformin treatment in patients with type 2 diabetes and CAD led to a significant suppression of the IL-1ß elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213.

Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels.

PubMed

Bays, Harold E; Sartipy, Peter; Xu, John; Sjöström, Carl David; Underberg, James A

Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (≥150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria. The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups. Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Poor habitual sleep efficiency is associated with increased cardiovascular and cortisol stress reactivity in men.

PubMed

Massar, Stijn A A; Liu, Jean C J; Mohammad, Nabilah B; Chee, Michael W L

2017-07-01

Inadequate sleep and psychological stress can both elevate physiological stress markers, such as cortisol. Prior studies that have applied induced psychosocial stress after a night of experimental sleep deprivation have found these effects to be compounded. We examined whether the relationship between stress reactivity and poor sleep also extends to habitual sleep patterns. Fifty-nine adult male participants were recruited. Habitual sleep patterns were monitored with actigraphy for a week. Participants subsequently underwent the Trier Social Stress Test. Cardiovascular responses and salivary cortisol were measured at baseline, during stress, and during recovery. Subjects who showed poor habitual sleep efficiency during the week before stress induction responded with higher stress-related elevations of blood pressure and cortisol levels as compared to subjects with high sleep efficiency. This relationship between poor sleep efficiency and elevated blood pressure persisted during the post-stress recovery period. Similar associations between total sleep time in the week prior to the stress induction and physiological reactivity did not reach significance. Our findings indicate that habitual low sleep efficiency exaggerates cardiovascular and neuroendocrine effects of psychosocial stress, in a male population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy.

PubMed

Robinson, Angela Byun; Tangpricha, Vin; Yow, Eric; Gurion, Reut; McComsey, Grace A; Schanberg, Laura E

2014-01-01

Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk. Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT). Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean-max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP. Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population. NCT00065806.

Hyperthyroidism in patients with ischaemic heart disease after iodine load induced by coronary angiography: Long-term follow-up and influence of baseline thyroid functional status.

PubMed

Bonelli, Nadia; Rossetto, Ruth; Castagno, Davide; Anselmino, Matteo; Vignolo, Francesca; Parasiliti Caprino, Mirko; Gaita, Fiorenzo; Ghigo, Ezio; Garberoglio, Roberto; Grimaldi, Roberto; Maccario, Mauro

2018-02-01

To study the effect of a iodine load on thyroid function of patients with ischaemic heart disease (IHD) and the long-term influence of unknown subclinical hyperthyroidism. Subclinical hyperthyroidism is considered an independent risk factors for cardiovascular morbidity of patients with IHD. They routinely undergo coronary angiography with iodine contrast media (ICM) which may induce or even worsen hyperthyroidism. A cross-sectional study followed by a longitudinal study on patients with subclinical hyperthyroidism. 810 consecutive IHD outpatients without known thyroid diseases or treatment with drugs influencing thyroid activity undergoing elective coronary angiography. We evaluated thyroid function either before and 1 month after ICM; patients with thyrotoxicosis at baseline or after ICM were then followed up for 1 year. 58 patients had hyperthyroidism at baseline (HB, 7.2%), independently associated to FT4 levels, thyroid nodules and family history of thyroid diseases. After ICM, the prevalence of hyperthyroidism was 81 (10%). Hyperthyroidism after ICM was positively predicted by baseline fT4 levels, thyroid nodules, age over 60, male gender, family history of thyroid diseases. Three months after ICM, 34 patients (4.2%) still showed hyperthyroidism (22 from HB, 13 treated with methimazole). One year after ICM, hyperthyroidism was still present in 20 patients (2.5%, all from HB, 13 treated). The prevalence of spontaneous subclinical hyperthyroidism in IHD is surprisingly elevated and is further increased by iodine load, particularly in patients with thyroid nodules and familial history of thyroid diseases, persisting in a not negligible number of them even after one year. © 2017 John Wiley & Sons Ltd.

Mercury concentrations and distribution in soil, water, mine waste leachates, and air in and around mercury mines in the Big Bend region, Texas, USA

USGS Publications Warehouse

Gray, John E.; Theodorakos, Peter M.; Fey, David L.; Krabbenhoft, David P.

2015-01-01

Samples of soil, water, mine waste leachates, soil gas, and air were collected from areas mined for mercury (Hg) and baseline sites in the Big Bend area, Texas, to evaluate potential Hg contamination in the region. Soil samples collected within 300 m of an inactive Hg mine contained elevated Hg concentrations (3.8–11 µg/g), which were considerably higher than Hg in soil collected from baseline sites (0.03–0.05 µg/g) distal (as much as 24 km) from mines. Only three soil samples collected within 300 m of the mine exceeded the probable effect concentration for Hg of 1.06 µg/g, above which harmful effects are likely to be observed in sediment-dwelling organisms. Concentrations of Hg in mine water runoff (7.9–14 ng/L) were generally higher than those found in springs and wells (0.05–3.1 ng/L), baseline streams (1.1–9.7 ng/L), and sources of drinking water (0.63–9.1 ng/L) collected in the Big Bend region. Concentrations of Hg in all water samples collected in this study were considerably below the 2,000 ng/L drinking water Hg guideline and the 770 ng/L guideline recommended by the U.S. Environmental Protection Agency (USEPA) to protect aquatic wildlife from chronic effects of Hg. Concentrations of Hg in water leachates obtained from leaching of mine wastes varied widely from <0.001 to 760 µg of Hg in leachate/g of sample leached, but only one leachate exceeded the USEPA Hg industrial soil screening level of 31 µg/g. Concentrations of Hg in soil gas collected at mined sites (690–82,000 ng/m3) were highly elevated compared to soil gas collected from baseline sites (1.2–77 ng/m3). However, air collected from mined areas at a height of 2 m above the ground surface contained concentrations of Hg (4.9–64 ng/m3) that were considerably lower than Hg in soil gas from the mined areas. Although concentrations of Hg emitted from mine-contaminated soils and mine wastes were elevated, persistent wind in southwest Texas disperses Hg in the air within a few meters of the ground surface.

Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts

NASA Technical Reports Server (NTRS)

Stowe, R. P.; Pierson, D. L.; Barrett, A. D.

2001-01-01

OBJECTIVE: The objective of this study was to determine the effects of stress and spaceflight on levels of neuroendocrine hormones and Epstein-Barr virus (EBV)-specific antibodies in astronauts. METHODS: Antiviral antibody titers and stress hormones were measured in plasma samples collected from 28 astronauts at their annual medical exam (baseline), 10 days before launch (L-10), landing day (R+0), and 3 days after landing (R+3). Urinary stress hormones were also measured at L-10 and R+0. RESULTS: Significant increases (p <.01) in EBV virus capsid antigen antibodies were found at all three time points (L-10, R+0, and R+3) as compared with baseline samples. Anti-EBV nuclear antigen antibodies were significantly decreased at L-10 (p <.05) and continued to decrease after spaceflight (R+0 and R+3, p <.01). No changes were found in antibodies to the nonlatent measles virus. The 11 astronauts who showed evidence of EBV reactivation had significant increases in urinary epinephrine and norepinephrine as compared with astronauts without EBV reactivation. CONCLUSION: These findings indicate that physical and psychological stresses associated with spaceflight resulted in decreased virus-specific T-cell immunity and reactivation of EBV.

Distress Tolerance and Social Support in Adolescence: Predicting Risk for Internalizing and Externalizing Symptoms Following a Natural Disaster

PubMed Central

Cohen, Joseph R.; Danielson, Carla Kmett; Adams, Zachary W.; Ruggiero, Kenneth J.

2016-01-01

The purpose of the multi-measure, multi-wave, longitudinal study was to examine the interactive relation between behavioral distress tolerance (DT) and perceived social support (PSS) in 352 tornado-exposed adolescents aged 12–17 years (M=14.44; SD=1.74). At baseline, adolescents completed a computer-based task for DT, and self-report measures of PSS, depressed mood, posttraumatic stress disorder (PTSD), substance use, and interpersonal conflict. Symptoms also were assessed 4 and 12 months after baseline. Findings showed that lower levels of DT together with lower levels of PSS conferred risk for elevated symptoms of prospective depression (t(262)= −2.04, p=.04; reffect size=0.13) and PTSD (t(195)= −2.08, p=.04; reffect size=0.15) following a tornado. However, only PSS was significant in substance use t(139)=2.20, p=.03; reffect size=0.18) and conflict (t(138)=−4.05, p<.0001; reffect size=0.33) in our sample. Implications regarding adolescent DT, the transdiagnostic nature of PSS, and the clinical applications of our findings in the aftermath of a natural disaster are discussed. PMID:28163364

Recommendations for the Regionalizing of Coffee Cultivation in Colombia: A Methodological Proposal Based on Agro-Climatic Indices

PubMed Central

García L., Juan Carlos; Posada-Suárez, Húver; Läderach, Peter

2014-01-01

The Colombian National Federation of Coffee Growers (FNC) conducted an agro-ecological zoning study based on climate, soil, and terrain of the Colombian coffee-growing regions (CCGR) located in the tropics, between 1° and 11.5° N, in areas of complex topography. To support this study, a climate baseline was constructed at a spatial resolution of 5 km. Twenty-one bioclimatic indicators were drawn from this baseline data and from yield data for different coffee genotypes evaluated under conditions at eight experimental stations (ESs) belonging to the National Center for Coffee Research (CENICAFÉ). Three topographic indicators were obtained from a digital elevation model (DEM). Zoning at a national level resulted in the differentiation of 12 agro-climatic zones. Altitude notably influenced zone differentiation, however other factors such as large air currents, low-pressure atmospheric systems, valleys of the great rivers, and physiography also played an important role. The strategy of zoning according to coffee-growing conditions will enable areas with the greatest potential for the development of coffee cultivation to be identified, criteria for future research to be generated, and the level of technology implementation to be assessed. PMID:25436456

Recommendations for the regionalizing of coffee cultivation in Colombia: a methodological proposal based on agro-climatic indices.

PubMed

García L, Juan Carlos; Posada-Suárez, Húver; Läderach, Peter

2014-01-01

The Colombian National Federation of Coffee Growers (FNC) conducted an agro-ecological zoning study based on climate, soil, and terrain of the Colombian coffee-growing regions (CCGR) located in the tropics, between 1° and 11.5° N, in areas of complex topography. To support this study, a climate baseline was constructed at a spatial resolution of 5 km. Twenty-one bioclimatic indicators were drawn from this baseline data and from yield data for different coffee genotypes evaluated under conditions at eight experimental stations (ESs) belonging to the National Center for Coffee Research (CENICAFÉ). Three topographic indicators were obtained from a digital elevation model (DEM). Zoning at a national level resulted in the differentiation of 12 agro-climatic zones. Altitude notably influenced zone differentiation, however other factors such as large air currents, low-pressure atmospheric systems, valleys of the great rivers, and physiography also played an important role. The strategy of zoning according to coffee-growing conditions will enable areas with the greatest potential for the development of coffee cultivation to be identified, criteria for future research to be generated, and the level of technology implementation to be assessed.

Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.

PubMed

Izano, Monika; Wei, Esther K; Tai, Caroline; Swede, Helen; Gregorich, Steven; Harris, Tamara B; Klepin, Heidi; Satterfield, Suzanne; Murphy, Rachel; Newman, Anne B; Rubin, Susan M; Braithwaite, Dejana

2016-03-01

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults. © 2015 UICC.

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

PubMed Central

Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

2014-01-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

PubMed

Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

2015-03-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.

Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

PubMed

Sameshima, Hiroshi; Ikenoue, Tsuyomu

2005-01-01

We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (< 7.1) in low-risk pregnancies. We selected two secondary and two tertiary-level institutions where 10,030 women delivered. Among them, 5522 were low-risk pregnancies. The last 2 hours of FHR patterns before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlation between the incidence of LD (occasional, < 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (< 7.1) were evaluated. Statistical analyses included a contingency table with chi2 and the Fisher test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (< 7.1) was exponentially elevated from 0% at no deceleration, 1% in occasional LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

Correlative analysis of plasma and urine neopterin levels in the pre- and post-menopausal women with periodontitis, following nonsurgical periodontal therapy.

PubMed

Prasanna, Jammula Surya; Sumadhura, Chinta; Karunakar, Parupalli; Rekharani, Koduganti; Himabindu, Gireddy; Manasa, Ambati

2017-01-01

Periodontitis is an inflammatory condition which is distinguished by the devastation of the supported tooth structures. In such inflammatory conditions, some biomarkers such as neopterin will be secreted and elevated in the body fluids, which can be used as a diagnostic marker for the present and future disease activity. Assessment of the neopterin as a biomarker in inflammatory conditions such as menopause and periodontitis. A cross-sectional interventional study. Sixty female individuals with a mean age of 40-60 years with chronic periodontitis were included in this study. All were categorized into two groups of thirty each, depending on their menstrual history: Group I - thirty premenopausal women and Group II - thirty postmenopausal women. Urine and plasma were collected from both groups to estimate neopterin levels. ELISA kit was used to assess the neopterin levels at baseline and after 3 months of nonsurgical periodontal therapy (NSPT). IBM SPSS version 21 software. A significant depreciation in the mean values of all the parameters from baseline to 3 months ( P < 0.001), in the intragroup analysis, was observed. Plasma (0.006) and urine (0.004) reduction was seen. In both the groups, in 3 months after NSPT, decreased neopterin levels were found, suggesting that the NSPT is the definitive therapy. Further, suggesting that, neopterin levels in the plasma and urine can be used as an index to identify the periodontal inflammation and destruction.

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low fat but not a low carbohydrate diet in obese women

PubMed Central

Gray, Dona L.; O’Brien, Kevin D.; D’Alessio, David A.; Brehm, Bonnie J.; Deeg, Mark A.

2013-01-01

Context Although circulating glycosylphosphatidylinositol-specific phospholipase D, a minor high density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating glycosylphosphatidylinositol-specific phospholipase D levels. Objective Determine the effect of weight loss and changes in insulin sensitivity on plasma glycosylphosphatidylinositol-specific phospholipase D levels. Participants Forty two non-diabetic obese women. Intervention Three month dietary intervention randomizing patients to a low fat or a low carbohydrate diet. Main outcome measures Plasma glycosylphosphatidylinositol-specific phospholipase D levels and insulin sensitivity as estimated by the homeostasis model assessment. Results The very low carbohydrate diet group lost more weight after 3 months (−7.6 ± 3.2 vs. −4.2 ± 3.5 kg, P < 0.01) although the decrease in insulin resistance was similar between groups. Weight loss with either diet did not alter plasma glycosylphosphatidylinositol-specific phospholipase D levels. However, baseline glycosylphosphatidylinositol-specific phospholipase D levels correlated with the change in insulin sensitivity in response to the low fat diet while baseline insulin sensitivity correlated the change in insulin sensitivity in response to the low carbohydrate diet. Conclusions Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low fat diet on insulin sensitivity. PMID:18328347

Dynamic release and clearance of circulating microparticles during cardiac stress.

PubMed

Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

2014-01-03

Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Relationship between fasting glucose levels and in-hospital mortality in Chinese patients with acute myocardial infarction and diabetes mellitus: a retrospective cohort study.

PubMed

Liang, Hao; Guo, Yi Chen; Chen, Li Ming; Li, Min; Han, Wei Zhong; Zhang, Xu; Jiang, Shi Liang

2016-08-02

Previous studies have demonstrated that elevated admission and fasting glucose (FG) is associated with worse outcomes in patients with acute myocardial infarction (AMI). However, the quantitative relationship between FG levels and in-hospital mortality in patients with AMI remains unknown. The aim of the study is to assess the prevalence of elevated FG levels in hospitalized Chinese patients with AMI and diabetes mellitus and to determine the quantitative relationship between FG levels and the in-hospital mortality as well as the optimal level of FG in patients with AMI and diabetes mellitus. A retrospective study was carried out in 1856 consecutive patients admitted for AMI and diabetes mellitus from 2002 to 2013. Clinical variables of baseline characteristics, in-hospital management and in-hospital adverse outcomes were recorded and compared among patients with different FG levels. Among all patients recruited, 993 patients (53.5 %) were found to have FG ≥100 mg/dL who exhibited a higher in-hospital mortality than those with FG < 100 mg/dL (P < 0.001). Although there was a high correlation between FG levels and in-hospital mortality in all patients (r = 0.830, P < 0.001), the relationship showed a J-curve configuration with an elevated mortality when FG was less than 80 mg/dL. Using multivariate logistic regression models, we identified that age, FG levels and Killip class of cardiac function were independent predictors of in-hospital mortality in AMI patients with diabetes mellitus. More than half of patients with AMI and diabetes mellitus have FG ≥100 mg/dL and the relationship between in-hospital mortality and FG level was a J-curve configuration. Both FG ≥ 100 mg/dL and FG <80 mg/dL were identified to be independent predictors of in-hospital mortality and thus the optimal FG level in AMI patients with diabetes mellitus appears to be 80-100 mg/dL.

Pitavastatin: clinical effects from the LIVES Study.

PubMed

Teramoto, Tamio

2011-11-01

Although clinical trials provide useful information on drug safety and efficacy, results do not always reflect those observed in the real world. The Japanese long-term prospective post-marketing surveillance LIVALO Effectiveness and Safety (LIVES) Study was designed to assess the efficacy and safety of pitavastatin in clinical practice in ~20,000 patients. After 104 weeks, pitavastatin was associated with significant reductions in low-density lipoprotein-cholesterol (LDL-C) (29.1%) that largely occurred within 4 weeks of treatment initiation. In patients with abnormal triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) levels at baseline, pitavastatin reduced TG and increased HDL-C by 22.7% and 19.9%, respectively. Overall, 88.2% of the primary prevention low-risk patients attained their Japan Atherosclerosis Society LDL-C target, compared with 82.7% of intermediate-risk patients, 66.5% of high-risk patients and 50.3% of secondary prevention patients. Only 10.4% of pitavastatin-treated patients experienced adverse events (AEs), of which approximately 84% were mild and around 1% was severe. Increases in blood creatine phosphokinase (2.7%), alanine aminotransferase (1.8%), myalgia (1.1%), aspartate aminotransferase (1.5%) and gamma-glutamyltransferase (1.0%) were the most common AEs and only 7.4% of patients discontinued pitavastatin due to AEs. Regression analysis demonstrated that age was not a significant factor for the incidence of any AE or myopathy-associated events. A subanalysis of initial LIVES data focussing on the effects of pitavastatin on HDL-C levels showed that HDL-C was elevated by 5.9% in all patients and by 24.6% in those with low (

Chromium exposure and incidence of metabolic syndrome among American young adults over a 23-year follow-up: the CARDIA Trace Element Study

PubMed Central

Bai, Jianling; Xun, Pengcheng; Morris, Steve; Jacobs, David R.; Liu, Kiang; He, Ka

2015-01-01

Studies suggest that chromium deficiency is associated with elevated levels of fasting blood glucose, circulating insulin, cholesterol and triglycerides, and decreased proportion of lean body mass. However, data directly relating chromium levels to metabolic syndrome (MetS) risk are lacking. A total of 3,648 American adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, aged 20–32 years, were prospectively examined for the incidence of MetS and its five components from 1987–88 to 2010–11. Baseline toenail chromium levels were measured with instrumental neutron-activation analysis. Incident MetS was defined by the NCEP-ATP III criteria. During the 23-year follow-up, 878 incident MetS cases were identified. Baseline toenail chromium was inversely associated with incidence of MetS as well as its blood lipid components. The multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of MetS comparing the highest to the lowest quartiles of toenail chromium levels was 0.80 (0.66–0.98; Plinear trend = 0.006). The adjusted HRs were 0.82 (0.68–0.98; Ptrend = 0.045) for having abnormal triglycerides levels and 0.75 (0.64–0.88; Ptrend  = 0.030) for having abnormal HDL cholesterol levels. Toenail chromium levels were inversely and longitudinally associated with incidence of MetS in American young adults. This inverse association was mainly explained by its relation to blood lipids. PMID:26489690

Efficacy of a chairside diagnostic test kit for estimation of C-reactive protein levels in periodontal disease.

PubMed

Nagarale, Girish; Ravindra, S; Thakur, Srinath; Setty, Swati

2010-10-01

C-reactive protein [CRP] levels increase to hundreds of mg/mL within hours following infection. Studies have shown that serum CRP levels were elevated in periodontal disease. However, in all the previous studies, CRP levels were measured by using high-sensitivity CRP assay kits with minimal detection limits of 0.1 to 3 mg/L, which was much below the normal value of 10 mg/L. These high-sensitivity CRP assays need a proper laboratory setup, and these methods cannot be used as a routine chair-side test in the dental office. The purpose of this study was to investigate the serum CRP levels in subjects with periodontal disease by using a rapid chair-side diagnostic test kit with a lower detection limit of 6 mg/L and to compare the CRP levels before and after periodontal therapy. A total of 45 systemically healthy subjects were selected for the study. Subjects were divided into three groups: group A: healthy controls, group B: gingivitis, group C: periodontitis. Serum levels of CRP were determined by using a latex slide agglutination method with commercially available kit with lower detection limit of 6 mg/L. CRP was negative in all the 15 subjects in groups A and B at baseline, 7th and 30th day. CRP was positive only in 2 subjects in Group C at baseline and 7th day. Estimation of serum CRP by using a rapid chair-side diagnostic test kit is not of any significance in subjects with periodontitis.

Efficacy of a chairside diagnostic test kit for estimation of C-reactive protein levels in periodontal disease

PubMed Central

Nagarale, Girish; Ravindra, S.; Thakur, Srinath; Setty, Swati

2010-01-01

Background: C-reactive protein [CRP] levels increase to hundreds of mg/mL within hours following infection. Studies have shown that serum CRP levels were elevated in periodontal disease. However, in all the previous studies, CRP levels were measured by using high-sensitivity CRP assay kits with minimal detection limits of 0.1 to 3 mg/L, which was much below the normal value of 10 mg/L. These high-sensitivity CRP assays need a proper laboratory setup, and these methods cannot be used as a routine chair-side test in the dental office. Aim: The purpose of this study was to investigate the serum CRP levels in subjects with periodontal disease by using a rapid chair-side diagnostic test kit with a lower detection limit of 6 mg/L and to compare the CRP levels before and after periodontal therapy. Materials and Methods: A total of 45 systemically healthy subjects were selected for the study. Subjects were divided into three groups: group A: healthy controls, group B: gingivitis, group C: periodontitis. Serum levels of CRP were determined by using a latex slide agglutination method with commercially available kit with lower detection limit of 6 mg/L. Results: CRP was negative in all the 15 subjects in groups A and B at baseline, 7th and 30th day. CRP was positive only in 2 subjects in Group C at baseline and 7th day. Conclusion: Estimation of serum CRP by using a rapid chair-side diagnostic test kit is not of any significance in subjects with periodontitis. PMID:21731244

Circulating Branched-chain Amino Acid Concentrations Are Associated with Obesity and Future Insulin Resistance in Children and Adolescents

PubMed Central

McCormack, Shana E.; Shaham, Oded; McCarthy, Meaghan A.; Deik, Amy A.; Wang, Thomas J.; Gerszten, Robert E.; Clish, Clary B.; Mootha, Vamsi K.; Grinspoon, Steven K.; Fleischman, Amy

2012-01-01

Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether pediatric obesity is associated with elevations in fasting circulating concentrations of branched-chain amino acids (isoleucine, leucine, and valine), and whether these elevations predict future insulin resistance. Research Design and Methods Sixty-nine healthy subjects, ages 8 to18 years, were enrolled as a cross-sectional cohort. A subset who were pre- or early-pubertal, ages 8 to 13 years, were enrolled in a prospective longitudinal cohort for 18 months (n=17 with complete data). Results Elevations in the concentrations of BCAA’s were significantly associated with BMI Z-score (Spearman’s Rho 0.27, p=0.03) in the cross-sectional cohort. In the subset of subjects followed longitudinally, baseline BCAA concentrations were positively associated with HOMA-IR measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex, and pubertal stage (p=0.046). Conclusions Elevations in the concentrations of circulating branched-chain amino acids are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. PMID:22961720

Immune responses of eastern fence lizards (Sceloporus undulatus) to repeated acute elevation of corticosterone.

PubMed

McCormick, Gail L; Langkilde, Tracy

2014-08-01

Prolonged elevations of glucocorticoids due to long-duration (chronic) stress can suppress immune function. It is unclear, however, how natural stressors that result in repeated short-duration (acute) stress, such as frequent agonistic social encounters or predator attacks, fit into our current understanding of the immune consequences of stress. Since these types of stressors may activate the immune system due to increased risk of injury, immune suppression may be reduced at sites where individuals are repeatedly exposed to potentially damaging stressors. We tested whether repeated acute elevation of corticosterone (CORT, a glucocorticoid) suppresses immune function in eastern fence lizards (Sceloporus undulatus), and whether this effect varies between lizards from high-stress (high baseline CORT, invaded by predatory fire ants) and low-stress (low baseline CORT, uninvaded) sites. Lizards treated daily with exogenous CORT showed higher hemagglutination of novel proteins by their plasma (a test of constitutive humoral immunity) than control lizards, a pattern that was consistent across sites. There was no significant effect of CORT treatment on bacterial killing ability of plasma. These results suggest that repeated elevations of CORT, which are common in nature, produce immune effects more typical of those expected at the acute end of the acute-chronic spectrum and provide no evidence of modulated consequences of elevated CORT in animals from high-stress sites. Copyright © 2014 Elsevier Inc. All rights reserved.