Montoya, Bibiana; Briga, Michael; Jimeno, Blanca; Moonen, Sander; Verhulst, Simon
2018-05-01
High baseline glucose levels are associated with pathologies and shorter lifespan in humans, but little is known about causes and consequences of individual variation in glucose levels in other species. We tested to what extent baseline blood glucose level is a repeatable trait in adult zebra finches, and whether glucose levels were associated with age, manipulated environmental conditions during development (rearing brood size) and adulthood (foraging cost), and lifespan. We found that: (1) repeatability of glucose levels was 30%, both within and between years. (2) Having been reared in a large brood and living with higher foraging costs as adult were independently associated with higher glucose levels. Furthermore, the finding that baseline glucose was low when ambient temperature was high, and foraging costs were low, indicates that glucose is regulated at a lower level when energy turnover is low. (3) Survival probability decreased with increasing baseline glucose. We conclude that baseline glucose is an individual trait negatively associated with survival, and increases due to adverse environmental conditions during development (rearing brood size) and adulthood (foraging cost). Blood glucose may be, therefore, part of the physiological processes linking environmental conditions to lifespan.
Gimbo, Rodrigo Y; Fávero, Gisele C; Franco Montoya, Luz N; Urbinati, Elisabeth C
2015-04-01
We investigated if the energy deficit following a 30-day starvation period could affect the ability of fish to mount immune responses after experimental exposure to Aeromonas hydrophila. Fish were submitted to two feeding strategies during 30 days: starvation and continuously feeding. Fish were then sampled to allow for the assessment of baseline metabolic and immune system indicators, were next intraperitonially inoculated with A. hydrophila, and finally were sampled at 3 and 24 h after the challenge. The respiratory activity of leukocytes was lower in starved fish at baseline, increasing after bacterial inoculation to levels similar to those seen among fed fish. Levels of serum lysozyme were higher in starved fish at baseline. The same response profile was observed 3 h after inoculation, but among fed fish, these levels increased to values similar to those of starved fish 24 h after infection. Among starved fish, lysozyme concentration did not change over the course of the experiment. The serum ACH activity was lower in starved fish at baseline and increased after bacterial inoculation in both fish groups. Baseline levels of blood glucose of starved fish were lower than those of fed fish and increased 3 h after bacterial inoculation in both fish groups, decreasing in both groups at 24 h after inoculation. Baseline liver glycogen levels were similar in both fish groups and higher than at 3 and 24 h after inoculation. Three hours after bacterial inoculation, liver glycogen was less reduced in fed fish. Baseline levels of blood triglycerides were lower in starved fish and the profile remained unchanged 3 h after inoculation. There was a gradual decrease in fed fish, and the levels of starved fish remained unchanged throughout the observation period. Blood glycerol levels at baseline were higher in starved fish than in fed fish and remained unaltered at 3 h after inoculation. However those levels increased at 24 h. In fed fish there was a gradual increase of glycerol levels up to 24 h after bacterial inoculation. Baseline liver lipid levels of starved fish were lower and this difference in the response profile remained unchanged 3 and 24 h after inoculation. The liver lipid levels of starved fish decreased after inoculation, and remained unchanged in fed fish. As observed in liver lipid, muscle lipid levels of starved fish were lower than in fed fish, throughout the experiment. Starved fish levels remained unchanged; however fed fish levels decreased 24 h after bacterial inoculation. Levels of cortisol were higher in starved fish at baseline and increased in both fish groups 3 h after bacterial inoculation, reaching intermediary levels 24 h after inoculation. Our results show that in pacu, although mounting an immune response triggered after bacterial exposure is an energy-expensive process, fish under energetic deficit status were able to display protection against infection. Copyright © 2015 Elsevier Ltd. All rights reserved.
Hankin, Benjamin L.
2009-01-01
This study takes a developmental psychopathological approach to examine mechanisms through which baseline levels of positive emotionality (PE) and negative emotionality (NE) prospectively predict increases in anhedonic depressive symptoms in a community sample of 350 adolescents (6th–10th graders). Dependent stressors mediated the relationship between baseline levels of NE and anhedonic depressive symptoms after controlling for initial symptoms. Supportive relationships mediated the relationship between baseline levels of PE and anhedonic depressive symptoms, after controlling for baseline symptoms. In addition, NE × PE interacted to predict later anhedonic depressive symptoms, such that adolescents with low levels of PE and high levels of NE experienced the greatest increase in anhedonic depressive symptoms. Last, supportive relationships interacted with baseline PE to predict prospective changes in anhedonic depressive symptoms, such that adolescents with low PE and low supportive relationships experienced the greatest increase in anhedonic depressive symptoms. Results are discussed in terms of current theoretical models of the link between temperament and depression. PMID:19184402
Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo
2016-01-01
Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293
Blood pressure changes over 7 years in a large workforce cohort in New Zealand.
Metcalf, Patricia; Scragg, Robert; Jackson, Rod
2006-11-17
The aim of this study was to determine factors associated with changes in blood pressure levels over 7 years. The baseline Workforce Diabetes Survey was carried out between 1988 and 1990 on workers predominantly aged =40 years, and a follow-up survey of 4053 participants was carried out between 1995 and 1997. Overall, mean systolic and diastolic blood pressure levels increased by 6.0 (5.2%) and 3.1 (4.9%) mmHg, respectively, between the two surveys. The prevalence of GP-diagnosed raised blood pressure more than doubled over the 7 years--from 16.7% at baseline to 36.4% at follow-up. The two-thirds of participants whose blood pressure increased between the two surveys had on average lower baseline blood pressure levels, and were of shorter stature compared to those whose blood pressure levels showed no change or decreased (all p<0.05). A multivariate regression model of change in blood pressure over the 7 years showed that increase in systolic blood pressure levels was associated with lower baseline blood pressure levels; male gender; higher baseline weight and urinary albumin levels and greater increase in weight and urinary albumin levels over the 7 years; being of lower stature; being a never smoker; having newly or previously diagnosed diabetes; and being on current blood pressure lowering medication. The principal modifiable factor associated with increasing blood pressure over the 7 years was higher baseline weight and a greater increase in weight during that time period. This study highlights the importance of prevention of weight gain as a key public health strategy and for managing raised blood pressure, which is one of the major determinants of the burden of CVD in New Zealand.
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.
Douven, Elles; Köhler, Sebastian; Schievink, Syenna H J; van Oostenbrugge, Robert J; Staals, Julie; Verhey, Frans R J; Aalten, Pauline
2018-03-01
To examine the influence of vascular cognitive impairment (VCI) on the course of poststroke depression (PSD) and poststroke apathy (PSA). Included were 250 stroke patients who underwent neuropsychological and neuropsychiatric assessment 3 months after stroke (baseline) and at a 6- and 12-month follow-up after baseline. Linear mixed models tested the influence of VCI in at least one cognitive domain (any VCI) or multidomain VCI (VCI in multiple cognitive domains) at baseline and domain-specific VCI at baseline on levels of depression and apathy over time, with random effects for intercept and slope. Almost half of the patients showed any VCI at baseline, and any VCI was associated with increasing apathy levels from baseline to the 12-month follow-up. Patients with multidomain VCI had higher apathy scores at the 6- and 12-month follow-up compared with patients with VCI in a single cognitive domain. Domain-specific analyses showed that impaired executive function and slowed information processing speed went together with increasing apathy levels from baseline to 6- and 12-month follow-up. None of the cognitive variables predicted the course of depressive symptoms. Baseline VCI is associated with increasing apathy levels from baseline to the chronic stroke phase, whereas no association was found between baseline VCI and the course of depressive symptoms. Health professionals should be aware that apathy might be absent early after stroke but may evolve over time in patients with VCI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Derwent, Richard G.; Manning, Alistair J.; Simmonds, Peter G.; Spain, T. Gerard; O'Doherty, Simon
2018-04-01
Observations of surface ozone, O3, have been made at the Mace Head Atmospheric Research Station on the North Atlantic Ocean coastline of Ireland over a 30-year period from April 1987 through to April 2017. Using meteorological analyses and a sophisticated Lagrangian dispersion model, the hourly observations have been sorted by air mass histories to separate out the observations for northern hemisphere mid-latitude baseline air masses. Monthly average baseline levels showed a pronounced seasonal cycle with spring maxima and summer minima. Baseline levels have shown an increase during the 1980s and 1990s which has been stronger in the winter and spring and weaker in the summer. The rate of this increase has slowed to the extent that baseline levels have been relatively constant through the 2000s and started to decline in 2010s. The unsorted O3 data has shown different long-term trends from the baseline data because of the influence of European regional NOx and VOC emissions which have reduced wintertime O3 levels below the baseline levels and enhanced summertime O3 levels above them. Episodic peak O3 levels have declined steadily during the study period but 50 ppb 1 h exceedances are likely to continue for the foreseeable future.
Jacobson, Ira M; Washington, Mary K; Buti, Maria; Thompson, Alexander; Afdhal, Nezam; Flisiak, Robert; Akarca, Ulus Salih; Tchernev, Konstantin G; Flaherty, John F; Aguilar Schall, Raul; Myers, Robert P; Subramanian, G Mani; McHutchison, John G; Younossi, Zobair; Marcellin, Patrick; Patel, Keyur
2017-07-01
Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov registration numbers: NCT00117676 and NCT00116805. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.
Naito, A; Izumi, H; Karita, K; Tamai, M
2001-12-01
We clarified whether the intraocular pressure (IOP) response elicited by stimulation of the cervical sympathetic nerve (CSN) is influenced by changes in the baseline of IOP level and by beta-adrenergic blockade. The CSN was stimulated electrically for 30 seconds (10 V, 0.1-100 Hz, 2 milliseconds pulse duration) in urethane (100 mg/kg i.v.)-chloralose (50 mg/kg i.v.)-anesthetized, paralyzed cats. The IOP was monitored manometrically, and a controlled saline infusion was delivered into the anterior chamber to gradually increase IOP. CSN stimulation was delivered at the various baseline IOP levels so obtained. When required, a beta-adrenergic blocker timolol (2%) was delivered into the conjunctival cul-de-sac. The normal IOP in our cats was 25+/-3 mmHg. This value decreased transiently on CSN stimulation. The amplitude of this IOP response depended on stimulus frequency and the pre-stimulus baseline IOP level. Topical administration of timolol increased the IOP response to CSN stimulation at a given baseline level. These results suggest that beta-adrenergic blockade increases the alpha-adrenergic mediated-IOP reduction elicited by CSN stimulation at given baseline IOP level.
Using parathyroid hormone spikes during parathyroidectomy to guide intraoperative decision-making.
Carr, Azadeh A; Yen, Tina W; Wilson, Stuart D; Evans, Douglas B; Wang, Tracy S
2017-03-01
Intraoperative parathyroid hormone (IOPTH) level monitoring is a useful adjunct to parathyroidectomy for primary hyperparathyroidism (pHPT). Occasionally, increases ("spikes") in IOPTH levels from the preoperative baseline parathyroid hormone may occur, which may lead to longer operative times or more extensive neck exploration or both. The aim of this study was to determine if the extent of IOPTH level increase predicts single gland disease (SGD). This is a retrospective review of a prospective parathyroid database of patients undergoing parathyroidectomy for sporadic pHPT from 1999-2013. Extent of parathyroid hormone spike was calculated by the difference in IOPTH level at the time of gland excision and baseline: group 1 had a decrease in IOPTH level, group 2 had IOPTH level increase one to three times above the baseline, and group 3 had IOPTH level increase greater than three times above the baseline. Of the 900 patients in the cohort, there were 634 patients (70%) in group 1, 234 (26%) in group 2, and 32 (4%) in group 3. SGD was identified in 88%, 78%, and 100% of patients in groups 1, 2, and 3, respectively. The median gland weight in group 3 (920 mg) was significantly larger than those in groups 1 and 2 (440 and 460 mg, respectively; P < 0.001). IOPTH level spikes occur in nearly one-third of patients undergoing parathyroidectomy for sporadic pHPT. Patients with extensive IOPTH level increase are more likely to have larger SGD, whereas patients with moderate IOPTH level increases have increased incidence of multigland disease. In patients with a significant increase in IOPTH levels and larger glands, no further surgical exploration may be indicated. Copyright © 2016 Elsevier Inc. All rights reserved.
Wrosch, Carsten; Sabiston, Catherine M
2013-03-01
This longitudinal study examined whether goal adjustment capacities (i.e., goal disengagement and goal reengagement) would predict breast cancer survivors' emotional well-being and physical health by facilitating high levels of physical activity and low levels of sedentary activity. Self-reports of goal adjustment capacities were measured among 176 female breast cancer survivors at baseline. Self-reports of physical activity, sedentary activity, daily affect, and daily physical health symptoms (e.g., nausea or pain) were measured at baseline and 3-month follow-up. Goal reengagement predicted high levels of positive affect and low levels of physical symptoms at baseline and increases in positive affect over 3 months. The combination of high goal disengagement and high goal reengagement was associated with particularly large 3-month increases in positive affect. The effects of goal reengagement on baseline affect and physical health were mediated by high baseline levels of physical activity, and the interaction effect on 3-month changes in positive affect was mediated by low baseline levels of sedentary activity. Goal adjustment capacities can exert beneficial effects on breast cancer survivors' well-being and physical health by facilitating adaptive levels of physical and sedentary activity. Integrating goal adjustment processes into clinical practice may be warranted. Copyright © 2012 John Wiley & Sons, Ltd.
Sullivan, Lisa M.; Fox, Caroline S.; Wilson, Peter W.F.; Nathan, David M.; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Meigs, James B.
2014-01-01
Abstract Background: Multiple abnormal metabolic traits are found together or “cluster” within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures. Methods: In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0–4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia). Results: At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, P<0.0001. In models with BMI predictors only, for every quintile difference in baseline BMI, the 7-year trait score increase was 0.14 traits, and for every quintile increase in BMI during 7-year follow-up, the trait score increased by 0.3 traits. Baseline level and change in fasting insulin were similarly related to trait score change. In models adjusted for age–sex–baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits). Conclusions: Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits. PMID:25007010
Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.
2011-01-01
Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709
Zhao, Shumei; Choksuchat, Chainarong; Zhao, Yueqin; Ballagh, Susan A; Kovalevsky, George A; Archer, David F
2009-06-01
Endometrial spotting and/or bleeding (ESB) occurs in levonorgestrel subcutaneous implant (LNG SI) users. Matrix metalloproteinases (MMPs) may play a role in ESB. Women between 18 and 40 years with regular menstrual cycles had a baseline evaluation followed by LNG SI insertion and randomization to doxycycline (DOX; 20 mg) or placebo (PL) twice a day. MMP-2, MMP-9 and tissue inhibitor of MMP-1 (TIMP-1) in serum and the endometrium were estimated at baseline and at 1, 3 and 6 months after insertion. LNG increased serum MMP-9, while DOX decreased MMP-9 levels compared to PL after 1 month (p<.05). DOX decreased endometrial MMP-9 at 1 and 6 months compared to baseline and PL (p<.05). DOX increased endometrial TIMP-1 at 6 months compared with baseline and PL (p<.05). MMP-2 levels were unchanged. LNG SI increased serum MMP-9 and TIMP-1 levels, while DOX decreased both serum and endometrial MMP-9 levels.
Fukui, Aiko; Kawabe, Naoto; Hashimoto, Senju; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Takagawa, Yuka; Kamei, Hiroyuki; Yoshioka, Kentaro
2015-07-01
To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.
Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Bansal, Sukhvinder S; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D; Macdougall, Iain C
2016-01-01
Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.
Fifteen years of GH replacement improves body composition and cardiovascular risk factors.
Elbornsson, Mariam; Götherström, Galina; Bosæus, Ingvar; Bengtsson, Bengt-Åke; Johannsson, Gudmundur; Svensson, Johan
2013-05-01
Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. The mean initial GH dose of 0.55 (S.E.M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced.
DeFilippis, Andrew P; Harper, Charles R; Cotsonis, George A; Jacobson, Terry A
2009-01-01
We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.
Lopes-Virella, Maria F; Baker, Nathaniel L; Hunt, Kelly J; Cleary, Patricia A; Klein, Richard; Virella, Gabriel
2013-08-01
The current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria. Levels of inflammation and endothelial cell dysfunction biomarkers were measured in 1,237 of 1,441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline. To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, micro-, and macroalbuminuria were the outcomes of interest. In the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and -2 lead to a 30-50% increase in the odds to develop macroalbuminuria. Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and -2 but not for IL-6 or PAI-1. Our study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and -2, are important predictors of macroalbuminuria in patients with type 1 diabetes.
Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.
Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola
2017-07-01
The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kostapanos, Michael S; Milionis, Haralampos J; Lagos, Konstantinos G; Rizos, Christos B; Tselepis, Alexandros D; Elisaf, Moses S
2008-08-20
The influence of various statins on low-density-lipoprotein (LDL)-particle phenotype has been reportedly trivial or moderate. We assessed the effect of rosuvastatin (the newest statin available) on the LDL subfraction profile in patients with primary hyperlipidemia. One hundred and twenty patients with primary hyperlipidemia without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification ('control' group, N=60) or therapeutic lifestyle modification plus rosuvastatin 20 mg/day (N=60). Laboratory evaluation was performed at baseline and 12 weeks post-treatment. LDL subfraction analysis was carried out electrophoretically using of high-resolution 3% polyacrylamide gel tubes and the Lipoprint LDL System. Rosuvastatin induced a redistribution of LDL-cholesterol from small-dense LDL particles to large-buoyant ones and increased the mean LDL particle size. This beneficial effect was observed only in patients with baseline triglyceride levels >or=150 mg/dl (mean LDL particle size 255+/-7 A vs 260+/-5 A, P<0.01), whereas the LDL subfraction profile was not altered in those with triglyceride levels <150 mg/dl. Stepwise multivariate linear regression analysis revealed that baseline triglyceride levels (R(2)=0.29, P=0.001) followed by baseline insulin resistance as assessed by the HOmeostasis Model Assessment (HOMA) (R(2)=0.25, P=0.001) were independently associated with the rosuvastatin-induced increase in the mean LDL particle size. In conclusion, rosuvastatin at 20 mg/day favorably modified the relative distribution of LDL-cholesterol distribution on LDL subfractions as well as on the mean LDL particle size in patients treated for primary dyslipidemia. Baseline triglyceride levels as well as baseline HOMA-index were found to be the major predictors of this beneficial action of rosuvastatin.
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.
Hirsch, Jana A.; Moore, Kari A.; Clarke, Philippa J.; Rodriguez, Daniel A.; Evenson, Kelly R.; Brines, Shannon J.; Zagorski, Melissa A.; Diez Roux, Ana V.
2014-01-01
Lack of longitudinal research hinders causal inference on the association between the built environment and walking. In the present study, we used data from 6,027 adults in the Multi-Ethnic Study of Atherosclerosis who were 45–84 years of age at baseline to investigate the association of neighborhood built environment with trends in the amount of walking between 2000 and 2012. Walking for transportation and walking for leisure were assessed at baseline and at 3 follow-up visits (median follow-up = 9.15 years). Time-varying built environment measures (measures of population density, land use, number of destinations, bus access, and street connectivity) were created using geographic information systems. We used linear mixed models to estimate the associations between baseline levels of and a change in each built environment feature and a change in the frequency of walking. After adjustment for potential confounders, we found that higher baseline levels of population density, area zoned for retail, social destinations, walking destinations, and street connectivity were associated with greater increases in walking for transportation over time. Higher baseline levels of land zoned for residential use and distance to buses were associated with less pronounced increases (or decreases) in walking for transportation over time. Increases in the number of social destinations, the number of walking destinations, and street connectivity over time were associated with greater increases in walking for transportation. Higher baseline levels of both land zoned for retail and walking destinations were associated with greater increases in leisure walking, but no changes in built environment features were associated with leisure walking. The creation of mixed-use, dense developments may encourage adults to incorporate walking for transportation into their everyday lives. PMID:25234431
Ormstad, Heidi; Dahl, Johan; Verkerk, Robert; Andreassen, Ole A; Maes, Michael
2016-08-01
Lowered plasma tryptophan (TRP) and TRP/competing amino acid (CAA) ratio may be involved in the pathophysiology of major depression (MDD). Increased cortisol and immune-inflammatory mediators in MDD may affect the availability of TRP to the brain. We investigated whether baseline or post-treatment TRP, CAAs and TRP/CAA ratio are associated with a treatment response in MDD and whether these effects may be mediated by cortisol or immune biomarkers. We included 50 medication-free MDD patients with a depressive episode (DSM diagnosis) and assessed symptom severity with the Inventory of Depressive Symptomatology (IDS) before and after treatment as usual for 12 weeks (endpoint). Plasma levels of TRP, CAAs, the ratio, cortisol, CRP and 6 selected cytokines were assayed. The primary outcome was a 50% reduction in the IDS, while the secondary was a remission of the depressive episode. In IDS non-responders, CAAs increased and the TRP/CAA ratio decreased, while in IDS responders CAAs decreased and the TRP/CAA ratio increased from baseline to endpoint. In patients who were still depressed at endpoint TRP and CAAs levels had increased from baseline, while in remitted patients no such effects were found. Increases in CAAs were inversely correlated with changes in interleukin-1 receptor antagonist levels. The results show that increased CAA levels from baseline to endpoint are associated with a non-response to treatment in MDD patients. This suggests that the mechanism underpinning the CAA-related treatment resistance may be related to changes in immune pathways. CAA levels and amino acid metabolism may be new drug targets in depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund
2018-03-01
Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p < 0.001), independently of insulin-treatment, baseline serum glucose, baseline brain metabolic distress (CMD-lactate-to-pyruvate-ratio (LPR) > 40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.
Kenny, Anne M; Biskup, Bradley; Robbins, Bertha; Marcella, Glenn; Burleson, Joseph A
2003-12-01
To study the effects of vitamin D supplementation in healthier populations of men. : Randomized, controlled trial. General clinical research center. Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.
Kim, Taehee; Rhee, Connie M; Streja, Elani; Obi, Yoshitsugu; Brunelli, Steven M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar
2017-02-01
The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.
Malinovschi, A; Alving, K; Kalm-Stephens, P; Janson, C; Nordvall, L
2012-03-01
The fraction of nitric oxide in exhaled air (FE(NO)) is increased in rhinitis and asthma. We have previously suggested that elevated FE(NO) levels in the absence of asthma symptoms may be a sign of 'early asthma'. In the present study, we hypothesize that elevated exhaled NO levels may also precede rhinitis symptoms. To investigate in a cohort of adolescents whether or not increased exhaled NO levels at the age of 13-14 years predicted new-onset or persistent rhinitis within a 4-year period. A total of 959 randomly selected adolescents (13-14 years) completed a questionnaire on respiratory symptoms at baseline and follow-up, 4 years later. Exhaled NO was measured at baseline. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 657 participants were eligible for the present study. Higher FE(NO) levels at baseline were associated with increased risk for new-onset (P = 0.009) and persistent rhinitis (P = 0.03) within a 4-year period. The risk of new-onset rhinitis was 2.32 (1.23, 4.37) [OR (95% CI)] times higher if FE(NO) > 90th percentile of the group without rhinitis at baseline. This increased risk for new-onset rhinitis was significant [2.49 (1.24, 5.01)] after excluding subjects with allergic symptoms. The risk of persistent rhinitis was 5.11 (1.34, 19.57) times higher if FE(NO) > 90th percentile of the group without rhinitis at baseline. Elevated exhaled nitric oxide levels predicted incident and persistent rhinitis in this population-based study of adolescents. Moreover, these findings were consistent after excluding subjects with allergic symptoms. Thus, it appears that elevation of exhaled NO precedes airway symptoms and predicts development of rhinitis in subjects without allergic symptoms or family history of allergic disease. © 2011 Blackwell Publishing Ltd.
Comparing the occlusal contact area of individual teeth during low-level clenching.
Nishimori, Hideta; Iida, Takashi; Kamiyama, Hirona; Komoda, Yoshihiro; Obara, Ryoko; Uchida, Takashi; Kawara, Misao; Komiyama, Osamu
2017-09-14
The aim of this study was to investigate the occlusal contact area (OCA) in individual teeth during low-level tooth clenching in 24 healthy participants. Before measurements were made, the 100% maximum voluntary contraction (MVC) was determined. At baseline, all subjects were instructed to close their mouth and touch the opposing teeth with minimal force. Occlusal contact was recorded during three jaw motor tasks (baseline, 20% MVC, and 40% MVC) using a blue silicone material. OCA thickness was determined from images and defined on five levels: level 1 (0-149 µm), level 2 (0-89 µm), level 3 (0-49 µm), level 4 (0-29 µm), and level 5 (0-4 µm). Premolar and molar OCAs increased significantly from baseline to 20% MVC and 40% MVC. The OCA of each anterior tooth did not change significantly with increasing clenching intensity at all levels. Our findings suggest that premolar and molar OCAs may be altered by low-intensity clenching, affecting the teeth and periodontal tissues.
Baliarsingh, S; Jaiswal, M
2014-02-01
Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects. Within a 19-month period, baseline and weekly samples from 15 CPDA-1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin. One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0·50, P < 0·01) of storage; four units increase at 2 weeks (r2 = 0·64, P < 0·001) and 3 weeks (r2 = 0·51, P < 0·01) of storage; six units at 4 weeks (r2 = 0·53, P < 0·01) of storage. Baseline whole blood haemoglobin showed a moderate association with baseline potassium (r2 = 0·36, P < 0·05) and 2-week potassium (r2 = 0·35, P < 0·05) values. For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the ‘first-in-first-out’ (FIFO) policy with ‘early release of blood-bags with high initial potassium’ might be helpful in improving the release of suitable blood units from blood-banks.
Shao, Qin; Casin, Kevin M.; Mackowski, Nathan; Murphy, Elizabeth; Steenbergen, Charles
2017-01-01
Nitric oxide (NO) plays an important role in cardioprotection, and recent work from our group and others has implicated protein S-nitrosylation (SNO) as a critical component of NO-mediated protection in different models, including ischemic pre- and post-conditioning and sex-dependent cardioprotection. However, studies have yet to examine whether protein SNO levels are similarly increased with pharmacologic preconditioning in male and female hearts, and whether an increase in protein SNO levels, which is protective in male hearts, is sufficient to increase baseline protection in female hearts. Therefore, we pharmacologically preconditioned male and female hearts with the adenosine A1 receptor agonist N6-cyclohexyl adenosine (CHA). CHA administration prior to ischemia significantly improved functional recovery in both male and female hearts compared to baseline in a Langendorff-perfused heart model of ischemia-reperfusion injury (% of preischemic function ± SE: male baseline: 37.5±3.4% vs. male CHA: 55.3±3.2%; female baseline: 61.4±5.7% vs. female CHA: 76.0±6.2%). In a separate set of hearts, we found that CHA increased p-Akt and p-eNOS levels. We also used SNO-resin-assisted capture with LC-MS/MS to identify SNO proteins in male and female hearts, and determined that CHA perfusion induced a modest increase in protein SNO levels in both male (11.4%) and female (12.3%) hearts compared to baseline. These findings support a potential role for protein SNO in a model of pharmacologic preconditioning, and provide evidence to suggest that a modest increase in protein SNO levels is sufficient to protect both male and female hearts from ischemic injury. In addition, a number of the SNO proteins identified with CHA treatment were also observed with other forms of cardioprotective stimuli in prior studies, further supporting a role for protein SNO in cardioprotection. PMID:28493997
Yamada, Shunsuke; Ueki, Kenji; Tokumoto, Masanori; Suehiro, Takaichi; Kimura, Hiroshi; Taniguchi, Masatomo; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko
2016-02-01
Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
NASA Astrophysics Data System (ADS)
Wang, Wenjia; Li, Qiang; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng
2007-02-01
Laser speckle imaging technique was used to characterize the spatiotemporal changes in cerebral blood flow (CBF) in rat cortex induced by the local ultraprofound hypothermia(0°C) with the duration time of 1 min, 2 min, 5 min, 7 min and 10 min. The experimental results showed significant difference of the spatiotemporal characteristics of changes in CBF between short term and long term of ultraprofound hypothermia. For the short duration of ultraprofound hypothermia (1 min, 2 min and 5 min), the hypothermia cause the CBF decrease firstly, and then the CBF increase rapidly when the temperature is recovered to 37°C, exceeding the baseline level and lasting 10+/-3 min, finally return to the baseline. This trend of changes in CBF is similar in the regions of artery, vein and parenchyma, but with different amplitude. For the duration time of 7 min, the changes in CBF also exhibit the similar decrease induced by ultraprofound hypothermia and the rapid increase induced by the temperature recovering, however the increase does not show the overshoot, but only reach around 75% of the baseline level. For the duration of 10 min of ultraprofound hypothermia, the CBF does not increase rapidly when the temperature is recovered to 37°C, but remains at the low level of CBF for 12+/-2 min, and then increases gradually at artery sites, or increases rapidly and then decrease slightly later at the vein and parenchyma sites. Similar as the case in the duration time of 7 min, the final CBF only recovers to about 75% of the baseline level. The experimental results suggest that the CBF can not recover to the baseline after a long duration of ultraprofound hypothermia longer than 7 min.
García-Carrasco, Mario; Mendoza-Pinto, Claudia; Ayón-Aguilar, Jorge; Soto-Santillán, Pamela; Rodríguez-Gallegos, Alma; Escamilla-Márquez, Marco Antonio; Méndez-Martínez, Socorro
2016-10-01
To determine changes over time of serum levels of 25-hydroxy vitamin D (25(OH)D) in Mexican patients with SLE and their relationship with disease activity. Longitudinal and observational study. Women with SLE were included. Serum levels of 25(OH)D were measured at baseline and after two years; the disease activity was measured with MEX-SLEDAI. Patients with initial suboptimal levels of 25(OH)D received supplements or increased doses of calcitriol. 105 women with SLE were included, mean age 49.4 ± 11 years. Serum levels of 25(OH)D were higher at two years (baseline 20 ± 6.8 vs. follow-up 22.7 ± 7.7; p = < 0.001). There were no differences between disease activity scores at baseline and two years (baseline 1.7 ± 1.9 vs. follow-up 1.1 ± 1.7; p = 0.7). Serum levels of 25(OH)D did not correlate with disease activity during the follow up, p = 0.7. No correlation was found between changes in MEX-SLEDAI scores and serum levels of 25(OH)D, p = 0.87. Mexican women with SLE had increased serum levels of 25(OH)D. No correlation between serum levels of 25(OH)D and disease activity was found.
Baseline adjustments for binary data in repeated cross-sectional cluster randomized trials.
Nixon, R M; Thompson, S G
2003-09-15
Analysis of covariance models, which adjust for a baseline covariate, are often used to compare treatment groups in a controlled trial in which individuals are randomized. Such analysis adjusts for any baseline imbalance and usually increases the precision of the treatment effect estimate. We assess the value of such adjustments in the context of a cluster randomized trial with repeated cross-sectional design and a binary outcome. In such a design, a new sample of individuals is taken from the clusters at each measurement occasion, so that baseline adjustment has to be at the cluster level. Logistic regression models are used to analyse the data, with cluster level random effects to allow for different outcome probabilities in each cluster. We compare the estimated treatment effect and its precision in models that incorporate a covariate measuring the cluster level probabilities at baseline and those that do not. In two data sets, taken from a cluster randomized trial in the treatment of menorrhagia, the value of baseline adjustment is only evident when the number of subjects per cluster is large. We assess the generalizability of these findings by undertaking a simulation study, and find that increased precision of the treatment effect requires both large cluster sizes and substantial heterogeneity between clusters at baseline, but baseline imbalance arising by chance in a randomized study can always be effectively adjusted for. Copyright 2003 John Wiley & Sons, Ltd.
Navarese, Eliano P; Robinson, Jennifer G; Kowalewski, Mariusz; Kolodziejczak, Michalina; Andreotti, Felicita; Bliden, Kevin; Tantry, Udaya; Kubica, Jacek; Raggi, Paolo; Gurbel, Paul A
2018-04-17
Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials. To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions. Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies. Two investigators abstracted data and appraised risks of bias. Intervention groups were categorized as "more intensive" (more potent pharmacologic intervention) or "less intensive" (less potent, placebo, or control group). The coprimary end points were total mortality and cardiovascular mortality. Random-effects meta-regression and meta-analyses evaluated associations between baseline LDL-C level and reductions in mortality end points and secondary end points including major adverse cardiac events (MACE). In 34 trials, 136 299 patients received more intensive and 133 989 received less intensive LDL-C lowering. All-cause mortality was lower for more vs less intensive therapy (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]), but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with greater reductions in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96]; P = .001; absolute risk difference [ARD], -1.05 incident cases per 1000 person-years [95% CI, -1.59 to -0.51]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Cardiovascular mortality was lower for more vs less intensive therapy (3.48% vs 4.07%; RR, 0.84 [95% CI, 0.79 to 0.89]) but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with a greater reduction in cardiovascular mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.86 [95% CI, 0.80 to 0.94]; P < .001; ARD, -1.0 incident cases per 1000 person-years [95% CI, -1.51 to -0.45]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Trials with baseline LDL-C levels of 160 mg/dL or greater had the greatest reduction in all-cause mortality (RR, 0.72 [95% CI, 0.62 to 0.84]; P < .001; 4.3 fewer deaths per 1000 person-years) in a meta-analysis. More intensive LDL-C lowering was also associated with progressively greater risk reductions with higher baseline LDL-C level for myocardial infarction, revascularization, and MACE. In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels. This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C-lowering therapy may occur for patients with higher baseline LDL-C levels.
Gueugnon, Carine; Mougin, Fabienne; Nguyen, Nhu Uyen; Bouhaddi, Malika; Nicolet-Guénat, Marie; Dumoulin, Gilles
2012-05-01
This study investigated (a) changes in ghrelin and peptide YY (PYY) concentrations during a weight reduction programme and (b) baseline ghrelin and PYY levels as predictors of weight loss in 32 severely obese adolescents (BMI z score = 4.1). Subjects spent an academic year in an institution for childhood obesity. Fasting ghrelin and PYY, leptin, insulin levels and insulin resistance were measured at baseline (month 0) and during the programme (months 3, 6, 9). In addition, 15 normal-weight teenagers served as reference for the baseline assessments. At baseline, obese teenagers had lower ghrelin and PYY concentrations than normal-weight adolescents (P < 0.05). Moreover, they showed significantly higher leptin, insulin levels and homeostasis model assessment (HOMA) (P < 0.0001). During the lifestyle modification, there was a significant decrease in body weight among obese teenagers, associated with an increase in ghrelin (apparent from month 6; P < 0.05), a decrease in leptin (from month 3; P < 0.05) and a decrease in insulin and HOMA (from month 3; P < 0.0001), without any significant change in PYY. Anthropometrical changes were correlated neither with baseline ghrelin levels nor with changes in ghrelin and PYY after the lifestyle modification. However, higher baseline PYY tended to correlate with greater anthropometrical changes (P < 0.1). In adolescents with severe obesity, a long-term combination of supervised aerobic exercises and a balanced diet led to weight reduction and increased ghrelin concentrations, without any change in PYY concentrations. Moreover, baseline PYY concentrations might be considered as predictors of weight loss.
Champagne, Cory; Tift, Michael; Houser, Dorian; Crocker, Daniel
2015-01-01
Stressful disturbances activate the hypothalamic–pituitary–adrenal (HPA) axis and result in the release of glucocorticoid (GC) hormones. This characteristic stress response supports immediate energetic demands and subsequent recovery from disturbance. Increased baseline GC concentrations may indicate chronic stress and can impair HPA axis function during exposure to additional stressors. Levels of GCs, however, vary seasonally and with life-history stage, potentially confounding their interpretation. Our objective was to evaluate HPA axis function across variations in baseline GC levels. Northern elephant seals show substantial baseline variation in GC levels during their annual moulting period. We therefore conducted measurements early, in the middle and at the end of moulting; we simulated an acute stressor by administering adrenocorticotrophic hormone and evaluated the changes in circulating hormones and metabolites over the following 2 h. The stress response was characterized by increases in both cortisol and aldosterone (F7,105 = 153 and 25.3, respectively; P < 0.001). These hormones increased in parallel and the slopes of their relationship varied by study group, suggesting they are regulated in a co-ordinated manner during acute stress in this species. There was no detectable difference in the total release of cortisol or aldosterone among study groups, indicating that the HPA axis remained sensitive to stimulation by adrenocorticotrophic hormone despite varying baseline levels of GCs. Acute stress influenced carbohydrate and fat metabolism in all study groups, but protein catabolism was affected to a far lesser degree. These findings suggest that elephant seals, and potentially other pinniped species, are resilient to moderate variations in baseline GC levels and remain capable of mounting a response to additional stressors. PMID:27293689
Zeigenfuss, Linda C.; Johnson, Therese L.
2015-12-17
Increases in the number of small-diameter, tree-sized (stems greater than 2.5 meter height) aspen stems were observed but only inside fences that excluded ungulates. In unfenced areas, stand structure was stagnant, with many medium- and large-diameter (older) stems and no replacement of small-diameter stems. By 2013, aspen saplings (stems less than or equal to 2.5 meter height) were recruiting on 29 percent of sampled sites, an increase from 13 percent of sites at baseline, but this was mainly due to growth inside fences. Upland herbaceous offtake dropped below baseline levels (61 percent) on both core and noncore winter range in 2010–14. Less than 10 percent of the upland areas had intense herbivory (greater than 85 percent offtake), and less than 30 percent of the landscape had offtake greater than 70 percent after 2009. Offtake levels in 2013 and 2014 indicated an increase in grazing pressure on upland sites compared to 2010–12 levels, but this change may have been in response to loss of large patches of both herbaceous and woody forage in Moraine Park following the 2012 Fern Lake Fire. Winter willow offtake remained steady from 2009 to 2014, and although there were no substantial increases in offtake, there were also no consistent declines. Winter-range willow offtake was below the baseline level of 35 percent only in 2013 and 2014. Willow heights have stayed at or above baseline levels of 0.9 meter. Average heights of willow increased compared to baseline measures within fenced habitat on the core winter range and on noncore (all unfenced) winter range. Willow cover increased at least 75 percent compared to baseline within core winter-range fenced areas and roughly 25 percent in noncore winter range. Overall, during the first 5 years of implementation, the EVMP at Rocky Mountain National Park seems to be making steady progress toward the vegetation objectives set out by the EVMP. Habitat fencing has been the most effective means of improving aspen and willow habitat conditions.
El-Sheikh, Mona; Hinnant, J. Benjamin; Erath, Stephen
2010-01-01
Trajectories of delinquency symptoms across middle and late childhood were examined through latent growth modeling, with a focus on the role of interactions among parental marital conflict, child sex, and multiple indices (baseline, reactivity) of either parasympathetic nervous system (PNS) activity, indexed by respiratory sinus arrhythmia (RSA), or sympathetic nervous system (SNS) activity, indexed by skin conductance level (SCL) as predictors of growth. At T1, 128 girls and 123 boys (Mean age 8.23 yrs ± .73) and their parents participated. The sample was comprised of 64% European-American (EA) and 36% African-American (AA) children. Families participated in 2nd and 3rd waves of data collection with a one-year lag between each wave. Interactions among marital conflict, sex, baseline RSA, and RSA reactivity from baseline to a frustrating lab task were significant predictors of growth in delinquent behavior from age 8 to age 10, with overall patterns indicating increasing symptoms for boys who live in high conflict homes and have an RSA response profile comprised of lower RSA during the baseline and RSA augmentation (increase from baseline to the frustrating task). Furthermore, increases in delinquency symptoms over time were observed for children from high conflict homes with an SCL profile characterized by higher baseline levels and lower reactivity (less pronounced SCL increases from baseline) to the frustrating task. Findings highlight the importance of contemporaneous assessments of resting and reactivity levels when examining relations between the environment, physiological functioning, and psychopathology. Results are discussed in the context of biology by environment interactions as relevant to the development of psychopathology. PMID:20919788
The effects of heat and massage application on autonomic nervous system.
Lee, Young-Hee; Park, Bit Na Ri; Kim, Sung Hoon
2011-11-01
The objective of this study is to evaluate the effects of heat and massage application on autonomic nervous system. One hundred thirty-nine subjects volunteered and completed this study. Heat and massage was daily applied for 40 minutes, 5 days a week for 2 weeks. Primary-dependent measures included heart rate variability, sympathetic skin response, and serum cortisol and norepinephrine levels. Serum cortisol levels were significantly decreased at 2 weeks compared to baseline (p=0.003). Plasma norepinephrine levels at 4 weeks were significantly decreased compared to baseline (p=0.010). Heart rate, using the power spectra, increased significantly after 2 weeks compared to baseline. Of autonomic nerve conduction measures, latency was significantly increased at 2 and 4 weeks compared to baseline (p=0.023, 0.012), and amplitude was significantly decreased at 4 weeks compared to baseline (p=0.008). There were no serious adverse events such as burns or other major complications. The results of this study suggest that heat and massage applications provide relaxation to the autonomic nervous system without serious adverse events.
Blom, Dirk J; Djedjos, C Stephen; Monsalvo, Maria Laura; Bridges, Ian; Wasserman, Scott M; Scott, Rob; Roth, Eli
2015-09-25
Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. To determine the effects of evolocumab on vitamin E and steroid hormone levels. After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01516879. © 2015 American Heart Association, Inc.
Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara
Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less
Augoulea, A; Tsakonas, E; Triantafyllopoulos, I; Rizos, D; Armeni, E; Tsoltos, N; Tournis, S; Deligeoroglou, E; Antoniou, A; Lambrinoudaki, I
2017-03-01
To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm 2 to 0.75±0.09 g/cm 2 ; BIS: 0.69±0.06 g/cm 2 to 0.71±0.07 g/cm 2 ; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm 2 to 0.89±0.14 g/cm 2 , p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.
Hirsch, Jana A; Moore, Kari A; Clarke, Philippa J; Rodriguez, Daniel A; Evenson, Kelly R; Brines, Shannon J; Zagorski, Melissa A; Diez Roux, Ana V
2014-10-15
Lack of longitudinal research hinders causal inference on the association between the built environment and walking. In the present study, we used data from 6,027 adults in the Multi-Ethnic Study of Atherosclerosis who were 45-84 years of age at baseline to investigate the association of neighborhood built environment with trends in the amount of walking between 2000 and 2012. Walking for transportation and walking for leisure were assessed at baseline and at 3 follow-up visits (median follow-up = 9.15 years). Time-varying built environment measures (measures of population density, land use, number of destinations, bus access, and street connectivity) were created using geographic information systems. We used linear mixed models to estimate the associations between baseline levels of and a change in each built environment feature and a change in the frequency of walking. After adjustment for potential confounders, we found that higher baseline levels of population density, area zoned for retail, social destinations, walking destinations, and street connectivity were associated with greater increases in walking for transportation over time. Higher baseline levels of land zoned for residential use and distance to buses were associated with less pronounced increases (or decreases) in walking for transportation over time. Increases in the number of social destinations, the number of walking destinations, and street connectivity over time were associated with greater increases in walking for transportation. Higher baseline levels of both land zoned for retail and walking destinations were associated with greater increases in leisure walking, but no changes in built environment features were associated with leisure walking. The creation of mixed-use, dense developments may encourage adults to incorporate walking for transportation into their everyday lives. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans
NASA Technical Reports Server (NTRS)
Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.
1993-01-01
The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous micro- circulation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, 0 deg, -6 deg (HDT), -12 deg, -6 deg, 0 deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P < 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar-X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.
Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans
NASA Technical Reports Server (NTRS)
Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.
1993-01-01
The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous microcirculation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, O deg, -6 deg (HDT), -12 deg, -6 deg, O deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P less than 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.
Zamora-Ros, R; Serafini, M; Estruch, R; Lamuela-Raventós, R M; Martínez-González, M A; Salas-Salvadó, J; Fiol, M; Lapetra, J; Arós, F; Covas, M I; Andres-Lacueva, C
2013-12-01
The intake of antioxidant-rich foods may increase the blood levels of non enzymatic antioxidant capacity (NEAC). NEAC takes into account all antioxidants from food and synergistic effects between them. We examined the effect of a 1-year intervention with Mediterranean diet on plasma NEAC and assessed whether it was related to baseline NEAC levels. Five hundred sixty-four participants at high cardiovascular risk were randomly selected from the PREDIMED (Prevención con DIeta MEDiterránea) Study, a large 3-arm randomized clinical trial. Blood NEAC levels were measured at baseline and after 1-year of dietary intervention with 1) a Mediterranean diet supplemented with virgin olive oil (MED + VOO); 2) a Mediterranean diet supplemented with nuts (MED + nuts), or 3) a control low-fat diet. Plasma NEAC was analyzed using FRAP (ferric reducing antioxidant potential) and TRAP (total radical-trapping antioxidant parameter) assays. Plasma FRAP levels increased after 1-year of intervention with MED + VOO [72.0 μmol/L (95% CI, 34.2-109.9)] and MED + nuts [48.9 μmol/L (24.3-73.5)], but not after the control low-fat diet [13.9 μmol/L (-11.9 to 39.8)]. Participants in the lowest quartile of plasma FRAP at baseline significantly increased their levels after any intervention, while those in the highest quartile decreased. Similar results occurred with TRAP levels. This study shows that a 1-year of MED diet intervention increases plasma TAC level in subjects at high risk for cardiovascular disease. Moreover, the effectiveness of dietary supplementation with antioxidants may be related to baseline levels of plasma NEAC. © 2013 Elsevier B.V. All rights reserved.
Mitigating Task Saturation in Critical Care Air Transport Team Red Flag Checklist
2015-04-14
Cincinnati. Team and individual performances were scored using a validated assessment tool for NOTECHS. Salivary cortisol levels were measured at baseline...deployment experience (pɘ.04) continued to be significant. Salivary cortisol levels increased by 0.124μg/dL over baseline as the result of the...Figure Page 1 Salivary cortisol levels for all 48 participants in the simulations ........................................3
Morotti, Andrea; Charidimou, Andreas; Phuah, Chia-Ling; Jessel, Michael J; Schwab, Kristin; Ayres, Alison M; Romero, Javier M; Viswanathan, Anand; Gurol, M Edip; Greenberg, Steven M; Anderson, Christopher D; Rosand, Jonathan; Goldstein, Joshua N
2016-11-01
Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH). To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion. Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016. Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively. A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders. Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.
Rhee, Eun-Jung; Cho, Jung-Hwan; Kwon, Hyemi; Park, Se Eun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Lee, Won-Young
2017-12-01
The hemoglobin glycation index (HGI) is known to be correlated with the risk for cardiovascular disease. To analyze the association between incident coronary artery calcification (CAC) and the changes in HGI among participants without diabetes, over 4 years. A retrospective study of 2052 nondiabetic participants in whom the coronary artery calcium score was measured repeatedly over 4 years, as part of a health checkup program in Kangbuk Samsung Hospital in Korea, and who had no CAC at baseline. The HGI was defined as the difference between the measured and predicted hemoglobin A1c (HbA1c) levels. A total of 201 participants developed CAC after 4 years, and the mean baseline HGI was significantly higher in those patients. The incidence of CAC gradually increased from the first to the fourth quartile groups of baseline HGI. The odds ratio (OR) for incident CAC was the highest among the four groups divided by the quartiles of the baseline HGI and was significant after adjustment for confounding variables (vs first quartile group: OR, 1.632; 95% confidence interval, 1.024 to 2.601). The incidence of and risk for CAC development were significantly higher than in other groups compared with the low-to-low group after adjustment for confounding factors; however, when baseline HbA1c level was included in the model, only participants with a low-to-high HGI over 4 years showed a significantly increased OR for CAC development compared with the low-to-low group (OR, 1.722; 95% confidence interval, 1.046 to 2.833). The participants with a high baseline HGI and consistently high HGI showed a higher risk for incident CAC than those with a low baseline HGI. An increased HGI over 4 years significantly increased the risk for CAC regardless of the baseline HbA1c levels. Copyright © 2017 Endocrine Society
Melehan, K L; Hoyos, C M; Yee, B J; Wong, K K; Buchanan, P R; Grunstein, R R; Liu, P Y
2016-01-01
Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing. © 2015 American Society of Andrology and European Academy of Andrology.
Lee, Jong-Young; Ryu, Seungho; Sung, Ki-Chul
2018-01-01
Background The association between baseline and temporal changes in physical activity and incident hypertension or diabetes mellitus in initially non-hypertensive or non-diabetic subjects is rarely known. Methods Among individuals who underwent consecutive comprehensive health screenings, their physical activity level was measured using a self-reported international physical activity questionnaire. First, subjects were classified into four categories: no regular physical activity with a sedentary lifestyle; minimal physical activity (<75 min/week); insufficient physical activity (≥75 min but <150 min/week); and sufficient physical activity (≥150 min/week). Second, subjects were sub-grouped, based on temporal changes in physical activity level between baseline and consecutive follow-up: increase, no change, and decrease. Results Finally, among 174,314 subjects (mean age 36.7 ± 6.9 years), 5544 (3.18%) and 21,276 (12.2%) developed incident diabetes mellitus and arterial hypertension, respectively. After a multivariate adjustment, sufficient baseline physical activity was associated with significantly lower risk for incident hypertension (hazard ratio 0.89; 95% confidence interval (CI) 0.81 to 0.97), but the difference was not significant, and showed a lower trend in diabetes mellitus incidence (hazard ratio 0.87; 95% CI 0.69 to 1.04) in reference to no regular physical activity group. Regardless of the baseline physical activity level, subjects with a temporal increase in physical activity showed significantly decreased risk for incident hypertension (hazard ratio 0.93; 95% CI 0.87 to 0.99) and diabetes mellitus (hazard ratio 0.83; 95% CI 0.74 to 0.92) compared with those with a temporal decrease in their physical activity level. Conclusion Both sufficient baseline physical activity level and its temporal increase were associated with a lower risk of incident hypertension and diabetes mellitus in a large, relatively healthy, cohort.
Hadji, P; Kauka, A; Bauer, T; Tams, J; Hasenburg, A; Kieback, D G
2012-10-01
The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.
Right-frontal cortical asymmetry predicts increased proneness to nostalgia.
Tullett, Alexa M; Wildschut, Tim; Sedikides, Constantine; Inzlicht, Michael
2015-08-01
Nostalgia is often triggered by feelings-such as sadness, loneliness, or meaninglessness-that are typically associated with withdrawal motivation. Here, we examined whether a trait tendency to experience withdrawal motivation is associated with nostalgia proneness. Past work indicates that baseline right-frontal cortical asymmetry is a neural correlate of withdrawal-related motivation. We therefore hypothesized that higher baseline levels of right-frontal asymmetry would predict increased proneness to nostalgia. We assessed participants' baseline levels of frontal cortical activity using EEG. Results supported the hypothesis and demonstrated that the association between relative right-frontal asymmetry and increased nostalgia remained significant when controlling for the Big Five personality traits. Overall, these findings indicate that individuals with a stronger dispositional tendency to experience withdrawal-related motivation are more prone to nostalgia. © 2015 Society for Psychophysiological Research.
Burosumab Therapy in Children with X-Linked Hypophosphatemia.
Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A
2018-05-24
X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).
Wan, Miaojian; Hu, Rong; Xie, Xiaoyuan; Gong, Zijian; Yi, Jinling; Chen, Haiyan; Xie, Lin; Guan, Xiaomin; Guan, Lei; Lai, Wei
2017-10-01
Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet (SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses (MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese. © 2017 The American Society of Photobiology.
Rossouw, Jacques E; Johnson, Karen C; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W; Manson, JoAnn E; Lakshminarayan, Kamakshi; Merino, Jose G; Lynch, John
2012-01-01
Background and Purpose To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT). Methods Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT. Results Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008. Conclusions Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT. PMID:22363056
Procalcitonin levels in sepsis and its association with clinical outcome in southern India.
Rebello, Alex; Thabah, Molly Mary; Dutta, Tarun Kumar; Bobby, Zachariah; Harish, B N; Mehalingam, Vadivelan
2017-10-01
Procalcitonin has been found to be a good marker for the diagnosis of sepsis. However, data on procalcitonin levels to predict the clinical outcome in patients with sepsis are limited. The aim of our study was to estimate serum procalcitonin levels in patients with sepsis and to identify its relationship with the clinical outcome. This was a prospective observational study conducted on 112 patients with sepsis admitted to the medical wards and medical intensive care unit of a tertiary care teaching hospital. Serum procalcitonin was measured at baseline before antibiotic administration and on day 5. The clinical outcome studied was death or survival on day 28. Baseline mean serum procalcitonin was highest in patients with septic shock and lowest in patients having sepsis without organ dysfunction. Mean values of procalcitonin at baseline and on day 5 were significantly higher in non-survivors when compared with survivors. There was a significant difference in the change in procalcitonin levels from baseline to day 5 between survivors and non-survivors, with survivors having declining values on day 5 while non-survivors had increasing values from baseline. The baseline APACHE II and SOFA scores also showed a significant correlation with the baseline procalcitonin level. Declining values of procalcitonin therefore indicate a favourable clinical outcome in patients with sepsis.
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
Strategic Key Word Instruction: Increasing Fluency in Connected Expository Text
ERIC Educational Resources Information Center
Coulter, Gail; Lambert, Michael C.
2015-01-01
The effects of preteaching key words on fluency in connected text were examined with three third-grade general education participants. Researchers used a multiple base-line design (i.e., Baseline and Wordlist Intervention) and found that preteaching increased fluency in connected text written above the participant's instructional level of reading…
Mediation of a corticosterone-induced reproductive conflict.
Love, Oliver P; Breuner, Creagh W; Vézina, François; Williams, Tony D
2004-06-01
Current research in birds suggests that a conflict should exist during reproduction for the role of the glucocorticoid corticosterone (CORT). While elevated levels have been correlated with the increased energetic demand of raising offspring, elevated CORT levels have traditionally been implicated in reproductive abandonment. We examined the relationship between CORT and nest desertion in breeding wild female European starlings (Sturnus vulgaris) incorporating analyses of both total circulating levels and 'free', unbound CORT through analysis of corticosteroid-binding globulin (CBG). Free baseline CORT levels of nest-abandoning birds were significantly higher than nonabandoning birds within each stage, with chick-rearing birds exhibiting the highest free baseline CORT levels, while concurrently remaining the most resistant stage to nest desertion. Elevated free baseline CORT levels in chick-rearing birds were not due to increased total CORT secretion, but rather to a decrease in CBG levels. Overall, our results suggest that CORT and CBG interact to play a role in mediating the increased energetic demand of offspring, while minimizing the chances of nest desertion, thereby alleviating any potential behavioral conflict for CORT during reproduction. Furthermore, these results demonstrate that the traditional view of the role of CORT during reproduction is much more complex than previously appreciated. Together with mounting evidence, we suggest that elevated corticosteroid levels are an inherent and necessary part of reproduction in nonmammalian tetrapods.
Jablan, Jasna; Inić, Suzana; Stosnach, Hagen; Hadžiabdić, Maja Ortner; Vujić, Lovorka; Domijan, Ana-Marija
2017-05-01
The aim of the present study was to explore impact of endurance exercise on urinary level of minerals and trace elements as well as on some oxidative stress and biochemical parameters. Urine samples were collected from participants (n=21) of mountain ultra-marathon race (53km; Medvednica, Zagreb, Croatia), before (baseline value), immediately after, 12h and 24h after the race. In urine samples level of minerals (Ca, P, K and Na) and trace elements (Se, Zn, Mn, Cu, Fe and Co) were assessed using the bench top Total reflection X-ray Fluorescence (TXRF) spectrometer. Oxidative stress was determined as level of malondialdehyde (MDA). Immediately after the race level of minerals, trace elements, MDA, creatinine, ketones, erythrocytes and specific gravity increased compared to their baseline value. In 24h follow-up trace elements involved in antioxidant defence, MDA and biochemical parameters returned to their baseline values, Cu and Co remained increased as after the race, Fe and K tended to return to baseline values while Ca, P and Na continued to increase. Mountain ultra-marathon resulted in alteration of physiologically important minerals and trace elements that for some minerals and trace elements persist, indicating their involvement in recovery processes. However, due to their loss in urine, level of minerals and trace elements in athletes participating in endurance exercise should be monitored. Copyright © 2017 Elsevier GmbH. All rights reserved.
Cardiovascular responses to energy drinks in a healthy population: The C-energy study.
Kozik, Teri M; Shah, Sachin; Bhattacharyya, Mouchumi; Franklin, Teresa T; Connolly, Therese Farrell; Chien, Walter; Charos, George S; Pelter, Michele M
2016-07-01
Energy drink consumption has increased significantly over the past decade and is associated with greater than 20,000 emergency department visits per year. Most often these visits are due to cardiovascular complaints ranging from palpitations to cardiac arrest. To determine if energy drinks alter; blood pressure, electrolytes, activated bleeding time (ACT), and/or cardiac responses measured with a 12-lead electrocardiographic (ECG) Holter. Continuous ECG data was collected for five hours (30 minutes baseline and 4 hours post consumption [PC]). Subjects consumed 32 ounces of energy drink within one hour and data (vital signs and blood samples) was collected throughout the study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data. Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (baseline=132, ±7.83; PC=151, ±11.21; P=.001); QTc interval (baseline=423, ±22.74; PC=503, ±24.56; P<.001); magnesium level (baseline 2.04, ± 0.09; PC=2.13, ±0.15; P=.05); and calcium level (baseline=9.31, ±.28; PC=9.52, ±.22; P=.018) significantly increased from baseline. While potassium and ACT fluctuated (some subjects increased their levels while others decreased) these changes were not significant. Eight of the fourteen subjects (57%) developed a QTc >500 milliseconds PC. Other T-wave changes were noted in 9/14 (64.3%) subjects PC. Energy drinks increased systolic blood pressure, altered electrolytes, and resulted in repolarization abnormalities. These physiological responses can lead to arrhythmias and other abnormal cardiac responses highlighting the importance that emergency room personnel assess for energy drink consumption and potential toxicity. Copyright © 2016. Published by Elsevier Inc.
The effects of response cost and response restriction on a multiple-response repertoire with humans
Crosbie, John
1993-01-01
In two experiments a multiple-response repertoire of four free-operant responses was developed with university students as subjects using monetary gain as reinforcement. Following baseline, one of the responses was reduced either by making monetary loss contingent upon it (response cost) or by removing it from the repertoire (response restriction). In Experiment 1 a multielement baseline design was employed in which baseline and restriction or response-cost contingencies alternated semirandomly every 3 minutes. In Experiment 2 a reversal design was employed (i.e., baseline, restriction or response cost, then baseline), and each response required a different amount of effort. Both experiments had the following results: (a) The target response decreased substantially; (b) most nontarget responses increased, and the rest remained near their baseline levels; and (c) no support was found for Dunham's hierarchical, most frequent follower, or greatest temporal similarity rules. For several subjects, the least probable responses during baseline increased most, and the most probable responses increased least. Furthermore, in Experiment 2, responses with the lowest frequency of reinforcement increased most (for all 7 subjects), and those with the greatest frequency of reinforcement increased least (for 5 subjects). PMID:16812683
Pepper, Ruth J; Draibe, Juliana B; Caplin, Ben; Fervenza, Fernando C; Hoffman, Gary S; Kallenberg, Cees G M; Langford, Carol A; Monach, Paul A; Seo, Philip; Spiera, Robert; William St Clair, E; Tchao, Nadia K; Stone, John H; Specks, Ulrich; Merkel, Peter A; Salama, Alan D
2017-01-01
S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment. © 2016, American College of Rheumatology.
Murawska-Cialowicz, E; Wojna, J; Zuwala-Jagiello, J
2015-12-01
Brain-derived neurotrophic factor (BDNF) is a protein that stimulates processes of neurogenesis, the survival of neurons and microglia, stimulates neuroplasticity, and takes part in the differentiation of cells developed in the hippocampus. BDNF is also released from skeletal muscles during exercise and can facilitate cross-talk between the nervous and muscular system. Irisin, the exercise hormone, is also released from skeletal muscles and is involved in oxidation processes in the organism. It is a vital issue from the point of view of prophylaxis and treatment through exercise of age-related diseases (e.g. senile dementia), obesity, type-2 diabetes. The aim of the study was to assess the changes in BDNF and irisin levels in young people after a 3-month CrossFit training program. At baseline and after the training, levels of BDNF and irisin were assayed before and after Wingate and progressive tests. Physical performance, body mass and composition, and muscle circumferences were also measured. There were noted: an improvement in aerobic capacity, an increase in VO2max, a reduction in adipose tissue percentage in women and an increase in LBM in all subjects. After CrossFit training the resting BDNF level increased significantly in all subjects while the resting level of irisin decreased in women, without changes in men. The resting level of BDNF at baseline was higher in men than in women. At baseline we observed an increased level of BDNF in women after Wingate and progressive tests, but in men only after the progressive test. After 3 months of CrossFit training the level of BDNF increased in all subjects, and also was higher in men than in women. In women we did not observe significant differences after both tests in comparison to rest. After the training BDNF was lower in men after Wingate and progressive tests than at rest. At baseline irisin level decreased in women after the Wingate and progressive tests. Changes in men were not observed after both tests. There were no differences in irisin levels between the baseline and 3 months after the training after Wingate and progressive tests. A beneficial influence of CrossFit training on the subjects' body composition, anaerobic capacity and cardiovascular fitness as well as an increase in BDNF makes it possible to assume that this type of training could have a very high application value, especially in a therapeutic process leading to improving a patient's wellbeing.
Adiponectin Levels and Longitudinal Changes in Metabolic Syndrome: The Healthy Twin Study.
Song, Yun-Mi; Lee, Kayoung; Sung, Joohon
2015-09-01
We investigated the association of plasma adiponectin levels with longitudinal changes in metabolic syndrome and the metabolic syndrome-related traits [insulin and homeostasis model assessment of insulin resistance (HOMA-IR)], as well as their genetic and environmental correlations. A total of 1030 Koreans (380 men and 650 women; 44.0 ± 12.7 years old) without diabetes of the Healthy Twin Study visited at baseline (2005-2010) and returned for a follow-up examination 3.7 ± 1.2 years later. Baseline plasma adiponectin, metabolic syndrome components [waist circumference (WC), glucose, blood pressure, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs)] and metabolic syndrome-related traits were measured at baseline and follow-up. After adjusting for age, sex, smoking, alcohol consumption, physical activity, caloric intake, education level, body mass index (BMI), family history of diabetes, and changes in BMI, 1 standard deviation increment in baseline adiponectin levels was associated with 38-63% lower odds of incident and persistent metabolic syndrome. After additionally adjusting for the baseline levels of each trait, baseline adiponectin levels were inversely associated with WC, blood pressure, insulin, HOMA-IR, and TGs values at follow-up. After adjusting for age, sex, and baseline values of each trait or sum of metabolic syndrome components, baseline adiponectin levels exhibited significantly inverse genetic and environmental correlations with insulin, HOMA-IR, and HDL-C values and the sum of metabolic syndrome components at follow-up. High adiponectin levels reduce the risk of developing metabolic syndrome and having persistent metabolic syndrome and increase of metabolic syndrome-related traits over time. These associations may be explained by pleiotropic genetic mechanisms.
Pretreatment data is highly predictive of liver chemistry signals in clinical trials.
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.
Parrish, Deidra D; Blevins, Meridith; Megazzini, Karen M; Shepherd, Bryan E; Mohammed, Mukhtar Y; Wester, C William; Vermund, Sten H; Aliyu, Muktar H
2014-04-01
We conducted a study to assess trends in haemoglobin recovery among HIV-infected patients initiated on zidovudine-based combination antiretroviral therapy (cART) stratified by baseline haemoglobin level. Haemoglobin data from non-pregnant adult patients initiating cART in rural north-central Nigeria between June 2009 and May 2011 were analysed using a linear mixed effects model to assess the interaction between time, zidovudine-containing regimen and baseline haemoglobin level on the outcome of subsequent haemoglobin level. Best-fit curves were created for baseline haemoglobin in the 10th, 25th, 75th and 90th percentiles. We included 313 patients with 736 measures of haemoglobin in the analysis (239 on zidovudine and 74 on non-zidovudine-containing regimens). Median haemoglobin increased over time in both groups, with differences in haemoglobin response over time related to baseline haemoglobin levels and zidovudine use (p = 0.003). The groups of patients on zidovudine at the 10th and 90th percentiles had downward sloping curves while all other groups had upward trending haemoglobin levels. Although haemoglobin levels increased overall for patients on zidovudine-containing regimens, for those in the 10th and 90th percentiles haemoglobin levels trended downward over time. These results have implications for decisions regarding when to initiate, switch from or avoid the use of zidovudine.
Strength training and physical activity in boys: a randomized trial.
Meinhardt, Udo; Witassek, Fabienne; Petrò, Renato; Fritz, Chris; Eiholzer, Urs
2013-12-01
In developed societies levels of daily physical activity (PA) among school-age children are decreasing. This implies risk factors for cardiovascular and metabolic diseases. Specific strategies to improve levels of PA are needed. In prepubertal boys there is evidence that strength training increases spontaneous PA outside of training. A total of 102 schoolchildren (age 10-14 years) in Switzerland were randomly assigned to physical education classes or to participate twice weekly at a guided strength training program for 19 weeks. Spontaneous PA energy expenditure (PAEE; 3axial accelerometry for 7 days), leg and arm strength, and body composition (dual energy radiograph absorptiometry) were measured at baseline, after 19 weeks of training intervention, and after 3 months of washout. There were no significant differences between the groups at baseline. In the intervention group, PAEE increased by 10% from baseline to end of training in boys (P = .02), but not in girls. Leg and arm strength were increased owing to training intervention in both boys and girls. All other variables were unchanged. Baseline PAEE was significantly negatively correlated with changes of PAEE. Targeted strength training significantly increases daily spontaneous PA behavior in boys. The less active children showed the greatest increase in spontaneous PAEE. Girls showed a similar increase in strength, but not in spontaneous PAEE. This may be explained by their earlier pubertal development. Strength training may be a promising strategy in schools to counteract decreasing levels of PA.
Shani, Michal; Vinker, Shlomo; Dinour, Dganit; Leiba, Merav; Twig, Gilad; Holtzman, Eliezer J; Leiba, Adi
2016-10-01
The risk associated with serum uric acid (SUA) levels within the normal range is unknown, especially among lean and apparently healthy adults. Evaluating whether high-normal SUA levels, 6.8 mg/dL and below, are associated with an increased diabetes risk, compared with low-normal SUA. This was a cohort study with 10 years of followup involving all clinics of the largest nationally distributed Health Maintenance Organization in Israel. Participants included 469,947 examinees, 40-70 years old at baseline, who had their SUA measured during 2002. We excluded examinees who had hyperuricemia (SUA > 6.8 mg/dL), impaired fasting glucose, overweight or obesity and chronic cardiovascular or renal disorders. The final cohort was composed of 30 302 participants. Participants were followed up to a new diagnosis of diabetes during the study period. Odds ratio of developing diabetes among participants with high-normal baseline SUA were compared with low-normal (2 ≤ uric acid < 3 and 3 ≤ uric acid < 4 in women and men, respectively). In a logistic regression model adjusted for age, body mass index, socioeconomic status, smoking, baseline estimated glomerular filtration rate, and baseline glucose, SUA levels of 4-5 mg/dL for women were associated with 61% increased risk for incident diabetes (95% confidence interval, 1.1-2.3). At the highest normal levels for women (SUA, 5-6 mg/dL) the odds ratio was 2.7 (1.8-4.0), whereas men had comparable diabetes risk at values of 6-6.8 mg/dL (hazard ratio, 1.35; 95% confidence interval, 0.9-2.1). SUA levels within the normal range are associated with an increased risk for new-onset diabetes among healthy lean women when compared with those with low-normal values.
Modeling Nonlinear Errors in Surface Electromyography Due To Baseline Noise: A New Methodology
Law, Laura Frey; Krishnan, Chandramouli; Avin, Keith
2010-01-01
The surface electromyographic (EMG) signal is often contaminated by some degree of baseline noise. It is customary for scientists to subtract baseline noise from the measured EMG signal prior to further analyses based on the assumption that baseline noise adds linearly to the observed EMG signal. The stochastic nature of both the baseline and EMG signal, however, may invalidate this assumption. Alternately, “true” EMG signals may be either minimally or nonlinearly affected by baseline noise. This information is particularly relevant at low contraction intensities when signal-to-noise ratios (SNR) may be lowest. Thus, the purpose of this simulation study was to investigate the influence of varying levels of baseline noise (approximately 2 – 40 % maximum EMG amplitude) on mean EMG burst amplitude and to assess the best means to account for signal noise. The simulations indicated baseline noise had minimal effects on mean EMG activity for maximum contractions, but increased nonlinearly with increasing noise levels and decreasing signal amplitudes. Thus, the simple baseline noise subtraction resulted in substantial error when estimating mean activity during low intensity EMG bursts. Conversely, correcting EMG signal as a nonlinear function of both baseline and measured signal amplitude provided highly accurate estimates of EMG amplitude. This novel nonlinear error modeling approach has potential implications for EMG signal processing, particularly when assessing co-activation of antagonist muscles or small amplitude contractions where the SNR can be low. PMID:20869716
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.
Pătraș, Laura; Pap, Péter L.; Vincze, Orsolya; Mureșan, Cosmin; Németh, József; Lendvai, Ádám Z.
2018-01-01
Glucocorticoid (GC) hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long) as well as on their circulating levels (baseline vs. stress-induced). Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation) and physiological state (humoral innate immune system activity and oxidative balance). We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT) or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde) and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days) elevation of baseline CORT might have a positive and stimulatory effect on animal physiology. PMID:29432437
Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.
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.
Evidence for baseline glucocorticoids as mediators of reproductive investment in a wild bird.
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.
Nakajima, Kei; Suwa, Kaname
2015-01-01
Obese individuals with normal HbA1c levels and low-body-weight individuals with high-normal HbA1c levels are frequently encountered in clinical settings, but the effects of these phenotypes on the onset of diabetes are poorly understood. Therefore, we addressed this issue in a longitudinal study. We analyzed clinical parameters, including body mass index (BMI) and HbA1c levels, in 5325 non-diabetic Japanese people aged 20-75 years who underwent four medical checkups between 1999 (baseline) and 2007. The subjects were then classified into six baseline BMI categories, each of which was divided into two HbA1c groups, resulting in a total of 12 groups. In 405 obese subjects with a normal baseline HbA1c (BMI ≥ 27.0 kg/m(2), HbA1c 5.2-5.6%), the mean HbA1c level increased during the study period, and 50.9% developed prediabetes/diabetes. In contrast, in 77 low-body-weight subjects with a high-normal baseline HbA1c (BMI ≤ 18.9 kg/m(2), HbA1c 5.7-6.4%), the mean HbA1c level remained constant. Similar changes occurred in the other groups during the study, resulting in a linear increase in HbA1c levels with increasing BMI. Our results suggest that approximately half of the obese individuals with HbA1c in the normal range develop prediabetes or diabetes within 8 years, whereas low-body-weight individuals with high-normal HbA1c are less likely to exhibit worsening in glycemia. Thus, excess body weight may be the primary therapeutic target to prevent the early onset of diabetes, regardless of the individual's HbA1c.
Increased exhaled breath condensate 8-isoprostane after a swimming session in competitive swimmers.
Morissette, Mathieu C; Murray, Nicolas; Turmel, Julie; Milot, Julie; Boulet, Louis-Philippe; Bougault, Valérie
2016-08-01
This study aimed to evaluate the levels of 8-isoprostane (8-IsoP) in the airways of competitive swimmers at baseline and after a swimming session according to their airway responsiveness. Twenty-three swimmers and six lifeguards had a baseline spirometry and bronchoprovocative challenges. During a second visit, swimmers performed a usual swimming session while lifeguards stayed in the same pool environment for the same time period. Forced expiratory volume in one second (FEV1) was measured before and 5 min after the end of the session. Exhaled breath condensate (EBC) was sampled before and 10 min after the session and EBC 8-IsoP levels were analysed by enzyme immunoassay. Change in EBC 8-IsoP from baseline to post-swimming session was calculated. We observed no relationships between airway hyper-responsiveness and 8-IsoP values before or after swimming in swimmers. The levels of 8-IsoP were significantly higher after the training session (mean value 2.9, s = 0.5 pg mL(-1)) than at baseline (mean value 1.9, s = 0.4 pg mL(-1)) in swimmers only (p = .012). EBC 8-IsoP levels after the swimming session significantly correlated with the percent change in FEV1 after swimming. EBC 8-IsoP levels were increased after training in swimmers but not in lifeguards, suggesting that exercise-induced hyperpnoea in a chlorinated pool environment increases airways oxidative stress.
Quanjer, Philip H; Ruppel, Gregg L; Langhammer, Arnulf; Krishna, Abhishek; Mertens, Frans; Johannessen, Ane; Menezes, Ana M B; Wehrmeister, Fernando C; Perez-Padilla, Rogelio; Swanney, Maureen P; Tan, Wan C; Bourbeau, Jean
2017-05-01
Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment. BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV 1 , FVC, and FEV 1 /FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score. Change (Δ) in FEV 1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV 1 was significantly lower in African Americans. In 1,106 subjects with low FEV 1 (200-1,621 mL) the FEV 1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. ΔFEV 1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction. Expressing FEV 1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV 1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Viitasalo, A; Pihlajamaki, J; Lindi, V; Atalay, M; Kaminska, D; Joro, R; Lakka, T A
2015-04-01
PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.
Job strain and changes in the body mass index among working women: A prospective study
Fujishiro, Kaori; Lawson, Christina C.; Hibert, Eileen Lividoti; Chavarro, Jorge E.; Rich-Edwards, Janet W.
2015-01-01
Objectives The relationship between job strain and weight gain has been unclear, especially for women. Using data from over 52 000 working women, we compare the association between change in job strain and change in BMI across different levels of baseline BMI. Subjects/Methods We used data from participants in the Nurses’ Health Study II (n=52 656, mean age = 38.4), an ongoing prospective cohort study. Using linear regression, we modeled the change in BMI over 4 years as a function of the change in job strain, baseline BMI, and the interaction between the two. Change in job strain was characterized in four categories combining baseline and follow-up levels: consistently low strain [low at both points], decreased strain [high strain at baseline only], increased strain [high strain at follow-up only], and consistently high strain [high at both points]. Age, race/ethnicity, pregnancy history, job types, and health behaviors at baseline were controlled for in the model. Results In adjusted models, women who reported high job strain at least once during the four-year period had a greater increase in BMI (ΔBMI=0.06–0.12, p<0.05) than those who never reported high job strain. The association between the change in job strain exposure and the change in BMI depended on the baseline BMI level (p=0.015 for the interaction): the greater the baseline BMI, the greater the BMI gain associated with consistently high job strain. The BMI gain associated with increased or decreased job strain was uniform across the range of baseline BMI. Conclusions Women with higher BMI may be more vulnerable to BMI gain when exposed to constant work stress. Future research focusing on mediating mechanisms between job strain and BMI change should explore the possibility of differential responses to job strain by initial BMI. PMID:25986779
Effect of vitamin D replacement on immunological biomarkers in patients with multiple sclerosis.
Mrad, May F; El Ayoubi, Nabil K; Esmerian, Maria O; Kazan, Jalal M; Khoury, Samia J
2017-08-01
We aimed to investigate the immunologic effects of vitamin D replacement in RRMS patients. In a controlled single center study, patients deficient in 25-hydroxyvitamin D (serum level<25ng/ml) received 10,000IU/week cholecalciferol for 3months. Sufficient vitamin D patients (serum level>35ng/ml) were followed for the same period. Assessments were performed at baseline and at 3months. 25-hydroxyvitamin D levels increased significantly from baseline to month-3 in the deficient group after treatment and remained stable in the sufficient group. We observed a decreased interferon-γ (IFNγ) secretion by CD4 + T cells in vitamin D deficient group but not in the sufficient group, and a negative correlation between baseline serum vitamin D and IFNγ production. There was no change in the frequency of T helper or regulatory T cell subsets in either group. Increasing serum levels of 25-hydroxyvitamin D are associated with decreased production of IFNγ by CD4 + T cells. Copyright © 2017 Elsevier Inc. All rights reserved.
Reinforcement and substitution in humans: a multiple-response analysis1
Bernstein, Daniel J.; Ebbesen, Ebbe B.
1978-01-01
Three adult human subjects engaged in activities such as reading, sewing, artwork, and candlemaking while living alone in a laboratory apartment 24 hours per day for several weeks. After a baseline period in which the activities were fully available, access to a particular activity (contingent response) was made dependent on engaging in another less-preferred activity (instrumental response). The contingencies produced substantial increases in instrumental responding, and responding decreased toward baseline levels when the dependency was removed. Under the contingent conditions, time earned for the concurrent activity was always less than the baseline level. To determine the contribution of this reduction to the instrumental increase, access to the contingent activity was restricted in the absence of any dependency. The results indicated that increases among responses that filled the newly available time could be selective, e.g., artwork increased when reading was restricted but candlemaking did not. It was concluded that the reductions in the contingent response that accompany contingencies usually do not exclusively determine instrumental increases, but selective increases can contribute to the increase in time devoted to the instrumental response. PMID:16812105
Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70
Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander
2006-01-01
Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596
Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.
Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander
2005-03-01
Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.
Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M
2016-10-01
Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Finne, Live Bakke; Christensen, Jan Olav; Knardahl, Stein
2016-01-01
Occupational health research has mainly addressed determinants of negative health effects, typically employing individual-level self-report data. The present study investigated individual- and department-level (means of each work unit) effects of psychological/social work factors on mental distress and positive affect. Employees were recruited from 63 Norwegian organizations, representing a wide variety of job types. A total of 4158 employees, in 918 departments, responded at baseline and at follow-up two years later. Multilevel linear regressions estimated individual- and department-level effects simultaneously, and accounted for clustering of data. Baseline exposures and average exposures over time ([T1+T2]/2) were tested. All work factors; decision control, role conflict, positive challenge, support from immediate superior, fair leadership, predictability during the next month, commitment to organization, rumors of change, human resource primacy, and social climate, were related to mental distress and positive affect at the individual and department level. However, analyses of baseline exposures adjusted for baseline outcome, demonstrated significant associations at the individual level only. Baseline "rumors of change" was related to mental distress only and baseline "predictability during the next month" was not a statistical significant predictor of either outcome when adjusted for outcome at baseline. Psychological and social work factors were generally related to mental distress and positive affect in a mirrored way. Impact of exposures seemed most pervasive at the individual level. However, department-level relations were also discovered. Supplementing individual-level measures with aggregated measures may increase understanding of working conditions influence on employees`health and well-being. Organizational improvements focusing on the work factors in the current study should be able to reduce distress and enhance positive affect. Furthermore, both targeting individual employees and redesigning working conditions at the work unit level seems important.
Klaphake, Eric; Fecteau, Kellie; DeWit, Martine; Greenacre, Cheryl; Grizzle, Judith; Jones, Michael; Zagaya, Nancy; Abney, L Kim; Oliver, Jack
2009-12-01
The luteinizing hormone-releasing hormone agonist leuprolide acetate is used commonly to anage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plas a and fecal hormone levels in a psittacine species, a single 800 microg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17beta-estradiol and androstenedione levels and fecal 17beta-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17beta-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17beta-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17beta-estradiol, and fecal 17beta-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.
Kyle, Simon D; Miller, Christopher B; Rogers, Zoe; Siriwardena, A Niroshan; Macmahon, Kenneth M; Espie, Colin A
2014-02-01
To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Within-subject, noncontrolled treatment investigation. Sleep research laboratory. Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia.
Sun, Fei; Park, Nan Sook; Wardian, Jana; Lee, Beom S; Roff, Lucinda L; Klemmack, David L; Parker, Michael W; Koenig, Harold G; Sawyer, Patricia L; Allman, Richard M
2013-11-01
This study focuses on the identification of multiple latent trajectories of pain intensity, and it examines how religiousness is related to different classes of pain trajectory. Participants were 720 community-dwelling older adults who were interviewed at four time points over a 3-year period. Overall, intensity of pain decreased over 3 years. Analysis using latent growth mixture modeling (GMM) identified three classes of pain: (1) increasing ( n = 47); (2) consistently unchanging ( n = 292); and (3) decreasing ( n = 381). Higher levels of intrinsic religiousness (IR) at baseline were associated with higher levels of pain at baseline, although it attenuated the slope of pain trajectories in the increasing pain group. Higher service attendance at baseline was associated with a higher probability of being in the decreasing pain group. The increasing pain group and the consistently unchanging group reported more negative physical and mental health outcomes than the decreasing pain group.
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.
Irisin in response to acute and chronic whole-body vibration exercise in humans.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Castaldini, C.; DeRosier, R.; Waterland, L.R.
1986-02-01
The report discusses emission results from comprehensive flue-gas sampling of a gas- and oil-fired industrial boiler equipped with Exxon's Thermal DeNOx Ammonia Injection Process for NOx reduction. Comprehensive emission measurements included continuous monitoring of flue gas emissions; source assessment sampling system (SASS) tests; EPA Method 5/17 for solid and condensible particulate emissions and ammonia emissions; controlled condensation system for SO2 and SO3; and N2O emission sampling. Ammonia injection at a NH3/NO molar ratio of 2.52 gave a NOx reduction of 41% from an uncontrolled level of 234 ppm to a controlled level of 137 ppm. NH3 emissions increased from 11more » ppm for the baseline to an average of 430 ppm for ammonia injection. Nitrous oxide, N2O, was reduced 68% from a 50 ppm baseline level to a 17 ppm controlled level. Total particulate emissions increased by an order of magnitude from a baseline of 17.7 ng/J to a controlled level of 182 ng/J.« less
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.
Frederiksen, Thomas W.; Ramlau-Hansen, Cecilia H.; Stokholm, Zara A.; Grynderup, Matias B.; Hansen, Åse M.; Kristiansen, Jesper; Vestergaard, Jesper M.; Bonde, Jens P.; Kolstad, Henrik A.
2017-01-01
Aims: To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. Materials and Methods: In 2001–2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009–2010, we were able to follow up on 271 out of the 554 baseline workers (49%). Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Results: Over the 10-year period, mean noise levels declined from 83.9 dB(A) to 82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (−0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): −0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). Conclusions: We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs. PMID:29192620
Frederiksen, Thomas W; Ramlau-Hansen, Cecilia H; Stokholm, Zara A; Grynderup, Matias B; Hansen, Åse M; Kristiansen, Jesper; Vestergaard, Jesper M; Bonde, Jens P; Kolstad, Henrik A
2017-01-01
To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. In 2001-2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009-2010, we were able to follow up on 271 out of the 554 baseline workers (49%). Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Over the 10-year period, mean noise levels declined from 83.9 dB(A) to 82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (-0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): -0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs.
Nest predation and circulating corticosterone levels within and among species
Fontaine, Joseph J.; Arriero, Elena; Schwabl, Hubert; Martin, Thomas E.
2011-01-01
Variation in the risk of predation to offspring can influence the expression of reproductive strategies both within and among species. Appropriate expression of reproductive strategies in environments that differ in predation risk can have clear advantages for fitness. Although adult-predation risk appears to influence glucocorticosteroid levels, leading to changes in behavioral and life-history strategies, the influence of offspring-predation risk on adult glucocorticosteroid levels remains unclear. We compared total baseline corticosterone concentrations in Gray-headed Juncos (Junco hyemalis dorsalis) nesting on plots with and without experimentally reduced risk of nest predation. Despite differences in risk between treatments, we failed to find differences in total baseline corticosterone concentrations. When we examined corticosterone concentrations across a suite of sympatric species, however, higher risk of nest predation correlated with higher total baseline corticosterone levels. As found previously, total baseline corticosterone was negatively correlated with body condition and positively correlated with date of sampling. However, we also found that corticosterone levels increased seasonally, independent of stage of breeding. Nest predation can alter the expression of birds' reproductive strategies, but our findings suggest that total baseline corticosterone is not the physiological mechanism regulating these responses.
Nest predation and circulating corticosterone levels within and among species
Fontaine, J.J.; Arriero, E.; Schwabl, H.; Martin, T.E.
2011-01-01
Variation in the risk of predation to offspring can influence the expression of reproductive strategies both within and among species. Appropriate expression of reproductive strategies in environments that differ in predation risk can have clear advantages for fitness. Although adult-predation risk appears to influence glucocorticosteroid levels, leading to changes in behavioral and life-history strategies, the influence of offspring-predation risk on adult glucocorticosteroid levels remains unclear. We compared total baseline corticosterone concentrations in Gray-headed Juncos (Junco hyemalis dorsalis) nesting on plots with and without experimentally reduced risk of nest predation. Despite differences in risk between treatments, we failed to find differences in total baseline corticosterone concentrations. When we examined corticosterone concentrations across a suite of sympatric species, however, higher risk of nest predation correlated with higher total baseline corticosterone levels. As found previously, total baseline corticosterone was negatively correlated with body condition and positively correlated with date of sampling. However, we also found that corticosterone levels increased seasonally, independent of stage of breeding. Nest predation can alter the expression of birds' reproductive strategies, but our findings suggest that total baseline corticosterone is not the physiological mechanism regulating these responses. ?? The Cooper Ornithological Society 2011.
Pretreatment data is highly predictive of liver chemistry signals in clinical trials
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
Anxiety and stress can predict pain perception following a cognitive stress.
Hoeger Bement, Marie; Weyer, Andy; Keller, Manda; Harkins, April L; Hunter, Sandra K
2010-08-04
Hoeger Bement, M.K., A. Weyer, M. Keller, A. Harkins, and S.K. Hunter. Anxiety and stress can predict pain perception following a cognitive stressor. PHYSIOL BEHAV 000-000. The purpose of this study was to investigate the influence of a cognitive stressor on pain perception and determine individual characteristics that may predict the pain response. Twenty-five subjects participated in three sessions: one familiarization and two experimental. The experimental sessions involved measurement of pain perception before and after 1) mental math tasks (stressor session) and 2) quiet rest (control session). Pain threshold and ratings were assessed with a mechanical noxious stimulus. Changes in stress and anxiety were examined with self-reported and physiological measures including questionnaires, visual analogue scales, and salivary cortisol levels. During the control session, stress and anxiety decreased and pain reports remain unchanged. During the stressor session, stress and anxiety increased and pain reports were variable among subjects. Based on the pain response to mental math, subjects were divided into three groups (increase, decrease or no change in pain). The increase-pain group (n=8) had lower baseline stress and anxiety, lower baseline pain reports, and large anxiety response following the mental math. In contrast, the decrease-pain group (n=9) had higher baseline stress and anxiety levels, higher baseline pain reports, and a large increase in cortisol levels. Thus, the differential response in the changes in pain perception was related to anxiety and stress levels prior to and during the cognitive stressor, indicating that psychosocial characteristics can help determine the stress-induced pain response. Copyright 2010 Elsevier Inc. All rights reserved.
Weng, Ting-Chia; Chang, Chia-Hsuin; Dong, Yaa-Hui; Chang, Yi-Cheng; Chuang, Lee-Ming
2015-01-01
Objective To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12 and folate levels. Data collection and analysis Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. Results Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. Conclusions RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range. PMID:26185175
Short-term effects of a high nitrate diet on nitrate metabolism in healthy individuals.
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.
Kimura, Utako; Kinoshita, Ayako; Osawa, Aki; Negi, Osamu; Haruna, Kunitaka; Mizuno, Yuki; Suga, Yasushi
2012-05-01
Ablative fractional laser skin resurfacing (FLSR) has recently been used for the amelioration of acne scars, and previous studies have shown clinical effectiveness. Despite its extensive use, few studies have focused on the associated changes in biophysical properties of the epidermis. Herein, we evaluate transepidermal water loss, sebum levels, skin hydration, and skin elasticity, following FLSR treatments with an Er:YSGG laser device (Pearl FractionalTM, Cutera Inc., Brisbane, CA), employing non-invasive measurements. Five Japanese patients with facial acne scars underwent one FLSR session. Some acne scars appeared to become less obvious as a consequence of the treatment. All patients were aware of a feeling of skin tightness in treated areas. Objective measurements on the lower lateral angle of the eye and on the inner cheeks were evaluated at baseline and at 3 days, 1 week, and 4 weeks after FLSR. Transepidermal water loss showed a significant two-fold (100%) increase at day 3, but had returned to almost the baseline level at week 4 in both areas. Sebum secretion showed a 50% increase at day 3, but had returned to the baseline level after day 7. Skin hydration showed a significant decrease at day 3, but had returned to the baseline level by day 7, and showed significant improvement at the end of the study. Skin elasticity (R2) was still at baseline on day 3, but showed some improvement--an increase of at least 30%--at the end of the study. Based on our findings, we believe that FLSR should be performed no more than once a month to allow sufficient time for the damaged skin to recover its barrier function in most areas of the face.
Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model
Ebersole, J L; Steffen, M J; Holt, S C; Kesavalu, L; Chu, L; Cappelli, D
2010-01-01
This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals. PMID:21070210
Predictors of Ibandronate Efficacy for the Management of Osteoporosis: A Meta-Regression Analysis
Ma, Zeren; Li, Yong; Zhou, Ming; Huang, Kedi; Hu, Hejun; Liu, Xiaoping; Xu, Xiaosheng
2016-01-01
Background Aim of the present study was to identify the predictors of ibandronate efficacy in subjects with osteoporosis or decreased bone mineral density (BMD). Method Several electronic databases were searched by using specific keywords for the acquisition of research articles reporting the efficacy of ibandronate in subjects with osteoporosis or decreased BMD. Metaregression analyses were carried out by using changes in the BMD of lumbar spine and total hip following ibandronate treatment as dependent (outcome) variables against several independent (explanatory) variables. Results Data were extracted from 34 studies (11,090 ibandronate treated subjects) which fulfilled eligibility criteria. A history of previous fracture/s was reported by 46% of these subjects. In overall population, longer treatment duration from 1 to 5 years, increasing age, history of previous fractures, lower baseline T score, and higher baseline levels of C-terminal telopeptide of type 1 collagen (CTX) predicted higher ibandronate efficacy in improving BMD of the lumbar spine as well as of the total hip. Lower baseline levels of vitamin D and higher baseline levels of bone specific alkaline phosphatase (BSAP) predicted higher efficacy of ibandronate for lumbar spine only. In postmenopausal women with osteoporosis or decreased BMD, in addition to above-mentioned predictors, better efficacy of ibandronate was also associated with increasing time since menopause for both lumbar spine and total hip and lower body weight for lumbar spine only. Conclusion Longer treatment duration from 1 to 5 years, increasing age, lower baseline T scores, and higher serum CTX levels are identified as the predictors of better efficacy of ibandronate in the study subjects with osteoporosis or decreased BMD. PMID:26930292
Quicke, Jonathan G; Foster, Nadine E; Ogollah, Reuben O; Croft, Peter R; Holden, Melanie A
2017-08-01
To investigate how attitudes and beliefs about exercise relate to physical activity behavior in older adults with knee pain attributable to osteoarthritis (OA). We conducted secondary data analyses of a randomized controlled trial of exercise interventions (ISRCTN: 93634563). Participants were adults ≥45 years old with knee pain attributable to OA (n = 514). Crude and adjusted cross-sectional and longitudinal associations between baseline Self-Efficacy for Exercise (SEE), Positive Outcome Expectations for Exercise (POEE), Negative Outcome Expectations for Exercise scores, and physical activity level, at baseline, 3 months, and 6 months (measured by self-report using the Physical Activity Scale for the Elderly [PASE]), and important increases in physical activity level (from baseline to 6-month followup) were investigated using multiple linear and logistic regression. Cross-sectional associations were found between SEE and PASE scores (β = 4.14 [95% confidence interval (95% CI) 0.26, 8.03]) and POEE and PASE scores (β = 16.71 [95% CI 1.87, 31.55]), adjusted for sociodemographic and clinical covariates. Longitudinal associations were found between baseline SEE and PASE scores at 3 months (β = 4.95 [95% CI 1.02, 8.87]) and 6 months β = 3.71 (0.26, 7.16), and baseline POEE and PASE at 3 months (β = 34.55 [95% CI 20.13, 48.97]) and 6 months (β = 25.74 [95% CI 11.99, 39.49]), adjusted for baseline PASE score and intervention arm. However, no significant associations with important increases in physical activity level were found. Greater exercise self-efficacy and more positive exercise outcome expectations were associated with higher current and future physical activity levels. These may be targets for interventions aimed at increasing physical activity. © 2017 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
Foster, Nadine E.; Ogollah, Reuben O.; Croft, Peter R.; Holden, Melanie A.
2017-01-01
Objective To investigate how attitudes and beliefs about exercise relate to physical activity behavior in older adults with knee pain attributable to osteoarthritis (OA). Methods We conducted secondary data analyses of a randomized controlled trial of exercise interventions (ISRCTN: 93634563). Participants were adults ≥45 years old with knee pain attributable to OA (n = 514). Crude and adjusted cross‐sectional and longitudinal associations between baseline Self‐Efficacy for Exercise (SEE), Positive Outcome Expectations for Exercise (POEE), Negative Outcome Expectations for Exercise scores, and physical activity level, at baseline, 3 months, and 6 months (measured by self‐report using the Physical Activity Scale for the Elderly [PASE]), and important increases in physical activity level (from baseline to 6‐month followup) were investigated using multiple linear and logistic regression. Results Cross‐sectional associations were found between SEE and PASE scores (β = 4.14 [95% confidence interval (95% CI) 0.26, 8.03]) and POEE and PASE scores (β = 16.71 [95% CI 1.87, 31.55]), adjusted for sociodemographic and clinical covariates. Longitudinal associations were found between baseline SEE and PASE scores at 3 months (β = 4.95 [95% CI 1.02, 8.87]) and 6 months β = 3.71 (0.26, 7.16), and baseline POEE and PASE at 3 months (β = 34.55 [95% CI 20.13, 48.97]) and 6 months (β = 25.74 [95% CI 11.99, 39.49]), adjusted for baseline PASE score and intervention arm. However, no significant associations with important increases in physical activity level were found. Conclusion Greater exercise self‐efficacy and more positive exercise outcome expectations were associated with higher current and future physical activity levels. These may be targets for interventions aimed at increasing physical activity. PMID:27696795
Garland, Eric L; Beck, Anna C; Lipschitz, David L; Nakamura, Yoshio
2015-06-01
Cancer survivors experience significant stress and diminished well-being long after treatment. Dispositional mindfulness is linked with salutary coping with stress and enhanced well-being, with potentially beneficial effects on stress-related hormones. In the present study, we evaluated dispositional mindfulness as a predictor of changes in waking salivary cortisol levels among a sample of cancer survivors. Mindfulness, well-being, and saliva samples were collected at baseline and at 4- and 12-week follow-ups. Latent growth curve analysis was conducted to examine baseline dispositional mindfulness as a predictor of changes in waking salivary cortisol over time, and regression analyses examined associations between well-being and cortisol. Findings indicated that cancer survivors who reported lower baseline levels of dispositional mindfulness exhibited increases in waking cortisol over time, whereas those who reported higher baseline dispositional mindfulness showed comparatively stable waking cortisol over the study period. Furthermore, increases in waking cortisol were associated with decreased well-being over the study period. This study provides preliminary evidence that cancer survivors with higher levels of dispositional mindfulness may be buffered from deleterious changes in cortisol secretion. Enhanced dispositional mindfulness may promote salutary neuroendocrine function among cancer survivors and thereby improve well-being during the survivorship process.
Amygdala Hyperactivity at Rest in Paranoid Individuals With Schizophrenia.
Pinkham, Amy E; Liu, Peiying; Lu, Hanzhang; Kriegsman, Michael; Simpson, Claire; Tamminga, Carol
2015-08-01
The amygdala's role in threat perception suggests that increased activation of this region may be related to paranoid ideation. However, investigations of amygdala function in paranoid individuals with schizophrenia, compared with both healthy individuals and nonparanoid individuals with schizophrenia, have consistently reported reduced task-related activation. The reliance of blood-oxygen-level-dependent functional MRI on a contrast between events and baseline, and the inability to quantitatively measure this baseline, may account for these counterintuitive findings. The present study tested for differences in baseline levels of amygdala activity in paranoid and nonparanoid individuals with schizophrenia using arterial spin labeling perfusion MRI. Resting cerebral blood flow (CBF) and task-related activation of the amygdala were measured in 25 healthy individuals, 16 individuals with schizophrenia who were actively paranoid at the time of scanning, and 16 individuals with schizophrenia who were not paranoid. Analysis of relative CBF values extracted from the amygdala bilaterally revealed significantly increased activity in the left amygdala in paranoid patient volunteers compared with healthy comparison subjects and nonparanoid patient volunteers. Increased CBF was also evident in the right amygdala but did not reach the level of statistical significance. Paranoid volunteers also showed significantly decreased task-related activation of the amygdala compared with the two other groups. These findings suggest that amygdala hyperactivation may underlie paranoia in schizophrenia. Additionally, the reported differences between paranoid and nonparanoid patient volunteers emphasize the importance of considering symptom-based subgroups and baseline levels of activity in future investigations of neural activation in schizophrenia.
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.
Histological outcomes of anal high-grade cytopredictions.
Roberts, Jennifer Margaret; Jin, Fengyi; Poynten, Isobel Mary; Law, Carmella; Templeton, David James; Thurloe, Julia Kathleen; Garland, Suzanne Marie; Grulich, Andrew Edwin; Farnsworth, Annabelle; Hillman, Richard John
2018-02-01
Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period. The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point. Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point. In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2018;126:136-44. © 2017 American Cancer Society. © 2017 American Cancer Society.
Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.
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.
Impact of Sea Level Rise on Storm Surge and Inundation in the Northern Gulf of Mexico
NASA Astrophysics Data System (ADS)
Veeramony, J.
2016-12-01
Assessing the impact of climate change on surge and inundation due to tropical cyclones is important for coastal adaptation as well as mitigation efforts. Changes in global climate increase vulnerability of coastal environments to the threat posed by severe storms in a number of ways. Both the intensity of future storms as well as the return periods of more severe storms are expected to increase signficantly. Increasing mean sea levels lead to more areas being inundated due to storm surge and bring the threat of inundation further inland. Rainfall associated with severe storms are also expected to increase substantially, which will add to the intensity of inland flooding and coastal inundation. In this study, we will examine the effects of sea level rise and increasing rainfall intensity using Hurricane Ike as the baseline. The Delft3D modeling system will be set up in nested mode, with the outermost nest covering the Gulf of Mexico. The system will be run in a coupled mode, modeling both waves and the hydrodynamics. The baseline simulation will use the atmospheric forcing which consists of the NOAA H*Wind (Powell et all 1998) for the core hurricane characteristics blended with reanalyzed background winds to create a smooth wind field. The rainfall estimates are obtained from TRMM. From this baseline, a set of simulations will be performed to show the impact of sea level rise and increased rainfall activity on flooding and inundation along theTexas-Lousiana coast.
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.
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.
Factors Associated with D-Dimer Levels in HIV-Infected Individuals
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
Martin, Anthony Richard; Coombes, Peter John; Harrison, Tracey Lee; Hugh Dunstan, R
2010-01-01
Microbial properties of harvested rainwater were assessed at two study sites at Newcastle on the east coast of Australia. The investigation monitored daily counts of heterotrophic bacteria (HPC), total coliforms and E. coli during a mid-winter month (July). Immediately after a major rainfall event, increases in bacterial loads were observed at both sites, followed by gradual reductions in numbers to prior baseline levels within 7 days. Baseline HPC levels ranged from 500-1000 cfu/mL for the sites evaluated, and the loads following rain peaked at 3590-6690 cfu/mL. Baseline levels of total coliforms ranged from 0-100 cfu/100 mL and peaked at 480-1200 cfu/100 mL following rain. At Site 1, there was no evidence of E. coli loading associated with the rain events assessed, and Site 2 had no detectable E.coli colonies at baseline, with a peak load of 17 cfu/100 mL following rain which again diminished to baseline levels. It was concluded that rainfall events contributed to the bacterial load in rainwater storage systems, but processes within the rainwater storage ensured these incoming loads were not sustained.
Suh, Joome; Sinclair, Elizabeth; Peterson, Julia; Lee, Evelyn; Kyriakides, Tassos C; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Price, Richard W; Gisslen, Magnus; Spudich, Serena
2014-12-03
Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Antiretroviral-naïve subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD)4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P <0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P <0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.
Addison, Christina L; Ding, Keyue; Seymour, Lesley; Zhao, Huijun; Laurie, Scott A; Shepherd, Frances A; Goss, Glenwood D; Bradbury, Penelope A
2015-11-01
Prognostic and predictive ability of circulating vascular endothelial growth factor (VEGF), stromal derived factor (SDF)-1α and soluble VEGF receptors (sVEGFR) 2 and 3, were evaluated in non-small cell lung cancer (NSCLC) patients enrolled in NCIC Clinical Trials Group BR. 24 comparing chemotherapy with or without cediranib. Biomarker levels were assessed by ELISA in serum from 149/296 enrolled patients at baseline and 146/149 patients after one treatment cycle. Experimental cut-offs for baseline measures determined using a graphic method were: < or ≥1 ng/ml, SDF-1α: ≤ or >3.5 ng/ml, sVEGFR2: < or ≥11 ng/ml and sVEGFR3: < or ≥35.5 ng/ml. Changes in markers from baseline to on-treatment were predefined as increased ≥10%, stable within 10% or decreased ≥10%. Cox regression models were used to correlate biomarkers with patient characteristics and outcomes including progression-free survival (PFS) and overall survival (OS). No baseline biomarker was prognostic for OS, however, high baseline sVEGFR2 was prognostic for better PFS (p=0.0008) in the chemotherapy alone arm. Low baseline sVEGFR2 or sVEGFR3 were predictive of PFS benefit from cediranib (interaction p=0.06 and p=0.05, respectively). While on treatment, VEGF-A increases were associated with better PFS (p=0.02) and OS (p=0.01) for cediranib treated patients. Decreases in sVEGFR2 (p=0.01) or sVEGFR3 (p=0.02) were also predictive of better OS in cediranib treated patients. Low baseline sVEGFR2 and sVEGFR3 were predictive for PFS benefit from cediranib, whereas increases in VEGF-A and decreases in sVEGFR2 or sVEGFR3 levels from baseline to on-treatment were predictive of an OS benefit from cediranib in chemotherapy treated NSCLC patients. Validation of these results is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.
Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; DeFronzo, Ralph A
2014-06-01
Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. © 2014 by the American Diabetes Association.
Baseline Adiponectin Levels Do Not Influence the Response to Pioglitazone in ACT NOW
Tripathy, Devjit; Clement, Stephen C.; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Gastaldelli, Amalia; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Musi, Nicolas; Reaven, Peter D.
2014-01-01
OBJECTIVE Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. RESEARCH DESIGN AND METHODS A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. RESULTS Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. CONCLUSIONS Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. PMID:24705615
Increasing arousal enhances inhibitory control in calm but not excitable dogs
Bray, Emily E.; MacLean, Evan L.; Hare, Brian A.
2015-01-01
The emotional-reactivity hypothesis proposes that problem-solving abilities can be constrained by temperament, within and across species. One way to test this hypothesis is with the predictions of the Yerkes-Dodson law. The law posits that arousal level, a component of temperament, affects problem solving in an inverted U-shaped relationship: optimal performance is reached at intermediate levels of arousal and impeded by high and low levels. Thus, a powerful test of the emotional-reactivity hypothesis is to compare cognitive performance in dog populations that have been bred and trained based in part on their arousal levels. We therefore compared a group of pet dogs to a group of assistance dogs bred and trained for low arousal (N = 106) on a task of inhibitory control involving a detour response. Consistent with the Yerkes-Dodson law, assistance dogs, which began the test with lower levels of baseline arousal, showed improvements when arousal was artificially increased. In contrast, pet dogs, which began the test with higher levels of baseline arousal, were negatively affected when their arousal was increased. Furthermore, the dogs’ baseline levels of arousal, as measured in their rate of tail wagging, differed by population in the expected directions. Low-arousal assistance dogs showed the most inhibition in a detour task when humans eagerly encouraged them while more highly aroused pet dogs performed worst on the same task with strong encouragement. Our findings support the hypothesis that selection on temperament can have important implications for cognitive performance. PMID:26169659
Increasing arousal enhances inhibitory control in calm but not excitable dogs.
Bray, Emily E; MacLean, Evan L; Hare, Brian A
2015-11-01
The emotional-reactivity hypothesis proposes that problem-solving abilities can be constrained by temperament, within and across species. One way to test this hypothesis is with the predictions of the Yerkes-Dodson law. The law posits that arousal level, a component of temperament, affects problem solving in an inverted U-shaped relationship: Optimal performance is reached at intermediate levels of arousal and impeded by high and low levels. Thus, a powerful test of the emotional-reactivity hypothesis is to compare cognitive performance in dog populations that have been bred and trained based in part on their arousal levels. We therefore compared a group of pet dogs to a group of assistance dogs bred and trained for low arousal (N = 106) on a task of inhibitory control involving a detour response. Consistent with the Yerkes-Dodson law, assistance dogs, which began the test with lower levels of baseline arousal, showed improvements when arousal was artificially increased. In contrast, pet dogs, which began the test with higher levels of baseline arousal, were negatively affected when their arousal was increased. Furthermore, the dogs' baseline levels of arousal, as measured in their rate of tail wagging, differed by population in the expected directions. Low-arousal assistance dogs showed the most inhibition in a detour task when humans eagerly encouraged them, while more highly aroused pet dogs performed worst on the same task with strong encouragement. Our findings support the hypothesis that selection on temperament can have important implications for cognitive performance.
Finne, Live Bakke; Christensen, Jan Olav; Knardahl, Stein
2016-01-01
Occupational health research has mainly addressed determinants of negative health effects, typically employing individual-level self-report data. The present study investigated individual- and department-level (means of each work unit) effects of psychological/social work factors on mental distress and positive affect. Employees were recruited from 63 Norwegian organizations, representing a wide variety of job types. A total of 4158 employees, in 918 departments, responded at baseline and at follow-up two years later. Multilevel linear regressions estimated individual- and department-level effects simultaneously, and accounted for clustering of data. Baseline exposures and average exposures over time ([T1+T2]/2) were tested. All work factors; decision control, role conflict, positive challenge, support from immediate superior, fair leadership, predictability during the next month, commitment to organization, rumors of change, human resource primacy, and social climate, were related to mental distress and positive affect at the individual and department level. However, analyses of baseline exposures adjusted for baseline outcome, demonstrated significant associations at the individual level only. Baseline “rumors of change” was related to mental distress only and baseline “predictability during the next month” was not a statistical significant predictor of either outcome when adjusted for outcome at baseline. Psychological and social work factors were generally related to mental distress and positive affect in a mirrored way. Impact of exposures seemed most pervasive at the individual level. However, department-level relations were also discovered. Supplementing individual-level measures with aggregated measures may increase understanding of working conditions influence on employees`health and well-being. Organizational improvements focusing on the work factors in the current study should be able to reduce distress and enhance positive affect. Furthermore, both targeting individual employees and redesigning working conditions at the work unit level seems important. PMID:27010369
O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam
2016-01-01
Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040
O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam
2016-10-01
Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.
Le Leu, Richard K; Winter, Jean M; Christophersen, Claus T; Young, Graeme P; Humphreys, Karen J; Hu, Ying; Gratz, Silvia W; Miller, Rosalind B; Topping, David L; Bird, Anthony R; Conlon, Michael A
2015-07-01
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O(6)MeG adducts relative to its baseline by 21% (P < 0.01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P < 0.001) and HRM + HAMSB (P < 0.05) diets when compared with their respective baseline levels, but was lower following the HRM + HAMSB diet compared with the HRM diet (P < 0.05). Relative to its baseline, the HRM + HAMSB diet increased the excretion of SCFA by over 20% (P < 0.05) and increased the absolute abundances of the Clostridium coccoides group (P < 0.05), the Clostridium leptum group (P < 0.05), Lactobacillus spp. (P < 0.01), Parabacteroides distasonis (P < 0.001) and Ruminococcus bromii (P < 0.05), but lowered Ruminococcus torques (P < 0.05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P < 0.01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O(6)MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
Stanford, Joseph B.; Murtaugh, Maureen A.; Greenwood, Jessica L.J.; Gren, Lisa H.; Hegmann, Kurt T.; Thiese, Matthew S.
2015-01-01
Objective To ascertain worker health characteristics and psychosocial factors associated with changes in body weight and total cholesterol (TC) among two production operation populations. Methods We performed descriptive and predictive analysis of questionnaire data and biomedical measurements from two prospective cohort studies. Our key outcomes were changes in weight, and TC over 5–10 years between baseline and exit assessments. Results 146 subjects were analyzed. Increases in weight were associated with belief in being overweight and baseline overweight and obesity. Increases in TC levels were associated with female gender, belief that TC levels were “not good,” and feeling depressed. Conclusion Most of the reported associations with increases in weight and TC levels are amenable to interventions and may be a target for workplace intervention programs. PMID:26147542
Sun, Fei; Park, Nan Sook; Wardian, Jana; Lee, Beom S.; Roff, Lucinda L.; Klemmack, David L.; Parker, Michael W.; Koenig, Harold G.; Sawyer, Patricia L.; Allman, Richard M.
2013-01-01
This study focuses on the identification of multiple latent trajectories of pain intensity, and it examines how religiousness is related to different classes of pain trajectory. Participants were 720 community-dwelling older adults who were interviewed at four time points over a 3-year period. Overall, intensity of pain decreased over 3 years. Analysis using latent growth mixture modeling (GMM) identified three classes of pain: (1) increasing (n = 47); (2) consistently unchanging (n = 292); and (3) decreasing (n = 381). Higher levels of intrinsic religiousness (IR) at baseline were associated with higher levels of pain at baseline, although it attenuated the slope of pain trajectories in the increasing pain group. Higher service attendance at baseline was associated with a higher probability of being in the decreasing pain group. The increasing pain group and the consistently unchanging group reported more negative physical and mental health outcomes than the decreasing pain group. PMID:24187410
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.
Martinucci, I; de Bortoli, N; Savarino, E; Piaggi, P; Bellini, M; Antonelli, A; Savarino, V; Frazzoni, M; Marchi, S
2014-04-01
Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs). Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times. Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p < 0.001). Evaluating baseline impedance levels in patients with heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus. © 2014 John Wiley & Sons Ltd.
A controlled HIV/AIDS-related health education programme in Managua, Nicaragua.
Pauw, J; Ferrie, J; Rivera Villegas, R; Medrano Martínez, J; Gorter, A; Egger, M
1996-05-01
To evaluate the impact of a community-wide intervention to increase HIV/AIDS-related knowledge, change attitudes and increase safer-sex practices in Managua, Nicaragua. Household-based health education intervention trial comprising a knowledge, attitudes and practices (KAP) survey at baseline, a health education intervention and a follow-up KAP survey. Four neighbourhoods were included, two received the intervention, and the other two served as controls. Randomly selected residents aged 15-45 years were interviewed at baseline (n = 2160) and follow-up (n = 2271) using an identical questionnaire. The intervention consisted of a health education campaign that emphasized HIV transmission and condom use. OUTCOME AND ANALYSIS: Knowledge levels regarding transmission and prevention of HIV infection, self-reported use of condoms, levels of worries about HIV/AIDS and perceptions of personal risk of HIV infection. Comparisons between baseline and follow-up employed chi 2 tests with continuity correction. The influence of the intervention was examined in multivariate logistic models including an appropriate interaction term. Intervention and control samples were comparable with regard to sex, age, and age at first intercourse. Significantly less intervention residents had formal education (P < 0.001). At baseline, outcome variables were generally similar in control and intervention samples. Condom use increased from 9 to 16% (P = 0.003) among intervention women, but only from 9 to 11% (P = 0.5) in control women (test for interaction, P = 0.08). Among men, increases were from 31 to 41% (P < 0.001) and from 30 to 37% (P = 0.06), respectively (test for interaction, P = 0.3). Levels of worries about HIV/AIDS decreased in all groups, but perception of individual risk increased only among intervention women (test for interaction, P = 0.02). This household-targeted health education intervention appears to have had some effect; however, sustained efforts are needed further to improve levels of knowledge and to increase condom use in Managua.
Short-Term Effects of a High Nitrate Diet on Nitrate Metabolism in Healthy Individuals
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
Kawamoto, R; Ninomiya, D; Kasai, Y; Senzaki, K; Kusunoki, T; Ohtsuka, N; Kumagi, T
2018-02-19
Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased serum uric acid (SUA) levels are associated with MetS and its components. However, whether baseline and changes in SUA predict incidence of MetS and its components remains unclear. The subjects comprised 407 women aged 71 ± 8 years from a rural village. We have identified participants who underwent a similar examination 11 years ago, and examined the relationship between baseline and changes in SUA, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report. Of these subjects, 83 (20.4%) women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS; both baseline and changes in SUA as well as history of cardiovascular disease, low-density lipoprotein cholesterol, and estimated glomerular filtration ratio (eGFR) were independently and significantly associated with the number of MetS components during an 11-year follow-up. The adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82-2.65), and 3.11 (1.66-5.83), and 1.00, 1.88 (1.03-3.40), and 2.49 (1.38-4.47), respectively. In addition, the combined effect between increased baseline and changes in SUA was also a significant and independent determinant for the accumulation of MetS components (F = 20.29, p < 0.001). The ORs for incident MetS were significant only in subjects with age ≥ 55 years, decline in eGFR, and no baseline MetS. These results suggested that combined assessment of baseline and changes in SUA levels provides increased information for incident MetS, independent of other confounding factors in community-dwelling women.
Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.
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.
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.
Pirat, Bahar; Korkmaz, Mehmet Emin; Eroğlu, Serpil; Tayfun, Egemen; Yildirir, Aylin; Uluçam, Melek; Ozin, Bülent; Müderrisoğlu, Haldun
2004-12-01
This study was designed to compare the effects of simvastatin versus a combination of simvastatin with vitamin C or E on serum lipid profile, particularly, high-density lipoprotein (HDL)-cholesterol (C) level, in patients with a low HDL-C level. Fifty-nine women and 49 men, who had a baseline HDL-C level equal to or lower than 40 mg/dl were randomized to one of the following study treatment groups: Group S (n=39) simvastatin 20 mg/day, Group S+C (n=33) simvastatin 20 mg/day + vitamin C 500 mg/day, and Group S+E (n=36) simvastatin 20 mg/day + vitamin E 400 IU/day. The groups' lipid profiles were obtained at baseline, 3rd and 6th months. Comparing with baseline values, total-C and low-density cholesterol (LDL-C) values significantly reduced (p<0.001) and HDL-C values significantly increased (Group S--33.9+/-3.9 mg/dl vs. 39.8+/-6.9 mg/dl, Group S+C--34.2+/-3.5 mg/dl vs. 38.1+/-6.1 mg/dl, Group S+E--33.1+/-3.6 mg/dl vs. 34.8+/-5.9 mg/dl, p<0.001) on therapy within the groups; however, there were no significant differences among the groups with regards to these parameters. The HDL-C levels increased from baseline by 14.0%, 11.7% and 10.2% in Group S, S+C, and S+E, respectively (p>0.05). A combination of simvastatin with antioxidant vitamins does not offer any beneficial effect over simvastatin alone. Particularly vitamin E seems to blunt the simvastatin induced HDL-C increase.
Epel, Elissa S.; Kristeller, Jean; Moran, Patricia J.; Dallman, Mary; Lustig, Robert H.; Acree, Michael; Bacchetti, Peter; Laraia, Barbara A.; Hecht, Frederick M.; Daubenmier, Jennifer
2016-01-01
We evaluated changes in mindful eating as a potential mechanism underlying the effects of a mindfulness-based intervention for weight loss on eating of sweet foods and fasting glucose levels. We randomized 194 obese individuals (M age = 47.0 ± 12.7 years; BMI = 35.5 ± 3.6; 78 % women) to a 5.5-month diet-exercise program with or without mindfulness training. The mindfulness group, relative to the active control group, evidenced increases in mindful eating and maintenance of fasting glucose from baseline to 12-month assessment. Increases in mindful eating were associated with decreased eating of sweets and fasting glucose levels among mindfulness group participants, but this association was not statistically significant among active control group participants. Twelve-month increases in mindful eating partially mediated the effect of intervention arm on changes in fasting glucose levels from baseline to 12-month assessment. Increases in mindful eating may contribute to the effects of mindfulness-based weight loss interventions on eating of sweets and fasting glucose levels. PMID:26563148
Mason, Ashley E; Epel, Elissa S; Kristeller, Jean; Moran, Patricia J; Dallman, Mary; Lustig, Robert H; Acree, Michael; Bacchetti, Peter; Laraia, Barbara A; Hecht, Frederick M; Daubenmier, Jennifer
2016-04-01
We evaluated changes in mindful eating as a potential mechanism underlying the effects of a mindfulness-based intervention for weight loss on eating of sweet foods and fasting glucose levels. We randomized 194 obese individuals (M age = 47.0 ± 12.7 years; BMI = 35.5 ± 3.6; 78% women) to a 5.5-month diet-exercise program with or without mindfulness training. The mindfulness group, relative to the active control group, evidenced increases in mindful eating and maintenance of fasting glucose from baseline to 12-month assessment. Increases in mindful eating were associated with decreased eating of sweets and fasting glucose levels among mindfulness group participants, but this association was not statistically significant among active control group participants. Twelve-month increases in mindful eating partially mediated the effect of intervention arm on changes in fasting glucose levels from baseline to 12-month assessment. Increases in mindful eating may contribute to the effects of mindfulness-based weight loss interventions on eating of sweets and fasting glucose levels.
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.
Effects of noradrenaline on human vagal baroreflexes
NASA Technical Reports Server (NTRS)
Airaksinen, K. E.; Huikuri, H. V.; Huhti, L.; Kuusela, T. A.; Tahvanainen, K. U.; Tulppo, M.; Makikallio, T.; Eckberg, D. L.
2001-01-01
BACKGROUND: Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function. AIM: To understand better the role of NA in cardiovascular homeostasis. METHODS: We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz. RESULTS: The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (+/- SD) baseline level of 17.3+/-6.6 to 34.1+/-20.8 ms/mmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0+/-12.9 to 10.1+/-7.4 during the low NA infusion rate and to 6.2+/-6.2% during the high rate (P < 0.05 and 0.01, respectively). CONCLUSIONS: Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.
Income inequality among American states and the incidence of major depression.
Pabayo, Roman; Kawachi, Ichiro; Gilman, Stephen E
2014-02-01
Although cross-sectional and ecological studies have shown that higher area-level income inequality is related to increased risk for depression, few longitudinal studies have been conducted. This investigation examines the relationship between state-level income inequality and major depression among adults participating in a population-based, representative longitudinal study. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=34 653). Respondents completed structured diagnostic interviews at baseline (2001-2002) and follow-up (2004-2005). Weighted multilevel modelling was used to determine if U.S. state-level income inequality (measured by the Gini coefficient) was a significant predictor of depression at baseline and at follow-up, while controlling for individual-level and state-level covariates. We also repeated the longitudinal analyses, excluding those who had a history of depression or at baseline, in order to test whether income inequality was related to incident depression. State-level inequality was associated with increased incidence of depression among women but not men. In comparison to women residing in states belonging to the lowest quintile of income inequality, women were at increased risk for depression in the second (OR=1.18, 95% CI 0.86 to 1.62), third (OR=1.22, 95% CI 0.91 to 1.62), fourth (OR=1.37, 95% CI 1.03 to 1.82) and fifth (OR=1.50, 95% CI 1.14 to 1.96) quintiles at follow-up (p<0.05 for the linear trend). Living in a state with higher income inequality increases the risk for the development of depression among women.
Rumination prospectively predicts executive functioning impairments in adolescents.
Connolly, Samantha L; Wagner, Clara A; Shapero, Benjamin G; Pendergast, Laura L; Abramson, Lyn Y; Alloy, Lauren B
2014-03-01
The current study tested the resource allocation hypothesis, examining whether baseline rumination or depressive symptom levels prospectively predicted deficits in executive functioning in an adolescent sample. The alternative to this hypothesis was also evaluated by testing whether lower initial levels of executive functioning predicted increases in rumination or depressive symptoms at follow-up. A community sample of 200 adolescents (ages 12-13) completed measures of depressive symptoms, rumination, and executive functioning at baseline and at a follow-up session approximately 15 months later. Adolescents with higher levels of baseline rumination displayed decreases in selective attention and attentional switching at follow-up. Rumination did not predict changes in working memory or sustained and divided attention. Depressive symptoms were not found to predict significant changes in executive functioning scores at follow-up. Baseline executive functioning was not associated with change in rumination or depression over time. Findings partially support the resource allocation hypothesis that engaging in ruminative thoughts consumes cognitive resources that would otherwise be allocated towards difficult tests of executive functioning. Support was not found for the alternative hypothesis that lower levels of initial executive functioning would predict increased rumination or depressive symptoms at follow-up. Our study is the first to find support for the resource allocation hypothesis using a longitudinal design and an adolescent sample. Findings highlight the potentially detrimental effects of rumination on executive functioning during early adolescence. Copyright © 2013 Elsevier Ltd. All rights reserved.
Rumination prospectively predicts executive functioning impairments in adolescents
Connolly, Samantha L.; Wagner, Clara A.; Shapero, Benjamin G.; Pendergast, Laura L.; Abramson, Lyn Y.; Alloy, Lauren B.
2014-01-01
Background and objectives The current study tested the resource allocation hypothesis, examining whether baseline rumination or depressive symptom levels prospectively predicted deficits in executive functioning in an adolescent sample. The alternative to this hypothesis was also evaluated by testing whether lower initial levels of executive functioning predicted increases in rumination or depressive symptoms at follow-up. Methods A community sample of 200 adolescents (ages 12–13) completed measures of depressive symptoms, rumination, and executive functioning at baseline and at a follow-up session approximately 15 months later. Results Adolescents with higher levels of baseline rumination displayed decreases in selective attention and attentional switching at follow-up. Rumination did not predict changes in working memory or sustained and divided attention. Depressive symptoms were not found to predict significant changes in executive functioning scores at follow-up. Baseline executive functioning was not associated with change in rumination or depression over time. Conclusions Findings partially support the resource allocation hypothesis that engaging in ruminative thoughts consumes cognitive resources that would otherwise be allocated towards difficult tests of executive functioning. Support was not found for the alternative hypothesis that lower levels of initial executive functioning would predict increased rumination or depressive symptoms at follow-up. Our study is the first to find support for the resource allocation hypothesis using a longitudinal design and an adolescent sample. Findings highlight the potentially detrimental effects of rumination on executive functioning during early adolescence. PMID:23978629
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.
Benfield, Rebecca D; Hortobágyi, Tibor; Tanner, Charles J; Swanson, Melvin; Heitkemper, Margaret M; Newton, Edward R
2010-07-01
Hydrotherapy (immersion or bathing) is used worldwide to promote relaxation and decrease parturient anxiety and pain in labor, but the psychophysiological effects of this intervention remain obscure. A pretest-posttest design with repeated measures was used to examine the effects of hydrotherapy on maternal anxiety and pain, neuroendocrine responses, plasma volume shift (PVS), and uterine contractions (CXs) during labor. Correlations among variables were examined at three time points (preimmersion and twice during hydrotherapy). Eleven term women (mean age 24.5 years) in spontaneous labor were immersed to the xiphoid in 37 degrees C water for 1 hr. Blood samples and measures of anxiety and pain were obtained under dry baseline conditions and repeated at 15 and 45 min of hydrotherapy. Uterine contractions were monitored telemetrically. Hydrotherapy was associated with decreases in anxiety, vasopressin (V), and oxytocin (O) levels at 15 and 45 min (all ps < .05). There were no significant differences between preimmersion and immersion pain or cortisol (C) levels. Pain decreased more for women with high baseline pain than for women with low baseline levels at 15 and 45 min. Cortisol levels decreased twice as much at 15 min of hydrotherapy for women with high baseline pain as for those with low baseline pain. beta-endorphin (betaE) levels increased at 15 min but did not differ between baseline and 45 min. During immersion, CX frequency decreased. A positive PVS at 15 min was correlated with contraction duration. Hydrotherapy during labor affects neuroendocrine responses that modify psychophysiological processes.
Lauri, Gianfranco; Rossi, Chiara; Rubino, Mara; Cosentino, Nicola; Milazzo, Valentina; Marana, Ivana; Cabiati, Angelo; Moltrasio, Marco; De Metrio, Monica; Grazi, Marco; Campodonico, Jeness; Assanelli, Emilio; Riggio, Daniela; Sandri, Maria Teresa; Bonomi, Alice; Veglia, Fabrizio; Marenzi, Giancarlo
2016-06-01
Pericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. We prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0-2), intermediate (3-4), or high (5-7) severity score. Out of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=-0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). The results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Arnold, L Eugene; Young, Andrea S; Belury, Martha A; Cole, Rachel M; Gracious, Barbara; Seidenfeld, Adina M; Wolfson, Hannah; Fristad, Mary A
2017-04-01
To examine fatty acid profiles, their response to omega-3 fatty acid (Ω3) supplementation, and associations with clinical status and treatment response in youth with mood disorders. In a placebo-controlled 2X2 design, 7-14 year-olds (N = 95) in parallel pilot trials (depression N = 72; bipolar N = 23) were randomly assigned to 12 weeks of Ω3 supplementation (1.4 g eicosapentaenoic acid [EPA], 0.2 g docosahexaenoic acid [DHA], and 0.27 g other Ω3 per day); psychoeducational psychotherapy (PEP); their combination; or placebo (mainly oleic and linoleic acid) alone. Blood was drawn at baseline (N = 90) and endpoint (n = 65). Fatty acid levels were expressed as percent of total plasma fatty acids. Correlational and moderator/mediator analyses were done with SPSS Statistics 23. At baseline: (1) DHA correlated negatively with alpha-linolenic acid (ALA) (r = -0.23, p = 0.029); (2) Arachidonic acid (AA, Ω6) correlated negatively with global functioning (r = -0.24, p = 0.022); (3) Total Ω3 correlated negatively with age (r = -0.22, p = 0.036) and diastolic blood pressure (r = -0.31, p = 0.006). Moderation: Baseline ALA moderated response to Ω3 supplementation: ALA levels above the sample mean (lower DHA) predicted significantly better placebo-controlled response (p = 0.04). Supplementation effects: Compared to placebo, 2 g Ω3 per day increased EPA blood levels sevenfold and DHA levels by half (both p < 0.001). Body weight correlated inversely with increased EPA (r = -0.52, p = 0.004) and DHA (r = -0.54, p = 0.003) and positively with clinical mood response. Mediation: EPA increase baseline-to-endpoint mediated placebo-controlled global function and depression improvement: the greater the EPA increase, the less the placebo-controlled Ω3 improvement. Ω3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored.
Jennings, Jeanine E; Ramkumar, Thiruvamoor; Mao, Jingnan; Boyd, Jessica; Castro, Mario; Field, Joshua J; Strunk, Robert C; DeBaun, Michael R
2008-08-01
Cysteinyl leukotrienes (CsyLTs) are inflammatory mediators produced by white blood cells. Leukotriene LTE(4) is the stable metabolite of CsyLTs, which can be measured in urine. We tested two hypotheses among children with sickle cell disease (SCD): (1) baseline urinary LTE(4) levels are elevated in children with SCD when compared with controls; and (2) baseline LTE(4) levels are associated with an increased incidence rate of hospitalization for SCD-related pain. Baseline LTE(4) levels were measured in children with SCD (cases) and children without SCD matched for age and ethnicity (controls). Medical records of cases were reviewed to assess the frequency of hospitalization for pain within 3 years of study entry. LTE(4) levels were obtained in 71 cases and 22 controls. LTE(4) levels were higher in cases compared with controls (median LTE(4): 100 vs. 57 pg/mg creatinine, P < 0.001). After adjustment for age and asthma diagnosis, a greater incidence rate of hospitalization for pain was observed among children with SCD in the highest LTE(4) tertile when compared with the lowest (114 vs. 52 episodes per 100 patient-years, P = 0.038). LTE(4) levels are elevated in children with SCD when compared with controls. LTE(4) levels are associated with an increased rate of hospitalizations for pain. Copyright 2008 Wiley-Liss, Inc.
Perry, Nicole B.; Nelson, Jackie A.; Swingler, Margaret M.; Leerkes, Esther M.; Calkins, Susan D.; Marcovitch, Stuart; O’Brien, Marion
2017-01-01
Trajectories of baseline RSA (respiratory sinus arrhythmia), an index of reactivity, and vagal withdrawal, an index of regulation, across the preschool period were examined. In addition, maternal emotional support was investigated as a potential time-varying predictor of these trajectories. Physiological measures were obtained during frustration tasks, and a maternal emotional support measure was assessed via maternal report and direct observation. Children’s baseline RSA and vagal withdrawal scores were moderately stable across the preschool period. Growth models indicated that children’s baseline RSA scores changed linearly over the preschool years, and there was significant variability in withdrawal trajectories. Greater maternal emotional support predicted higher initial withdrawal levels and lower emotional support was associated with the greatest increase in withdrawal over time. This suggests that children of higher emotionally supportive mothers reached higher levels of physiological regulation earlier in development and therefore did not show the same increase across preschool as children of less supportive mothers. Maternal emotional support was not significantly related to trajectories of baseline RSA. PMID:22573287
Instant Recess®: a practical tool for increasing physical activity during the school day.
Whitt-Glover, Melicia C; Ham, Sandra A; Yancey, Antronette K
2011-01-01
An increased prevalence of overweight/obesity among children has led to school district level policies to increase physical activity (PA) among elementary school students. Interventions are needed that increase activity levels without sacrificing time spent in academics. We evaluated a policy implementation intervention for to increase in-school PA in elementary schools in Forsyth County, North Carolina, in a randomized study with a delayed intervention control group. The study included third- through fifth-grade classrooms in eight elementary schools. Instant Recess® was used to introduce 10-minute PA breaks in classrooms on schedules determined by teachers. Direct observation was used to measure activity levels, other student behaviors, and teacher behaviors related to PA in the classrooms. Twenty-eight visits to schools were made during the spring and fall semesters of 2009. At baseline 11% to 44% of intervention and control schools were engaged in classroom-based PA. PA increased from baseline to spring follow-up in intervention schools and was maintained the following fall. Control schools decreased PA from baseline to spring and increased PA once they began the intervention. Students in classrooms engaged in Instant Recess exhibited statistically significant increases in light (51%) and moderate-intensity (16%) PA and increases in time spent in on-task behavior (11%). Control schools experienced similar benefits after they began implementing Instant Recess. Instant Recess is useful for increasing PA and improving behavior among elementary school children. Additional research may be needed to understand how to create policies supporting classroom activity breaks and how to assess policy adherence.
Lothery, Cassie J.; Thompson, Charles F.; Lawler, Megan L.; Sakaluk, Scott K.
2014-01-01
Incubating birds must allocate their time and energy between maintaining egg temperature and obtaining enough food to meet their own metabolic demands. We tested the hypothesis that female house wrens (Troglodytes aedon) face a trade-off between incubation and self-maintenance by providing females with supplemental food during incubation. We predicted that food supplementation would increase the amount of time females devoted to incubating their eggs, lower their baseline plasma corticosterone levels (a measure of chronic stress), and increase their body mass, haematocrit (a measure of anaemia), and reproductive success relative to control females. As predicted, food-supplemented females spent a greater proportion of time incubating their eggs than control females. Contrary to expectation, however, there was no evidence that food supplementation significantly influenced female baseline plasma corticosterone levels, body mass, haematocrit, or reproductive success. However, females with high levels of corticosterone at the beginning of incubation were more likely to abandon their nesting attempt after capture than females with low levels. Corticosterone significantly increased between the early incubation and early nestling stages of the breeding cycle in all females. These results suggest that although food supplementation results in a modest increase in incubation effort, it does not lead to significantly lower levels of chronic stress as reflected in lower baseline corticosterone levels. We conclude that female house wrens that begin the incubation period with low levels of plasma corticosterone can easily meet their own nutritional needs while incubating their eggs, and that any trade-off between incubation and self-feeding does not influence female reproductive success under the conditions at the time of our study. PMID:25184281
Tan, Z.; Lal, R.; Liu, S.
2006-01-01
Conservation management of croplands at the plot scale has demonstrated a great potential to mitigate the greenhouse effect through sequestration of atmospheric carbon (C) into soil. This study estimated the potential of soil to sequester C through the conversion of croplands from conventional tillage (CT) to no-till (NT) in the East Central United States between 1992 and 2012. This study used the baseline soil organic C (SOC) pool (SOCP) inventory and the empirical models that describe the relationships of the SOCP under CT and NT, respectively, to their baseline SOCP in the upper 30-cm depth of soil. The baseline SOCP were obtained from the State Soil Geographic database, and the cropland distribution map was generated from the 1992 National Land Cover Database. The results indicate that if all the croplands under CT in 1992 were converted to NT, the SOCP would increase by 16.8% by 2012, which results in a total C sink of 136 Tg after 20 years. A greater sequestration rate would occur in soils with lower baseline SOCP, but the sink strength would be weaker with increasing SOCP levels. The CT-induced C sources tend to become larger in soils with higher baseline levels, which can be significantly reduced by adopting NT. We conclude that baseline SOC contents are an indicator of C sequestration potential with NT practices. ?? 2006 Lippincott Williams & Wilkins, Inc.
Kyle, Simon D.; Miller, Christopher B.; Rogers, Zoe; Siriwardena, A. Niroshan; MacMahon, Kenneth M.; Espie, Colin A.
2014-01-01
Study Objectives: To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Design: Within-subject, noncontrolled treatment investigation. Setting: Sleep research laboratory. Participants: Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. Interventions: Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Measurement and results: Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). Conclusion: For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia. Citation: Kyle SD; Miller CB; Rogers Z; Siriwardena AN; MacMahon KM; Espie CA. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. SLEEP 2014;37(2):229-237. PMID:24497651
Xu, Min; Lv, Xiaofei; Xie, Lan; Huang, Xiaolin; Huang, Ya; Chen, Ying; Peng, Kui; Wang, Po; Wang, Weiqing; Qi, Lu; Bi, Yufang; Sun, Yimin; Ning, Guang
2016-02-01
Glucokinase regulatory protein gene (GCKR) variant rs780092 is a novel genetic variant associated with serum triacylglycerol (TG) identified in a genome-wide association study in East Asians. We aimed to investigate associations of rs780092 with incident type 2 diabetes and dyslipidaemia, and the longitudinal changes in glucose and lipid levels. A community-based prospective cohort study was conducted at baseline in 2008, including 5,613 non-diabetic participants (37% male, mean age 57.6 years) with 5 years of follow-up. Blood glucose and lipid was measured at baseline and follow-up. Each rs780092 T-allele was associated with a 17% lower risk of incident type 2 diabetes (HR 0.83 [95% CI 0.73, 0.95]) and 36% higher risk of incident hypertriacylglycerolaemia (OR 1.36 [95% CI 1.08, 1.72]), after adjustment for baseline fasting glucose and TG and other confounders. The T-allele was associated with a 5 year increasing level of log10 TG (β ± SE, 0.01 ± 0.004, p = 0.005). Mediation analysis showed that both baseline TG and the 5 year increase in log10 TG were significant mediators in the associations of rs780092 with risk of diabetes. The risk of incident type 2 diabetes associated with 1 SD increase in total and LDL-cholesterol was 35% and 22% lower in TT carriers compared with CC carriers, respectively (both p for interaction ≤ 0.04). The GCKR rs780092 variant showed opposite-directional associations with type 2 diabetes and hypertriacylglycerolaemia in a Chinese population. Both baseline level and 5 year change in serum TG were mediators of the association between the genetic variant and type 2 diabetes.
Fiber Intake and PAI-1 in type 2 diabetes: Look AHEAD Trial Findings at Baseline and Year 1
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
Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K
2017-04-01
To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.
Faller, Hermann; Strahl, André; Richard, Matthias; Niehues, Christiane; Meng, Karin
2017-11-01
Previous research has demonstrated associations between satisfaction with information and reduced emotional distress in cancer patients. However, as most studies were cross-sectional, the direction of this relationship remained unclear. We therefore aimed to test whether information satisfaction predicted subsequent depression and anxiety levels, and, reciprocally, depression and anxiety levels predicted subsequent information satisfaction, thus clarifying the direction of impact. We performed a secondary analysis of a prospective cohort study with 436 female breast cancer patients (mean age 51 years). We measured information satisfaction with 2 self-developed items, symptoms of depression with the 2-item Patient Heath Questionnaire and symptoms of anxiety with the 2-item Generalized Anxiety Disorder Scale. We created 2 structural equation models, 1 for depression and 1 for anxiety, that examined the prediction of 1-year depression (or anxiety) levels by baseline information satisfaction and, in the same model, 1-year information satisfaction by baseline depression (or anxiety) levels (cross-lagged panel analysis). Baseline information satisfaction predicted 1-year levels of both depression (beta = -0.17, P < .01) and anxiety (beta = -0.13, P < .01), adjusting for the baseline scores of the outcome variables. Conversely, baseline levels of depression (beta = -0.12, P < .05) and anxiety (beta = -0.16, P < .01) predicted 1-year information satisfaction, adjusting for its baseline score. Our results suggest a bidirectional relationship between information satisfaction and symptoms of depression and anxiety. Thus, provision of information may reduce subsequent depression and anxiety, while reducing depression and anxiety levels may increase satisfaction with received information. Combining the provision of information with emotional support may be particularly beneficial. Copyright © 2016 John Wiley & Sons, Ltd.
van Loon, Janine E; Sonneveld, Michelle A H; Praet, Stephan F E; de Maat, Moniek P M; Leebeek, Frank W G
2014-01-01
Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.
Emanuele, Enzo; Bertona, Marco; Pareja-Galeano, Helios; Fiuza-Luces, Carmen; Morales, Javier Salvador; Sanchis-Gomar, Fabian; Lucia, Alejandro
2016-07-01
Muscle wasting in patients with cancer has been linked to an increased activity of nuclear factor κB (NF-κB) and higher circulating levels of activin-A (ActA), a negative growth factor for muscle mass. Baicalin is a natural flavonoid that can reduce skeletal muscle atrophy in animal models of cancer cachexia by inhibiting NF-κB. This pilot open-label study assessed the effects of baicalin supplementation (50 mg daily for 3 months) in cancer patients who showed involuntary weight loss >5% over the past 6 months. A total of 20 patients were investigated. Participants were evaluated at baseline and at the end of the 3-month study period for the following endpoints: 1) changes from baseline in serum NF-κB and ActA levels; and 2) change from baseline in lean body mass (LBM). We observed significant reduction in both NF-κB (p<0.05) and ActA (p<0.05) serum levels from baseline to 3 months. At 3 months, patients also showed a significant mean increase in LBM (+0.8 kg, p<0.05 compared with baseline). Our pilot open-label data suggest that baicalin supplementation is potentially useful for contrasting lean body mass reduction in cancer patients with involuntary weight loss, an effect which is likely mediated by the inhibition of negative growth factors for muscle mass.
Effect of an acute bout of aerobic exercise on chemerin levels in obese adults
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
Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi
2017-11-01
Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Effects of intraaortic balloon augmentation in a porcine model of endotoxemic shock.
Engoren, Milo; Habib, Robert H
2004-03-01
Patients with septic shock commonly have myocardial dysfunction associated with lactic acid production and troponin I release. The purpose of this study was to evaluate the effects on intraaortic balloon pump (IABP) support on myocardial dysfunction. Prospective, randomized controlled study. Animal research laboratory. Ten pigs had arterial, pulmonary arterial, and coronary catheters inserted. After receiving endotoxin infusion over 30 min, half the animals received IABP support. Coronary sinus lactic acid levels (P< 0.05 for both 90 min versus baseline and 60 min versus baseline) and arterial lactic acid levels (P < 0.05 for both 90 min versus baseline and 60 min versus baseline) increased with time but did not differ between IABP and sham groups. While overall there was no difference with time in myocardial lactic acid consumption or production (calculated as arterial lactic acid level minus coronary sinus lactic acid level), the IABP group showed net myocardial lactic acid consumption at 90 min, while the sham group showed myocardial lactic acid production. Three of five animals in each group showed troponin I release. The levels were similar and did not differ between groups. IABP had no benefits in this porcine model of endotoxemic shock.
Fuchs, Charles S; Goldberg, Richard M; Sargent, Daniel J; Meyerhardt, Jeffrey A; Wolpin, Brian M; Green, Erin M; Pitot, Henry C; Pollak, Michael
2008-12-15
Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer. The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer. Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome. Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.
The Heritability of Macular Response to Supplemental Lutein and Zeaxanthin: A Classic Twin Study
Hammond, Christopher J.; Liew, S. H. Melissa; Van Kuijk, Frederik J.; Beatty, Stephen; Nolan, John M.; Spector, Tim D.; Gilbert, Clare E.
2012-01-01
Purpose. Antioxidant supplements may reduce age-related macular degeneration (AMD) progression. The macular carotenoids are of particular interest because of their biochemical, optical, and anatomic properties. This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z). Methods. A total of 322 healthy female twin volunteers, aged 16–50 years (mean 40 ± 8.7) was enrolled in a prospective, nonrandomized supplement study. Macular pigment optical density (MPOD) measurements using two techniques (2-wavelength fundus autofluorescence [AF] and heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z, were recorded at baseline, and at 3 and 6 months following daily supplementation with 18 mg L and 2.4 mg Z for a study period of 6 months. Results. At baseline, mean MPOD was 0.44 density units (SD 0.21, range 0.04–1.25) using HFP, and 0.41 density units (SD 0.15) using AF. Serum L and Z levels were raised significantly from baseline following 3 months' supplementation (mean increase 223% and 633%, respectively, P < 0.0001 for both), with no MPOD increase. After 6 months' supplementation, a small increase in MPOD was seen (mean increase 0.025 ± 0.16, P = 0.02, using HFP). Subdivision of baseline MPOD into quartiles revealed that baseline levels made no difference to the treatment effect. Genetic factors explained 27% (95% confidence interval [CI] 7–45) of the variation in MPOD response. Distribution profiles of macular pigment did not change in response to supplementation. Conclusions. MPOD response to supplemental L and Z for a period of 6 months was small (an increase over baseline of 5.7% and 3.7%, measured using HFP and AF, respectively), and was moderately heritable. Further study is indicated to investigate the functional and clinical impact of supplementation with the macular carotenoids. PMID:22700713
Giugliani, Roberto; Lampe, Christina; Guffon, Nathalie; Ketteridge, David; Leão-Teles, Elisa; Wraith, James E; Jones, Simon A; Piscia-Nichols, Cheri; Lin, Ping; Quartel, Adrian; Harmatz, Paul
2014-08-01
Mucopolysaccharidosis VI (MPS VI) is a clinically heterogeneous and progressive disorder with multiorgan manifestations caused by deficient N-acetylgalactosamine-4-sulfatase activity. A cross-sectional Survey Study in individuals (n = 121) affected with MPS VI was conducted between 2001 and 2002 to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of disease. We conducted a Resurvey Study (ClinicalTrials.gov: NCT01387854) to obtain 10-year follow-up data, including medical histories and clinical assessments (n = 59), and survival status over 12 years (n = 117). Patients received a mean (SD) of 6.8 (2.2) years of galsulfase ERT between baseline (Survey Study) and follow-up. ERT patients increased in height by 20.4 cm in the 4-7-year-old baseline age group and by 16.8 cm in the 8-12-year-old baseline age group. ERT patients <13 years-old demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 sec (FEV1) by 55%, and those ≥13 years-old increased FVC by 12.8% and maintained FEV1. Patients with >200 µg/mg baseline uGAG levels increased FVC by 48% in the <13-year-old baseline age group and by 15% in the ≥13-year-old baseline age group. ERT patients who completed the 6-min walk test demonstrated a mean (SD) increase of 65.7 (100.6) m. Cardiac outcomes did not significantly improve or worsen. Observed mortality rate among naïve patients was 50% (7/14) and 16.5% (17/103) in the ERT group (unadjusted hazard ratio, 0.24; 95% CI, 0.10-0.59). Long-term galsulfase ERT was associated with improvements in pulmonary function and endurance, stabilized cardiac function and increased survival. © 2014 Wiley Periodicals, Inc.
Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo
2002-04-01
To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH administration, a significant cortisol peak was detected in patients and controls, whereas no significant difference in cortisol area-under-the-curve (AUC) was found between the groups. In contrast, ACTH induced a significantly higher (p < 0.05) peak of 17-OHP and AUC in PMR patients than in controls. This study found reduced production of adrenal hormones (cortisol, DHEAS) at baseline in patients with active and untreated PMR. The defect seems mainly related to altered adrenal responsiveness to the ACTH stimulation (i.e., increased 17-OHP), at least in untreated patients. The 12 month glucocorticoid treatment of patients reduced the production of inflammatory mediators (i.e., IL-6) in a stable manner that persisted after glucocorticoids were tapered.
Engert, Veronika; Smallwood, Jonathan; Singer, Tania
2014-12-01
Stress is a major health burden in today's society. Research shows that negative cognitive styles are associated with increased stress reactivity, low mood and accelerated cellular aging. Our study sought to unravel the relationship between the content of self-generated thoughts and psychosocial stress measured in terms of hypothalamic-pituitary-adrenal axis and sympathetic activity. Features of self-generated thoughts were assessed using thought sampling while participants performed cognitive tasks following a stress induction or in a baseline condition. More negatively toned emotional thoughts and more social temporal thoughts with a past focus were associated with increased cortisol and alpha-amylase levels, both after stress and at baseline. More social temporal thoughts with a future focus, on the other hand, had an overall attenuating effect on the levels of both stress markers. Our results indicate a fundamental link between the thoughts and stress levels we experience. Understanding the mechanisms governing this mind-body association may have important implications for understanding and counteracting the high incidence of stress-related disorders in today's society. Copyright © 2014 Elsevier B.V. All rights reserved.
Kiechle, Karin; Bazarian, Jeffrey J; Merchant-Borna, Kian; Stoecklein, Veit; Rozen, Eric; Blyth, Brian; Huang, Jason H; Dayawansa, Samantha; Kanz, Karl; Biberthaler, Peter
2014-01-01
The on-field diagnosis of sports-related concussion (SRC) is complicated by the lack of an accurate and objective marker of brain injury. To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion. Longitudinal cohort study. From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels. Forty-six athletes (30 Munich, 16 Rochester) underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich) sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002). Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively). A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC. Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.
Pinhas-Hamiel, Orit; Tzadok, Michal; Hirsh, Galit; Boyko, Valentina; Graph-Barel, Chana; Lerner-Geva, Liat; Reichman, Brian
2010-07-01
This study was done to identify factors influencing long-term metabolic control in youth with type 1 diabetes mellitus (T1DM) treated with an insulin pump. Data were obtained from retrospective chart review of 113 patients (52 males) with T1DM treated with an insulin pump for up to 7 years. Their mean +/- SD age at diagnosis of T1DM was 9.7 +/- 5.1 years, and that at pump therapy initiation was 13.8 +/- 6.1 years. Linear trends and changes in hemoglobin A1c (HbA1c) levels following pump insertion were evaluated according to gender, metabolic control prior to initiation of pump therapy, time from diagnosis of diabetes until pump therapy, age at initiation, and the duration of pump treatment. Mean HbA1c levels of patients with good baseline metabolic control (HbA1c level
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.
Fecal corticoid monitoring in whooping cranes (Grus americana) undergoing reintroduction
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.
Postprandial Monocyte Activation in Individuals With Metabolic Syndrome
Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu
2016-01-01
Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945
Gorman, Shelley; Zafirau, Mark Zafir; Lim, Ee Mun; Clarke, Michael W; Dhamrait, Gursimran; Fleury, Naomi; Walsh, John P; Kaufmann, Martin; Jones, Glenville; Lucas, Robyn M
2017-09-01
The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used, but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9 nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)] but generally remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinically normal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.
Individual changes in clozapine levels after smoking cessation: results and a predictive model.
Meyer, J M
2001-12-01
Published reports document 20-40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital-wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml +/- 598.8 ng/ml) occurred upon smoking cessation (p < .034) from a baseline level of 550.2 ng/ml (+/- 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (+/- 105.2 ng/ml) for the remaining cases (p < .001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F = 34.9;p = .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events.
HDL-C Response Variability to Niacin ER in US Adults
Christian, Jennifer B.; Olson, Eric J.; Allen, Jeffery K.; Lowe, Kimberly A.
2013-01-01
Background. Niacin is the most effective treatment currently available for raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels have an effect on the HDL-C response of niacin ER and to identify factors that predict response to niacin ER at the 500 mg dose. Material and Methods. The change in HDL-C effect between baseline and follow-up levels was quantified in absolute change as well as dichotomized into high versus low response (high response was defined as an HDL-C effect of >15% increase and low response was HDL-C <5%) in a sample of 834 individuals. Results. Both males and females with low HDL-C levels at baseline exhibited a response to treatment in the multivariate model (males, HDL-C <40 mg/dL: OR = 5.18, 95% CI: 2.36–11.39; females, HDL-C <50 mg/dL: OR = 5.40, 95% CI: 1.84–15.79). There was also a significant difference in the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg niacin ER dose group for both males (mean HDL-C effect = 0.08, P < 0.001) and females (mean HDL-C effect = 0.10, P = 0.019). Conclusion. Baseline HDL-C levels are the biggest predictor of response to niacin ER treatment for both males and females among the factors evaluated. PMID:23533734
Rud, Micaela A; Do, Thao N; Siegel, Jessica A
2016-10-28
Methamphetamine (MA) is an addictive psychomotor stimulant that affects the central nervous system and alters behavior. The effects of MA are modulated by age, and while much research has examined the effects of MA use in adults, relatively little research has examined the effects in adolescents. As the brain is developing during adolescence, it is important that we understand the effects of MA exposure in adolescence. This research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test and plasma corticosterone levels in adolescent male C57BL/6J mice. Baseline locomotor and anxiety-like behaviors were assessed in the open field test. Immediately following baseline measurements, mice were exposed to saline or 4mg/kg MA and locomotor and anxiety-like behavior were measured. Serum was collected immediately after testing and plasma corticosterone levels measured. There were no group differences in baseline behavioral measurements. MA-exposed adolescent mice showed increased locomotor activity and anxiety-like behavior in the open field compared with saline controls. There was no effect of MA on plasma corticosterone levels. These data suggest that acute MA exposure during adolescence increases locomotor activity and anxiety-like behavior, but does not alter plasma corticosterone levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Effect of supplemental vitamin D and calcium on serum sclerostin levels.
Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa; Palermo, Nancy J
2014-04-01
Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults. We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years. Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay. In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels. Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.
Pejovic, Slobodanka; Basta, Maria; Vgontzas, Alexandros N; Kritikou, Ilia; Shaffer, Michele L; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O; Chrousos, George P
2013-10-01
One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.
Pejovic, Slobodanka; Basta, Maria; Kritikou, Ilia; Shaffer, Michele L.; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O.; Chrousos, George P.
2013-01-01
One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown. PMID:23941878
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
Benfield, Rebecca D.; Hortobágyi, Tibor; Tanner, Charles J.; Swanson, Melvin; Heitkemper, Margaret M.; Newton, Edward R.
2013-01-01
Background Hydrotherapy (immersion, or bathing) is used worldwide to promote relaxation and decrease parturient anxiety and pain in labor, but the psychophysiological effects of this intervention remain obscure. Design A pre-test post-test design with repeated measures was used to examine the effects of hydrotherapy on maternal anxiety and pain, neuroendocrine responses, plasma volume shift and uterine contractions during labor. Correlations among variables were examined at three time points (pre-immersion and twice during hydrotherapy). Methods Eleven term women (mean age 24.5 years) in spontaneous labor were immersed to the xiphoid in 37°C water for 1 hr. Blood samples and measures of anxiety and pain were obtained under dry baseline conditions and repeated at 15 and 45 min of hydrotherapy. Uterine contractions were monitored telemetrically. Results Hydrotherapy was associated with decreases in anxiety, vasopressin and oxytocin levels at 15 and 45 min (all p < .05). There were no significant differences between pre-immersion and immersion pain or cortisol levels. Pain decreased more for women with high baseline pain than for women with low baseline levels at 15 and 45 min. Cortisol levels decreased twice as much at 15 min of hydrotherapy for women with high baseline pain as for those with low baseline pain. Beta-endorphin levels increased at 15 min but did not differ between baseline and 45 min. During immersion, uterine-contraction frequency decreased. A positive plasma volume shift at 15 min was correlated with contraction duration. Conclusions Hydrotherapy during labor affects neuroendocrine responses that modify psychophysiological processes. PMID:20453024
NT-proBNP and Heart Failure Risk Among Individuals With and Without Obesity: The ARIC Study
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
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.
Effect of walking on sand on gait kinematics in individuals with multiple sclerosis.
van den Berg, Maayken E L; Barr, Christopher J; McLoughlin, James V; Crotty, Maria
2017-08-01
Walking in the real-world involves negotiating challenging or uneven surfaces, including sand. This can be challenging for people with Multiple Sclerosis (PWMS) due to motor deficits affecting the lower extremities. The study objective was to characterise kinematic gait adaptations made by PWMS when walking on sand and describe any immediate post-adaptation effects. 17 PWMS (mean age 51.4 ± 5.5, Disease Steps 2.4 ± 1.0), and 14 age-and gender matched healthy adults (HA) took part in a case-control study. 3D gait analysis was conducted using an eight-camera Vicon motion capture system. Each participant completed walking trials over level ground (baseline), sand (gait adaptation response), and again level ground (post-adaptation). Spatiotemporal data and kinematic data for the hip knee and ankle were recorded. At baseline PWMS showed significantly less total lower limb flexion (p<0.05) compared to HA. PWMS adapted to walking on sand by significantly increasing hip and knee flexion and ankle dorsiflexion (p<0.05) during swing, resulting in an overall 23° greater total lower limb flexion (p<0.05), reaching values within normal range. During the return to level ground walking values of temporal-spatial and kinematic parameters returned towards baseline values. PWMS adapted to walking on sand by increasing lower limb flexion during swing, and returned to their gait pattern to near baseline levels, in a manner similar to but with values not equalling HA. Further work is required to determine whether this mode of walking has potential to act as a gait retraining strategy to increase flexion of the lower limb. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi
2012-09-01
To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.
Myrianthefs, P; Boutzouka, E; Venetsanou, K; Papalois, A; Kouloukousa, M; Kittas, C; Baltopoulos, G
2006-05-01
The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. TNF-alpha and IL-10 were measured in BALF and serum at baseline, 2 h, and 4 h of MV. One animal in LVZP (2 h) and two in HVP (3 h) group died before the end of the experiment. TNF-alpha level in BALF was significantly higher in LVZP and LVP at 4 h compared to baseline and the other groups. IL-10 level in BALF was significantly higher in LVP at 4h compared to baseline and the other groups. There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.
Seo, A Young; Shin, Cheol Min; Kim, Nayoung; Yoon, Hyuk; Park, Young Soo; Lee, Dong Ho
2015-07-01
To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux. The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1 week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement. In the study subjects (n = 51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time % (r = -0.660, P < 0.001). Also, all reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD + DB length (r = 0.327 and 0.324, P = 0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4 ± 862.7 vs. 1,752.2 ± 611.1 Ω, P = 0.004). A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.
Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance
Rahman, Shadab A.; Shapiro, Colin M.; Wang, Flora; Ainlay, Hailey; Kazmi, Syeda; Brown, Theodore J.
2013-01-01
Circadian phase resetting is sensitive to visual short wavelengths (450–480 nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480 nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age ± SD: 31.3 ± 4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2 h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p < 0.01) and sleep efficiency (p = 0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p = 0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40 min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p < 0.05) and middle (p < 0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p < 0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca) PMID:23834705
Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2.
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.
Borrego Utiel, Francisco José; Bravo Soto, Juan Antonio; Merino Pérez, María José; González Carmelo, Isabel; López Jiménez, Verónica; García Álvarez, Teresa; Acosta Martínez, Yelenei; Mazuecos Blanca, María Auxiliadora
2015-01-01
Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Castaldini, C.; DeRosier, R.; Waterland, L.R.
1986-02-01
The report discusses emission results from comprehensive flue gas sampling of a gas- and oil-fired industrial boiler equipped with Exxon's Thermal DeNO/sub x/ Ammonia Injection Process for NO/sub x/ reduction. Comprehensive emission measurements included continuous monitoring of flue gas emissions; source assessment sampling system (SASS) tests; EPA Method 5/17 for solid and condensible particulate emissions and ammonia emissions; controlled condensation system for SO/sub 2/ and SO/sub 3/; and N/sub 2/O emission sampling. Ammonia injection at a NH/sub 3//NO molar ratio of 2.52 gave a NO/sub x/ reduction of 41% from an uncontrolled level of 234 ppm to a controlled levelmore » of 137 ppm. NH/sub 3/ emissions increased from 11 ppm for the baseline to an average of 430 ppm for ammonia injection. Nitrous oxide, N/sub 2/O was reduced 68% from a 50 ppm baseline level to a 17 ppm controlled level. Total particulate emissions increased by an order of magnitude from a baseline of 17.7 ng/J to a controlled level of 182 ng/J. The increase is in part attributed to formation of ammonia sulfate and bisulfate from residual ammonia and SO/sub x/. Total organic emissions were at a moderate level and showed a relative concentration in the nonvolatile category. Organic emissions of CO and trace inorganic elements were not significantly affected by ammonia injection.« less
The Association between Selenium and Lipid Levels: a Longitudinal Study in Rural Elderly Chinese
Chen, Chen; Jin, Yinlong; Unverzagt, Frederick W.; Cheng, Yibin; Hake, Ann M.; Liang, Chaoke; Ma, Feng; Su, Liqin; Liu, Jingyi; Bian, Jianchao; Li, Ping; Gao, Sujuan
2014-01-01
A protective effect of selenium on lipid levels has been reported in populations with relatively low selenium status. However, recent studies found that high selenium exposure may lead to adverse cardiometabolic effects, particularly in selenium-replete populations. We examined the associations of selenium status with changes in lipid levels in a 7-year follow up of an elderly Chinese cohort including participants from selenium-deplete areas. Study population consisted of 140 elderly Chinese aged 65 or older with nail selenium levels measured at baseline (2003-2005). Lipid concentrations were measured in fasting blood samples collected at baseline and the 7-year follow-up (2010-2012). Analysis of covariance (ANCOVA) models was used to determine the association between baseline selenium status and changes in lipid levels from baseline to follow-up adjusting for other covariates. Mean (±standard deviation) baseline selenium concentration was 0.41±0.2mg/kg. In prospective analysis, we found that individuals in the highest selenium quartile group showed 1.11 SD decrease on total-cholesterol (p<0.001), 0.41 SD increase on HDL-cholesterol (p<0.001) and 0.52 SD decrease on triglyceride after 7 years than those in the lowest selenium quartile group. The similar trends were seen with significant lipids changes in the 2th and 3th quartile groups. Selenium has modestly beneficial effects on blood lipid levels in a population with relatively low selenium status. Our result suggests adequate dietary selenium intake as a potential prevention strategy for lowering lipid levels in selenium deplete populations. PMID:25263027
Carranza Lira, Sebastián; Arce Herrera, Rosa María; González González, Patricia
2007-11-01
The educative models and strategies to achieve a significant learning have a wide variety. The development of clinical aptitude for clinical research papers lecture has an important place to maintain the physician actualized and for resident formation. To evaluate the degree of development of the aptitude for the reading of clinical research articles in 2nd grade residents of the gynecology and obstetrics speciality alter an educative strategy. In 16 2nd year gynecology and obstetrics residents, a previously validated instrument was applied for the evaluation of critical lecture of clinical research articles in general medicine previous and after and educative strategy. Statistical analysis was with Kruskal-Wallis analysis of variance. Also Wilcoxon test was used to assess the differences between baseline and final results. The median of age was 27 (24-31) years, gender 56.3% women and 43.8% men. A statistically significant increase in global score was observed after the educative strategy. After it only there was a significant increase in the indicator to interpret. After evaluating the domain degrees according to the indicator to interpret, in baseline evaluation it predominated the very low level and at the final evaluation the very low and low levels. In the indicator to judge at baseline the majority were in the very low level, and at the end in very low and low levels. According to the indicator to propose at baseline all were in the level expected by hazard, and at the end a minimal proportion was at very low level. These results traduce a discrete improvement in critical lecture process, which makes to consider the educative strategy that was used, since the objective to improve critical lecture capacity was not achieved.
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.
Covassin, Tracey; Elbin, Robert J; Stiller-Ostrowski, Jennifer L; Kontos, Anthony P
2009-01-01
Computerized neurocognitive testing is becoming popular among clinicians evaluating sport-related concussions across all levels of sport. Baseline neurocognitive testing has been recommended to provide more accurate representation of the preconcussion cognitive status of individual athletes. However, little is known about the use of baseline neurocognitive testing in concussion assessment and management. To examine implementation and practice trends of sports medicine professionals using baseline neurocognitive testing at the high school and collegiate levels. Quantitative survey research. Online survey. Certified athletic trainers (ATs) from approximately 1209 US institutions listed on the ImPACT Web site were recruited. A total of 399 ATs completed the survey, for a response return rate of 32.7%. Survey questions addressed educational level, years of certification, employment setting, percentage of athletes baseline tested, and accuracy of baseline tests. Other items addressed postconcussive neurocognitive testing protocols and scenarios for return-to-play decisions based on neurocognitive testing. Nearly all ATs (94.7%) administered baseline computerized neurocognitive testing to their athletes. However, only 51.9% examined these baseline tests for validity. The majority of ATs indicated that they administer baseline neurocognitive tests most frequently to football players (88.4%), followed by women's soccer players (78.8%) and men's soccer players (71.2%). Nearly all respondents (95.5%) stated that they would not return a symptomatic athlete to play if the athlete's neurocognitive scores were back to baseline. However, when asked if they would return an athlete who is symptom free but who scores below his or her baseline, 86.5% responded no, 9.8% responded yes, and 3.8% indicated that it depended on the importance of the competition. The use of baseline testing, baseline testing readministration, and postconcussion protocols among ATs is increasing. However, the ATs in this study reported that they relied more on symptoms than on neurocognitive test scores when making return-to-play decisions.
Olivier, A; Girerd, N; Michel, J B; Ketelslegers, J M; Fay, R; Vincent, J; Bramlage, P; Pitt, B; Zannad, F; Rossignol, P
2017-08-15
Increased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. In a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. When included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). Both increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. In the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while further opening new avenues for biomarker-guided targeted therapies. Copyright © 2017 Elsevier B.V. All rights reserved.
Monosodium glutamate intake increases hemoglobin level over 5 years among Chinese adults.
Shi, Zumin; Yuan, Baojun; Taylor, Anne W; Dal Grande, Eleonora; Wittert, Gary A
2012-09-01
The aim of this analysis was to determine the relationship between monosodium glutamate (MSG) intake and change in hemoglobin (Hb) levels and the risk of anemia over 5 years in 1197 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN). MSG intake and Hb were quantitatively assessed in 2002 and followed up in 2007. Diet and lifestyle factors were assessed at both time points. There was a positive association between MSG intake and increase in Hb among men but not women. In the multivariate model adjusting for demographic and lifestyle factors as well as baseline dietary pattern, the beta values and 95% confidence interval for Hb changes across quartiles of MSG intake were 0, 0.67(0.04-1.29), 0.99(0.38-1.60), 0.73(0.13-1.34) among men (p for trend 0.091); 0, -0.01(-0.45-0.43), 0.23(-0.25-0.71), and -0.45(-0.96-0.05) among women (p for trend 0.087). Among anemic participants at baseline, there was a significant inverse association between MSG intake and the risk of anemia at follow-up. Comparing extreme quartiles of MSG intake among those anemic at baseline, the relative risk for persistent anemia at follow-up was 0.49 (95% CI: 0.28-0.86, p < 0.01). The association was independent of dietary patterns and lifestyle factors. A dose-response relationship between MSG intake and increase in Hb levels among anemic participants was seen. MSG intake may have independent Hb-increasing effects, especially among men and those anemic at baseline.
Mook-Kanamori, D O; Römisch-Margl, W; Kastenmüller, G; Prehn, C; Petersen, A K; Illig, T; Gieger, C; Wang-Sattler, R; Meisinger, C; Peters, A; Adamski, J; Suhre, K
2014-04-01
Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia (defined as having a fasting triglyceride level above 1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses. Increased levels of leucine, arginine, valine, proline, phenylalanine, isoleucine and lysine were significantly associated with an increased risk of hypertriglyceridemia. These associations remained significant when restricting to those individuals who did not develop T2D in the 7-year follow-up. The increase per standard deviation of amino acid level was between 26 and 40 %. Seven amino acids were associated with an increased risk of developing hypertriglyceridemia after 7 years. Further studies are necessary to elucidate the complex role of these amino acids in the pathogenesis of metabolic disorders.
2013-01-01
Background The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. Methods Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. Results Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. Conclusions There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers’ release. PMID:24156746
Madliger, Christine L; Love, Oliver P
2016-01-01
Abstract Labile physiological variables, such as stress hormones [i.e. glucocorticoids (GCs)], allow individuals to react to perturbations in their environment and may therefore reflect the effect of disturbances or positive conservation initiatives in advance of population-level demographic measures. Although the application of GCs as conservation biomarkers has been of extensive interest, few studies have explicitly investigated whether baseline GC concentrations respond to disturbances consistently across individuals. However, confirmation of consistent responses is of paramount importance to assessing the ease of use of GCs in natural systems and to making valid interpretations regarding population-level change (or lack of change) in GC concentrations. We investigated whether free-ranging female tree swallows (Tachycineta bicolor) display individually specific changes in baseline glucocorticoid concentrations naturally over the breeding season (from incubation to offspring provisioning) and in response to a manipulation of foraging profitability (representing a decrease in access to food resources). We show that baseline GC concentrations are repeatable within individuals over reproduction in natural conditions. However, in response to a reduction in foraging ability, baseline GC concentrations increase at the population level but are not repeatable within individuals, indicating a high level of within-individual variation. Overall, we suggest that baseline GCs measured on a subset of individuals may not provide a representative indication of responses to environmental change at the population level, and multiple within-individual measures may be necessary to determine the fitness correlates of GC concentrations. Further validation should be completed across a variety of taxa and life-history stages. Moving beyond a traditional cross-sectional approach by incorporating repeated-measures methods will be necessary to assess the suitability of baseline GCs as biomarkers of environmental change and population persistence, particularly from a logistical and ease-of-use perspective for conservation managers. PMID:27757239
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan, Mohini; Braley, Gabriel; Pittman, Brian; Cooper, Thomas; Perry, Edward; Krystal, John; D’Souza, Deepak Cyril
2010-01-01
Background Cannabis is one of the most widely used illicit substances, and there is growing interest in the therapeutic applications of cannabinoids. While known to modulate neuroendocrine function, the precise acute and chronic dose-related effects of cannabinoids in humans are not well-known. Furthermore, the existing literature on the neuroendocrine effects of cannabinoids is limited by small sample sizes (n=6–22), heterogeneous samples with regard to cannabis exposure (lumping users and nonusers), lack of controlling for chronic cannabis exposure, differing methodologies, and limited dose–response data. Delta-9-tetrahydrocannabinol (Δ-9-THC) was hypothesized to produce dose-related increases in plasma cortisol levels and decreases in plasma prolactin levels. Furthermore, relative to controls, frequent users of cannabis were hypothesized to show altered baseline levels of these hormones and blunted Δ-9-THC-induced changes of these hormones. Materials and methods Pooled data from a series of laboratory studies with multiple doses of intravenous Δ-9-THC in healthy control subjects (n=36) and frequent users of cannabis (n=40) was examined to characterize the acute, chronic, and acute on chronic effects of cannabinoids on plasma cortisol and prolactin levels. Hormone levels were measured before (baseline) and 70 min after administration of each dose of Δ-9-THC. Data were analyzed using linear mixed models with +70 min hormonal levels as the dependant variable and baseline hormonal level as the covariate. Results At socially relevant doses, Δ-9-THC raised plasma cortisol levels in a dose-dependent manner but frequent users showed blunted increases relative to healthy controls. Frequent users also had lower baseline plasma prolactin levels relative to healthy controls. Conclusions These group differences may be related to the development of tolerance to the neuroendocrine effects of cannabinoids. Alternatively, these results may reflect inherent differences in neuroendocrine function in frequent users of cannabis and not a consequence of cannabis use. PMID:19083209
Davis, John C; Van der Heijde, Désirée M F M; Dougados, Maxime; Braun, Jurgen; Cush, John J; Clegg, Daniel O; Inman, Robert D; de Vries, Todd; Tsuji, Wayne H
2005-09-01
To examine the baseline demographic and disease characteristics that might influence improvement as measured by the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) in patients with ankylosing spondylitis (AS). A multicenter Phase 3 study was performed to compare the safety and efficacy of 24 weeks of etanercept 25 mg subcutaneous injection twice weekly (n = 138) and placebo (n = 139) in patients with AS. The ASAS 20 was measured at multiple time points. Using a significance level of 0.05, a repeated measures logistic regression model was used to determine which baseline factors influenced response in the etanercept-treated patients during the 24-week double blind portion of the trial. The following baseline factors were used in the model: demographic and disease severity variables, concomitant medications, extra-articular manifestations, and HLA-B27 status. The predictive capability of the model was then tested on the patients receiving placebo after they had received open-label etanercept treatment. Baseline factors that were significant predictors of an ASAS 20 response in etanercept-treated patients were C-reactive protein (CRP), back pain score, and Bath Ankylosing Spondylitis Functional Index (BASFI) score. Although clinical response to etanercept was seen at all levels of baseline disease activity, responses were consistently more likely with higher CRP levels or back pain scores and less likely with increased BASFI scores at baseline. Higher CRP values and back pain scores and lower BASFI scores at baseline were significant predictors of a higher ASAS 20 response in patients with AS receiving etanercept but predictive value was of insufficient magnitude to determine treatment in individual patients.
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.
Park, Hye-Jeong; Kim, Jihyun; Han, Eun Jin; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung
2016-06-01
Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years. © 2015 John Wiley & Sons Ltd.
ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.
Gopalaswamy, Vinaya; Dhibar, Deba Prasad; Gupta, Vipin; Arya, Ashutosh Kumar; Khandelwal, Niranjan; Bhansali, Anil; Garg, Sudhir Kumar; Agarwal, Neelam; Rao, Sudhaker D; Bhadada, Sanjay Kumar
2017-06-01
Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 μg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 μg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. Weekly teriparatide therapy (60 μg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.
NASA Astrophysics Data System (ADS)
Gaffney, Jeffrey S.; Marley, Nancy A.; Blake, Donald R.
2012-09-01
While it is well known that combustion of ethanol as a biofuel will lead to enhanced emissions of methane, ethene (ethylene), acetaldehyde, formaldehyde, and oxides of nitrogen (primarily NO) when compared to gasoline alone, especially during cold starts or if catalytic converters are not operating properly, the impacts of increases in atmospheric ethene levels from combustion of fuels with higher ethanol content has not received much attention. Ethene is a well known and potent plant growth hormone and exposure to agricultural crops and natural vegetation results in yield reductions especially when combined with higher levels of PAN and ozone also expected from the increased use of ethanol/gasoline blends. We report here some baseline measurements of ethene obtained in 2002 in the southwestern and south central United States. These data indicate that current ethene background levels are less than 1 ppb. Anticipated increases in fuel ethanol content of E30 or greater is expected to lead to higher atmospheric levels of ethene on regional scales due to its atmospheric lifetime of 1.5-3 days. These background measurements are discussed in light of the potential enhancement of ethene levels expected from the anticipated increases in ethanol use as a renewable biofuel.
Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping
2014-01-01
Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957
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.
Cho, Jung Hwan; Lee, Da Young; Lee, Eun Seo; Kim, Jihyun; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung
2016-11-01
Results from previous studies support the association of lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we analyzed the association between baseline Lp(a) levels and future progression of coronary artery calcification (CAC) in apparently healthy Korean adults. A total of 2611 participants (mean age: 41years, 92% mend) who underwent a routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a) was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC was defined as a change in CACS >0 over four years. Bivariate correlation analyses with baseline Lp(a) and other metabolic parameters revealed age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive correlation, while body weight, fasting glucose level, blood pressure and triglyceride level were negatively correlated with baseline Lp(a) level. After four years of follow-up, 635 subjects (24.3%) had CAC progression. The participants who had CAC progression were older, composed of more men, more obese, and had higher fasting glucose levels and worse baseline lipid profiles compared to those who did not have CAC progression. The mean serum Lp(a) level was significantly higher in subjects who had CAC progression compared to those who did not (32.5 vs. 28.9mg/dL, p<0.01). When the risk for CAC progression according to baseline Lp(a) was calculated, those with Lp(a) level≥50mg/dL had an odds ratio of 1.333 (95% CI 1.027-1.730) for CAC progression compared to those with Lp(a)<50mg/dL after adjusting for confounding factors. In this study, the subjects who had higher Lp(a) were at significantly higher risk for CAC progression after four years of follow-up, suggesting the role of high Lp(a) in CAC progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Iron Status and the Acute Post-Exercise Hepcidin Response in Athletes
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
Emotional outlook on life predicts increases in physical activity among initially inactive men.
Baruth, Meghan; Lee, Duck-Chul; Sui, Xuemei; Church, Timothy S; Marcus, Bess H; Wilcox, Sara; Blair, Steven N
2011-04-01
This study examined the relationship between emotional outlook on life and change in physical activity among inactive adults in the Aerobics Center Longitudinal Study. A total of 2,132 sedentary adults completed a baseline medical examination and returned for a follow-up examination at least 6 months later. Participants self-reported physical activity level and emotional outlook on life. Emotional outlook on life was significantly and positively related to physical activity participation at the follow-up visit in men but not women. Men who were usually very happy and optimistic at baseline had significantly greater increases in physical activity compared to men who were not happy. Men with a more positive outlook on life (e.g., happier) may be more likely to increase physical activity levels. Physical activity interventions targeting men may be more successful if they first increase happiness.
Khurana, Rahul N; LaBree, Laurie D; Scott, Garrett; Smith, Ronald E; Yiu, Samuel C
2006-09-01
To investigate the effect of esterified estrogens combined with methyltestosterone (EECM) (Estratest, Solvay, Pharmaceuticals, Inc, Baudette, Minnesota, USA) on intraocular pressure (IOP) in postmenopausal women. Observational case series. The IOP of 13 consecutive postmenopausal women with dry eye syndrome were recorded before and during EECM therapy (1.25 mg of esterified estrogens and 2.5 mg of methyltestosterone for several months). The mean IOP increased from a baseline of 15.0 mm Hg before treatment to 18.2 mm Hg on EECM therapy (P < .0001) after a median duration of 11.3 months (range, 0.9 to 24 months). The increase in IOP was statistically significant at the 0.05 level of significance within three months and continued over 12 months. Two patients whose pressures increased (>4 mm Hg) returned to baseline levels after EECM was discontinued. Esterified estrogens combined with methyltestosterone produce a clinically significant increase in IOP in postmenopausal women with dry eye syndrome.
Rezvani, Reza; Cianflone, Katherine; McGahan, John P.; Berglund, Lars; Bremer, Andrew A.; Keim, Nancy L.; Griffen, Steven C.; Havel, Peter J.; Stanhope, Kimber L.
2013-01-01
Objective We determined the effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity. Design and Methods 32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. Results Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. Conclusions The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption. PMID:23512943
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
Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence
Adam, Emma K.; Doane, Leah D.; Zinbarg, Richard E.; Mineka, Susan; Craske, Michelle G.; Griffith, James W.
2010-01-01
Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40 minutes after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including Major Depressive Disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD. In a sample of 230 late adolescents, clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered one year earlier, including: waking cortisol levels, bedtime cortisol levels, the size of the CAR, average cortisol, and the slope of the diurnal cortisol rhythm across the waking day. Age and gender, health and health behaviors, baseline neuroticism, exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates, to help ensure effects are attributable to the CAR rather than related variables. A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD. No other baseline cortisol measures were significant prospective predictors of MDD. In summary, the CAR is a significant prospective risk factor for the development of MDD in young adults, providing some support for the possibility that a heightened CAR may play a role in the etiology of Major Depressive Disorder. PMID:20079576
Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lessin, Lawrence S; Kamensky, Victor; Lin, Juan; Wassertheil-Smoller, Sylvia; Rohan, Thomas E
2016-05-15
Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Drinking Level Versus Drinking Pattern and Cigarette Smoking Among Older Adults.
Holahan, Charles J; Brennan, Penny L; Schutte, Kathleen K; Holahan, Carole K; Hixon, J Gregory; Moos, Rudolf H
2018-04-01
There is a lack of research on the role of alcohol consumption in cigarette smoking among older adults, and the few studies on alcohol use and smoking with older adults have failed to distinguish between average level and pattern of drinking as predictors of smoking. The main purpose of this study was to examine the independent contributions of average level versus pattern of drinking as predictors of cigarette smoking among older adults. A subsidiary purpose was to examine the link between continued smoking and mortality among older smokers. We investigated average level and pattern of drinking as predictors of current smoking among 1,151 older adults at baseline and of continued smoking and mortality among the subset of 276 baseline smokers tracked across 20 years. We used multiple linear and logistic regression analyses and, to test mediation, bias-corrected bootstrap confidence intervals. A high level of average drinking and a pattern of episodic heavy drinking were concurrently associated with smoking at baseline. However, only episodic heavy drinking was prospectively linked to continued smoking among baseline smokers. Continued smoking among baseline smokers increased the odds of 20-year mortality and provided an indirect pathway through which heavy episodic drinking related to mortality. Smokers who misuse alcohol are a challenging population for smoking cessation efforts. Older adults who concurrently misuse alcohol and smoke cigarettes provide a unique target for public health interventions. Copyright © 2018 by the Research Society on Alcoholism.
Abioye, Ajibola I.; Ulenga, Nzovu; Msham, Salum; Kaishozi, George; Gunaratna, Nilupa S; Mwiru, Ramadhani; Smith, Erin; Dhillon, Christina Nyhus; Spiegelman, Donna; Fawzi, Wafaie
2017-01-01
There is widespread vitamin and mineral deficiency problem in Tanzania with known deficiencies of at least vitamin A, iron, folate and zinc, resulting in lasting negative consequences especially on maternal health, cognitive development and thus the nation’s economic potential. Folate deficiency is associated with significant adverse health effects among women of reproductive age, including a higher risk of neural tube defects. Several countries, including Tanzania, have implemented mandatory fortification of wheat and maize flour but evidence on the effectiveness of these programs in developing countries remains limited. We evaluated the effectiveness of Tanzania’s food fortification program by examining folate levels for women of reproductive age, 18–49 years. A prospective cohort study with 600 non-pregnant women enrolled concurrent with the initiation of food fortification and followed up for 1 year thereafter. Blood samples, dietary intake and fortified foods consumption data were collected at baseline, and at 6 and 12 months. Plasma folate levels were determined using a competitive assay with folate binding protein. Using univariate and multivariate linear regression, we compared the change in plasma folate levels at six and twelve months of the program from baseline. We also assessed the relative risk of folate deficiency during follow-up using log-binomial regression. The mean (±SE) pre–fortification plasma folate level for the women was 5.44-ng/ml (±2.30) at baseline. These levels improved significantly at six months [difference: 4.57ng/ml (±2.89)] and 12 months [difference: 4.27ng/ml (±4.18)]. Based on plasma folate cut-off level of 4 ng/ml, the prevalence of folate deficiency was 26.9% at baseline, and 5% at twelve months. One ng/ml increase in plasma folate from baseline was associated with a 25% decreased risk of folate deficiency at 12 months [(RR = 0.75; 95% CI = 0.67–0.85, P<0.001]. In a setting where folate deficiency is high, food fortification program with folic acid resulted in significant improvements in folate status among women of reproductive age. PMID:28797054
Heat increment of feeding in Steller sea lions, Eumetopias jubatus.
Rosen, D A; Trites, A W
1997-11-01
The heat increment of feeding (HIF) was measured in six captive, juvenile Steller sea lions (Eumetopias jubatus), fed meals of either 2 or 4 kg of herring. HIF was calculated as the post-prandial increase in metabolism above baseline levels, and was measured using open-circuit (gas) respirometry. It averaged 12.4 +/- 0.9% (SE) of ingested energy intake for the 4-kg meal trials, and 9.9 +/- 0.9% for the 2-kg meal size. The effect lasted 8-10 hr for the larger meal size. Metabolism peaked 3.7 hr after feeding, and was 2.13 times higher than baseline levels. For the 2-kg meal size, the effect lasted 6-8 hr, with metabolism peaking 2.8 hr after ingestion at 1.76 times baseline levels. Our estimates of HIF for Steller sea lions are at the lower end of estimates for terrestrial mammals, and are consistent with estimates for other marine mammals.
Blood lead levels and bone turnover with weight reduction in women.
Riedt, Claudia S; Buckley, Brian T; Brolin, Robert E; Ambia-Sobhan, Hasina; Rhoads, George G; Shapses, Sue A
2009-01-01
High bone turnover states are known to raise blood lead levels (BPb). Caloric restriction will increase bone turnover, yet it remains unknown if weight reduction increases BPb due to mobilization of skeletal stores. We measured whole blood Pb levels ((206)Pb) by inductively coupled plasma mass spectrometry in 73 women (age 24-75 years; BMI 23- 61 kg/m(2)) before and after 6 months of severe weight loss (S-WL), moderate weight loss (M-WL), or weight maintenance (WM). Baseline BPb levels were relatively low at 0.2-6.0 microg/dl, and directly associated with age (r=0.49, P<0.0001). After severe WL (-37.4+/-9.3 kg, n=17), BPb increased by 2.1+/-3.9 microg/dl (P<0.05), resulting in BPb levels of 1.3-12.5 microg/dl. M-WL (-5.6+/-2.7 kg, n=39) and WM (0.3+/-1.3 kg, n=17) did not result in an increase in BPb levels (0.5+/-3.2 and 0.0+/-0.7 microg/dl, M-WL and WM, respectively). BPb levels increased more with greater WL (r=0.24, P<0.05). Bone turnover markers increased only with severe WL and were directly correlated with WL. At baseline, higher calcium intake was associated with lower BPb (r=-0.273, P<0.02), however, this association was no longer present after 6 months. Severe weight reduction in obese women increases skeletal bone mobilization and BPb, but values remain well below levels defined as Pb overexposure.
Young, Andrea S.; Belury, Martha A.; Cole, Rachel M.; Gracious, Barbara; Seidenfeld, Adina M.; Wolfson, Hannah; Fristad, Mary A.
2017-01-01
Abstract Objective: To examine fatty acid profiles, their response to omega-3 fatty acid (Ω3) supplementation, and associations with clinical status and treatment response in youth with mood disorders. Methods: In a placebo-controlled 2X2 design, 7–14 year-olds (N = 95) in parallel pilot trials (depression N = 72; bipolar N = 23) were randomly assigned to 12 weeks of Ω3 supplementation (1.4 g eicosapentaenoic acid [EPA], 0.2 g docosahexaenoic acid [DHA], and 0.27 g other Ω3 per day); psychoeducational psychotherapy (PEP); their combination; or placebo (mainly oleic and linoleic acid) alone. Blood was drawn at baseline (N = 90) and endpoint (n = 65). Fatty acid levels were expressed as percent of total plasma fatty acids. Correlational and moderator/mediator analyses were done with SPSS Statistics 23. Results: At baseline: (1) DHA correlated negatively with alpha-linolenic acid (ALA) (r = −0.23, p = 0.029); (2) Arachidonic acid (AA, Ω6) correlated negatively with global functioning (r = −0.24, p = 0.022); (3) Total Ω3 correlated negatively with age (r = −0.22, p = 0.036) and diastolic blood pressure (r = −0.31, p = 0.006). Moderation: Baseline ALA moderated response to Ω3 supplementation: ALA levels above the sample mean (lower DHA) predicted significantly better placebo-controlled response (p = 0.04). Supplementation effects: Compared to placebo, 2 g Ω3 per day increased EPA blood levels sevenfold and DHA levels by half (both p < 0.001). Body weight correlated inversely with increased EPA (r = −0.52, p = 0.004) and DHA (r = −0.54, p = 0.003) and positively with clinical mood response. Mediation: EPA increase baseline-to-endpoint mediated placebo-controlled global function and depression improvement: the greater the EPA increase, the less the placebo-controlled Ω3 improvement. Conclusion: Ω3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored. PMID:28157380
High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes.
Custer, Aimee; Sufrinko, Alicia; Elbin, R J; Covassin, Tracey; Collins, Micky; Kontos, Anthony
2016-02-01
Some healthy athletes report high levels of baseline concussion symptoms, which may be attributable to several factors (eg, illness, personality, somaticizing). However, the role of baseline symptoms in outcomes after sport-related concussion (SRC) has not been empirically examined. To determine if athletes with high symptom scores at baseline performed worse than athletes without baseline symptoms on neurocognitive testing after SRC. Cohort study. High school and collegiate athletic programs. A total of 670 high school and collegiate athletes participated in the study. Participants were divided into groups with either no baseline symptoms (Postconcussion Symptom Scale [PCSS] score = 0, n = 247) or a high level of baseline symptoms (PCSS score > 18 [top 10% of sample], n = 68). Participants were evaluated at baseline and 2 to 7 days after SRC with the Immediate Post-concussion Assessment and Cognitive Test and PCSS. Outcome measures were Immediate Post-concussion Assessment and Cognitive Test composite scores (verbal memory, visual memory, visual motor processing speed, and reaction time) and total symptom score on the PCSS. The groups were compared using repeated-measures analyses of variance with Bonferroni correction to assess interactions between group and time for symptoms and neurocognitive impairment. The no-symptoms group represented 38% of the original sample, whereas the high-symptoms group represented 11% of the sample. The high-symptoms group experienced a larger decline from preinjury to postinjury than the no-symptoms group in verbal (P = .03) and visual memory (P = .05). However, total concussion-symptom scores increased from preinjury to postinjury for the no-symptoms group (P = .001) but remained stable for the high-symptoms group. Reported baseline symptoms may help identify athletes at risk for worse outcomes after SRC. Clinicians should examine baseline symptom levels to better identify patients for earlier referral and treatment for their injury. Additional investigation of baseline symptoms is warranted to help delineate the type and severity of premorbid symptoms.
Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens; Poulsen, Henrik Enghusen; Jensen, Peter Østrup; Johansen, Helle Krogh; Qvist, Tavs; Kræmer, Dorthe; Høiby, Niels; Ciofu, Oana
2015-03-01
Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplementation with anti-oxidants is potentially beneficial for CF patients. The effect of 4 weeks of oral N-acetylcysteine (NAC) treatment (2400 mg/day divided into two doses) on biochemical parameters of oxidative stress was investigated in an open-label, controlled, randomized trial on 21 patients; 11 patients in the NAC group and 10 in the control group. Biochemical parameters of oxidative burden and plasma levels of antioxidants were assessed at the end of the study and compared to the baseline values in the two groups. A significant increase in the plasma levels of the antioxidant ascorbic acid (p=0.037) and a significant decrease in the levels of the oxidized form of ascorbic acid (dehydroascorbate) (p=0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change significantly compared to baseline in either of the groups. A better lung function was observed in the NAC treated group with a mean (SD) change compared to baseline of FEV1% predicted of 2.11 (4.6), while a decrease was observed in the control group (change -1.4 (4.6)), though not statistically significant. Treatment with N-acetylcysteine 1200 mg×2/day for 30 days significantly decreased the level of oxidized vitamin C and increased the level of vitamin C (primary end-points) and a not statistically significant improvement of lung function was observed in this group of patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Meuwese, Christiaan L.; Dekker, Friedo W.; Lindholm, Bengt; Qureshi, Abdul R.; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J.
2012-01-01
Summary Background and objectives Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. Design, setting, participants, & measurements In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models. Results During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Conclusions Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect. PMID:22246282
Meuwese, Christiaan L; Dekker, Friedo W; Lindholm, Bengt; Qureshi, Abdul R; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J
2012-01-01
Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan-Meier curves and Cox proportional hazard models. During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect.
Xu, Xiao; Tian, Xue; Chen, Yuan; Yang, Zhi-Kai; Qu, Zhen; Dong, Jie
2018-04-19
Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study. Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined. At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort. A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.
Hidalgo-Lopez, Esmeralda; Pletzer, Belinda
2017-01-01
Estradiol and progesterone levels vary along the menstrual cycle and have multiple neuroactive effects, including on the dopaminergic system. Dopamine relates to executive functions in an "inverted U-shaped" manner and its levels are increased by estradiol. Accordingly, dopamine dependent changes in executive functions along the menstrual cycle have been previously studied in the pre-ovulatory phase, when estradiol levels peak. Specifically it has been demonstrated that working memory is enhanced during the pre-ovulatory phase in women with low dopamine baseline levels, but impaired in women with high dopamine baseline levels. However, the role of progesterone, which peaks in the luteal cycle phase, has not been taken into account previously. Therefore, the main goals of the present study were to extend these findings (i) to the luteal cycle phase and (ii) to other executive functions. Furthermore, the usefulness of the eye blink rate (EBR) as an indicator of dopamine baseline levels in menstrual cycle research was explored. 36 naturally cycling women were tested during three cycle phases (menses-low sex hormones; pre-ovulatory-high estradiol; luteal-high progesterone and estradiol). During each session, women performed a verbal N-back task, as measure of working memory, and a single trial version of the Stroop task, as measure of response inhibition and cognitive flexibility. Hormone levels were assessed from saliva samples and spontaneous eye blink rate was recorded during menses. In the N-back task, women were faster during the luteal phase the higher their progesterone levels, irrespective of their dopamine baseline levels. In the Stroop task, we found a dopamine-cycle interaction, which was also driven by the luteal phase and progesterone levels. For women with higher EBR performance decreased during the luteal phase, whereas for women with lower EBR performance improved during the luteal phase. These findings suggest an important role of progesterone in modulating dopamine-cycle interactions. Additionally, we identified the eye blink rate as a non-invasive indicator of baseline dopamine function in menstrual cycle research.
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.
NASA Astrophysics Data System (ADS)
Cīrule, Dina; Krama, Tatjana; Krams, Ronalds; Elferts, Didzis; Kaasik, Ants; Rantala, Markus J.; Mierauskas, Pranas; Luoto, Severi; Krams, Indrikis A.
2017-12-01
Animals normally respond to stressful environmental stimuli by releasing glucocorticoid hormones. We investigated whether baseline corticosterone (CORT), handling-induced corticosterone concentration(s), and body condition indices of members of willow tit ( Poecile montanus) groups differed while wintering in old growth forests and managed young forests in mild weather conditions and during cold spells. Willow tits spend the winter season in non-kin groups in which dominant individuals typically claim their priority to access resources, while subordinate individuals may experience greater levels of stress and higher mortality, especially during cold spells. We captured birds to measure baseline CORT and levels of handling-induced CORT secretion after 20 min of capture. Willow tits in the young forests had higher baseline CORT and a smaller increase in CORT in response to capture than individuals in the old forests. Baseline CORT was higher in females and juvenile birds compared to adult males, whereas handling-induced CORT secretion did not differ between birds of different ages. During cold spells, baseline CORT of willow tits increased and handling-induced CORT secretion decreased, especially in birds in young forests. Willow tits' survival was higher in the old forests, with dominant individuals surviving better than subordinates. Our results show that changes in CORT secretion reflect responses to habitat quality and climate harshness, indicating young managed coniferous forests as a suboptimal habitat for the willow tit.
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.
Charles, Emmanuel; Nawyn, John P.; Voronin, Lois M.; Gordon, Alison D.
2011-01-01
Withdrawals from the Potomac-Raritan-Magothy aquifer system in New Jersey, which includes the Upper, Middle, and Lower Potomac-Raritan-Magothy aquifers, are the principal source of groundwater supply in northern Gloucester and northeastern Salem Counties in the New Jersey Coastal Plain. Water levels in these aquifers have declined in response to pumping. With increased population growth and development expected in Gloucester County and parts of Salem County over the next 2 decades (2005-2025), withdrawals from these aquifers also are expected to increase. A steady-state groundwater-flow model, developed to simulate flow in the Potomac-Raritan-Magothy aquifer system in northern Gloucester and northeastern Salem Counties, was calibrated to withdrawal conditions in 1998, when groundwater withdrawals from the Potomac-Raritan-Magothy aquifer system in the model area were more than 10,100 Mgal/yr (million gallons per year). Withdrawals from water-purveyor wells accounted for about 63 percent of these withdrawals, and withdrawals from industrial self-supply wells accounted for about 32 percent. Withdrawals from agricultural-irrigation, commercial self-supply, and domestic self-supply wells accounted for the remaining 5 percent. Results of the 2000 baseline groundwater-flow simulation, incorporating average annual 1999-2001 groundwater withdrawals, indicate that the average simulated water levels in the Upper, Middle, and Lower Potomac-Raritan-Magothy aquifers are 31, 27, and 30 feet below the National Geodetic Vertical Datum of 1929 (NGVD 29), respectively, and the lowest simulated water levels are 77, 65, and 59 feet below NGVD 29, respectively. In the full-allocation scenario, the maximum State-permitted (allocated) groundwater withdrawals totaled 16,567 Mgal/yr, an increase of 72 percent from the 2000 baseline simulation. Results of the full-allocation simulation indicate that the average simulated water levels in the Upper, Middle, and Lower Potomac-Raritan-Magothy aquifers are 49, 43, and 48 feet below NGVD 29, respectively, which are 18, 16, and 18 feet lower, respectively, than in the 2000 baseline simulation. The lowest simulated water levels are 156, 95, and 69 feet below NGVD 29, respectively, which are 79, 30, and 10 feet lower, respectively, than in the 2000 baseline simulation. Simulated net flow from the Potomac-Raritan-Magothy aquifer system to streams is 8,441 Mgal/yr in the 2000 baseline simulation but is 6,018 Mgal/yr in the full-allocation scenario, a decrease of 29 percent from the 2000 baseline simulation. Simulated net flow in the 2000 baseline simulation is 1,183 Mgal/yr from the aquifer system to the Delaware River but in the full-allocation scenario is 1,816 Mgal/yr from the river to the aquifer system. Four other simulations were conducted that incorporated full-allocation conditions at water-purveyor wells in Critical Area 2 but increased or decreased withdrawals at selected water-purveyor wells outside Critical Area 2 and agricultural-irrigation and industrial-self-supply wells in the study area. The results of the four simulations also indicate net flow from the Delaware River to the Potomac-Raritan-Magothy aquifer system. A growth scenario was developed to simulate future withdrawals in 2025 estimated from population projections for municipalities in the Salem-Gloucester study area. Simulated withdrawals for this scenario totaled 10,261 Mgal/yr, an increase of 6 percent from the 2000 baseline simulation. This total includes about 25 Mgal/yr withdrawn from the Englishtown aquifer system for domestic self-supply. This scenario incorporated full-allocation withdrawals at water-purveyor wells in Critical Area 2, and increased withdrawals at water-purveyor wells outside Critical Area 2. Results of this simulation indicate that the average simulated water levels in the Upper, Middle, and Lower Potomac-Raritan-Magothy aquifers are 32, 29, and 32 feet below NGVD 29, respectively, which are 1, 2, and
Pedersen, Eric R.; Neighbors, Clayton; Atkins, David C.; Lee, Christine M.; Larimer, Mary E.
2016-01-01
Research documents increased and problematic alcohol use during study abroad experiences for college students yet no research documents effective preventive programs with these students. The present randomized controlled trial was designed to prevent increased and problematic alcohol use abroad by correcting misperceptions of peer drinking norms abroad and by promoting positive and healthy adjustment into the host culture (i.e., sojourner adjustment) through brief online personalized feedback interventions. A sample of 343 study abroad college students was randomly assigned to one of four conditions including a personalized normative feedback intervention (PNF), a sojourner adjustment feedback intervention (SAF), a combined PNF + SAF intervention, and an assessment-only control condition. Generalized estimated equation analyses accounting for baseline drinking and consequences revealed an intervention effect for PNF that was mitigated by baseline drinking level, such that PNF was best for those with lighter baseline drinking, but heavier baseline drinkers receiving PNF alone or PNF + SAF drank comparatively similar or more heavily abroad to those in the control condition. However, PNF + SAF condition participants with greater baseline levels of consequences reported comparatively less consequences abroad than their control participants. Thus, PNF alone may be helpful for lighter drinkers at predeparture and the addition of SAF to PNF may help prevent consequences abroad for those reporting more consequences prior to departure abroad. This research represents an important first step in designing and implementing efficacious interventions with at-risk study abroad college students, for which no current empirically-based programs exist. PMID:28080092
Pedersen, Eric R; Neighbors, Clayton; Atkins, David C; Lee, Christine M; Larimer, Mary E
2017-03-01
Research documents increased and problematic alcohol use during study abroad experiences for college students yet no research documents effective preventive programs with these students. The present randomized controlled trial was designed to prevent increased and problematic alcohol use abroad by correcting misperceptions of peer drinking norms abroad and by promoting positive and healthy adjustment into the host culture (i.e., sojourner adjustment) through brief online personalized feedback interventions. A sample of 343 study abroad college students was randomly assigned to 1 of 4 conditions including a personalized normative feedback intervention (PNF), a sojourner adjustment feedback intervention (SAF), a combined PNF + SAF intervention, and an assessment-only control condition. Generalized estimated equation analyses accounting for baseline drinking and consequences revealed an intervention effect for PNF that was mitigated by baseline drinking level, such that PNF was best for those with lighter baseline drinking, but heavier baseline drinkers receiving PNF alone or PNF + SAF drank comparatively similar or more heavily abroad to those in the control condition. However, PNF + SAF condition participants with greater baseline levels of consequences reported comparatively less consequences abroad than their control participants. Thus, PNF alone may be helpful for lighter drinkers at predeparture and the addition of SAF to PNF may help prevent consequences abroad for those reporting more consequences prior to departure abroad. This research represents an important first step in designing and implementing efficacious interventions with at-risk study abroad college students, for which no current empirically based programs exist. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.
De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja
2006-06-01
Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.
Endotoxemia and the host systemic response during experimental gingivitis.
Wahaidi, Vivian Y; Kowolik, Michael J; Eckert, George J; Galli, Dominique M
2011-05-01
To assess endotoxemia episodes and subsequent changes in serum inflammatory biomarkers using the experimental gingivitis model. Data from 50 healthy black and white adult males and females were compared for serum concentrations of endotoxin, and serum biomarkers [neutrophil oxidative activity, interleukin (IL)-1β, IL-6, IL-8, C-reactive protein (CRP), and fibrinogen] at baseline, at 3 weeks of experimental gingivitis, and after 2 weeks of recovery. Means were compared using repeated measures analysis of variance. Endotoxemia was reported in 56% of the serum samples at 3 weeks of induced gingivitis. At 2 weeks of recovery, endotoxin levels decreased to levels similar to those reported at baseline. Neutrophil oxidative activity increased significantly following 3 weeks of gingivitis versus baseline (p<0.05). In the endotoxin-negative group this increase was associated with the black subjects whereas in the endotoxin-positive group change in neutrophil activity was driven by the female subpopulation. Serum cytokines, CRP, and fibrinogen levels did not change during the study. Experimental gingivitis was associated with endotoxemia and hyperactivity of circulating neutrophils, but not with changes in systemic levels of cytokines and acute-phase proteins. This may be attributed to the mild nature and the short duration of the induced gingivitis. © 2011 John Wiley & Sons A/S.
Endotoxemia and the host systemic response during experimental gingivitis
Wahaidi, Vivian Y.; Kowolik, Michael J.; Eckert, George J.; Galli, Dominique M.
2011-01-01
Aim To assess endotoxemia episodes and subsequent changes in serum inflammatory biomarkers using the experimental gingivitis model Materials and Methods Data from 50 healthy black and white adult males and females were compared for serum concentrations of endotoxin, and serum biomarkers [neutrophil oxidative activity, interleukin (IL)-1β, IL-6, IL-8, C-reactive protein, and fibrinogen] at baseline, at 3 weeks of experimental gingivitis, and after 2 weeks of recovery. Means were compared using repeated measures ANOVA. Results Endotoxemia was reported in 56% of the serum samples at three weeks of induced gingivitis. At two weeks of recovery, endotoxin levels decreased to levels similar to those reported at baseline. Neutrophil oxidative activity increased significantly following three weeks of gingivitis versus baseline (p<0.05). In the endotoxin-negative group this increase was associated with the black subjects whereas in the endotoxin-positive group change in neutrophil activity was driven by the female subpopulation. Serum cytokines, CRP, and fibrinogen levels did not change during the study. Conclusions Experimental gingivitis was associated with endotoxemia and hyperactivity of circulating neutrophils, but not with changes in systemic levels of cytokines and acute phase proteins. This may be attributed to the mild nature and the short duration of the induced gingivitis. PMID:21320151
Shigehara, Kazuyoshi; Koh, Eitetsu; Sakamoto, Jiro; Yaegashi, Hiroshi; Izumi, Koji; Ueno, Satoru; Kitagawa, Yasuhide; Maeda, Yuji; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Nakashima, Takao; Namiki, Mikio
2014-03-01
We investigated the effects of the relative increase in testosterone by dutasteride administration in patients with benign prostatic hyperplasia and hypogonadism on urinary symptoms or androgen-responsive general health. Seventy-six patients were enrolled, and were taking 0.5 mg dutasteride daily for 52 weeks. Before and after treatment, all participants underwent blood test, and body mass index, prostate volume (PV), bone mineral density (BMD), post-voiding residual (PVR) volume, and muscle volume were measured. All patients responded to the questionnaires: International prostatic symptom score (IPSS), Overactive Bladder Symptom score (OABSS). Patients were divided into two groups according to the increase rate of total testosterone (TT): group A, ≥20% increase in TT level; group B, <20% increase or decrease. Baseline TT and free testosterone (FT) levels were significantly lower in group A than group B. Both groups showed marked improvement in PV and PVR. Group A showed significant improvement in IPSS and OABSS with a significant increase of FT level, whereas group B showed no significant change. Dutasteride treatment contributed to a significant increase in BMD in group A. Dutasteride treatment significantly improved urinary symptoms and BMD in patients with low baseline serum TT and FT levels.
Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics.
Fentoğlu, Özlem; Kirzioğlu, Fatma Yeşim; Tözüm Bulut, Memduha; Kurgan, Şivge; Koçak, Havva; Sütcü, Recep; Kale Köroğlu, Banu; Günhan, Meral
2015-01-01
To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis.
Changes in stress hormones and metabolism during a 105-day simulated Mars mission.
Strollo, Felice; Vassilieva, Galina; Ruscica, Massimiliano; Masini, Mariangela; Santucci, Daniela; Borgia, Luisa; Magni, Paolo; Celotti, Fabio; Nikiporuc, Igor
2014-08-01
The Mars-105 project was aimed at simulating crew's activities, workload, and communication during a mission to Mars, evaluating the homeostatic adaptations to prolonged confinement and cohabitation. Fasting plasma glucose (FPG) and insulin, C-peptide, leptin, cortisol, and NGF and BDNF plasma levels were monitored in six healthy nonsmoking male subjects taking part in a 105-d Mars mission simulation. Samples were collected from each subject before (0 wk), during (2.5 wk; 5 wk; 10 wk; 15 wk), and after confinement (+1 wk). Confinement resulted in impaired glucometabolic parameters, since FPG increased during the first 5 wk (baseline: 85.2 ± 10.8 mg · dl⁻¹; 2.5 wk: 98.4 ± 4.7 mg · dl⁻¹; 5 wk: 92.5 ± 6.0 mg · dl⁻¹) and insulin dropped at 2.5 wk (baseline: 14.4 ± 4.8 mU · L⁻¹; 2.5 wk: 7.7 ± 2.1 mU · L⁻¹), subsequently returning to baseline values. HOMA-IR paralleled plasma insulin, dropping to 1.8 ± 0.5 at 2.5 wk (baseline: 3.0 ± 1.2). At all time-points tested, plasma leptin levels were decreased (baseline: 4.4 ± 3.3 ng · dl⁻¹; 2.5 wk: 1.6 ± 1.2 ng · dl⁻¹; 5 wk: 1.3 ± 0.8 ng · dl⁻¹; 10 wk: 1.5 ± 1.1 ng · dl⁻¹; 15 wk:1.7 ± 0.8 ng · dl⁻¹), whereas cortisol levels were increased (baseline: 10.8 ± 4.9 ng · dl⁻¹; 2.5 wk: 16.8 ± 3.5 ng · dl⁻¹; 5 wk: 18.1 ± 7.6 ng · dl⁻¹; 10 wk: 18.1 ± 8.3 ng · dl⁻¹; 15 wk:14.2 ± 4.4 ng · dl⁻¹), resulting in a negative correlation between these hormones. BDNF levels increased only at 5 and 10 wk (baseline: 67.1 ± 36.0 pg · ml⁻¹; 5 wk: 164 ± 54 pg · ml⁻¹; and 10 wk: 110.2 ± 28.9 pg · ml⁻¹). The data obtained with the Mars-105 experiment suggest that environmental stress has a strong impact upon metabolic and stress response, indicating the need for further studies and the implementation of specific countermeasures.
Aso, Yoshimasa; Terasawa, Tomoko; Kato, Kanako; Jojima, Teruo; Suzuki, Kunihiro; Iijima, Toshie; Kawagoe, Yoshiaki; Mikami, Shigeru; Kubota, Yoshiro; Inukai, Toshihiko; Kasai, Kikuo
2013-11-01
A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (β = 0.382, P = 0.007) and HOMA-IR (β = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 μg/mL (interquartile range, from 2.80 to 6.65 μg/mL) at baseline to 4.17 μg/mL (interquartile range, from 2.48 to 6.96 μg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle. Copyright © 2013 Mosby, Inc. All rights reserved.
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.
Vitamin A status of Filipino preschool children given a massive oral dose.
Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I
1996-12-01
The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.
Akay, Aynur Pekcanlar; Resmi, Halil; Güney, Sevay Alsen; Erkuran, Handan Özek; Özyurt, Gonca; Sargin, Enis; Topuzoglu, Ahmet; Tufan, Ali Evren
2018-01-01
Brain-derived neurotrophic factor (BDNF) is an important neurotrophin in the brain that modulates dopaminergic neurons. In this study, we aimed to investigate the changes in serum BDNF levels of children with attention-deficit/hyperactivity disorder (ADHD) in response to OROS methylphenidate treatment. We also aimed to determine whether there were any pre-post-differences between ADHD subtypes and comorbid psychiatric disorders in serum BDNF levels. Fifty male children with ADHD and 50 male healthy controls within the age range of 6-12 years were recruited to the study. The psychiatric diagnoses were determined by applying a structured interview with Kiddie schedule for affective disorders and schizophrenia for school-age children-present and lifetime version. The symptom severity of ADHD was measured using the Clinical Global Impression ADHD Severity Scale (CGI-S). Physicians completed Du Paul ADHD questionnaires. The levels of serum BDNF were assessed before and after 8 weeks of treatment with effective dosages of OROS methylphenidate. In the present study, the mean serum BDNF levels of boys with ADHD and of the healthy controls were 2626.33 ± 1528.05 and 2989.11 ± 1420.08 pg/mL, respectively. Although there were no statistically significant difference between the ADHD group and healthy controls at baseline (p = 0.22), the increase of serum BDNF was statistically significant from baseline to endpoint in the ADHD group (p = 0.04). The mean serum BDNF levels at baseline and endpoint of the ADHD group were 2626.33 ± 1528.05 and 3255.80 ± 1908.79 pg/mL, respectively. The serum BDNF levels of ADHD-inattentive subtype were significantly lower at baseline (p = 0.02), whereas BDNF levels post-treatment showed no significant difference. The increase of serum BDNF levels with methylphenidate treatment after 8 weeks was significantly higher in the inattentive group (p = 0.005). The increase of serum BDNF levels with methylphenidate treatment after 8 weeks in boys with ADHD may support the potential role of BDNF in the pathophysiology of ADHD. The role of BDNF in ADHD subtypes in particular should be evaluated with further, larger studies.
Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi
2015-01-01
The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445
Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi
2015-05-06
The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.
Roads are associated with a blunted stress response in a North American pit viper.
Owen, Dustin A S; Carter, Evin T; Holding, Matthew L; Islam, Kamal; Moore, Ignacio T
2014-06-01
Whereas numerous studies have examined roads as anthropogenic stressors in birds and mammals, comparatively few studies have been undertaken on reptiles. We investigated plasma corticosterone (CORT) levels at baseline and following 30min of restraint stress in free-ranging copperhead snakes (Agkistrodon contortrix) captured within the forest interior or while in contact with public roads. There was no difference in baseline CORT levels between snakes in the forest and on roads. Copperheads responded to restraint stress by increasing plasma levels of CORT; however snakes on roads exhibited a lower CORT stress response compared to forest snakes. Additionally, among snakes captured on roads there was a negative association between road traffic and baseline CORT, stressed CORT, and the magnitude of the CORT response. Our results suggest that roads are associated with a blunted stress response in copperheads. Reduced stress responses may be indicative of acclimation, the inhibited ability to mount a stress response in the face of prolonged chronic stress, or that road environments select for individuals with lower CORT responsiveness. Either scenario could result in increased road mortality if snakes do not perceive roads as a potential threat. Copyright © 2014 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Lüning, Sebastian; Vahrenholt, Fritz
2017-12-01
The Paris Agreement adopted in December 2015 during the COP21 conference stipulates that the increase in the global average temperature is to be kept well below 2°C above “pre-industrial levels” and that efforts are pursued to limit the temperature increase to 1.5°C above “pre-industrial levels”. In order to further increase public acceptance of these limits it is important to transparently place the target levels and their baselines in a paleoclimatic context of the past 150,000 years (Last Interglacial, LIG) and in particular of the last 10,000 years (Holocene; Present Interglacial, PIG). Intense paleoclimatological research of the past decade has firmed up that pre-industrial temperatures have been highly variable which needs to be reflected in the pre-industrial climate baseline definitions. The currently used reference level 1850-1900 represents the end of the Little Ice Age (LIA).The LIA represents the coldest phase of the last 10,000 years when mean temperatures deviated strongly negatively from the Holocene average and which therefore are hard to justify as a representative pre-industrial baseline. The temperature level reached during the interval 1940-1970 may serve as a better reference level as it appears to roughly correspond to the average pre-industrial temperature of the past two millennia. Placing the climate limits in an enlarged paleoclimatic context will help to demonstrate that the chosen climate targets are valid and represent dangerous extremes of the known natural range of Holocene temperature variability.
Gourlan, M; Sant, F; Boiche, J
2014-12-01
Regular physical activity (PA) practice represents a key component of obesity treatment. Drawing upon Self-Determination Theory, the purpose of this study was twofold. The first aim was to evaluate among obese adolescents the impact of a supervised exercise program supporting autonomy on their motivation to practice PA at the end of the intervention. The second aim was to evaluate the impact of the program on their level of PA one month after the end of the intervention. Eighteen obese adolescents (mean age=14.3 years, mean BMI=33.47 kg/m²) were recruited to participate in an 11-week residential obesity treatment program. They received a 45-minute supervised exercise session each week. Motivational regulations were assessed at baseline and at the end of the intervention (via the Exercise Motivation Scale). PA practice was assessed at baseline and one month after the end of the intervention (via the 7-day PA recall interview). The analyses revealed that adolescents' levels of autonomy increased, that their levels of intrinsic motivation tended to increase, and that their level of external regulation tended to decrease. In addition, the participants increased their habitual PA practice one month after the end of the intervention in comparison to baseline. This study highlights that supporting autonomy during supervised exercise sessions appears as an effective strategy to promote PA among obese adolescents because it fosters internalization of the behavior.
Riechert, Juliane; Chastel, Olivier; Becker, Peter H
2014-01-01
Hormones are involved in reproductive decisions, linking environmental cues and body condition and adapting behavior. Mass loss is often accompanied by decreased prolactin and increased corticosterone concentrations, influencing incubation and brooding behavior and ultimately triggering nest desertion. Using blood-sucking bugs (Dipetalogaster maxima), we measured baseline prolactin, corticosterone, and ketone body values in incubating common terns (Sterna hirundo) between 2006 and 2009 during energy-demanding periods: 50 pairs were sampled hungry (after an incubation bout) and again fed (after foraging). In a second approach, we sampled 57 other pairs (experienced and inexperienced birds) three times over their individual breeding period, because reproduction, especially chick rearing, is a very energy-demanding process. In line with the common physiological pattern of fasting, we found significantly lower baseline prolactin values in hungry terns, which were negatively related to mass loss over the incubation bout, whereas corticosterone and ketone body levels were marginally increased. Compared to that in the incubation phase, the prolactin level dropped after hatching of chicks in inexperienced birds, perhaps indicating lower parental expenditure. Corticosterone, on the other hand, increased after hatching in males, probably linked to higher foraging activity, as males mainly deliver food during the first days. These energy-demanding periods clearly influenced hormones and ketone bodies, maybe reinforced by the low energy margin of this small seabird species, but energy reserves were not depleted to a level affecting behavior or reproductive success.
Tin'kov, Aleksey N; Aksenov, Valeriy A
2002-01-01
The objective of the study was to evaluate the effects of intermittent hypobaric hypoxia (IHH) on plasma lipid concentrations of male coronary heart disease (CHD) patients. Forty-six male coronary patients were enrolled in the study. Thirty had a history of myocardial infarction and 16 had ischemic episodes documented by ergometer testing or Holter monitoring. The patients underwent acclimation to hypoxia by means of a protocol of intermittent exposure in a hypobaric chamber. Lipid profiles, including coefficient of atherogenity (CA) by A.N. Klimov, were assessed at baseline, on completion of the study, and at 3-, 6-, and 10-month follow-ups. Total cholesterol decreased by 7% on completion of the IHH and by 9% at 3 months and persisted on that level to month 6. HDL levels increased by 12% at 3-month follow-up and remained significantly higher than baseline until month 6. LDL levels declined on completion of IHH, but the changes from baseline were most prominent at 3-month (13%) and 6-month (11%) follow-ups. Similar changes were found in levels of VLDL and TG. CA declined by 26% on treatment completion and by 37% at 3-month follow-up and increased to baseline at 10 months. No changes in lipid profiles were found in patients with CA < 3 (n = 22). In subjects with CA > 3 (n = 24), beneficial effects were more pronounced. IHH in CHD patients with abnormal lipid metabolism leads to favorable changes of plasma lipid patterns persisting to month 6 following IHH.
A Statistical Simulation Approach to Safe Life Fatigue Analysis of Redundant Metallic Components
NASA Technical Reports Server (NTRS)
Matthews, William T.; Neal, Donald M.
1997-01-01
This paper introduces a dual active load path fail-safe fatigue design concept analyzed by Monte Carlo simulation. The concept utilizes the inherent fatigue life differences between selected pairs of components for an active dual path system, enhanced by a stress level bias in one component. The design is applied to a baseline design; a safe life fatigue problem studied in an American Helicopter Society (AHS) round robin. The dual active path design is compared with a two-element standby fail-safe system and the baseline design for life at specified reliability levels and weight. The sensitivity of life estimates for both the baseline and fail-safe designs was examined by considering normal and Weibull distribution laws and coefficient of variation levels. Results showed that the biased dual path system lifetimes, for both the first element failure and residual life, were much greater than for standby systems. The sensitivity of the residual life-weight relationship was not excessive at reliability levels up to R = 0.9999 and the weight penalty was small. The sensitivity of life estimates increases dramatically at higher reliability levels.
The effect of a therapeutic lithium level on a stroke-related cerebellar tremor.
Orleans, Rachel A; Dubin, Marc J; Kast, Kristopher A
2018-01-24
Lithium is a mood stabiliser used in the treatment of acute mania, bipolar disorder and as augmentation for unipolar major depression. Tremor is a common adverse effect associated with lithium at both therapeutic and toxic serum levels. We present a case of dose-dependent changes in the quality and intensity of a stroke-related, chronic cerebellar tremor with lithium treatment at serum levels within the therapeutic range. On admission, the patient in this case had a baseline fine, postural tremor, which increased in frequency and evolved to include myoclonic jerks once lithium therapy was initiated. Although the patient's serum lithium level was never in the toxic range, his tremor returned to baseline on reduction of his serum lithium level. This case highlights that a pre-existing, baseline tremor may lower the threshold for developing myoclonus. It also suggests that caution may be warranted with lithium therapy in the setting of known cerebellar disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Nikseresht, Mahmoud
2018-06-01
Nikseresht, M. Comparison of serum cytokine levels in men who are obese or men who are lean: effects of nonlinear periodized resistance training and obesity. J Strength Cond Res 32(6): 1787-1795, 2018-This study examined the capacity of nonlinear resistance training (NRT) to alter some cytokines and markers of insulin resistance in men who are obese. An additional aim was to compare these variables between men who are obese and men who are lean. Age- and fitness-matched men who are obese were randomly allocated to NRT (n = 12) and control (CON, n = 10) groups. An age- and fitness-matched control group of lean men (n = 11) were also recruited for baseline comparison. The NRT (12 weeks, 3 d·wk, 5-11 exercises) performed at different intensities (40-95% of 1 repetition maximum) with flexible periodization. Serum insulin, glucose, interleukin (IL)-6, IL-10, IL-17A, and IL-20 levels were measured at baseline and after training. Men who were obese had significantly lower IL-20 and higher glucose, insulin, insulin resistance (homeostasis model assessment, HOMA-IR), IL-10, and IL-6 than lean participants at baseline (all, p ≤ 0.05). There were significant negative correlations between IL-10 with anthropometric markers and HOMA-IR at baseline, whereas these variables were inversely correlated with IL-20. After training, V[Combining Dot Above]O2peak and 1 repetition maximum for bench press and knee extension of the NRT increased significantly compared with CON, which was accompanied by significant reductions in anthropometric markers, insulin and HOMA-IR. IL-6 and IL-17A did not change significantly in response to training, but IL-10 and IL-20 increased significantly compared with baseline. An inverse relationship between the percent IL-20 increase and the percent waist circumference decrease suggests that adipocytes, or other metabolic factors such as glucose, may exert a lowering-effect on IL-20.
Hwang, You-Cheol; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Kahn, Steven E; Leonetti, Donna L; Boyko, Edward J
2016-02-01
Atherogenic dyslipidemia is frequently observed in persons with a greater amount of visceral adipose tissue (VAT). However, it is still uncertain whether VAT is independently associated with the future development of atherogenic dyslipidemia. The aim of this study was to determine whether baseline and changes in VAT and subcutaneous adipose tissue (SAT) are associated with future development of atherogenic dyslipidemia independent of baseline lipid levels and standard anthropometric indices. Community-based prospective cohort study with 5 years of follow-up. A total of 452 Japanese Americans (240 men, 212 women), aged 34-75 years were assessed at baseline and after 5 years of follow-up. Abdominal fat areas were measured by computed tomography. Atherogenic dyslipidemia was defined as one or more abnormalities in high-density lipoprotein (HDL) cholesterol, triglycerides, or non-HDL cholesterol levels. Baseline VAT and change in VAT over 5 years were independently associated with log-transformed HDL cholesterol, log-transformed triglyceride, and non-HDL cholesterol after 5 years (standardized β = -0.126, 0.277, and 0.066 for baseline VAT, respectively, and -0.095, 0.223, and 0.090 for change in VAT, respectively). However, baseline and change in SAT were not associated with any future atherogenic lipid level. In multivariate logistic regression analysis, incremental change in VAT (odds ratio [95% confidence interval], 1.73 [1.20-2.48]; P = .003), triglycerides (4.01 [1.72-9.33]; P = .001), HDL cholesterol (0.32 [0.18-0.58]; P < .001), and non-HDL cholesterol (7.58 [4.43-12.95]; P < .001) were significantly associated with the future development of atherogenic dyslipidemia independent of age, sex, diastolic blood pressure, homeostasis model assessment insulin resistance, body mass index (BMI), change in BMI, SAT, and baseline atherogenic lipid levels. Baseline and change in VAT were independent predictors for future development of atherogenic dyslipidemia. However, BMI, waist circumference, and SAT were not associated with future development of atherogenic dyslipidemia.
Bayram, F; Elbuken, G; Korkmaz, C; Aydogdu, A; Karaca, Z; Cakır, I
2016-02-01
Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH. © Georg Thieme Verlag KG Stuttgart · New York.
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.
NASA Technical Reports Server (NTRS)
Skillen, Michael D.; Crossley, William A.
2008-01-01
This report presents an approach for sizing of a morphing aircraft based upon a multi-level design optimization approach. For this effort, a morphing wing is one whose planform can make significant shape changes in flight - increasing wing area by 50% or more from the lowest possible area, changing sweep 30 or more, and/or increasing aspect ratio by as much as 200% from the lowest possible value. The top-level optimization problem seeks to minimize the gross weight of the aircraft by determining a set of "baseline" variables - these are common aircraft sizing variables, along with a set of "morphing limit" variables - these describe the maximum shape change for a particular morphing strategy. The sub-level optimization problems represent each segment in the morphing aircraft's design mission; here, each sub-level optimizer minimizes fuel consumed during each mission segment by changing the wing planform within the bounds set by the baseline and morphing limit variables from the top-level problem.
Benefits of intensive resistance training in patients with chronic polymyositis or dermatomyositis.
Alexanderson, Helene; Dastmalchi, Maryam; Esbjörnsson-Liljedahl, Mona; Opava, Christina H; Lundberg, Ingrid E
2007-06-15
To investigate the benefits and safety of an intensive muscular training program in patients with chronic polymyositis (PM) and dermatomyositis (DM). Nine patients with chronic PM or DM (median age 53 years, range 44-61) were included. Assessments of impairment (10-15 voluntary repetition maximum [VRM], the Functional Index 2 [FI-2], the Grippit, and pain rated on the Borg CR-10 scale), activity limitation (Myositis Activities Profile), and participation restriction (patients' disease impact on well-being) were performed 4 weeks prior to baseline, at baseline, and after 7 weeks of exercise. A 6-item core set of disease activity measures was administered and muscle biopsy samples of vastus lateralis were obtained at baseline and after 7 weeks of exercise. Response criteria at an individual level were set for disability and disease activity. The patients exercised 3 days per week for 7 weeks on loads allowing 10 VRM. On a group level there were no significant differences between assessments at 4 weeks before baseline compared with baseline. The group improved significantly regarding 10-15 VRM and FI-2 at 7 weeks compared with baseline (P < 0.05). All patients were responders with respect to impairment and 2 were activity limitation responders whereas participation restriction remained unchanged in all. Two patients were responders with reduced disease activity and no patient had signs of increased muscle inflammation in the muscle biopsy sample after 7 weeks of exercise. Patients with chronic, stable PM and DM can perform this intensive resistive exercise program with beneficial effects on impairment and activity limitation without increased muscle inflammation.
Vicente-Herrero, M Teofila; Lladosa Marco, Silvia; Ramírez-Iñiguez de La Torre, M Victoria; Terradillos-García, M Jesús; López-González, Ángel Arturo
2014-05-01
Hearing loss due to noise is considered within the prevention plans of the most common occupational diseases. In addition to evaluation of working conditions, other personal factors increasing the risk of hypoacusis, such as diabetes, should be taken into account. To explore hearing loss in the workplace and its relationship to impaired fasting baseline blood glucose levels. An observational, cross-sectional study enrolling 1636 workers from service companies was conducted. Full audiometric evaluation was performed at different frequencies: high frequency (HF), early loss index (ELI), speech average loss (SAL), and monaural and binaural loss. Results were categorized by baseline blood glucose levels: G1 (<100mg/dl), G2 (100-125mg/dl), and G3 (>125mg/dl). Based on both HF and ELI, 11% of workers had clear indication of deafness. Women with G3 levels showed significant differences in the results of HF and ELI indexes as compared to the G1 group (P=.038 and .046, respectively). A positive association was found between hearing loss and G3 blood glucose levels in HF (OR: .338; p=.002), ELI (OR: .407; p=.007), and the monaural test in the left ear (OR: 4.77×10-5; p=.006). Despite the methodological limitations of this study, there is evidence for an increased risk of high frequency hearing loss in workers with high baseline blood glucose levels. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.
McGarvey, S T; Aligui, G; Graham, K K; Peters, P; Olds, G R; Olveda, R
1996-05-01
The hypothesis that infection with Schistosoma japonicum causes decreased nutritional status was studied in a randomized trial among 170 males and females, mean (SD) age 11.4 (3.5) years, residing in an endemic region of northeastern Leyte, Philippines. The S. japonicum-infected children were randomized to receive praziquantel or placebo and followed-up six months after randomization. Stature, weight, triceps, subscapular, and calf skinfold thicknesses and their sum, and hemoglobin level were measured at baseline and follow-up. Schistosoma japonicum eggs were detected in Kato-Katz stool smears and the intensity of infection was assessed by quantitative egg count. Intensities of hookworm, ascaris, and trichuris infections were also measured. The six-month levels of the anthropometric measures and hemoglobin were adjusted for age and their baseline levels and then compared between the praziquantel and placebo groups. Treatment interactions were also analyzed by sex. Baseline anthropometric and hemoglobin levels and parasite infection intensities were the same in the two groups. At six months, the praziquantel group had significantly higher hemoglobin levels (P < 0.001) and sum of skinfolds (P < 0.001) than the placebo group. Males had a significantly greater increase in hemoglobin levels with treatment than did females. The hemoglobin increase was not due to changes in hookworm intensity. The results show that schistosomiasis japonica caused decreased nutritional status in children and probably is partly responsible for the malnutrition and reduction in growth for age described in prior cross-sectional studies.
Hypoglycemia Reduction and Changes in Hemoglobin A1c in the ASPIRE In-Home Study.
Weiss, Ram; Garg, Satish K; Bode, Bruce W; Bailey, Timothy S; Ahmann, Andrew J; Schultz, Kenneth A; Welsh, John B; Shin, John J
2015-08-01
ASPIRE In-Home randomized 247 subjects with type 1 diabetes to sensor-augmented pump therapy with or without the Threshold Suspend (TS) feature, which interrupts insulin delivery at a preset sensor glucose value. We studied the effects of TS on nocturnal hypoglycemia (NH) in relation to baseline hemoglobin A1c (A1C) and change in A1C during the study. NH event rates and mean area under curve (AUC) of NH events were evaluated at different levels of baseline A1C (<7%, 7-8%, and >8%) and at different levels of changes in A1C (less than -0.3% [decreased], -0.3% to 0.3% [stable], and >0.3% [increased]), in the TS Group compared with the Control Group (sensor-augmented pump only). In the TS Group, 27.9% of the NH events were accompanied by a confirmatory blood glucose value, compared with 39.3% in the Control Group. Among subjects with baseline A1C levels of <7% or 7-8%, those in the TS Group had significantly lower NH event rates than those in the Control Group (P=0.001 and P=0.004, respectively). Among subjects with decreased or stable A1C levels, those in the TS Group had significantly lower NH event rates, and the events had lower AUCs (P≤0.001 for each). Among subjects with increased A1C levels, those in the TS Group had NH events with significantly lower AUCs (P<0.001). Use of the TS feature was associated with decreases in the rate and severity (as measured by AUC) of NH events in many subjects, including those with low baseline A1C levels and those whose A1C values decreased during the study period. Use of the TS feature can help protect against hypoglycemia in those wishing to intensify diabetes management to achieve target glucose levels.
Hypoglycemia Reduction and Changes in Hemoglobin A1c in the ASPIRE In-Home Study
Weiss, Ram; Garg, Satish K.; Bode, Bruce W.; Bailey, Timothy S.; Ahmann, Andrew J.; Schultz, Kenneth A.; Welsh, John B.
2015-01-01
Abstract Background: ASPIRE In-Home randomized 247 subjects with type 1 diabetes to sensor-augmented pump therapy with or without the Threshold Suspend (TS) feature, which interrupts insulin delivery at a preset sensor glucose value. We studied the effects of TS on nocturnal hypoglycemia (NH) in relation to baseline hemoglobin A1c (A1C) and change in A1C during the study. Materials and Methods: NH event rates and mean area under curve (AUC) of NH events were evaluated at different levels of baseline A1C (<7%, 7–8%, and >8%) and at different levels of changes in A1C (less than −0.3% [decreased], −0.3% to 0.3% [stable], and >0.3% [increased]), in the TS Group compared with the Control Group (sensor-augmented pump only). Results: In the TS Group, 27.9% of the NH events were accompanied by a confirmatory blood glucose value, compared with 39.3% in the Control Group. Among subjects with baseline A1C levels of <7% or 7–8%, those in the TS Group had significantly lower NH event rates than those in the Control Group (P=0.001 and P=0.004, respectively). Among subjects with decreased or stable A1C levels, those in the TS Group had significantly lower NH event rates, and the events had lower AUCs (P≤0.001 for each). Among subjects with increased A1C levels, those in the TS Group had NH events with significantly lower AUCs (P<0.001). Conclusions: Use of the TS feature was associated with decreases in the rate and severity (as measured by AUC) of NH events in many subjects, including those with low baseline A1C levels and those whose A1C values decreased during the study period. Use of the TS feature can help protect against hypoglycemia in those wishing to intensify diabetes management to achieve target glucose levels. PMID:26237308
Ushida, Yuka; Koshy, Geena; Kawashima, Yoko; Kiji, Makoto; Umeda, Makoto; Nitta, Hiroshi; Nagasawa, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi
2008-11-01
This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.
Message Framing and Physical Activity Promotion in Colorectal Cancer Survivors.
Hirschey, Rachel; Lipkus, Isaac; Jones, Lee; Mantyh, Christopher; Sloane, Richard; Demark-Wahnefried, Wendy
2016-11-01
To test effects of gain-framed versus loss-framed mailed brochures on increasing physical activity (PA) among colorectal cancer (CRC) survivors. . Randomized trial with repeated measures at baseline, 1 month, and 12 months postintervention. . Mail recruitment from tumor registries. . 148 inactive CRC survivors who had completed primary therapy. . PA and constructs from the Theory of Planned Behavior (TPB) were assessed at baseline, 1 month, and 12 months. Participants were randomized to receive pamphlets describing PA benefits (gain framed) or disadvantages of not being physically active (loss framed). Baseline characteristics were compared using descriptive statistics. Repeated measures linear models were used to test PA changes. . Minutes of PA and TPB constructs. . Significant PA increases were observed in both study arms. Results did not differ by message frame. At one month, about 25% of previously inactive participants increased activity to national recommendations. Those who increased PA compared to those who did not had higher baseline scores on subjective norms, perceived behavioral control, and PA intentions. . Independent of message framing, mailed brochures are highly effective in producing within-subject short- and long-term increases in PA. . CRC survivors may increase short- and long-term levels of PA by receiving inexpensive print brochures.
Leelarungrayub, Donrawee; Saidee, Kunteera; Pothongsunun, Prapas; Pratanaphon, Sainetee; YanKai, Araya; Bloomer, Richard J
2011-07-01
This study evaluated the change in blood oxidative stress, blood interleukin-2, and physical performance following 6 weeks of moderate intensity and duration aerobic dance exercise in 24 sedentary women. Blood samples were collected at rest twice before (baseline) and after the 6-week intervention for analysis of protein hydroperoxide (PrOOH), malondialdehyde (MDA), total anti-oxidant capacity (TAC), and interleukin-2 (IL-2) levels. Maximal treadmill run time (Time(max)) and maximal oxygen consumption (VO(2max)) were also measured. All variables were statistically analyzed with a repeated measurement ANOVA and Tukey post hoc. No differences were noted in any variable during the baseline period (p > 0.05). After aerobic dance exercise, VO(2max), Time(max), TAC and IL-2 were significantly increased, whereas MDA levels were decreased significantly (p < 0.05). PrOOH did not change either between baseline measures or after exercise. It can be concluded that aerobic dance exercise at a moderate intensity and duration can improve physical fitness, decrease MDA, and increase TAC and IL-2 in previously sedentary women. Copyright © 2010 Elsevier Ltd. All rights reserved.
Ono, Kim E; Burns, Thomas G; Bearden, Donald J; McManus, Susan M; King, Harold; Reisner, Andrew
2016-03-01
To date, few studies have delineated clear sex-based differences in symptom resolution after a sports-related concussion (SRC), and equivocal results have been identified in sex-based differences on baseline assessments. To assess whether female athletes displayed prolonged recovery and more symptoms at baseline and after an SRC compared with male athletes. Cohort study; Level of evidence, 3. The current study assessed 135 male and 41 female athletes (10-18 years old) who participated in high-impact sports in metropolitan Atlanta middle and high schools. All athletes completed a baseline assessment and at least 1 postconcussion assessment from the Immediate Post-Concussion Assessment and Cognitive Testing battery. Longitudinal hierarchical linear modeling was employed to examine individual-level variables and their associations with adolescents' rates of recovery in concussive symptoms after controlling for age and number of prior concussions. Aggregate symptoms were rated as higher in female athletes compared with male athletes at baseline (mean ± SD: females, 13.49 ± 11.20; males, 4.88 ± 8.74; F(1,175) = 10.59, P < .001) and immediately after a concussion (females: 16.75 ± 18.08; males: 10.58 ± 14.21; F(1,175) = 3.99, P = .05). There were no group differences in the slope of recovery between male and female athletes, indicating generally similar trajectories of change for both groups. Post hoc analyses revealed higher baseline levels of migraine and neuropsychological symptoms in female athletes. Although female athletes in the current study reported increased symptoms, identical recovery patterns were observed in both sexes, suggesting that sex-based differences in concussion recovery are better explained by increased symptom frequency among female athletes when compared with their male counterparts. © 2015 The Author(s).
Shojaee, Majid; Sabzghabaei, Anita; Alimohammadi, Hossein; Derakhshanfar, Hojjat; Amini, Afshin; Esmailzadeh, Bahareh
2017-01-01
Finding the probable governing pattern of PEEP and CVP changes is an area of interest for in-charge physicians and researchers. Therefore, the present study was designed with the aim of evaluating the relationship between the mentioned pressures. In this quasi-experimental study, patients under mechanical ventilation were evaluated with the aim of assessing the effect of PEEP change on CVP. Non-trauma patients, over 18 years of age, who were under mechanical ventilation and had stable hemodynamics, with inserted CV line were entered. After gathering demographic data, patients underwent 0, 5, and 10 cmH 2 O PEEPs and the respective CVPs of the mentioned points were recorded. The relationship of CVP and PEEP in different cut points were measured using SPSS 21.0 statistical software. 60 patients with the mean age of 73.95 ± 11.58 years were evaluated (68.3% male). The most frequent cause of ICU admission was sepsis with 45.0%. 5 cmH 2 O increase in PEEP led to 2.47 ± 1.53 mean difference in CVP level. If the PEEP baseline is 0 at the time of 5 cmH 2 O increase, it leads to a higher raise in CVP compared to when the baseline is 5 cmH 2 O (2.47 ± 1.53 vs. 1.57 ± 1.07; p = 0.039). The relationship between CVP and 5 cmH 2 O (p = 0.279), and 10 cmH 2 O (p = 0.292) PEEP changes were not dependent on the baseline level of CVP. The findings of this study revealed the direct relationship between PEEP and CVP. Approximately, a 5 cmH 2 O increase in PEEP will be associated with about 2.5 cmH 2 O raise in CVP. When applying a 5 cmH 2 O PEEP increase, if the baseline PEEP is 0, it leads to a significantly higher raise in CVP compared to when it is 5 cmH 2 O (2.5 vs. 1.6). It seems that sex, history of cardiac failure, baseline CVP level, and hypertension do not have a significant effect in this regard.
Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang
2017-10-03
The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.
Song, Jing; Nagae, Masaki; Soyano, Kiyoshi
2018-07-01
Field surveys of the impact of environmental estrogen (EE) pollution in aquatic wildlife have been conducted using vitellogenin (VTG) as a biomarker to evaluate the influence of EE. However, a standard baseline of VTG level that can be used to evaluate EE pollution has not been fully determined. To the best of our knowledge, the present study is the first to determine the standard baseline VTG level for evaluating the biological effects of EE pollution using the Japanese common goby (Acanthogobius flavimanus) as the target model fish. Plasma VTG and estradiol-17β (E 2 ) levels associated with the reproductive cycle of wild goby inhabiting an unpolluted environment were measured. Mean plasma VTG and E 2 levels exhibited similar changes, increasing in the yolk vesicle stage and peaking in the tertiary yolk stage in females. However, plasma VTG and E 2 levels showed no significant changes in males, remaining at low levels throughout the reproductive cycle. The highest VTG levels in females and males were 1.6 mg ml -1 and 124.87 ng ml -1 , respectively. These results indicate that the baseline level (normal level) in males was approximately 130 ng ml -1 at most. We concluded that the threshold between normal and abnormal levels with a 10% risk rate was 150 ng ml -1 in the wild male goby. Plasma VTG levels in males captured from Nagasaki Harbor were higher than the threshold in each reproductive developmental stage, indicating the possibility of EE pollution at this site. The biological standard baseline for VTG established in this study is useful for assessing EE pollution in natural waters. Copyright © 2018 John Wiley & Sons, Ltd.
Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang
2017-01-01
ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR. PMID:28267407
NASA Astrophysics Data System (ADS)
Mann, M. E.; Schurer, A. P.; Hawkins, E.; Tett, S. F.; Hegerl, G. C.
2017-12-01
During the Paris Conference in 2015, nations of the world strengthened the United NationsFramework Convention on Climate Change by agreeing to holding "the increase in the globalaverage temperature to well below 2°C above pre-industrial levels and pursuing efforts to limitthe temperature increase to 1.5°C. However, "pre-industrial" was not defined. Here weinvestigate the implications of different choices of the pre-industrial baseline on the likelihood ofexceeding these two temperature thresholds. We find that for the strongest mitigation scenarioRCP2.6 and a medium scenario RCP4.5 the probability of exceeding the thresholds and timingof exceedance is highly dependent on the pre-industrial baseline, for example the probability ofcrossing 1.5°C by the end of the century under RCP2.6, varies from 61% to 88% depending onhow the baseline is defined. In contrast, in the scenario with no mitigation, RCP8.5, boththresholds will almost certainly be exceeded by the middle of the century with the definition ofthe pre-industrial baseline of less importance. Allowable carbon emissions for thresholdstabilisation are similarly highly dependent on the pre-industrial baseline. For stabilisation at2°C, allowable emissions decrease by as much as 40% when earlier than 19th century climatesare considered as a baseline.
Acute stress induces increases in salivary IL-10 levels.
Szabo, Yvette Z; Newton, Tamara L; Miller, James J; Lyle, Keith B; Fernandez-Botran, Rafael
2016-09-01
The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1β, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1β/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.
Preliminary evidence that self-efficacy predicts physical activity in multiple sclerosis.
Motl, Robert W; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S
2009-09-01
Individuals with multiple sclerosis (MS) are less physically active than non diseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and prospective correlates of objectively measured physical activity in 16 individuals with a diagnosis of MS. The participants completed two measures of self-efficacy and then wore an accelerometer for a 5-day period at baseline and then at 3 months follow-up. Self-efficacy for continued physical activity was associated with baseline and follow-up levels of physical activity. Self-efficacy for overcoming barriers was associated with follow-up levels of physical activity and change in physical activity across a 3-month period. Researchers should consider self-efficacy as a possible component of an intervention that is designed to increase physical activity levels in those with MS. International Journal of Rehabilitation Research
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.
Helmink, Judith H M; Gubbels, Jessica S; van Brussel-Visser, Femke N; de Vries, Nanne K; Kremers, Stef P J
2013-05-08
The aim of this study was to explore the predictive value of baseline characteristics in relation to changes in physical activity (PA) and sedentary behaviour among diabetic and pre-diabetic patients participating in a primary care based exercise intervention. We used a descriptive case series among diabetic and pre-diabetic patients (n = 119, 50.8% male, mean age 65.5 (SD = 7.8)). Measurements took place with questionnaires at baseline and two years after the start of the intervention. Predictor variables included demographic factors, Body Mass Index, baseline PA and sitting time, and baseline socio-cognitive profile. At follow-up, respondents spent more time being physically active than at baseline. For the total group, the average sitting time remained almost unchanged between the two measurements. Further exploration showed that respondents who had relatively high levels of PA at the start of the intervention, increased their total sitting time, while respondents with relatively low levels of PA at the start decreased their sitting time. The socio-cognitive profile did not predict behaviour change. The intervention appeared to be suitable for people with a low-education level, but the results should be interpreted in view of the limitations of the study such as the non-controlled design, self-reported outcomes and selective drop-out of participants. Interventions for this specific target group may need to put more emphasis on the prevention of increased sitting time. The finding that the socio-cognitive profile did not predict behaviour change may underline the proposition that decisions to initiate and maintain PA behaviour change are to a large extend non-linear events. Acknowledging the possible non-linearity of the relationship between socio-cognitive determinants and behaviour change will help our understanding of this complex and dynamic process.
Zheng, Yan; Hu, Frank B; Ruiz-Canela, Miguel; Clish, Clary B; Dennis, Courtney; Salas-Salvado, Jordi; Hruby, Adela; Liang, Liming; Toledo, Estefania; Corella, Dolores; Ros, Emilio; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluis; Estruch, Ramón; Martínez-González, Miguel A
2016-09-15
Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. URL: www.controlled-trials.com. Unique identifier: ISRCTN 35739639. © 2016 The Authors and The Broad Institute. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Evaluation of nutrient status after laparoscopic sleeve gastrectomy 1, 3, and 5 years after surgery.
Saif, Taha; Strain, Gladys W; Dakin, Gregory; Gagner, Michel; Costa, Ricardo; Pomp, Alfons
2012-01-01
Laparoscopic sleeve gastrectomy evolved as a primary bariatric procedure with little information on its nutritional effects. Our objective was to assess the longer term micronutrient and vitamin status after laparoscopic sleeve gastrectomy at a university hospital. Measurements of ferritin, iron, total iron binding capacity, hemoglobin, hematocrit, parathyroid hormone, albumin, calcium, magnesium, phosphorus, zinc, folate, and vitamins A, B1, B12, and D were obtained at baseline and 1, 3, and 5 years after surgery. Two-sample t tests with multiple adjusted comparisons and Fisher's exact test were used to determine deficiency. A total of 82 patients (67% women), with a mean age of 46.4 years and a baseline body mass index 55.7 kg/m2 were included in the present study (35 at 1, 27 at 3, and 30 at 5 years postoperatively). The percentage of excess body mass index loss was 58.5% at year 1 in 35 patients, 63.1% at year 3 in 27 patients, and 46.1% at year 5 in 30 patients. The parathyroid hormone level decreased from 75.0 to 49.6 ng/mL in year 1 to 40.7 ng/mL in year 3. The year 5 levels increased to 99.6 ng/mL. The mean vitamin D level increased from 23.6 ng/mL to 35.0, 32.1 and 34.8 at years 1, 3, and 5 (P = .05 for baseline to year 1). The vitamin D level was less than normal in 42% of the patients at year 5. After normalization from baseline, by year 5, parathyroid hormone had increased in 58.3% of patients. At year 5, vitamin B1 was less than normal in 30.8% of patients, and hemoglobin and hematocrit were less than normal in for 28.6% and 25% of patients, respectively. Finally, 28.9% of patients reported taking supplements in year 1, 42.9% in year 3, and 63.3% in year 5. The other variables were not significantly different. Laparoscopic sleeve gastrectomy resulted in health improvements through year 3. At year 5, the nutrient levels had reverted toward the baseline values. These observations provide focus for necessary clinical monitoring. Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya
2018-05-30
Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.
Ooms, Linda; Leemrijse, Chantal; Collard, Dorine; Schipper-van Veldhoven, Nicolette; Veenhof, Cindy
2018-06-01
Health-enhancing physical activity (HEPA) promotion programs are implemented in sports clubs. The purpose of this study was to examine the characteristics of the insufficiently active participants that benefit from these programs. Data of three sporting programs, developed for insufficiently active adults, were used for this study. These sporting programs were implemented in different sports clubs in the Netherlands. Participants completed an online questionnaire at baseline and after six months (n = 458). Of this sample, 35.1% (n = 161) was insufficiently active (i.e. not meeting HEPA levels) at baseline. Accordingly, two groups were compared: participants who were insufficiently active at baseline, but increased their physical activity to HEPA levels after six months (activated group, n = 86) versus participants who were insufficiently active both at baseline and after six months (non-activated group, n = 75). Potential associated characteristics (demographic, social, sport history, physical activity) were included as independent variables in bivariate and multivariate logistic regression analyses. The percentage of active participants increased significantly from baseline to six months (from 64.9 to 76.9%, p < 0.05). The bivariate logistic regression analyses showed that participants in the activated group were more likely to receive support from family members with regard to their sport participation (62.8% vs. 42.7%, p = 0.02) and spent more time in moderate-intensity physical activity (128 ± 191 min/week vs. 70 ± 106 min/week, p = 0.02) at baseline compared with participants in the non-activated group. These results were confirmed in the multivariate logistic regression analyses: when receiving support from most family members, there is a 216% increase in the odds of being in the activated group (OR = 2.155; 95% CI: 1.118-4.154, p = 0.02) and for each additional 1 min/week spent in moderate-intensity physical activity, the odds increases with 0.3% (OR = 1.003; 95% CI: 1.001-1.006, p = 0.02). The results suggest that HEPA sporting programs can be used to increase HEPA levels of insufficiently active people, but it seems a challenge to reach the least active ones. It is important that promotional strategies and channels are tailored to the target group. Furthermore, strategies that promote family support may enhance the impact of the programs.
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.
Your brain on bikes: P3, MMN/N2b, and baseline noise while pedaling a stationary bike.
Scanlon, Joanna E M; Sieben, Alex J; Holyk, Kevin R; Mathewson, Kyle E
2017-06-01
Increasingly, there is a trend to measure brain activity in more ecologically realistic scenarios. Normally, the confines of the laboratory and sedentary tasks mitigate sources of electrical noise on EEG measurement. Moving EEG outside of the lab requires understanding of the impact of complex movements and activities on traditional EEG and ERP measures. Here, we recorded EEG with active electrodes while participants were either riding or sitting on a stationary bike in an electrical and sound-attenuated chamber in the lab. Participants performed an auditory oddball task, pressing a button when they detected rare target tones in a series of standard frequent tones. We quantified both the levels of spectral, single-trial baseline, and ERP baseline noise, as well as classic MMN/N2b and P3 ERP components measured during both biking and sitting still. We observed slight increases in posterior high frequency noise in the spectra, and increased noise in the baseline period during biking. However, morphologically and topographically similar MMN/N2b and P3 components were measured reliably while both biking and sitting. A quantification of the power to reliably measure ERPs as a function of the number of trials revealed slight increases in the number of trials needed during biking to achieve the same level of power. Taken in sum, our results confirm that classic ERPs can be measured reliably during biking activities in the lab. Future directions will employ these techniques outside the lab in ecologically valid situations. © 2017 Society for Psychophysiological Research.
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.
Hochberg, Marc C; Silverman, Stuart L; Barr, Charles E; Miller, Paul D
2010-01-01
Bone turnover markers may provide a more rapid indication of patient response to osteoporosis treatment than bone mineral density (BMD) measurements. This post hoc analysis of data from the MOBILE (Monthly Oral iBandronate In LadiEs) study assessed the relationship between increases in BMD at 12 mo from baseline after starting ibandronate treatment and changes in bone resorption marker serum C-terminal telopeptide of type I collagen (sCTX) from baseline at 3 and 6 mo. MOBILE enrolled postmenopausal women aged 55-80 yr with mean lumbar spine (LS) BMD T-score of -2.5 to -5.0. This analysis included women who received 150-mg monthly oral ibandronate (n=323). A high proportion of women were classified as BMD responders after 1 yr (BMD increase was >/=0%, i.e., 74-91% depending on skeletal site; BMD increase was >/=3%, i.e., 34-67%). Women with larger decreases in sCTX were more likely to be BMD responders. The percent increase in LS BMD at 12 mo was significantly associated with the percent decrease in sCTX at 3 mo from baseline (Pearson correlation coefficient: -0.19, p=0.0016). In linear regression models, percent decrease in sCTX at 3 mo from baseline was a significant predictor of 1-yr LS BMD response (R(2)=0.61, p=0.0007). These data suggest that 3-mo changes in sCTX levels are associated with 1-yr LS BMD increases in postmenopausal women treated with once-monthly oral ibandronate. The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
Kirsch, Susanne H; Herrmann, Wolfgang; Kruse, Vera; Eckert, Rudolf; Gräber, Stefan; Geisel, Jürgen; Obeid, Rima
2015-02-01
We aimed to study the effect of long-term supplementation of B-vitamins on folate forms in serum and whole blood (WB) in elderly German subjects. 59 participants (mean age 67 years) were randomized to daily receive either vitamin D3 (1200 IU), folic acid (500 μg), vitamin B12 (500 μg), vitamin B6 (50 mg), and calcium carbonate (456 mg) or vitamin D3 plus calcium carbonate. Serum and WB folate forms were measured before and after 6 and 12 months. B-vitamins supplementation for 6 months led to higher concentrations of 5-methyltetrahydrofolate (5-methylTHF) in serum (mean 49.1 vs. 19.6 nmol/L) and WB (1332 vs. 616 nmol/L). Also non-methyl-folate concentrations in serum and WB were higher after 6 months with B-vitamins supplementation. Unmetabolized folic acid (UFA) increased after supplementation. tHcy concentration was lowered after 1 year of B-vitamin supplementation (mean 13.1 vs. 9.6 μmol/L). A stronger reduction of tHcy after 1 year was found in participants who had baseline level >12.5 μmol/L (mean 17.0 vs. 11.9 μmol/L) compared to those with baseline tHcy lower than this limit (mean 9.1 vs. 7.4 μmol/L). In contrast, the increases in serum and WB 5-methylTHF were comparable between the two groups. One year B-vitamins supplementation increased the levels of 5-methylTHF and non-methyl-folate in serum and WB, normalized tHcy, but caused an increase in the number of cases with detectable UFA in serum. Lowering of tHcy was predicted by baseline tHcy, but not by baseline serum or WB 5-methylTHF.
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
Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber
2015-04-01
This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.
Yang, Zhong-jin; Price, Chrystal D.; Bosco, Gerardo; Tucci, Micheal; El-Badri, Nagwa S.; Mangar, Devanand; Camporesi, Enrico M.
2008-01-01
Background Cerebral blood flow (CBF) is auto-regulated to meet the brain's metabolic requirements. Oxycyte® is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte® on regional CBF (rCBF), by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte® on CBF. Methodology Male rats were intubated and ventilated with 100% O2 under isoflurane anesthesia. The regional (striatum) CBF (rCBF) was measured with a laser doppler flowmeter (LDF). Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte® plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct) values reached 5%. Principal Findings In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208±30%) when Hct levels were less than 10%. In the Oxycyte®-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118±18%) when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO2 to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO2 level. In the Oxycyte®-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO2 level dropped below 10 ml/dl (142±20% vs. 186±26%), and rCBF returned to almost baseline levels (106±15) when the CaO2 level was below 7 ml/dl. Conclusions/Significance Hemodilution with Oxycyte® was accompanied with higher CaO2 and PO2 than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin. PMID:18431491
Sponder, Michael; Campean, Ioana-Alexandra; Dalos, Daniel; Emich, Michael; Fritzer-Szekeres, Monika; Litschauer, Brigitte; Bergler-Klein, Jutta; Graf, Senta; Strametz-Juranek, Jeanette
2017-08-09
INTRODUCTION Since proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were introduced to the market, the interest in PCSK9 metabolism has increased dramatically. OBJECTIVES We investigated prospectively the influence of long-term physical activity on PCSK9, highand low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and lipoprotein(a) levels [Lp(a)]. PATIENTS AND METHODS A total of 109 participants were recruited and instructed to increase their sport pensum by 75 min/wk of vigorous-intensity or 150 min/wk of moderate-intensity endurance training (or a mixture) within the calculated training pulse for 8 months. Stress tests were performed at baseline and at the end of the study to prove and quantify the performance gain. PCSK9 levels were measured at baseline and after 2, 6, and 8 months by an enzyme-linked immunosorbent assay. HDL-C, LDL-C, and Lp(a) levels were measured at baseline and every 2 months. RESULTS The final study sample included 79 subjects, who showed a mean performance gain of 11.4%. Mean (SD) PCSK9 and HDL-C levels increased significantly from 224.7 (66.8) ng/ml to 243.4 (84.0) ng/ml (P = 0.04) and 58.3 (18.4) mg/dl to 61.1 (18.5) mg/dl (P = 0.014), respectively. Mean (SD) LDL-C levels decreased significantly from 115.0 (33.4) mg/dl to 109.8 (31.7) mg/dl (P = 0.04), but there was no significant change in mean (SD) Lp(a) levels: 37.9 (51.9) nmol/l to 43.3 (60.6) nmol/l; P = 0.218. CONCLUSIONS Our study showed a decrease in LDL-C levels induced by a long-term physical activity with a simultaneous increase in PCSK9 levels. PCSK9 is essential in lipid metabolism and should not be basically considered as harmful. It is possible that a certain amount of PCSK9 is beneficial to ensure an adequate lipid supply.
Duggal, Shalu; Simpson, Mary Elizabeth; Keiver, Kathy
2007-01-01
Chronic alcohol (ethanol) consumption during pregnancy results in maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level, and PTH does not increase in response to ethanol-induced hypocalcemia. However, it is not known whether ethanol actually prevents PTH from responding, or whether the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca maintained. The objective of this study was to determine whether chronic ethanol consumption impairs the ability of the pregnant female to increase PTH in response to acute hypocalcemia. Rats were fed isocaloric diets with ethanol (36% ethanol-derived calories, E group) or without ethanol [pair-fed (PF) and control (C) groups], before and throughout 21 days of gestation. On day 21 gestation, rats received an intraperitoneal injection of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (300 or 500 mumol/kg body weight) or saline (saline group), or no injection (baseline group). Blood was collected from the baseline group, and at 30 or 60 minutes postinjection (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH. Consistent with previous studies, ethanol consumption decreased blood iCa levels at baseline, but PTH levels did not differ among groups. Administration of EGTA significantly decreased blood iCa levels by 30 minutes, but ethanol did not prevent PTH from increasing in response to the hypocalcemia. In all diet groups, PTH levels were significantly increased by 30 minutes. Ethanol did, however, appear to decrease the maximum PTH level achievable in blood. These data suggest that chronic ethanol consumption does not impair the ability of the pregnant rat to raise serum PTH levels in response to acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair the ability of the pregnant female to sustain high PTH levels in response to chronic hypocalcemia.
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.
Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Baseline Findings.
Grady, Kathleen L; Hof, Kathleen Van't; Andrei, Adin-Cristian; Shankel, Tamara; Chinnock, Richard; Miyamoto, Shelley; Ambardekar, Amrut V; Anderson, Allen; Addonizio, Linda; Latif, Farhana; Lefkowitz, Debra; Goldberg, Lee; Hollander, Seth A; Pham, Michael; Weissberg-Benchell, Jill; Cool, Nichole; Yancy, Clyde; Pahl, Elfriede
2018-02-01
Young adult solid organ transplant recipients who transfer from pediatric to adult care experience poor outcomes related to decreased adherence to the medical regimen. Our pilot trial for young adults who had heart transplant (HT) who transfer to adult care tests an intervention focused on increasing HT knowledge, self-management and self-advocacy skills, and enhancing support, as compared to usual care. We report baseline findings between groups regarding (1) patient-level outcomes and (2) components of the intervention. From 3/14 to 9/16, 88 subjects enrolled and randomized to intervention (n = 43) or usual care (n = 45) at six pediatric HT centers. Patient self-report questionnaires and medical records data were collected at baseline, and 3 and 6 months after transfer. For this report, baseline findings (at enrollment and prior to transfer to adult care) were analyzed using Chi-square and t-tests. Level of significance was p < 0.05. Baseline demographics were similar in the intervention and usual care arms: age 21.3 ± 3.2 vs 21.5 ± 3.3 years and female 44% vs 49%, respectively. At baseline, there were no differences between intervention and usual care for use of tacrolimus (70 vs 62%); tacrolimus level (mean ± SD = 6.5 ± 2.3 ng/ml vs 5.6 ± 2.3 ng/ml); average of the within patient standard deviation of the baseline mean tacrolimus levels (1.6 vs 1.3); and adherence to the medical regimen [3.6 ± 0.4 vs 3.5 ± 0.5 (1 = hardly ever to 4 = all of the time)], respectively. At baseline, both groups had a modest amount of HT knowledge, were learning self-management and self-advocacy, and perceived they were adequately supported. Baseline findings indicate that transitioning HT recipients lack essential knowledge about HT and have incomplete self-management and self-advocacy skills.
Hirokawa, Kumi; Taniguchi, Toshiyo; Fujii, Yasuhito; Takaki, Jiro; Tsutsumi, Akizumi
2016-08-01
The purpose of this longitudinal study was to ascertain if changes in job demands modify associations between changes in testosterone levels and andropause symptoms in male Japanese workers. A baseline survey including job demands and the Aging Males' Symptoms scale, lifestyle factors, and blood levels of testosterone was conducted in 2007. Among 192 men (mean age ± SD 52.2 ± 7.6 years) who completed all relevant questionnaires and provided blood at baseline, 104 men (50.9 ± 7.2 years) were followed up in 2009. Changes of variables in 2 years were calculated (data of follow-up minus those of baseline). Testosterone levels were increased significantly, whereas job demands and somatic symptoms were reduced significantly, at follow-up. Changes in testosterone levels were negatively associated with changes in total andropause symptoms, psychological symptoms, and sexual symptoms (standardized β = -0.27, -0.24, and, -0.29, p < 0.05, respectively), after adjustment for confounders. Changes in job demands were positively associated with changes in somatic symptoms (standardized β = 0.21, p < 0.05). Significant interactions of changes in testosterone levels and job demands were noted for changes in psychological symptoms (standardized β = 0.26, p < 0.05). For men with a 1-SD reduction in job demands, negative associations between changes in testosterone levels and psychological symptoms were intensified, but not for men with a 1-SD increase in job demands. Andropause symptoms may be affected by changes in testosterone levels and job demands. Change in job demands may modify associations between changes in testosterone levels and andropause symptoms.
Miller, David A.; Vleck, Carol M.; Otis, David L.
2009-01-01
Endocrine systems have an important mechanistic role in structuring life-history trade-offs. During breeding, individual variation in prolactin (PRL) and corticosterone (CORT) levels affects behavioral and physiological processes that drive trade-offs between reproduction and self-maintenance. We examined patterns in baseline (BL) and stress induced (SI; level following a standard capture-restraint protocol) levels of PRL and CORT for breeding mourning doves (Zenaida macroura). We determined whether the relationship of adult condition and parental effort to hormone levels in wild birds was consistent with life-history predictions. Both BL PRL and BL CORT level in adults were positively related to nestling weight at early nestling ages, consistent with the prediction of a positive relationship of hormone levels to current parental effort of adults and associated increased energy demand. Results are consistent with the two hormones acting together at baseline levels to limit negative effects of CORT on reproduction while maintaining beneficial effects such as increased foraging for nestling feeding. Our data did not support predictions that SI responses would vary in response to nestling or adult condition. The magnitude of CORT response in the parents to our capture-restraint protocol was negatively correlated with subsequent parental effort. Average nestling weights for adults with the highest SI CORT response were on average 10–15% lighter than expected for their age in follow-up visits after the stress event. Our results demonstrated a relationship between individual hormone levels and within population variation in parental effort and suggested that hormonal control plays an important role in structuring reproductive decisions for mourning doves.
Miller, David A.; Vleck, Carol M.; Otis, David L.
2009-01-01
Endocrine systems have an important mechanistic role in structuring life-history trade-offs. During breeding, individual variation in prolactin (PRL) and corticosterone (CORT) levels affects behavioral and physiological processes that drive trade-offs between reproduction and self-maintenance. We examined patterns in baseline (BL) and stress induced (SI; level following a standard capture-restraint protocol) levels of PRL and CORT for breeding mourning doves (Zenaida macroura). We determined whether the relationship of adult condition and parental effort to hormone levels in wild birds was consistent with life-history predictions. Both BL PRL and BL CORT level in adults were positively related to nestling weight at early nestling ages, consistent with the prediction of a positive relationship of hormone levels to current parental effort of adults and associated increased energy demand. Results are consistent with the two hormones acting together at baseline levels to limit negative effects of CORT on reproduction while maintaining beneficial effects such as increased foraging for nestling feeding. Our data did not support predictions that SI responses would vary in response to nestling or adult condition. The magnitude of CORT response in the parents to our capture-restraint protocol was negatively correlated with subsequent parental effort. Average nestling weights for adults with the highest SI CORT response were on average 10–15% lighter than expected for their age in follow-up visits after the stress event. Our results demonstrated a relationship between individual hormone levels and within population variation in parental effort and suggested that hormonal control plays an important role in structuring reproductive decisions for mourning doves.
Powell-Wiley, Tiffany M; Moore, Kari; Allen, Norrina; Block, Richard; Evenson, Kelly R; Mujahid, Mahasin; Diez Roux, Ana V
2017-08-01
Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of neighborhood crime and safety with changes in adiposity (body mass index (BMI) and waist circumference). MESA is a longitudinal study of cardiovascular disease among adults aged 45-84 years at baseline in 2000-2002, from 6 US sites, with follow-up for MESA participants until 2012. Data for this study were limited to Chicago, Illinois, participants in the MESA Neighborhood Ancillary Study, for whom police-recorded crime data were available, and who had complete baseline data (n = 673). We estimated associations of individual-level safety, aggregated neighborhood-level safety, and police-recorded crime with baseline levels and trajectories of BMI and waist circumference over time using linear mixed modeling with random effects. We also estimated how changes in these factors related to changes in BMI and waist circumference using econometric fixed-effects models. At baseline, greater individual-level safety was associated with more adiposity. Increasing individual- and neighborhood-level safety over time were associated with decreasing BMI over the 10-year period, with a more pronounced effect observed in women for individual-level safety and men for neighborhood-level safety. Police-recorded crime was not associated with adiposity. Neighborhood-level safety likely influences adiposity change and subsequent cardiovascular risk in multiethnic populations. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.
Suzukawa, Maho; Matsumoto, Hisako; Ohshima, Nobuharu; Tashimo, Hiroyuki; Asari, Isao; Tajiri, Tomoko; Niimi, Akio; Nagase, Hiroyuki; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Shoji, Shunsuke; Ohta, Ken
2018-01-01
Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients. This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab. Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed. GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49.1 ± 12.5 pg/ml at 32 weeks, P = 0.008; PDGF: 4821 ± 2458 pg/ml at baseline vs. 4219 ± 1951 pg/ml at 32 weeks, P = 0.048). High baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics. Copyright © 2017 Elsevier Ltd. All rights reserved.
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.
Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi
2016-01-01
Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p < 0.001). There was a significant positive correlation between baseline serum thyroid stimulating hormone (TSH) level and EAT thickness in the SCH group. There was a significant reduction in mean EAT thickness in response to L-thyroxine treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p < 0.001). The decrease in EAT thickness after L-thyroxine treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.
Gurrin, Lyle C; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Laurie W; Allen, Katrina J
2008-12-01
There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in individuals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF >1000 microg/L. For males with SF 300-1000 microg/L at baseline, the predicted probability of progressing to SF >1000 microg/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, <15% were predicted to develop SF >1000 microg/L if left untreated. The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.
O'Connor, Kathryn L; Dain Allred, C; Cameron, Kenneth L; Campbell, Darren E; D'Lauro, Christopher J; Houston, Megan N; Johnson, Brian R; Kelly, Tim F; McGinty, Gerald; O'Donnell, Patrick G; Peck, Karen Y; Svoboda, Steven J; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P
2018-03-28
The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p's < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen's d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels.
Aeroacoustic Analysis of Fan Noise Reduction With Increased Bypass Nozzle Area
NASA Technical Reports Server (NTRS)
Woodward, Richard P.; Hughes, Christopher E.; Podboy, Gary G.
2005-01-01
An advanced model turbofan was tested in the NASA Glenn 9-by 15-Foot Low Speed Wind Tunnel (9x15 LSWT) to explore far field acoustic effects of increased bypass nozzle area. This fan stage test was part of the NASA Glenn Fan Broadband Source Diagnostic Test, second entry (SDT2) which acquired aeroacoustic results over a range of test conditions. The baseline nozzle was sized to produce maximum stage performance at cruise condition. However, the wind tunnel testing is conducted near sea level condition. Therefore, in order to simulate and obtain performance at other operating conditions, two additional nozzles were designed and tested one with +5 percent increase in weight flow (+5.4 percent increase in nozzle area compared with the baseline nozzle), sized to simulate the performance at the stage design point (takeoff) condition, and the other with a +7.5 percent increase in weight flow (+10.9 percent increase in nozzle area) sized for maximum weight flow with a fixed nozzle at sea level condition. Measured acoustic benefits with increased nozzle area were very encouraging, showing overall sound power level (OAPWL) reductions of 2 or more dB while the stage thrust actually increased by 2 to 3 percent except for the most open nozzle at takeoff rotor speed where stage performance decreased. Effective perceived noise levels for a 1500 ft engine flyover and 3.35 scale factor showed a similar noise reduction of 2 or more EPNdB. Noise reductions, principally in the level of broadband noise, were observed everywhere in the far field. Laser Doppler Velocimetry measurements taken downstream of the rotor showed that the total turbulent velocity decreased with increasing nozzle flow, which may explain the reduced rotor broadband noise levels.
Salvatore, Michael F.; Terrebonne, Jennifer; Fields, Victoria; Nodurft, Danielle; Runfalo, Cori; Latimer, Brian; Ingram, Donald K.
2015-01-01
Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging. PMID:26610387
Griffeth, Valerie E.M.; Perthen, Joanna E.; Buxton, Richard B.
2011-01-01
Functional magnetic resonance imaging (fMRI) provides an indirect reflection of neural activity change in the working brain through detection of blood oxygenation level dependent (BOLD) signal changes. Although widely used to map patterns of brain activation, fMRI has not yet met its potential for clinical and pharmacological studies due to difficulties in quantitatively interpreting the BOLD signal. This difficulty is due to the BOLD response being strongly modulated by two physiological factors in addition to the level of neural activity: the amount of deoxyhemoglobin present in the baseline state and the coupling ratio, n, of evoked changes in blood flow and oxygen metabolism. In this study, we used a quantitative fMRI approach with dual measurement of blood flow and BOLD responses to overcome these limitations and show that these two sources of modulation work in opposite directions following caffeine administration in healthy human subjects. A strong 27% reduction in baseline blood flow and a 22% increase in baseline oxygen metabolism after caffeine consumption led to a decrease in baseline blood oxygenation and was expected to increase the subsequent BOLD response to the visual stimulus. Opposing this, caffeine reduced n through a strong 61% increase in the evoked oxygen metabolism response to the visual stimulus. The combined effect was that BOLD responses pre- and post-caffeine were similar despite large underlying physiological changes, indicating that the magnitude of the BOLD response alone should not be interpreted as a direct measure of underlying neurophysiological changes. Instead, a quantitative methodology based on dual-echo measurement of blood flow and BOLD responses is a promising tool for applying fMRI to disease and drug studies in which both baseline conditions and the coupling of blood flow and oxygen metabolism responses to a stimulus may be altered. PMID:21586328
Elevated serum uric acid level predicts rapid decline in kidney function
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
Koopman, A D M; Rutters, F; Rauh, S P; Nijpels, G; Holst, J J; Beulens, J W; Alssema, M; Dekker, J M
2018-01-01
We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.
Rutters, F.; Rauh, S. P.; Nijpels, G.; Holst, J. J.; Beulens, J. W.; Alssema, M.; Dekker, J. M.
2018-01-01
We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus. PMID:29324870
Riccardi, Patrizia; Baldwin, Ron; Salomon, Ronald; Anderson, Sharlet; Ansari, Mohammad S; Li, Rui; Dawant, Benoit; Bauernfeind, Amy; Schmidt, Dennis; Kessler, Robert
2008-01-15
This study examined whether positron emission tomography (PET) studies with [18F] fallypride performed before and after alpha-methyl-para-tyrosine (AMPT) administration can be used to estimate baseline dopamine (DA) D2 receptor occupancy in striatal and extrastriatal regions. Six normal subjects underwent PET with [18 F] fallypride before and after administration of AMPT. The DA D2 receptor binding potentials (bp) were calculated with the reference region method. Percent changes in bp in striatal and extrastriatal regions were calculated with both region-of-interest analysis and on a voxel by voxel basis with parametric images of DA D2 receptor levels. The results of the current study indicate that AMPT treatment significantly increased the bp in the caudate, putamen, ventral striatum, and substantia nigra. A trend level increase was seen in the medial thalamus. This study demonstrates that PET with [18F] fallypride can be used to estimate baseline DA D2 receptor occupancy in striatal and extrastriatal regions.
Beauvais, Brad; Wells, Rebecca; Vasey, Joseph; DelliFraine, Jami L
2007-01-01
As the number of health centers increases through a federal initiative, questions remain about these primary care providers' capacity to provide sufficient care to the underserved. In the current study, the authors hypothesize that health centers with greater financial latitude or "slack" will provide medically appropriate primary care to greater proportions of their patients. Annual data from all US federally funded community health centers between 1998 and 2004 provide unusually rich data through which to test this hypothesis. Multilevel model results indicate positive associations between higher levels of net revenue and percentages of patients receiving preventive health care at baseline, as well as between initial net revenue and increases over time in post partum care access. Contrary to expectation, higher net revenue was also negatively associated with percentages of women getting post partum care at baseline. Also contrary to expectation, higher baseline levels of net revenue were associated with decreasing preventive care access over time. These mixed results imply that organizations' financial slack can affect quality, but in ways that vary across outcomes and over time.
NASA Technical Reports Server (NTRS)
Carlson, John R.; Asbury, Scott C.
1994-01-01
An experimental investigation was performed in the Langley 16-Foot Transonic tunnel to determine the effects of external and internal flap rippling on the aerodynamics of a nonaxisymmetric nozzle. Data were obtained at several Mach numbers from static conditions to 1.2 over a range of nozzle pressure ratios. Nozzles with chordal boattail angles of 10, 20, and 30 degrees, with and without surface rippling, were tested. No effect on discharge coefficient due to surface rippling was observed. Internal thrust losses due to surface rippling were measured and attributed to a combination of additional internal skin friction and shock losses. External nozzle drag for the baseline configurations were generally less than that for the rippled configurations at all free-stream Mach numbers tested. The difference between the baseline and rippled nozzle drag levels generally increased with increasing boat tail angle. The thrust-minus-drag level for each rippled nozzle configuration was less than the equivalent baseline configuration for each Mach number at the design nozzle pressure ratio.
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
Simpson, Norah S; Banks, Siobhan; Dinges, David F
2010-07-01
We evaluated the effects of sleep restriction on leptin levels in a large, diverse sample of healthy participants, while allowing free access to food. Prospective experimental design. After 2 nights of baseline sleep, 136 participants (49% women, 56% African Americans) received 5 consecutive nights of 4 hours time in bed (TIB). Additionally, one subset of participants received 2 additional nights of either further sleep restriction (n = 27) or increased sleep opportunity (n = 37). Control participants (n = 9) received 10 hr TIB on all study nights. Plasma leptin was measured between 10:30 a.m. and 12:00 noon following baseline sleep, after the initial sleep-restriction period, and after 2 nights of further sleep restriction or recovery sleep. Leptin levels increased significantly among sleep-restricted participants after 5 nights of 4 hr TIB (Z = -8.43, p < .001). Increases were significantly greater among women compared to men (Z = -4.77, p < .001) and among participants with higher body mass index (BMI) compared to those with lower (Z = -2.09, p = .036), though participants in all categories (sex, race/ethnicity, BMI, and age) demonstrated significant increases. There was also a significant effect of allowed TIB on leptin levels following the 2 additional nights of sleep restriction (p < .001). Participants in the control condition showed no significant changes in leptin levels. These findings suggest that sleep restriction with ad libitum access to food significantly increases morning plasma leptin levels, particularly among women.
Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H
2016-07-01
We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.
Kurban, Sevil; Mehmetoglu, Idris; Yerlikaya, Hümeyra F; Gönen, Sait; Erdem, Sami
2011-01-01
Objectives. Our aim was to determine the effect of chronic regular exercise on ischemia-modified albumin (IMA) levels and oxidative stress in type 2 diabetes mellitus (DM). Design and methods. Sixty patients with type 2 DM were randomly divided into two groups as exercise (17 M, 13 F) and non-exercise (12 M, 18 F) groups, each consisting of 30 patients. The exercise group underwent a 3-month aerobic regular exercise consisting of moderate-intensity power walking. The non-exercise subjects remained sedentary throughout the study period. Serum total antioxidant status (TAS), total oxidant status (TOS), and IMA levels of the groups were determined at baseline and 3 months later. Results. There was no significant change in TOS and IMA levels of exercise group but TAS levels were significantly increased (p < 0.05). Also, postexercise systolic (p < 0.001) and diastolic (p < 0.05) blood pressures of the exercise group were significantly lower than the baseline values. In addition, there was no significant change in TAS and TOS levels of the non-exercise group; however, IMA levels were significantly increased (p < 0.01). Conclusion. We have shown, for the first time, that exercise prevents increase in IMA levels in type 2 DM which might have resulted from increased levels of TAS and reduces the risk of ischemia in these patients. These findings show that chronic exercise is beneficial in the prevention of oxidative stress in patients with type 2 DM as documented by decreased IMA levels.
Evaluation of the accuracy of estimated baseline serum creatinine for acute kidney injury diagnosis.
Hatakeyama, Yutaka; Horino, Taro; Nagata, Keitaro; Kataoka, Hiromi; Matsumoto, Tatsuki; Terada, Yoshio; Okuhara, Yoshiyasu
2018-04-01
Modern epidemiologic studies of acute kidney injury (AKI) have been facilitated by the increasing availability of electronic medical records. However, pre-morbid reference serum creatinine (SCr) data are often unavailable in such records. Investigators substitute estimated baseline SCr with the eGFR 75 approach, instead of using actually measured baseline SCr. Here, we evaluated the accuracy of estimated baseline SCr for AKI diagnosis in the Japanese population. Inpatients and outpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using SCr levels. The non-AKI and AKI groups were selected using the following criteria: increase 1.5 times greater than baseline SCr ("baseline SCr") or increase 0.3 mg/dL greater than baseline SCr in 48 h ("increase in 48 h"). AKI accuracy defined by the estimated reference SCr, the average SCr value of the non-AKI population (eb-GFR-A approach), or the back-calculated SCr from fixed eGFR = 75 mL/min/1.73 m 2 (eGFR 75 approach, or, eb-GFR-B approach in this study), was evaluated. We analyzed data from 131,358 Japanese patients. The number of patients with reference baseline SCr in the non-AKI and AKI patients were 29,834 and 8952, respectively. For AKI patients diagnosed using "baseline SCr", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 63.5 and 57.7%, respectively, while in AKI diagnosed using "increase in 48 h", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 78.7 and 75.1%, respectively. In non-AKI patients, false-positive rates of AKI misdiagnosed via eb-GFR-A and eb-GFR-B were 7.4 and 6.8%, respectively. AKI diagnosis using the average SCr value of the general population may yield more accurate results than diagnosis using the eGFR 75 approach when the reference SCr is unavailable.
Lin, Annie W.; Lujan, Marla E.
2014-01-01
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age worldwide. In addition to deleterious effects on fertility imparted by PCOS, women with PCOS are at increased risk of obesity, diabetes, cardiovascular disease, depression, and certain cancers. Hormonal and metabolic aberrations in PCOS have the potential to influence dietary intake and physical activity levels. There are emerging global data that women with PCOS have different baseline dietary energy intakes compared with women without PCOS. These alterations in diet may exacerbate clinical symptoms and compound risk of chronic disease in patients. Few studies have compared baseline physical activity levels between women with and without PCOS. Although comparisons between studies are confounded by several factors, the data point to no differences in activity levels among PCOS and non-PCOS groups. This review provides an assessment of the current literature on baseline dietary intake and physical activity levels in women with PCOS. Future recommendations to strengthen research in this area are provided, given the implications to aid in the development of effective nutrition-focused interventions for PCOS. PMID:25469380
Pomara, Nunzio; Willoughby, Lisa M; Hashim, Audrey; Sershen, Henry; Sidtis, John J; Wesnes, Keith; Greenblatt, David J; Lajtha, Abel
2004-07-01
The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.
Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques
2011-09-01
The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.
Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S
2008-07-01
States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.
Ou-Yang, Li-Xue; Yang, Fan
2017-07-01
To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.
McKinney, Diana L; Frost-Pineda, Kimberly; Oldham, Michael J; Fisher, Michael T; Wang, Jingzhu; Gogova, Maria; Kobal, Gerd
2014-07-01
Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Coyne, Daniel W.; Ficociello, Linda H.; Parameswaran, Vidhya; Anderson, Ludmila; Vemula, Sharanya; Ofsthun, Norma J.; Mullon, Claudy; Maddux, Franklin W.; Kossmann, Robert J.; Sprague, Stuart M.
2017-01-01
Aims: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients. Materials and methods: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 – 3) and 6 months (SO 4 – 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed. Results: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 – 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 – 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%). Conclusions: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day. PMID:28587714
High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes
Custer, Aimee; Sufrinko, Alicia; Elbin, R. J.; Covassin, Tracey; Collins, Micky; Kontos, Anthony
2016-01-01
Context: Some healthy athletes report high levels of baseline concussion symptoms, which may be attributable to several factors (eg, illness, personality, somaticizing). However, the role of baseline symptoms in outcomes after sport-related concussion (SRC) has not been empirically examined. Objective: To determine if athletes with high symptom scores at baseline performed worse than athletes without baseline symptoms on neurocognitive testing after SRC. Design: Cohort study. Setting: High school and collegiate athletic programs. Patients or Other Participants: A total of 670 high school and collegiate athletes participated in the study. Participants were divided into groups with either no baseline symptoms (Postconcussion Symptom Scale [PCSS] score = 0, n = 247) or a high level of baseline symptoms (PCSS score > 18 [top 10% of sample], n = 68). Main Outcome Measure(s): Participants were evaluated at baseline and 2 to 7 days after SRC with the Immediate Post-concussion Assessment and Cognitive Test and PCSS. Outcome measures were Immediate Post-concussion Assessment and Cognitive Test composite scores (verbal memory, visual memory, visual motor processing speed, and reaction time) and total symptom score on the PCSS. The groups were compared using repeated-measures analyses of variance with Bonferroni correction to assess interactions between group and time for symptoms and neurocognitive impairment. Results: The no-symptoms group represented 38% of the original sample, whereas the high-symptoms group represented 11% of the sample. The high-symptoms group experienced a larger decline from preinjury to postinjury than the no-symptoms group in verbal (P = .03) and visual memory (P = .05). However, total concussion-symptom scores increased from preinjury to postinjury for the no-symptoms group (P = .001) but remained stable for the high-symptoms group. Conclusions:> Reported baseline symptoms may help identify athletes at risk for worse outcomes after SRC. Clinicians should examine baseline symptom levels to better identify patients for earlier referral and treatment for their injury. Additional investigation of baseline symptoms is warranted to help delineate the type and severity of premorbid symptoms. PMID:26885702
Unger, Jennifer B.; Meca, Alan; Lorenzo-Blanco, Elma I.; Baezconde-Garbanati, Lourdes; Cano, Miguel Ángel; Piña-Watson, Brandy; Szapocznik, José; Zamboanga, Byron L.; Córdova, David; Romero, Andrea J.; Lee, Tae Kyoung; Soto, Daniel W.; Villamar, Juan A.; Lizzi, Karina M.; Des Rosiers, Sabrina E.; Pattarroyo, Monica
2016-01-01
The present study was designed to examine trajectories of personal identity coherence and confusion among Hispanic recent-immigrant adolescents, as well as the effects of these trajectories on psychosocial and risk-taking outcomes. Personal identity is extremely important in anchoring young immigrants during a time of acute cultural change. A sample of 302 recently immigrated (5 years or less in the United States at baseline) Hispanic adolescents (Mage = 14.51 years at baseline; SD = 0.88 years, range 14–17) from Miami and Los Angeles (47 % girls) completed measures of personal identity coherence and confusion at the first five waves of a six-wave longitudinal study; and reported on positive psychosocial functioning, depressive symptoms, and externalizing problems at baseline and at Time 6. Results indicated that identity coherence increased linearly across time, but that there were no significant changes in confusion over time and no individual differences in confusion trajectories. Higher baseline levels of, and improvements in, coherence predicted higher levels of self-esteem, optimism, and prosocial behavior at the final study timepoint. Higher baseline levels of confusion predicted lower self-esteem, greater depressive symptoms, more aggressive behavior, and more rule breaking at the final study timepoint. These results are discussed in terms of the importance of personal identity for Hispanic immigrant adolescents, and in terms of implications for intervention. PMID:27882458
Schwartz, Seth J; Unger, Jennifer B; Meca, Alan; Lorenzo-Blanco, Elma I; Baezconde-Garbanati, Lourdes; Cano, Miguel Ángel; Piña-Watson, Brandy; Szapocznik, José; Zamboanga, Byron L; Córdova, David; Romero, Andrea J; Lee, Tae Kyoung; Soto, Daniel W; Villamar, Juan A; Lizzi, Karina M; Des Rosiers, Sabrina E; Pattarroyo, Monica
2017-04-01
The present study was designed to examine trajectories of personal identity coherence and confusion among Hispanic recent-immigrant adolescents, as well as the effects of these trajectories on psychosocial and risk-taking outcomes. Personal identity is extremely important in anchoring young immigrants during a time of acute cultural change. A sample of 302 recently immigrated (5 years or less in the United States at baseline) Hispanic adolescents (M age = 14.51 years at baseline; SD = 0.88 years, range 14-17) from Miami and Los Angeles (47 % girls) completed measures of personal identity coherence and confusion at the first five waves of a six-wave longitudinal study; and reported on positive psychosocial functioning, depressive symptoms, and externalizing problems at baseline and at Time 6. Results indicated that identity coherence increased linearly across time, but that there were no significant changes in confusion over time and no individual differences in confusion trajectories. Higher baseline levels of, and improvements in, coherence predicted higher levels of self-esteem, optimism, and prosocial behavior at the final study timepoint. Higher baseline levels of confusion predicted lower self-esteem, greater depressive symptoms, more aggressive behavior, and more rule breaking at the final study timepoint. These results are discussed in terms of the importance of personal identity for Hispanic immigrant adolescents, and in terms of implications for intervention.
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.
Schmidt, Morten; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A
2017-01-01
Objectives To examine adherence to serum creatinine and potassium monitoring and discontinuation guidelines following initiation of treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs); and whether high-risk patients are monitored. Design A general practice-based cohort study using electronic health records from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. Setting UK primary care, 2004–2014. Subjects 223 814 new ACEI/ARB users. Main outcome measures Proportion of patients with renal function monitoring before and after ACEI/ARB initiation; creatinine increase ≥30% or potassium levels >6 mmol/L at first follow-up monitoring; and treatment discontinuation after such changes. Using logistic regression models, we also examined patient characteristics associated with these biochemical changes, and with follow-up monitoring within the guideline recommendation of 2 weeks after treatment initiation. Results 10% of patients had neither baseline nor follow-up monitoring of creatinine within 12 months before and 2 months after initiation of an ACEI/ARB, 28% had monitoring only at baseline, 15% only at follow-up, and 47% both at baseline and follow-up. The median period between the most recent baseline monitoring and drug initiation was 40 days (IQR 12–125 days). 34% of patients had baseline creatinine monitoring within 1 month before initiating therapy, but <10% also had the guideline-recommended follow-up test recorded within 2 weeks. Among patients experiencing a creatinine increase ≥30% (n=567, 1.2%) or potassium level >6 mmol/L (n=191, 0.4%), 80% continued treatment. Although patients with prior myocardial infarction, hypertension or baseline potassium >5 mmol/L were at high risk of ≥30% increase in creatinine after ACEI/ARB initiation, there was no evidence that they were more frequently monitored. Conclusions Only one-tenth of patients initiating ACEI/ARB therapy receive the guideline-recommended creatinine monitoring. Moreover, the vast majority of the patients fulfilling postinitiation discontinuation criteria for creatinine and potassium increases continue on treatment. PMID:28069618
Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro
2017-08-01
To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.
Fernández-Juárez, Gema; Villacorta Perez, Javier; Luño Fernández, José Luis; Martinez-Martinez, Ernesto; Cachofeiro, Victoria; Barrio Lucia, Vicente; Tato Ribera, Ana M; Mendez Abreu, Angel; Cordon, Alfredo; Oliva Dominguez, Jesus Angel; Praga Terente, Manuel
2017-05-01
Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factorα (TNFα), are associated with early progression of diabetic nephropathy (DN). The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria. Between 2006 and 2011, we measured levels of circulating soluble TNFα receptor 1 (TNFR1) and soluble TNFα receptor 2 (TNFR2) at baseline and 4 and 12 months in 101 patients included in a multicenter randomized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination (dual blockade) to slow progression of established type 2 DN. The primary composite endpoint was a >50% increase in baseline serum creatinine, end-stage renal disease, or death. The median follow-up was 32 months (IQR, 18-48), during which time 28 patients (22.7%) achieved the primary endpoint. The TNFR1 level, but not the TNFR2 level, was correlated with other inflammatory markers. Cox regression analysis showed that the highest TNFR1 levels (HR, 2.60; 95%CI, 1.11-86.34) and baseline proteinuria (HR 1.32; 95%CI 1.15-1.52) were associated with the primary endpoint. The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers. Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN. The renin angiotensin blockers have no effect on these inflammatory markers. © 2016 Asian Pacific Society of Nephrology.
Tada, T; Kumada, T; Toyoda, H; Sone, Y; Takeshima, K; Ogawa, S; Goto, T; Wakahata, A; Nakashima, M; Nakamuta, M; Tanaka, J
2018-04-01
Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020). © 2018 John Wiley & Sons Ltd.
2013-01-01
Background Obesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results Age and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability. PMID:23391158
Maintaining Healthy Behavior: A Prospective Study of Psychological Well-Being and Physical Activity
Kim, Eric S.; Kubzansky, Laura D.; Soo, Jackie; Boehm, Julia K.
2016-01-01
Background Although higher psychological well-being has been linked with a range of positive biological processes and health outcomes, the prospective association between psychological well-being and physical activity among older adults has been understudied. Purpose We tested whether higher baseline psychological well-being predicted higher levels of physical activity over time. Methods Prospective data were from the English Longitudinal Study of Ageing, a nationally representative sample of English adults over the age of 50. Our sample included 9,986 adults who were assessed up to six times across an average of 11 years. Results After adjusting for sociodemographic factors, each standard deviation increase in baseline psychological well-being was associated with higher median physical activity in linear regression models that examined physical activity across all six waves (β=0.20; 95% confidence interval [CI]: 0.18–0.21) and in linear mixed effect models that examined repeated measures of physical activity over the entire follow-up period (β=0.20; 95% CI: 0.19–0.21). Further, higher baseline psychological well-being was associated with a slower rate of decline in physical activity among people who were active at baseline (hazard ratio [HR]=0.79, 95% CI: 0.76–0.82) and increasing physical activity among people who were inactive at baseline (HR=1.28, 95% CI: 1.22–1.35). Findings were maintained after adjusting for baseline health status and depression. Conclusions Psychological well-being was independently associated with attaining and maintaining higher physical activity levels over 11 years, suggesting that it may be a valuable target for interventions aimed at helping older adults acquire more physical activity. PMID:27822613
Leavy, Justine E; Rosenberg, Michael; Bauman, Adrian E; Bull, Fiona C; Giles-Corti, Billie; Shilton, Trevor; Maitland, Clover; Barnes, Rosanne
2013-08-01
Internationally, over the last four decades large-scale mass media campaigns have been delivered to promote physical activity and its associated health benefits. In 2002-2005, the first Western Australian statewide adult physical activity campaign Find Thirty. It's Not a Big Exercise was launched. In 2007, a new iteration of the campaign was proposed with new objectives, executions, and tag line Find Thirty every day(®). This article reports on the population-level effects of the Find Thirty every day (®) campaign from 2008 to 2010, with a focus on changes in awareness, intention, and physical activity. Evaluation of the campaign involved pre- and posttest serial cross-sectional surveys. Baseline data were collected in May 2008, and subsequent surveys in 2009 and 2010. Samples sizes were as follows: baseline (n = 972), first follow-up (n = 938), and second follow-up (n = 937). Data were derived from self-reported responses to a random-sample computer-assisted telephone interview. Total awareness increased from 30.4% at baseline to 48.5% at second follow-up. Total awareness was higher in women and low socioeconomic status adults. Intention was 21.0%, double that reported at baseline. There were positive significant changes from baseline to first follow-up across all four categories: walking, moderate, vigorous, and total physical activity. There also were positive significant changes for self-reported walking from baseline to second follow-up. Find Thirty every day (®) resulted in an increase in awareness, intention, walking, vigorous intensity, and total level of physical activity in priority target groups. Campaign effects should be further examined by subgroups to identify the most receptive population segments.
Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection
Lin, Wan-Yu; Dubuisson, Olga; Rubicz, Rohina; Liu, Nianjun; Allison, David B.; Curran, Joanne E.; Comuzzie, Anthony G.; Blangero, John; Leach, Charles T.; Göring, Harald; Dhurandhar, Nikhil V.
2013-01-01
OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders. PMID:23160725
Evaluation of inflammation during fixed orthodontic treatment.
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.
Loeb, Stacy; Roehl, Kimberly A; Antenor, Jo Ann V; Catalona, William J; Suarez, Brian K; Nadler, Robert B
2006-02-01
Limited data are available concerning the extent to which the initial prostate-specific antigen (PSA) measurement in men younger than age 60 predicts for the risk of prostate cancer (CaP) and how this compares to other known risk factors. From 1991 to 2001, 13,943 men younger than 60 years old participated in a CaP screening study. Men aged 40 to 49 years were eligible for the study if they had a positive family history or African-American heritage, and men older than 50 years were screened without respect to risk factors. The CaP detection rate, PSA velocity, pathologic features, and treatment outcomes were evaluated as a function of the baseline PSA level. The median PSA level was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6-fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years, respectively. A greater baseline PSA value was also associated with a significantly greater PSA velocity, more aggressive tumor features, a greater biochemical progression rate, and a trend toward a greater cancer-specific mortality rate. In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or suspicious digital rectal examination findings. A greater baseline PSA level was associated with significantly more adverse pathologic features and biochemical progression.
Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher S; Weintraub, Daniel; Mollenhauer, Brit; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl; Chahine, Lana M; Marek, Kenneth
2018-01-01
To examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC). Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging. 423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy. This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1-42 level is an important finding that will have to be replicated in other cohorts. ClinicalTrials.gov identifier: NCT01141023. © 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.
Cognitive Effort Requirements in Recall, Recognition, and Lexical Decision
1985-05-01
that the amount of integrative processing required for an item is a function of its preexisting or baseline familiarity level . Low frequency words... Lockhart , Craik , & Jacoby, 1976). In the present study, increased effort, and possibly increased distinctiveness, does not influence hit rates, which are...ing of items. Second, a lexical decision task, which does not require elabo- rative processing , leads to an overall poor level of recall. Furthermore
Eating increases oxidative damage in a reptile.
Butler, Michael W; Lutz, Thomas J; Fokidis, H Bobby; Stahlschmidt, Zachary R
2016-07-01
While eating has substantial benefits in terms of both nutrient and energy acquisition, there are physiological costs associated with digesting and metabolizing a meal. Frequently, these costs have been documented in the context of energy expenditure while other physiological costs have been relatively unexplored. Here, we tested whether the seemingly innocuous act of eating affects either systemic pro-oxidant (reactive oxygen metabolite, ROM) levels or antioxidant capacity of corn snakes (Pantherophis guttatus) by collecting plasma during absorptive (peak increase in metabolic rate due to digestion of a meal) and non-absorptive (baseline) states. When individuals were digesting a meal, there was a minimal increase in antioxidant capacity relative to baseline (4%), but a substantial increase in ROMs (nearly 155%), even when controlling for circulating nutrient levels. We report an oxidative cost of eating that is much greater than that due to long distance flight or mounting an immune response in other taxa. This result demonstrates the importance of investigating non-energetic costs associated with meal processing, and it begs future work to identify the mechanism(s) driving this increase in ROM levels. Because energetic costs associated with eating are taxonomically widespread, identifying the taxonomic breadth of eating-induced ROM increases may provide insights into the interplay between oxidative damage and life history theory. © 2016. Published by The Company of Biologists Ltd.
Differential responsiveness to a parenting intervention for mothers in substance abuse treatment.
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.
Oxidative stress and kidney injury in trans-radial catheterization.
Tsarouhas, Konstantinos; Tsitsimpikou, Christina; Papantoni, Xrisoula; Lazaridou, Dimitra; Koutouzis, Michael; Mazzaris, Savvas; Rezaee, Ramin; Mamoulakis, Charalambos; Georgoulias, Panagiotis; Nepka, Charitini; Rentoukas, Elias; Kyriakides, Zenon; Tsatsakis, Aristidis; Spandidos, Demetrios A; Kouretas, Demetrios
2018-05-01
Oxidative stress is linked to coronary artery disease and is a major mechanism in contrast-induced nephropathy. Trans-radial approach in coronary angiography (CA) with minimized peri-procedural bleeding is expected to reduce acute kidney injury incidence. In the present study, oxidative stress patterns observed in radial CA and their associations with early manifestations of kidney injury are described. A total of 20 stable coronary disease patients submitted to CA and 17 sex-matched patients undergoing computed tomography for myoskeletal reasons were enrolled. Reduced glutathione, catalase, thiobarbituric acid reactive species (TBARS) levels and total anti-oxidant status were measured at various time points postangiography. In ischemic patients baseline TBARS levels were 2-fold lower compared to controls, while carbonyls levels were 35% higher. Glutathione was almost 4-fold lower than the control group. Glutathione and lipid peroxidation in ischemic patients gradually increased after contrast medium administration and reached 180% (P<0.001) and 20% (P=0.021) after 4-6 h, respectively. Four patients presented early evidence of contrast-induced nephropathy postangiography, while no control patient developed acute kidney injury. In the multiple logistic regression analysis, only the creatinine levels at baseline influenced the frequency of early contrast-induced nephropathy development (β =0.36, 95% CI: 0.285-0.438, P=0.01). Glutathione low levels were dominant in the baseline values of ischemic patients who developed contrast-induced nephropathy. Glutathione levels rapidly increased while protein oxidation decreased at the expense of lipid peroxidation. In conclusion, early oxidative stress changes occur in trans-radial CA patients with a mild profile, sufficient to mobilize patient antioxidant defenses.
IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.
Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan
2018-05-04
Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.
Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose as daytime dwell.
Posthuma, N; ter Wee, P M; Donker, A J; Oe, P L; van Dorp, W; Peers, E M; Verbrugh, H A
1997-01-01
To evaluate the safety, efficacy, and biocompatibility of icodextrin- and glucose-containing dialysis fluid during continuous cycling peritoneal dialysis (CCPD), patients were treated for 2 years with either icodextrin- or glucose-containing dialysis fluid for their daytime dwell (14-15 hours). Prior to entry into the study, all patients used a standard glucose solution (Dianeal 1.36%, 2.27%, or 3.86%, Baxter, Utrecht, The Netherlands). Open, randomized, prospective, two-center study. University hospital and teaching hospital. Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18, those with peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a follow-up period of 12 months or longer in December 1996. Serum icodextrin metabolites: one to five glucose units (G1-G5), a high molecular weight fraction (G > 10), and total carbohydrate level, as well as a biochemical profile were determined every 3 months in combination with all other study variables. In icodextrin-treated patients, serum disaccharide (maltose) concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001). All icodextrin metabolites increased significantly from baseline, as illustrated by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p < 0.05). However, after 12 months the serum sodium concentration increased nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial decrease. Serum osmolality increased significantly from baseline in icodextrin users at 9 and 12 months, but did not differ significantly from glucose users in any visit. In icodextrin-treated patients, the calculated serum osmolal gap increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7 mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in millimoles/liter equaled the increase in osmolal gap. Body weight increased in icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse effects did not accompany these findings. Residual renal function remained stable during follow-up. The serum icodextrin metabolite levels in the present study increased markedly and were the same as those found previously in continuous ambulatory peritoneal dialysis patients treated with icodextrin, despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The initial decrease in serum sodium concentration was followed by an increase to a concentration not different from baseline at 12 months. The pathophysiology of this finding is speculated. Calculated osmolal gap in icodextrin patients increased significantly (p < 0.01) at every follow-up visit, and could be explained by the serum icodextrin metabolite increase. We encountered no clinical side effects of the observed levels of icodextrin metabolites.
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.
Zhang, Ren-Wen; Shao, Cui-Ping; Huo, Na; Li, Min-Ran; Xi, Hong-Li; Yu, Min; Xu, Xiao-Yuan
2015-09-07
To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients. One hundred and thirty-nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNα-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline. The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNα-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 ± 244.2 pg/mL vs 310.0 ± 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non-TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014). Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.
Ryan, John G; Fedders, Mark; Jennings, Terri; Vittoria, Isabel; Yanes, Melissa
2014-12-01
The extent to which reducing cost-related barriers affects diabetes outcomes and medication adherence among uninsured patients is not known. The purpose of these analyses was to understand the clinical impact and cost considerations of a prescription assistance program targeting low-income, minority patients with diabetes and at high risk for cost-related medication nonadherence. Patients received diabetes medications without copayments for 12 months. Change in diabetes control was calculated by using glycosylated hemoglobin (HbA1c) level at follow-up compared with baseline. Clinical data were collected from the electronic health record. Medication adherence for diabetes medications was estimated by using proportion of days covered (PDC). Incremental acquisition and per-patient costs, based on actual hospital medication costs, were calculated for different baseline HbA1c levels. Patients with baseline HbA1c levels ≥7%, ≥8%, and ≥9% experienced mean HbA1c reductions of 0.82% (P = 0.008), 1.02% (P = 0.010), and 1.47% (P = 0.010), respectively, during the 12-month period. The average PDC was 70.55%; 45.24% had a PDC ≥80%, indicating an adequate level of medication adherence. Medication adherence ≥80% was associated with ethnicity (P = 0.015), whereas mean PDC was associated with number of diabetes medication classes used (P = 0.031). Acquisition cost for 1242 prescriptions filled by 103 patients was $13,365.82, representing per-patient costs of $132.39; however, as baseline targets increased, acquisition costs decreased and per-patient costs increased from $10,682.59 and $169.56 to $6509.91 and $192.27, respectively. Clinically significant reductions in HbA1c levels were achieved for all patients, although greater reductions were achieved with modest per-patient cost increases when considering patients with uncontrolled diabetes. Incorporating a multifactorial intervention to address cost-related medication nonadherence with a behavior change component may yield greater reductions in HbA1c with improved diabetes outcomes and meaningful hospital-based cost savings. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.
Eating behaviors and weight over time in a prospective study: the Healthy Twin Study.
Song, Yun-Mi; Lee, Kayoung; Sung, Joohon
2014-01-01
We examined the relationships of combined initial restrained and external/emotional eating with initial BMI and change in weight and these subscales over time. BMI and the Dutch Eating Behavior Questionnaire were twicemeasured in 1361 Korean twins and families (482 men, 879 women) over a period of 2.7±0.9 years. Subjects were classified by combination of initial sex-specific restrained and external (or emotional) eating tertiles. Linear mixed models were performed after adjusting for confounders at baseline (household, sibling relations, sex, age, education level, smoking, alcohol use, energy intake, physical activity, and medical history). In adjusted models, initial BMI increased with increasing tertiles of initial restrained eating across initial external/emotional eating tertiles. Weight was less likely to increase over time with increasing tertiles of initial restrained eating in the lowest external eating tertile and middle tertile of emotional eating at baseline. Subscale scores decreased over time with increasing tertiles of corresponding subscales at baseline. These findings suggest that high dietary restraint and external/emotional eating may indicate concurrent high BMI and attenuated weight gain and decreases in corresponding subscales over time.
Otsuka, Rei; Kato, Yuki; Imai, Tomoko; Ando, Fujiko; Shimokata, Hiroshi
2015-03-01
Cross-sectional studies have shown age-related increases in blood docosahexaenoic and eicosapentaenoic acid and decreases in arachidonic acid. We describe serum docosahexaenoic, eicosapentaenoic, and arachidonic acid concentrations over 13 years (1997-2012) across four study waves and serum fatty acid composition over 4 years (2006-2012) between two study waves according to age groups by sex in the same subjects. We included 443 men and 435 women aged 40-79 years at baseline. Serum arachidonic acid concentrations increased in all sex and age groups over 13 years, and eicosapentaenoic or docosahexaenoic acid concentrations increased in males and females who were younger and middle-aged at baseline. Only serum arachidonic acid composition increased over 4 years in men and women who were 40-69 years at baseline, even after adjustment for arachidonic acid intake. These findings suggest a secular increase trend in serum arachidonic acid levels over 13 years among randomly selected community-dwelling middle-aged and elderly Japanese. Copyright © 2014 Elsevier Ltd. All rights reserved.
Noonan, Sinead A; Patil, Tejas; Gao, Dexiang; King, Gentry G; Thibault, Jessica R; Lu, Xian; Bunn, Paul A; Doebele, Robert C; Purcell, W Thomas; Barón, Anna E; Camidge, D Ross
2018-01-01
The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described. A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted. A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation). Of these, 82% had at least one marker (95% if all four markers were measured), with CA27.29 being the most commonly increased and CA19.9 the rarest. Only CA27.29 differed significantly by oncogene (it was less common in KRAS) (p = 0.016). The median times to nadir during tyrosine kinase inhibitor (TKI) therapy in EGFR and ALK cases were 16.4 and 20 weeks, respectively. Of the 41 patients with EGFR mutation or ALK or ROS1 rearrangement, 24 (59%) demonstrated an initial increase within the first 4 weeks of TKI therapy, 58% of whom then had their levels fall below baseline. An increase in marker level of 10% or more from nadir occurred in 53% of systemic and 22% of central nervous system-only progression. Serum tumor markers are frequently increased in lung adenocarcinoma regardless of driver oncogene. Changes within the first 4 weeks of therapy may be misleading. Progression is associated with marker increases, especially in sites other than the central nervous system. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Infliximab induces clonal expansion of γδ-T cells in Crohn's disease: a predictor of lymphoma risk?
Kelsen, Jens; Dige, Anders; Schwindt, Heinrich; D'Amore, Francesco; Pedersen, Finn S; Agnholt, Jørgen; Christensen, Lisbet A; Dahlerup, Jens F; Hvas, Christian L
2011-03-31
Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents.
Importance of the pre-industrial baseline for likelihood of exceeding Paris goals
NASA Astrophysics Data System (ADS)
Schurer, Andrew P.; Mann, Michael E.; Hawkins, Ed; Tett, Simon F. B.; Hegerl, Gabriele C.
2017-08-01
During the Paris conference in 2015, nations of the world strengthened the United Nations Framework Convention on Climate Change by agreeing to holding `the increase in the global average temperature to well below 2 °C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1.5 °C' (ref. ). However, `pre-industrial' was not defined. Here we investigate the implications of different choices of the pre-industrial baseline on the likelihood of exceeding these two temperature thresholds. We find that for the strongest mitigation scenario RCP2.6 and a medium scenario RCP4.5, the probability of exceeding the thresholds and timing of exceedance is highly dependent on the pre-industrial baseline; for example, the probability of crossing 1.5 °C by the end of the century under RCP2.6 varies from 61% to 88% depending on how the baseline is defined. In contrast, in the scenario with no mitigation, RCP8.5, both thresholds will almost certainly be exceeded by the middle of the century with the definition of the pre-industrial baseline of less importance. Allowable carbon emissions for threshold stabilization are similarly highly dependent on the pre-industrial baseline. For stabilization at 2 °C, allowable emissions decrease by as much as 40% when earlier than nineteenth-century climates are considered as a baseline.
da Silva, A E; dos Reis-Neto, E Torres; da Silva, N P; Sato, E I
2013-12-01
Acute exercise increases IL-6, IL-10 and TNF-α levels in healthy subjects. There is no study evaluating the effect of exercise on cytokines level in systemic lupus erythematosus (SLE) patients. Our aim was to assess IL-10, IL-6 and TNF-α levels at baseline and after acute physical exercise in patients with SLE. In total, 27 female SLE patients and 30 healthy controls were evaluated. Serum levels of IL-10, IL-6 and TNF-α at baseline and soon after the ergospirometric test were measured by ELISA test. Student's t-tests and Mann-Whitney test were used for intra- and inter-group comparisons; p values <0.05 were considered significant. Patients with SLE presented worse ergospirometric parameters compared with controls: VO2max (25.78 ± 5.51 vs. 32.74 ± 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 ± 12.36 vs. 185.15 ± 2.07 bpm, p = 0.001); maximum ventilation (65.51 ± 15.68 vs. 80.48 ± 18.98 l/min, p = 0.001) and maximum speed (7.70 ± 1.24 vs. 9.40 ± 1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6 (2.38 ± 1.70 vs. 1.71 ± 0.29 pg/ml, p = 0.035) and IL-10 (1.09 ± 1.55 vs. 0.30 ± 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls increased IL-6 level (1.71 ± 0.29 vs. 2.01 ± 0.27 pg/ml, p = 0.003) without change in IL-10 and TNF-α levels. However, no significant change in cytokine levels was observed in SLE patients after acute exercise. This is the first study evaluating the effect of acute exercise on cytokine levels in patients with SLE. In contrast to healthy controls, acute physical exercise did not increase the levels of IL-6 in patients with SLE, and seems to be safe in those patients with inactive or mild active disease.
2012-01-01
Background Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function. Methods Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment. Results Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks. Conclusion Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function. PMID:22824166
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.
Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Inui, Takashi; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao
2017-09-02
Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment. ClinicalTrials.gov, NCT00691028 . Retrospectively registered on 3 June 2008.
Impact of Incremental Perfusion Loss on Oxygen Transport in a Capillary Network Mathematical Model.
Fraser, Graham M; Sharpe, Michael D; Goldman, Daniel; Ellis, Christopher G
2015-07-01
To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport. A computational model was applied to capillary networks with dimensions 84 × 168 × 342 (NI) and 70 × 157 × 268 (NII) μm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis. A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3-4 fold. These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis. © 2015 John Wiley & Sons Ltd.
Estrada, V; Monge, S; Gómez-Garre, M D; Sobrino, P; Masiá, M; Berenguer, J; Portilla, J; Viladés, C; Martínez, E; Blanco, J R
2016-10-01
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels. © 2016 British HIV Association.
Marso, Steven P; Hardy, Elise; Han, Jenny; Wang, Hui; Chilton, Robert J
2018-04-01
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and - 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = - 0.3 to - 0.4). Baseline heart rate was the strongest predictor of increased heart rate. Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.
Croonenberghs, Jan; Verkerk, Robert; Scharpe, Simon; Deboutte, Dirk; Maes, Michael
2005-03-25
Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) may play a role in the pathophysiology of autistic disorder. This study examines the whole blood concentrations of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) in baseline conditions and during a challenge with L-5-OH-tryptophane (5-HTP; 4 mg/kg in non enteric-coated tablets), the precursor of 5-HT, in a study group of 18 male, post-pubertal, Caucasian autistic patients (age 13-19 y.; I.Q.>55) and 20 matched healthy volunteers. In baseline conditions, no significant differences in 5-HT or 5-HIAA levels could be found between autistic youngsters and normal controls. 5-HTP administration significantly increased the levels of 5-HT in autistic youngsters but not in normal controls. Following 5-HTP challenge the 5-HT levels were significantly higher in autistic patients than in healthy volunteers. After challenge with 5-HTP, no significant differences were found in the concentrations of 5-HIAA or the test substance between autistic youngsters and normal controls. Differences in the peripheral metabolism of 5-HT which may not be observed in baseline conditions but which became clear after loading with 5-HTP, suggest that an increased synthesis of 5-HT from its precursor 5-HTP might be a one factor responsible for differences in the serotonergic system between autistic post-pubertal youngsters and normal controls.
Derosa, Giuseppe; Mugellini, Amedeo; Ciccarelli, Leonardina; Crescenzi, Giuseppe; Fogari, Roberto
2003-02-01
Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control. In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy). This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment. One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI levels were seen in either group at 6 months, although FPI levels were significantly increased in the repaglinide group at 12 months (P < 0.05). Repaglinide significantly lowered levels of Lp(a), PAI-1, and Hcy after 12 months (all, P < 0.05 vs baseline). Glimepiride significantly lowered levels of Lp(a) and Hcy after 6 months (both, P < 0.05 vs baseline) and levels of Lp(a) (P < 0.01 vs baseline), Hcy (P < 0.01 vs baseline), and PAI-1 (P < 0.05 vs baseline) after 12 months. Repaglinide and glimepiride improved glycemic control and reduced levels of other metabolic parameters of interest in this population of patients with type 2 diabetes. It is possible that the reductions in Lp(a), PAI-1, and Hcy were the result of improved glucose metabolism; however, the possibility that repaglinide and glimepiride may have a direct effect on these parameters should not be excluded.
Smuthkochorn, Sorapan; Palomo, J Martin; Hans, Mark G; Jones, Corey S; Palomo, Leena
2017-07-01
Bone turnover associated with orthodontic tooth movement is evidenced by increased bone turnover markers in gingival crevicular fluid (GCF). Postmenopausal women have an increased concentration of serum bone turnover markers. The filtrate of this serum makes up GCF, but little is known of the bone turnover around teeth in this cohort. The objective of this investigation was to compare the GCF bone turnover markers in premenopausal vs postmenopausal women receiving orthodontic treatment at baseline and at orthodontic activation. Twenty-eight women were enrolled in the study and separated into 2 groups: premenopausal (16) and postmenopausal (12). Bone turnover was evaluated by GCF at baseline and 24 hours after orthodontic appliance activation. GCF concentrations of RANKL and OPN were measured using ELISA. Baseline and change in concentrations were compared between groups. Baseline RANKL and OPN were significantly different between the premenopausal and postmenopausal groups (P <0.05). Both markers increased significantly from baseline to 24 hours after orthodontic appliance activation in both groups (P <0.05). However, the response to orthodontic activation was not significantly different between groups. Although postmenopausal women have a different bone turnover profile at baseline than do their premenopausal counterparts, there is no difference in their response to orthodontic activation. This confers a level of security associated with orthodontic activation. Future studies are warranted to construct biomarker curves throughout orthodontic therapy. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.
Carboxyhemoglobin Levels Induced by Cigarette Smoking Outdoors in Smokers.
Schimmel, Jonathan; George, Naomi; Schwarz, John; Yousif, Sami; Suner, Selim; Hack, Jason B
2018-03-01
Non-invasive screening of carboxyhemoglobin saturation (SpCO) in the emergency department to detect occult exposure is increasingly common. The SpCO threshold to consider exposure in smokers is up to 9%. The literature supporting this cutoff is inadequate, and the impact of active smoking on SpCO saturation remains unclear. The primary objective was to characterize baseline SpCO in a cohort of smokers outdoors. Secondary objectives were to explore the impact of active smoking on SpCO and to compare SpCO between smokers and non-smokers. This was a prospective cohort pilot study in two outdoor urban public areas in the USA, in a convenience sample of adult smokers. SpCO saturations were assessed non-invasively before, during, and 2 min after cigarette smoking with pulse CO-oximetry. Analyses included descriptive statistics, correlations, and a generalized estimating equation model. Eighty-five smokers had mean baseline SpCO of 2.7% (SD 2.6) and peak of 3.1% (SD 2.9), while 15 controls had SpCO 1.3% (SD 1.3). This was a significant difference. Time since last cigarette was associated with baseline SpCO, and active smoking increased mean SpCO. There was correlation among individual smokers' SpCO levels before, during, and 2 min after smoking, indicating smokers tended to maintain their baseline SpCO level. This study is the first to measure SpCO during active smoking in an uncontrolled environment. It suggests 80% of smokers have SpCO ≤ 5%, but potentially lends support for the current 9% as a threshold, depending on clinical context.
Tanaka, Hiroyuki; Takano, Kazuhiko; Iijima, Hiroaki; Kubo, Hajime; Maruyama, Nobuko; Hashimoto, Toshio; Arakawa, Kenji; Togo, Masanori; Inagaki, Nobuya; Kaku, Kohei
2017-02-01
Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery. UMIN000019462. Mitsubishi Tanabe Pharma Corporation.
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
Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G
2011-09-01
To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.
2014-01-01
Background Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. Methods The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). Results Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. Conclusion Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis. PMID:24410736
Zhang, Le-Le; Fang, Jian-Qiao; Shao, Xiao; Lian, Lin-Li; Yu, Xiao-Jing; Dong, Zhen-Hua; Mo, Ya-Di
2015-01-01
To observe the effect of gastric dynamics by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia when controlled hypotension dropped to 60% of the mean arterial prenssure (MAP) baseline, and to provide experimental evidence for organ protection in clinical controlled hypotension. Eighteen male beagles were randomly divided into three groups, the general anesthesia group (blank), the general anesthesia induced controlled hypotension group (control), and the general anesthesia combined TEAS induced controlled hypotension group (experiment), 6 in each group. Controlled hypotension was performed in the latter two groups with isoflurane inhalation and intravenous injection of sodium nitroprusside (SNP). The mean arterial pressure (MAP) was lowered to 60% of the MAP baseline and kept for 60 min. Controlled hypotension was not performed in Beagles of the control group. For Beagles in the experiment group, TEAS [2/100 Hz, (4 ± 1) mA] was applied to bilateral Hegu (LI4), Quchi (LI11), Zusanli (ST36), and Sanyinjiao (SP6) from stable physiological conditions to the end of maintaining stages. Changes of EGG frequencies and EGG amplitudes were monitored. Serum levels of gastrin (GAS) and motilin (MTL) were also detected at corresponding time points during and after experiment. As for the pressure control effect of TEAS combined general anesthesia in the controlled hypotension, during the process of controlled hypotension (T1-T4), MAP levels of two controlled pressure groups remained relatively stable, and were kept at 60% of the MAP baseline. When the blood pressure dropped to the target low MAP and maintained at 60 min (T1-T4), EGG amplitudes of Beagles in all the three groups showed decreasing tendency. But it was more obviously lower than its basic level in the control group (P <0.05), while it was not obviously decreased in the experiment group (P < 0.05). EGG frequencies of Beagles in all the three groups showed no obvious change during this stage. By the end of the MAP rising stage (T8), the EGG amplitude of the experimental group was significantly higher than that of the control group and the blank group (P < 0.05), while it didn' t show any obvious increase in the control group. During this period, EGG frequencies of the two controlled hypotension groups decreased more than those of the blank group. Two h after rising blood pressure (at T9), EGG amplitudes and frequencies in the two controlled hypotension groups basically restored to their respective baselines and levels of the blank group at T9. At 2 h (T9) after controlled hypotension, serum levels of GAS and MTL were lower than those of basic levels in the two controlled hypotension groups (P <0.05). However, serum levels of GAS and MTL had an increasing trend in the two controlled hypotension groups at 24-72 h (T10-T12). Besides, the increasing speed and amplitude was better in experiment group than in the control group at T10-T12. However, there was no statistical difference between the two groups (P > 0.05). At 72 h (T12) serum levels of GAS and MTL had basically restored to their basic levels in the two controlled hypotension groups and that of the blank control group. EGG amplitudes could be effectively improved in TEAS combined general anesthesia for controlled hypotension at 60% of the MAP baseline, the recovery of the serum GAS level accelerated, gastric power improved and stomach protected.
Human cutaneous vascular responses to whole-body tilting, Gz centrifugation, and LBNP
NASA Technical Reports Server (NTRS)
Watenpaugh, Donald E.; Breit, Gregory A.; Buckley, Theresa M.; Ballard, Richard E.; Murthy, Gita; Hargens, Alan R.
2004-01-01
We hypothesized that gravitational stimuli elicit cardiovascular responses in the following order with gravitational stress equalized at the level of the feet, from lowest to highest response: short-(SAC) and long-arm centrifugation (LAC), tilt, and lower body negative pressure (LBNP). Up to 15 healthy subjects underwent graded application of the four stimuli. Laser-Doppler flowmetry measured regional skin blood flow. At 0.6 G(z) (60 mmHg LBNP), tilt and LBNP similarly reduced leg skin blood flow to approximately 36% of supine baseline levels. Flow increased back toward baseline levels at 80-100 mmHg LBNP yet remained stable during 0.8-1.0 G(z) tilt. Centrifugation usually produced less leg vasoconstriction than tilt or LBNP. Surprisingly, SAC and LAC did not differ significantly. Thigh responses were less definitive than leg responses. No gravitational vasoconstriction occurred in the neck. All conditions except SAC increased heart rate, according to our hypothesized order. LBNP may be a more effective and practical means of simulating cardiovascular effects of gravity than centrifugation.
Bangsgaard Bendtsen, Katja Maria; Krych, Lukasz; Sørensen, Dorte Bratbo; Pang, Wanyong; Nielsen, Dennis Sandris; Josefsen, Knud; Hansen, Lars H; Sørensen, Søren J; Hansen, Axel Kornerup
2012-01-01
Stress has profound influence on the gastro-intestinal tract, the immune system and the behavior of the animal. In this study, the correlation between gut microbiota composition determined by Denaturing Grade Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene amplicon pyrosequencing (454/FLX) and behavior in the Tripletest (Elevated Plus Maze, Light/Dark Box, and Open Field combined), the Tail Suspension Test, and Burrowing in 28 female BALB/c mice exposed to two weeks of grid floor induced stress was investigated. Cytokine and glucose levels were measured at baseline, during and after exposure to grid floor. Stressing the mice clearly changed the cecal microbiota as determined by both DGGE and pyrosequencing. Odoribacter, Alistipes and an unclassified genus from the Coriobacteriaceae family increased significantly in the grid floor housed mice. Compared to baseline, the mice exposed to grid floor housing changed the amount of time spent in the Elevated Plus Maze, in the Light/Dark Box, and burrowing behavior. The grid floor housed mice had significantly longer immobility duration in the Tail Suspension Test and increased their number of immobility episodes from baseline. Significant correlations were found between GM composition and IL-1α, IFN-γ, closed arm entries of Elevated Plus Maze, total time in Elevated Plus Maze, time spent in Light/Dark Box, and time spent in the inner zone of the Open Field as well as total time in the Open Field. Significant correlations were found to the levels of Firmicutes, e.g. various species of Ruminococccaceae and Lachnospiraceae. No significant difference was found for the evaluated cytokines, except an overall decrease in levels from baseline to end. A significant lower level of blood glucose was found in the grid floor housed mice, whereas the HbA1c level was significantly higher. It is concluded that grid floor housing changes the GM composition, which seems to influence certain anxiety-related parameters.
Psychological well-being and restorative biological processes: HDL-C in older English adults.
Soo, Jackie; Kubzansky, Laura D; Chen, Ying; Zevon, Emily S; Boehm, Julia K
2018-05-14
Psychological well-being is associated with better cardiovascular health, but the underlying mechanisms are unclear. This study investigates one possible mechanism by examining psychological well-being's prospective association with lipid levels, focusing on high-density lipoprotein cholesterol (HDL-C). Participants were 4757 healthy men and women ages ≥50 from the English Longitudinal Study of Ageing with clinical data from three times, three to five years apart. Psychological well-being was assessed at baseline using the Control, Autonomy, Satisfaction, and Pleasure scale; HDL-C, triglycerides, and total cholesterol were assayed from blood samples. Descriptive statistics and linear mixed models were used to examine associations between psychological well-being and lipid levels over time; the latter controlled for confounders and health behaviours. In descriptive analyses, HDL-C levels were initially higher in people with greater psychological well-being. Among those who met recommended levels of HDL-C at baseline, fewer individuals with higher versus lower psychological well-being dropped below HDL-C recommendations over time. Mixed models indicated that HDL-C increased over time (β = 0.64; 95% CI = 0.58 to 0.69) and higher baseline psychological well-being was associated with higher baseline HDL-C (β = 0.51; 95% CI = 0.03 to 0.99). A significant well-being by time interaction indicated individuals with higher versus lower well-being exhibited a more rapid rate of increase in HDL-C over follow-up. Higher psychological well-being was also significantly associated with lower triglycerides, but main effects for both HDL-C and triglycerides were attenuated after accounting for health behaviours. Higher psychological well-being is associated with healthier HDL-C levels; these effects may compound over time. This protective effect may be partly explained by health behaviours. Copyright © 2018 Elsevier Ltd. All rights reserved.
Sommer, J Ulrich; Kraus, Marius; Birk, Richard; Schultz, Johannes D; Hörmann, Karl; Stuck, Boris A
2014-03-01
Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium. In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion. The baseline CBF was 4.8 ± 0.6 Hz, and baseline MTT was 540 ± 221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p <0.05). The short-term groups with and without humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2 ± 0.4 Hz; 402 ± 176 s; p <0.01). The increase above baseline level was even more pronounced with humidification (9.3 ± 0.7 Hz; 313 ± 95 s; p <0.01). There was a statistically significant difference between both groups at long-term assessment with regard to CBF (p <0.01). Independent of airway humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function-both in terms of an increased CBF and a decreased MTT-was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.
Effects of video modeling on treatment integrity of behavioral interventions.
Digennaro-Reed, Florence D; Codding, Robin; Catania, Cynthia N; Maguire, Helena
2010-01-01
We examined the effects of individualized video modeling on the accurate implementation of behavioral interventions using a multiple baseline design across 3 teachers. During video modeling, treatment integrity improved above baseline levels; however, teacher performance remained variable. The addition of verbal performance feedback increased treatment integrity to 100% for all participants, and performance was maintained 1 week later. Teachers found video modeling to be more socially acceptable with performance feedback than alone, but rated both positively.
NASA Technical Reports Server (NTRS)
Blackburn, L. B.; Starke, E. A., Jr.
1989-01-01
Minor amounts of cadmium, indium or tin were added to a baseline alloy with the nominal composition of Al-2.4Cu-2.4Li-0.15Zr. These elements were added in an attempt to increase the age-hardening response of the material such that high strengths could be achieved through heat-treatment alone, without the need for intermediate mechanical working. The alloy variant containing indium achieved a higher peak hardness in comparison to the other alloy variations, including the baseline material, when aged at temperatures ranging from 160 C to 190 C. Tensile tests on specimens peak-aged at 160 indicated the yield strength of the indium-bearing alloy increased by approximately 15 percent compared to that of the peak-aged baseline alloy. In addition, the yield strength obtained in the indium-bearing alloy was comparable to that reported for similar baseline material subjected to a 6 percent stretch prior to peak-aging at 190 C. The higher strength levels obtaied for the indium-bearing alloy are attributed to increased number densities and homogeneity of both the T1 and theta-prime phases, as determined by TEM studies.
A Modified Dialogic Reading Intervention for Preschool Children with Autism Spectrum Disorder
ERIC Educational Resources Information Center
Fleury, Veronica P.; Schwartz, Ilene S.
2017-01-01
We examined the effect of a modified dialogic reading intervention on levels of verbal participation and vocabulary growth in nine preschool children with autism spectrum disorder (ASD) using single-case design methodology. Baseline book reading resulted in consistently low levels of verbal participation followed by an immediate increase in verbal…
Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Saha, Malay K; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Das, Ranjan Saurav; Mallick, Mausom; Mandal, Sutapa
2016-04-27
Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late. The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization. We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up. 125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 μg/mL at baseline to 2.65 μg/mL after two doses of HibCV, representing a 10.6-fold increase (p<0.0001). 76% percent of HIV-infected children mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 μg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children. Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response following two doses of HibCV. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pantuck, A J; Pettaway, C A; Dreicer, R; Corman, J; Katz, A; Ho, A; Aronson, W; Clark, W; Simmons, G; Heber, D
2015-09-01
The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
Docherty, Nancy M.; St-Hilaire, Annie; Aakre, Jennifer M.; Seghers, James P.; McCleery, Amanda; Divilbiss, Marielle
2011-01-01
Psychotic symptoms are exacerbated by social stressors in schizophrenia and schizoaffective disorder patients as a group. More specifically, critical attitudes toward patients on the part of family members and others have been associated with a higher risk of relapse in the patients. Some patients appear to be especially vulnerable in this regard. One variable that could affect the degree of sensitivity to a social stressor such as criticism is the individual’s level of anxiety. The present longitudinal study assessed 27 relatively stable outpatients with schizophrenia or schizoaffective disorder and the single “most influential other” (MIO) person for each patient. As hypothesized, (1) patients with high critical MIOs showed increases in psychotic symptoms over time, compared with patients with low critical MIOs; (2) patients high in anxiety at the baseline assessment showed increases in psychotic symptoms at follow-up, compared with patients low in anxiety, and (3) patients with high levels of anxiety at baseline and high critical MIOs showed the greatest exacerbation of psychotic symptoms over time. Objectively measured levels of criticism were more predictive than patient-rated levels of criticism. PMID:19892819
Scanning confocal slit photon counter measurements of post-PRK haze in two-year study
NASA Astrophysics Data System (ADS)
Taboada, John; Gaines, David; Perez, Mary A.; Waller, Steve G.; Ivan, Douglas J.; Baldwin, J. Bruce; LoRusso, Frank; Tutt, Ronald C.; Thompson, B.; Perez, Jose; Tredici, Thomas; Johnson, Dan A.
2001-06-01
In our study, a group of 80 United States Air Force, non- flying personnel will undergo photorefractive corneal surgery for moderate levels of myopia (< 6 diopters) and 20 will serve as controls. As of this report, approximately 56 have had the treatment. Of these, only about 59% of the treated eyes showed even a trace (.5) level of clinically assessed haze at any time. We report on the use of a recently developed instrument designed for the objective measurement of these low levels of haze in treated corneas. The sensitivity of the instrument is derived from the use of a scanning confocal slit photon counter. The use of a physical standard for calibration secures accuracy and reproducibility over an extensive period of time. Our haze measurements in this study revealed a very low level increase from baseline values for these patients. The typical increase over baseline was of the same magnitude as the variability in the observations, although the inherent variability in the measurements was approximately 0.25 times the value of the patient's haze variability.
Ji, Julie L; Holmes, Emily A; Blackwell, Simon E
2017-01-01
Optimism is associated with positive outcomes across many health domains, from cardiovascular disease to depression. However, we know little about cognitive processes underlying optimism in psychopathology. The present study tested whether the ability to vividly imagine positive events in one's future was associated with dispositional optimism in a sample of depressed adults. Cross-sectional and longitudinal analyses were conducted, using baseline (all participants, N=150) and follow-up data (participants in the control condition only, N=63) from a clinical trial (Blackwell et al., 2015). Vividness of positive prospective imagery, assessed on a laboratory-administered task at baseline, was significantly associated with both current optimism levels at baseline and future (seven months later) optimism levels, including when controlling for potential confounds. Even when depressed, those individuals able to envision a brighter future were more optimistic, and regained optimism more quickly over time, than those less able to do so at baseline. Strategies to increase the vividness of positive prospective imagery may aid development of mental health interventions to boost optimism. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Effect of Medicaid Policy Changes on Medication Adherence: Differences by Baseline Adherence.
Amin, Krutika; Farley, Joel F; Maciejewski, Matthew L; Domino, Marisa E
2017-03-01
In 2001, the North Carolina (NC) Medicaid program reduced the number of days prescription supply that enrollees could fill from 100 days to 34 days and increased copayments for brand-name medications. Previous work has shown that a change in these policies led to a decrease in medication adherence from 2.9 to 8.0 percentage points in specific populations with chronic conditions. Studies have also shown that days supply limits and copayment increases have heterogeneous effects based on enrollees' baseline characteristics, including baseline adherence. However, this phenomenon has not been studied in the Medicaid population. We undertook this study to assess the heterogeneous effect of the NC Medicaid policy changes in groups with varying levels of baseline adherence. To examine whether restrictions on days supply had heterogeneous effects in subgroups defined by medication adherence before the policy changes. A partial difference-in-difference-in-differences model with fixed effects was used to compare medication adherence before and after the NC Medicaid policy changes among Medicaid enrollees subject to the policy changes because of their use of long prescriptions (> 40 days) as compared with (a) NC Medicaid enrollees using short prescriptions (< 40 days) before policy adoption, as well as (b) Medicaid enrollees in Georgia restricted to a 31 days supply through the study period. Medicaid enrollees were included if they filled a prescription for 1 of the following medication classes: antihypertensives, lipid-lowering drugs, or antipsychotics. The effect of the policy changes on medication adherence, calculated using the proportion of days covered (PDC) each quarter by baseline adherence level and clinical condition group, was studied. Average adherence levels over the 18-month prechange period were used to stratify individuals into 3 baseline adherence groups: fully adherent (PDC ≥ 80%), partially adherent (50%-79%), and nonadherent (PDC ≤ 50%). Enrollees fully adherent at baseline observed a 2.0 (P = 0.001) and 1.2 (P < 0.001) percentage-point decline in adherence for the lipid-lowering drug and antihypertensive cohorts, respectively, in the period after the policy changes. The nonadherent and partially adherent cohorts in the statin group observed an increase in adherence by 1.7-2.6 (P < 0.05) percentage points in the post-index period. Adherence changes after cost containment policies have a heterogeneous effect on individuals with varying baseline adherence in the Medicaid population. Individuals fully adherent at baseline decreased adherence following policy changes, while individuals partially adherent and nonadherent at baseline either had no change or showed increases in adherence, possibly because of increased contact with pharmacists and clinicians required by shorter prescription lengths. Managed care strategies to control costs should take into consideration the heterogeneity of responses by the enrollees to these policies. Furthermore, policies that consider baseline characteristics of enrollees may be more effective in improving adherence. This study was partly funded by a grant from the Robert Wood Johnson Foundation for use in data creation. Maciejewski was supported by a Research Career Scientist Award from the Department of Veterans Affairs (RCS 10-391) and owns stock in Amgen. Farley reports consultancy fees from Daiichi Sankyo outside of the conduct of this study. The other authors report no financial or other conflicts of interest related to the subject of this article. The views expressed in this article are those of the authors and do not reflect the position or policy of the Centers for Medicare & Medicaid Services, University of North Carolina at Chapel Hill, Department of Veteran Affairs, or Duke University. Study design and concept were contributed by Amin and Domino, along with Farley and Maciejewski. Domino collected the data, and data interpretation was performed primarily by Amin, along with Domino, with assistance from Farley and Maciejewski. The manuscript was primarily written by Amin, along with Domino, and revised by all the authors.
Cohen, Robyn T; Rodeghier, Mark; Kirkham, Fenella J; Rosen, Carol L; Kirkby, Jane; DeBaun, Michael R; Strunk, Robert C
2016-11-01
The significance of fractional exhaled nitric oxide (Feno) levels in children with sickle cell anemia (SCA) is unclear, but increased levels can be associated with features of asthma and thus increased morbidity. We sought to determine factors associated with Feno and whether Feno levels are associated with increased rates of acute chest syndrome (ACS) and pain. All participants had SCA, were part of the prospective observational Sleep and Asthma Cohort study, and had the following assessments: Feno levels, spirometry, blood samples analyzed for hemoglobin, white blood cell counts, eosinophil counts and total serum IgE levels, questionnaires about child medical and family history, and review of medical records. The analytic sample included 131 children with SCA (median age, 11.2 years; age range, 6-18 years) followed for a mean of 16.2 years, including a mean of 5.1 years after baseline Feno data measurements. In multivariable analyses higher Feno levels were associated with ln(IgE) levels (P < .001) and the highest quartile of peripheral eosinophil counts (P = .03) but not wheezing symptoms, baseline spirometric indices, or response to bronchodilator. Multivariable analyses identified that the incident rate of ACS was associated with ln(Feno) levels (P = .03), as well as male sex (P = .025), wheezing causing shortness of breath (P = .002), and ACS at less than 4 years of age (P < .001). Feno levels were not associated with future pain episodes. Steady-state Feno levels were not associated with an asthma diagnosis, wheezing symptoms, lung function measures, or prior sickle cell morbidity but were associated with markers of atopy and increased risk of future ACS events. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volkmann, Elizabeth R; Tashkin, Donald P; Roth, Michael D; Clements, Philip J; Khanna, Dinesh; Furst, Daniel E; Mayes, Maureen; Charles, Julio; Tseng, Chi-Hong; Elashoff, Robert M; Assassi, Shervin
2016-12-30
Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD. A total of 142 SSc-ILD patients from Scleroderma Lung Study (SLS) II were randomized in a double-blind, parallel-arm trial, to receive mycophenolate (MMF) for 2 years or oral cyclophosphamide (CYC) for 1 year followed by 1 year of placebo. Plasma CXCL4 levels were measured at baseline, 12 months, and 24 months in SLS II participants (N = 136) and at a single time point in healthy controls (N = 67). A mixed-effects model evaluated the relationship between change in CXCL4 levels and SSc-ILD progression. The primary outcome was the course of the forced vital capacity. Baseline CXCL4 levels were significantly higher in SSc-ILD patients compared with healthy controls (2699 ± 1489 ng/ml vs 2233 ± 1351 ng/ml (mean ± SD); P = 0.019). However, no significant correlations were identified between CXCL4 levels and extent of ILD at baseline, as measured by the forced vital capacity, diffusing capacity of carbon monoxide, or radiographic extent of ILD. Plasma CXCL4 decreased significantly from baseline to 12 months in all patients (CYC: P < 0.001; MMF: P = 0.006) with no between-treatment differences (CYC vs MMF). Patients with the largest decline in CXCL4 levels during the first 12 months had an improved course of forced vital capacity %-predicted from 12 to 24 months (P = 0.040), even after adjusting for baseline disease severity and treatment arm assignment. Levels of CXCL4 were higher in patients with SSc-ILD compared with controls and decreased in all patients treated with immunosuppressive therapy. While CXCL4 levels were not correlated with extent of ILD at baseline, changes in CXCL4 at 12 months predicted future progression of SSc-ILD from 12 to 24 months. These findings suggest that intermediate-term changes in CXCL4 may have predictive significance for long-term progression of SSc-ILD in patients receiving immunosuppressive therapy. ClinicalTrials.gov NCT00883129 . Registered 16 April 2009.
Nota, N M; Dekker, M J H J; Klaver, M; Wiepjes, C M; van Trotsenburg, M A; Heijboer, A C; den Heijer, M
2017-08-01
The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L -1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. © 2016 Blackwell Verlag GmbH.
Baseline Response Levels Are a Nuisance in Infant Contingency Learning
ERIC Educational Resources Information Center
Millar, W. S.; Weir, Catherine
2015-01-01
The impact of differences in level of baseline responding on contingency learning in the first year was examined by considering the response acquisition of infants classified into baseline response quartiles. Whereas the three lower baseline groups showed the predicted increment in responding to a contingency, the highest baseline responders did…
Sowiński, Jerzy; Sawicka-Gutaj, Nadia; Gutaj, Paweł; Ruchała, Marek
2015-02-01
The aim of this study was to analyze the possible role of free triiodothyronine (FT3) in infertility and in levothyroxine-treated (LT4) euthyroid women with Hashimoto thyroiditis (HT). It is an observational retrospective case control study. Twenty one euthyroid women with HT on LT4 replacement therapy and a medical history of idiopathic infertility were included into the study. To achieve higher FT3 level, the dose of LT4 was increased in every patient. Fifteen fertile women with HT on LT4 replacement therapy served as a control group. At baseline in the study group mean thyroid stimulating hormone (TSH) level was 1.96 μU/ml ± 0.84 μU/ml and mean FT3 was 4.07 pmol/l ± 0.78 pmol/l. The mean TSH level after the increase of LT4 was 0.60 μU/ml ± 0.45 μU/ml (p < 0.0001), and the mean FT3 was 5.12 pmol/l ± 0.77 pmol/l (p = 0.0001). Baseline TSH in the study group was higher than in controls (p < 0.0001) and baseline FT3 in the study group was lower than in controls (p = 0.0003). Relatively low levels of FT3 in women with HT on LT4 replacement therapy may contribute to higher infertility rates.
Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas
2017-11-28
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.
Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle.
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.
Longitudinal levels and bouts of sedentary time among adolescent girls.
Carson, Valerie; Cliff, Dylan P; Janssen, Xanne; Okely, Anthony D
2013-10-21
Adolescent girls are one of the most sedentary demographic groups. A better understanding of their accumulation of sedentary time is needed to inform future interventions. The purpose of this study was to examine the longitudinal levels and bouts of objectively measured sedentary time accumulated during different days of the week and periods of the weekday among a large sample of adolescent girls. The results are based on 655 adolescent girls from the Girls in Sport Intervention and Research Project. Levels and bouts of sedentary time were derived from accelerometer data collected at baseline and 18-month follow-up. Total, weekday, weekend, school (i.e., morning bell to afternoon bell), after school (i.e., afternoon bell to 19:00), and evening (i.e. 19:01 to 23:59) sedentary time levels and bouts were calculated. Repeated-measures ANCOVAs were conducted to examine differences in sedentary time levels and bouts between days and time periods after adjusting for wear time, accelerometer model, and intervention group. Cross-sectional analyses revealed that levels and bouts of sedentary time were higher on weekdays compared to weekend days at baseline. Similar trends were observed at follow-up. In addition, percentage of wear time spent sedentary and bouts/hr of sedentary time were highest in the evening compared to the school and after school periods at both baseline and follow-up. Longitudinal analyses revealed that levels and bouts of sedentary time were higher at follow-up compared to baseline across the different days of the week and periods of the weekday examined, with the biggest increase (15%) occurring in the school period. Future interventions targeting sedentary time among adolescent girls should consider developing strategies to reduce and break up prolonged sedentary time during the school day and in the evening.
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.
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
Wen, Xiaozhong; Chen, Weiqing; Gans, Kim M; Colby, Suzanne M; Lu, Ciyong; Liang, Caihua; Ling, Wenhua
2010-01-01
Background The prevalence of adolescent smoking has been increasing rapidly in China. Theory-based smoking prevention programmes in schools may be an effective approach in preventing smoking among Chinese adolescents. Methods A school-level cluster randomized controlled trial was conducted among 7th and 8th grade students (N = 2343) in four junior high schools in southern China during 2004–06. The theory-based, multi-level intervention was compared with the standard health curriculum. Outcome measures comprised changes in students’ smoking-related knowledge, attitudes and behaviour. Results The mean knowledge scores from baseline to the 1- and 2-year follow-ups increased more in the intervention group than in the control group, whereas there was little change in attitude scores. At the 1-year follow-up (the total sample), the interventions reduced the probability of baseline experimental smokers’ escalating to regular smoker [7.9 vs 18.3%; adjusted odds ratio (OR) 0.34, 95% confidence interval (CI) 0.12–0.97, P = 0.043], but did not reduce the probability of baseline non-smokers’ initiating smoking (7.9 vs 10.6%; adjusted OR 0.86, 95% CI 0.54–1.38, P = 0.538). At the 2-year follow-up (only 7th grade students), similar proportions of baseline non-smokers initiated smoking in the intervention group and the control group (13.5 vs 13.1%), while a possibly lower proportion of baseline experimental smokers escalated to regular smoking in the intervention group than the control group (22.6 vs 40.0%; adjusted OR 0.43, 95% CI 0.12–1.57, P = 0.199). Conclusions This multi-level intervention programme had a moderate effect on inhibiting the escalation from experimental to regular smoking among Chinese adolescents, but had little effect on the initiation of smoking. The programme improved adolescents’ smoking-related knowledge, but did not change their attitudes towards smoking. PMID:20236984
Archer, D F; Thomas, M A; Conard, J; Merkatz, R B; Creasy, G W; Roberts, K; Plagianos, M; Blithe, D; Sitruk-Ware, R
2016-01-01
Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150mcg Nestorone® (NES) and 15mcg ethinyl estradiol (EE). A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. NES/EE CVR for up to 13cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC. Copyright © 2016 Elsevier Inc. All rights reserved.
Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W
2017-11-01
To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.
Pabayo, Roman; Kawachi, Ichiro; Gilman, Stephen E
2015-07-01
To examine prospectively the association between US state income inequality and incidence of heart attack. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,445). Respondents completed interviews at baseline (2001-2002) and follow-up (2004-2005). Weighted multilevel modeling was used to determine if US state-level income inequality (measured by the Gini coefficient) at baseline was a predictor of heart attack during follow-up, controlling for individual-level and state-level covariates. In comparison to residents of US states in the lowest quartile of income inequality, those living in the second [Adjusted Odds Ratio (AOR) = 1.71, 95 % CI 1.16-2.53)], third (AOR = 1.81, 95 % CI 1.28-2.57), and fourth (AOR = 2.04, 95 % CI 1.26-3.29) quartiles were more likely to have a heart attack. Similar findings were obtained when we excluded those who had a heart attack prior to baseline. This study is one of the first to empirically show the longitudinal relationship between income inequality and coronary heart disease. Living in a state with higher income inequality increases the risk for heart attack among US adults.
Assessment of adrenocortical reserve capacity and inflammatory parameters in critically ill dogs.
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.
Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo
2014-10-01
Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored. We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD. In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.
Effect of obesity on acute hemostatic responses to live-fire training drills.
Smith, Denise L; Horn, Gavin P; Petruzzello, Steven J; Freund, Gregory G; Woods, Jeffrey A; Cook, Marc D; Goldstein, Eric; Fernhall, Bo
2014-12-01
The objective of this study was to evaluate the impact of obesity and firefighting activities on coagulation and fibrinolytic activity in relatively young, apparently healthy firefighters. Firefighters performed simulated firefighting activities for 18 minutes in a live-fire training structure. Blood samples were obtained at baseline, before firefighting, and within a few minutes of completing the activity. Nearly all markers of coagulation and fibrinolytic activity increased immediately after firefighting with an overall shift toward a procoagulatory profile. Obese firefighters exhibited lower levels of tissue plasminogen activator activity (0.98 vs 0.63 IU/ml) and higher levels of plasminogen activator inhibitor-1 activity (2.2 vs 4.5 ng/ml) at baseline compared with normal-weight firefighters, suggesting that fibrinolytic activity was lower in obese firefighters. There were few interactions between body mass index and firefighting activity, thus our findings suggest that obese firefighters did not exhibit a greater procoagulatory response to live firefighting compared with normal-weight firefighters. Acute live firefighting produced increases in both fibrinolytic and coagulatory responses; although obesity was associated with a reduced fibrinolytic profile at baseline, the changes produced by acute firefighting were similar in obese and nonobese firefighters. Copyright © 2014 Elsevier Inc. All rights reserved.
Fox, M A; Panessiti, M G; Moya, P R; Tolliver, T J; Chen, K; Shih, J C; Murphy, D L
2013-12-01
A possible side effect of serotonin-enhancing drugs is the serotonin syndrome, which can be lethal. Here we examined possible hypersensitivity to two such drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA) and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B-WT mice, baseline tissue serotonin levels were increased ∼2.6-3.9-fold in MAOA/B-KO mice. Following 5-HTP, serotonin levels were further increased ∼4.5-6.2-fold in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated responses following serotonin-enhancing drugs that we previously observed in mice lacking the serotonin transporter (SERT). These findings provide a second genetic mouse model suggestive of possible human vulnerability to the serotonin syndrome in individuals with lesser-expressing MAO or SERT polymorphisms that confer serotonergic system changes.
Fox, MA; Panessiti, MG; Moya, PR; Tolliver, TJ; Chen, K; Shih, JC; Murphy, DL
2012-01-01
A possible side effect of serotonin-enhancing drugs is the serotonin syndrome, which can be lethal. Here we examined possible hypersensitivity to two such drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA) and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B-WT mice, baseline tissue serotonin levels were increased ~2.6–3.9-fold in MAOA/B-KO mice. Following 5-HTP, serotonin levels were further increased ~4.5–6.2-fold in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated responses following serotonin-enhancing drugs that we previously observed in mice lacking the serotonin transporter (SERT). These findings provide a second genetic mouse model suggestive of possible human vulnerability to the serotonin syndrome in individuals with lesser-expressing MAO or SERT polymorphisms that confer serotonergic system changes. PMID:22964922
Odin, Elisabeth A.; Carlsson, Göran U.; Kurlberg, Göran K.; Björkqvist, Hillevi G.; Tångefjord, Maria T.; Gustavsson, Bengt G.
2016-01-01
The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m2, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869
Disulfiram treatment increases plasma and red blood cell acetaldehyde in abstinent alcoholics.
Rosman, A S; Waraich, A; Baraona, E; Lieber, C S
2000-07-01
Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase. The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment. In the disulfiram-treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26 microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1 week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have clinically significant elevations. In abstaining subjects given disulfiram, acetaldehyde concentrations increase, possibly due to diminished catabolism of endogenously generated acetaldehyde. Disulfiram should be given cautiously, especially in patients with cirrhosis.
Lyoo, In Kyoon; Demopulos, Christina M; Hirashima, Fuyuki; Ahn, Kyung Heup; Renshaw, Perry F
2003-08-01
Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (31P) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder. Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.
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.
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.
Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.
Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin
2017-01-01
In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.
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
Fleseriu, Maria; Findling, James W; Koch, Christian A; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman
2014-10-01
Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Mifepristone (300-1200 mg) was administered once daily. ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.
Informal and formal trail monitoring protocols and baseline conditions: Acadia National Park
Marion, Jeffrey L.; Wimpey, Jeremy F.; Park, L.
2011-01-01
At Acadia National Park, changing visitor use levels and patterns have contributed to an increasing degree of visitor use impacts to natural and cultural resources. To better understand the extent and severity of these resource impacts and identify effective management techniques, the park sponsored this research to develop monitoring protocols, collect baseline data, and identify suggestions for management strategies. Formal and informal trails were surveyed and their resource conditions were assessed and characterized to support park planning and management decision-making.
Levels of fecal corticosterone in sandhill cranes during a human-led migration.
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.
Driving cessation and increased depressive symptoms.
Ragland, David R; Satariano, William A; MacLeod, Kara E
2005-03-01
To understand the consequences of driving cessation in older adults, the authors evaluated depression in former drivers compared with active drivers. Depression (as assessed using the Center for Epidemiological Studies Depression Scale), driving status, sociodemographic factors, health status, and cognitive function were evaluated for a cohort of 1953 residents of Sonoma County, California, aged 55 years and older, as part of a community-based study of aging and physical performance. The authors re-interviewed 1772 participants who were active drivers at baseline 3 years later. At baseline, former drivers reported higher levels of depression than did active drivers even after the authors controlled for age, sex, education, health, and marital status. In a longitudinal analysis, drivers who stopped driving during the 3-year interval (i.e., former drivers) reported higher levels of depressive symptoms than did those who remained active drivers, after the authors controlled for changes in health status and cognitive function. Increased depression for former drivers was substantially higher in men than in women. With increasing age, many older adults reduce and then stop driving. Increased depression may be among the consequences associated with driving reduction or cessation.
Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.
Galinowski, A; Castelnau, C; Spreux-Varoquaux, O; Bourdel, M C; Olie, J P; Loo, H; Poirier, M F
2000-11-01
1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.
Goyal, Aman; Singh, Surender; Tandon, Nikhil; Gupta, Nandita; Gupta, Yogendra Kumar
2014-12-01
Statins are commonly used for the management of dyslipidemia in type 2 diabetes mellitus patients. We hypothesized that atorvastatin could modulate the beta-cell function by altering the levels of proapoptotic and antiapoptotic lipoproteins and could also have an effect on insulin resistance. The aim of the present pilot study was to assess the effect of atorvastatin 10 mg on pancreatic beta-cell function and insulin resistance in patients with hyperlipidemia and type 2 diabetes by using the homeostasis model assessment-2 (HOMA2) index. Fifty-one type 2 diabetes patients receiving oral antidiabetes drugs, not taking statins, with baseline low-density lipoprotein cholesterol between 2.6 mmol/L and 4.1 mmol/L were included. Forty-three patients (21 in placebo group and 22 in atorvastatin group) completed the study and were taken up for final analysis. Fasting blood samples were obtained at baseline and at 12 weeks to determine levels of blood glucose, lipid profile, insulin, C-peptide and glycosylated hemoglobin (A1C). Atorvastatin nonsignificantly increased fasting serum insulin (+14.29%, p=0.18), accompanied by marginal nonsignificant increases in fasting plasma glucose and A1C. There was a decrease in HOMA2 percent beta-cell function (-2.9%, p=0.72) and increase in HOMA2 insulin resistance (+14%, p=0.16) in the atorvastatin group as compared with baseline, but the difference was not statistically significant. Atorvastatin in the dose used failed to produce significant change in pancreatic beta-cell function and insulin resistance in type 2 diabetes patients as assessed by the HOMA2 index. The possible explanations include absence of lipotoxicity at prevailing levels of dyslipidemia at baseline or inadequacy of statin dose used in the study. (Clinical Trials Registry-India: CTRI/2008/091/000099). Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.
Dale, Matthew A.; Ruhlman, Melissa K.; Zhao, Shijia; Meisinger, Trevor; Gu, Linxia; Swier, Vicki J.; Agrawal, Devendra K.; Greiner, Timothy C.; Carson, Jeffrey S.; Baxter, B. Timothy; Xiong, Wanfen
2015-01-01
Objective Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. Methods Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. Results Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. Conclusions These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA. PMID:26546710
Arenas, Ivan A; Navas-Acien, Ana; Ergui, Ian; Lamas, Gervasio A
2017-10-01
Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Copyright © 2017 Elsevier Inc. All rights reserved.
Faurholt-Jepsen, Daniel; Hansen, Kristina Beck; van Hees, Vincent T; Christensen, Line Brinch; Girma, Tsinuel; Friis, Henrik; Brage, Søren
2014-06-01
To assess physical activity at admission and during recovery from severe acute malnutrition. Ethiopian children who were admitted with severe acute malnutrition received a clinical examination each week to monitor their recovery during rehabilitation. Using accelerometry (24 h/d for 5 consecutive days) at admission and again after 10 days of rehabilitation, we assessed the level and changes of physical activity. Among 13 children included, the mean (SD) age was 31.1 months (15.5). At baseline, the day-night activity difference was relatively small, whereas the level of activity had substantially increased at follow-up. The diurnal mean acceleration level was significantly greater at follow-up for wrist (1158.8 vs 541.4 counts per minute, P = .003) but not hip movements (204.1 vs 141.5, P = .261). During daytime (6 a.m. to 10 p.m.), hip activity increased by 38% from baseline to follow-up (e(B) 1.38, 95% CI 1.17-1.62), and wrist activity more than doubled (e(B) 2.50, 95% CI 2.17-2.87). The level of physical activity among children with severe acute malnutrition is very low but increases rapidly during recovery. Accelerometry may be a useful approach in the recovery phase as an indicator of early improvement. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.
Li, Shao-Hua; Liu, Xu-Xia; Bai, Yong-Yi; Wang, Xiao-Jian; Sun, Kai; Chen, Jing-Zhou; Hui, Ru-Tai
2010-02-01
The effect of isoflavone on endothelial function in postmenopausal women is controversial. The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women. A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was > or = 5.2% (4 trials; WMD: 0.24%; 95% CI: -0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were <5.2% (5 trials; WMD: 2.22%; 95% CI: 1.15%, 3.30%; P < 0.0001), although significant heterogeneity was still detected in this low-baseline-FMD subgroup. Oral isoflavone supplementation does not improve endothelial function in postmenopausal women with high baseline FMD levels but leads to significant improvement in women with low baseline FMD levels.
Ninomiya, Haruhiko; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Nishiwaki, Kaichi; Matsumura, Itaru; Shichishima, Tsutomu; Okamoto, Shinichiro; Nishimura, Jun-Ichi; Ohyashiki, Kazuma; Nakao, Shinji; Ando, Kiyoshi; Kanda, Yoshinobu; Kawaguchi, Tatsuya; Nakakuma, Hideki; Harada, Daisuke; Akiyama, Hirozumi; Kinoshita, Taroh; Ozawa, Keiya; Omine, Mitsuhiro; Kanakura, Yuzuru
2016-11-01
Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 10 9 /L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.
Influence of level of education on disability free life expectancy by sex: the ILSA study.
Minicuci, N; Noale, M
2005-12-01
To assess the effect of education on Disability Free Life Expectancy among older Italians, using a hierarchical model as indicator of disability, with estimates based on the multistate life table method and IMaCh software. Data were obtained from the Italian Longitudinal Study on Aging which considered a random sample of 5632 individuals. Total life expectancy ranged from 16.5 years for men aged 65 years to 6 years for men aged 80. The age range for women was 19.6 and 8.4 years, respectively. For both sexes, increasing age was associated with a lower probability of recovery from a mild state of disability, with a greater probability of worsening for all individuals presenting an independent state at baseline, and with a greater probability of dying except for women from a mild state of disability. A medium/high educational level was associated with a greater probability of recovery only in men with a mild state of disability at baseline, and with a lower probability of worsening in both sexes, except for men with a mild state of disability at baseline. The positive effects of high education are well established in most research work and, being a modifiable factor, strategies focused on increasing level of education and, hence strengthening access to information and use of health services would produce significant benefits.
Beddhu, Srinivasan; Chertow, Glenn M; Cheung, Alfred K; Cushman, William C; Rahman, Mahboob; Greene, Tom; Wei, Guo; Campbell, Ruth C; Conroy, Margaret; Freedman, Barry I; Haley, William; Horwitz, Edward; Kitzman, Dalane; Lash, James; Papademetriou, Vasilios; Pisoni, Roberto; Riessen, Erik; Rosendorff, Clive; Watnick, Suzanne G; Whittle, Jeffrey; Whelton, Paul K
2018-01-09
In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level ( P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062. © 2017 American Heart Association, Inc.
Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.
van Vliet, Esther I; de Herder, Wouter W; de Rijke, Yolanda B; Zillikens, M Carola; Kam, Boen L R; Teunissen, Jaap J M; Peeters, Robin P; Krenning, Eric P; Kwekkeboom, Dik J
2013-12-01
The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.
Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.
Mussi, Chiara; Angelini, Carlo; Crippa, Stefano; Caprotti, Roberto; Fumagalli, Luca; Motta, Vittorio; Uggeri, Franco
2003-12-01
in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. 40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients. increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days. it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.
Chen, Hongying; Fan, Yong; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi
2017-09-01
The relationship between peripheral 5-HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown. A total 52 first-episode and drug-naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week. There was no difference in 5-HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline ( p = .24). Among 47 patients who completed 8-week naturalistic follow-up, 37 were responders to risperidone treatment. 5-HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8-week treatment with risperidone ( p = .29). However, 5-HT3A receptor mRNA level in responders increased significantly ( p = .04), but not in nonresponders ( p = .81). Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5-HT3A receptor may be involved in the mechanism of risperidone effect.
Self-Care Posters Serve as a Low-Cost Option for Physical Activity Promotion of Hospital Nurses.
Raney, Marcella; Van Zanten, Erin
2018-03-01
Hospital nurses play an important role in the nation's short- and long-term patient care. At the same time, nurses often experience high levels of occupational stress and participate in low levels of physical activity (PA). The purpose of this study was to examine the impact of self-monitoring and a poster campaign on the PA behaviors of hospital nurses. Motivational and instructional exercise posters were hung in break rooms of experimental units and replaced biweekly for 8 weeks. A total of 26 nurses (control: n = 13; experimental: n = 13) wore accelerometers for 3 workdays pre-, mid-, and postintervention. Participants were provided a step counter at baseline and a PA report at each stage. Moderate to vigorous PA (MVPA) and step count (SC) increased pre- to midintervention for control (MVPA: 14.8 ± 7.6%; SC: 19.1 ± 7.8%) and experimental (MVPA: 26.7 ± 18.5%, SC: 17.6 ± 8.3%) participants. Physical activity levels returned to baseline postintervention for control ( p > .05) and increased mid- to postintervention for experimental (MVPA: 16.2 ± 5.2%, SC: 10.7 ± 4.7%, p < .05) participants. In conclusion, a low-cost, self-care poster campaign may increase PA levels of hospital nurses when combined with personalized PA feedback.
Reaction and Adaptation to the Birth of a Child: A Couple-Level Analysis
ERIC Educational Resources Information Center
Dyrdal, Gunvor Marie; Lucas, Richard E.
2013-01-01
The present study explored how life satisfaction changes before and after childbirth among first-time parents from a nationally representative, longitudinal study of Germans. Life satisfaction increased before pregnancy to a peak just after birth and then returned to the baseline level within 2 years postpartum. The 2 members of the same couple…
A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.
Duttaroy, Smita; Thorell, Daniel; Karlsson, Lena; Börjesson, Mats
2012-02-01
While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.
Türkoğlu, Oya; Becerik, Sema; Tervahartiala, Taina; Sorsa, Timo; Atilla, Gül; Emingil, Gülnur
2014-05-20
The aim of the present study was to evaluate the effect of adjunctive chlorhexidine (CHX) mouthrinse on gingival crevicular fluid (GCF) MMP-8 and TIMP-1 levels in plaque-associated gingivitis. A total of 50 gingivitis patients were included in the present study. In addition to daily plaque control, CHX group rinsed with CHX, while placebo group rinsed with placebo mouthrinse for 4 weeks. GCF samples were collected, and clinical parameters including plaque index, papillary bleeding index, calculus index and pocket depth were recorded at baseline and 4 weeks. GCF MMP-8 and TIMP-1 levels were determined by immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA), respectively. In both groups, GCF MMP-8 levels of anterior and posterior sites at four weeks were not different from baseline (p > 0.05). There were no significant differences in GCF MMP-8 levels between the study groups at four weeks (p > 0.05). GCF TIMP-1 levels of anterior and posterior sites at four weeks were higher compared to baseline in both groups (p < 0.05). There was no significant difference in GCF TIMP level between the study groups at four weeks (p > 0.05). CHX usage had no significant effects on the GCF MMP-8 and TIMP-1 levels in plaque-associate gingivitis. However, daily plaque control resulted in the increase of GCF TIMP-1 levels regardless of CHX usage.
2014-01-01
Background The aim of the present study was to evaluate the effect of adjunctive chlorhexidine (CHX) mouthrinse on gingival crevicular fluid (GCF) MMP-8 and TIMP-1 levels in plaque-associated gingivitis. Methods A total of 50 gingivitis patients were included in the present study. In addition to daily plaque control, CHX group rinsed with CHX, while placebo group rinsed with placebo mouthrinse for 4 weeks. GCF samples were collected, and clinical parameters including plaque index, papillary bleeding index, calculus index and pocket depth were recorded at baseline and 4 weeks. GCF MMP-8 and TIMP-1 levels were determined by immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA), respectively. Results In both groups, GCF MMP-8 levels of anterior and posterior sites at four weeks were not different from baseline (p > 0.05). There were no significant differences in GCF MMP-8 levels between the study groups at four weeks (p > 0.05). GCF TIMP-1 levels of anterior and posterior sites at four weeks were higher compared to baseline in both groups (p < 0.05). There was no significant difference in GCF TIMP level between the study groups at four weeks (p > 0.05). Conclusions CHX usage had no significant effects on the GCF MMP-8 and TIMP-1 levels in plaque-associate gingivitis. However, daily plaque control resulted in the increase of GCF TIMP-1 levels regardless of CHX usage. PMID:24886536
New Year's res-illusions: food shopping in the new year competes with healthy intentions.
Pope, Lizzy; Hanks, Andrew S; Just, David R; Wansink, Brian
2014-01-01
How do the holidays--and the possible New Year's resolutions that follow--influence a household's purchase patterns of healthier foods versus less healthy foods? This has important implications for both holiday food shopping and post-holiday shopping. 207 households were recruited to participate in a randomized-controlled trial conducted at two regional-grocery chain locations in upstate New York. Item-level transaction records were tracked over a seven-month period (July 2010 to March 2011). The cooperating grocer's proprietary nutrient-rating system was used to designate "healthy," and "less healthy" items. Calorie data were extracted from online nutritional databases. Expenditures and calories purchased for the holiday period (Thanksgiving-New Year's), and the post-holiday period (New Year's-March), were compared to baseline (July-Thanksgiving) amounts. During the holiday season, household food expenditures increased 15% compared to baseline ($105.74 to $121.83; p<0.001), with 75% of additional expenditures accounted for by less-healthy items. Consistent with what one would expect from New Year's resolutions, sales of healthy foods increased 29.4% ($13.24/week) after the holiday season compared to baseline, and 18.9% ($9.26/week) compared to the holiday period. Unfortunately, sales of less-healthy foods remained at holiday levels ($72.85/week holiday period vs. $72.52/week post-holiday). Calories purchased each week increased 9.3% (450 calories per serving/week) after the New Year compared to the holiday period, and increased 20.2% (890 calories per serving/week) compared to baseline. Despite resolutions to eat more healthfully after New Year's, consumers may adjust to a new "status quo" of increased less-healthy food purchasing during the holidays, and dubiously fulfill their New Year's resolutions by spending more on healthy foods. Encouraging consumers to substitute healthy items for less-healthy items may be one way for practitioners and public health officials to help consumers fulfill New Year's resolutions, and reverse holiday weight gain.
Nogueira, Monize Aydar; Oliveira, Claudia Pinto; Ferreira Alves, Venâncio Avancini; Stefano, José Tadeu; Rodrigues, Lívia Samara Dos Reis; Torrinhas, Raquel Susana; Cogliati, Bruno; Barbeiro, Hermes; Carrilho, Flair José; Waitzberg, Dan Linetzky
2016-06-01
& aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Patients received three capsules daily, each containing 0.315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p ≤ 0.05). However in the placebo group, we also observed increased EPA and DHA (p ≤ 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01). In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809). Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Lo, Alexander X; Rundle, Andrew G; Buys, David; Kennedy, Richard E; Sawyer, Patricia; Allman, Richard M; Brown, Cynthia J
2016-11-01
To determine the relationship between neighborhood-level socioeconomic characteristics, life-space mobility, and incident falls in community-dwelling older adults. Prospective, observational cohort study with a baseline in-home assessment and 6-month telephone follow-up. Central Alabama. Community-dwelling adults aged 65 and older recruited from a random sample of Medicare beneficiaries (N = 1,000). Neighborhood disadvantage was measured using a composite index derived from baseline neighborhood-level residential census tract socioeconomic variables. Data on individual-level socioeconomic characteristics, clinical variables, and life-space collected at baseline were included as covariates in a multivariate model using generalized estimating equations to assess the association with incident falls in the 6 months after baseline. Of the 940 participants who completed baseline and follow-up assessments, 126 (13%) reported one or more new falls in the 6 months after baseline. There was an independent nonlinear association between neighborhood disadvantage (according to increasing quartiles of disadvantage) and incident falls after adjusting for confounders: The lowest quartile served as reference; 2nd quartile odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-4.6; 3rd quartile OR = 1.9, 95% CI = 1.0-3.7; 4th quartile OR = 3.2, 95% CI = 1.7-6.0. Each 10-point decrement in life-space (OR = 1.2, 95% CI = 1.0-1.3) was associated with a higher risk of falls. Greater neighborhood disadvantage was associated with greater risk of falls. Life-space also contributes separately to fall risk. Community-dwelling older adults in disadvantaged neighborhoods, particularly those with limited mobility, may benefit from a more-rigorous assessment of their fall risk by healthcare providers. Neighborhood level socioeconomic characteristics should also be an important consideration when identifying vulnerable populations that may benefit the most from fall prevention programs. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.
Kim, H-S; Lee, S H; Kim, H; Lee, S-H; Cho, J H; Lee, H; Yim, H W; Kim, S-H; Choi, I-Y; Yoon, K-H; Kim, J H
2016-06-01
Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables. © 2016 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.
Stressful life events and incident metabolic syndrome: the Hoorn study.
Rutters, Femke; Pilz, Stefan; Koopman, Anitra D M; Rauh, Simone P; Pouwer, Frans; Stehouwer, Coen D A; Elders, Petra J; Nijpels, Giel; Dekker, Jacqueline M
2015-01-01
Stressful life events are associated with the metabolic syndrome in cross-sectional studies, but prospective studies addressing this issue are rare and limited. We therefore evaluated whether the number of stressful life events is associated with incident metabolic syndrome. We assessed the association between the number of stressful life events experienced in the 5 years up until baseline and incident metabolic syndrome after 6.5 years at follow-up in the Hoorn study, a middle-aged and elderly population-based cohort. Participants with prevalent metabolic syndrome at baseline were excluded. Metabolic syndrome was defined according to the Adult Treatment Panel III, including fasting plasma glucose levels, HDL-C levels, triglyceride levels, waist circumference and hypertension. We included 1099 participants (47% male; age 60 ± 7 years). During 6.5 years of follow-up, 238 participants (22%) developed the metabolic syndrome. Logistic regression adjusted for age, sex, education level and follow-up duration showed a positive association between the number of stressful life events at baseline and incident metabolic syndrome [OR 1.13 (1.01-1.27) per event, p = 0.049]. In addition, a Poisson model showed a significant positive association between the number of stressful life events at baseline and the number of metabolic syndrome factors at follow-up [OR 1.05 (1.01-1.11) per event, p = 0.018]. Finally, we observed a significant association between the number of stressful life events at baseline and waist circumference at follow-up [adjusted for confounders β 0.86 (0.39-1.34) cm per event, p < 0.001]. Overall, we concluded that persons who reported more stressful life events at baseline had a significantly increased risk for developing metabolic syndrome during 6.5 years of follow-up, in a middle-aged and elderly population-based cohort.
Sanchez, O.A.; Duprez, D.A.; Bahrami, H.; Peralta, C.A.; Daniels, L.B.; Lima, J.A.; Maisel, A.; Folsom, A.R.; Jacobs, D.R.
2016-01-01
Aims This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. Methods lasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA).ΔNT-proBNP was calculated as NT-proBNPvisit3 − NT-proBNPbaseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n = 3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1) <54.4 pg/mL; (2) 54.4–85.9 pg/mL; and (3) 86–54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) −6.2 (−131–11.7) pg/mL; (2) 19.8 (11.8–30.1) pg/mL; (3) 44.0 (30.2–67.9) pg/mL; and (4) 111.2 (68.0–3749.9) pg/mL. Results The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P = 0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. Conclusion This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a ‘physiological range’ of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP. PMID:26047677
Diet Quality Is Linked to Insulin Resistance among Adults in China.
Wang, Zhihong; Adair, Linda S; Cai, Jianwen; Gordon-Larsen, Penny; Siega-Riz, Anna Maria; Zhang, Bing; Popkin, Barry M
2017-11-01
Background: Little is known about the impact of Chinese diet quality changes on diabetes-related markers. Objective: The present study examined the association of changes in overall diet quality with various biomarkers of diabetes among adults in China. Methods: The current analysis used longitudinal diet data from 1991 to 2006 and fasting blood samples from 2009 for 4734 adults aged 18-65 y from the China Health and Nutrition Survey. Dietary intake was assessed by using 3 consecutive 24-h recalls and household food weighing. The tailored Alternative Healthy Eating Index (tAHEI) was adapted from the 2010 Harvard Alternative Healthy Eating Index to measure overall diet quality. We categorized baseline tAHEI scores into tertiles and annual changes in the scores into 5 levels (high decrease, low decrease, maintain, low increase, and high increase). We performed mixed-effects regressions to assess the associations between baseline scores and changes in the tAHEI scores and diabetes or insulin markers. Results: Adults with high baseline tAHEI scores tended to be male, older, of lower socioeconomic status, and with higher physical activity levels. After adjustment for all of the covariates, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were 5.1% (95% CI: -0.100, -0.002) and 5.7% (95% CI: -0.113, -0.001) lower, respectively, for adults with high compared with low baseline tAHEI scores and 8.6% (95% CI: -0.155, -0.017) and 9.8% (95% CI: -0.177, -0.018) lower, respectively, for adults with a high increase in score compared with the "maintain" category. Null associations were observed between baseline scores and changes in the scores and fasting blood glucose, glycated hemoglobin (HbA1c), and diabetes prevalence. Conclusions: Baseline and changes in diet quality were independently associated with lower HOMA-IR and plasma insulin but not with fasting blood glucose and HbA1c in Chinese adults. Prospective studies on overall diet quality in relation to diabetes markers and risk of diabetes are needed. © 2017 American Society for Nutrition.
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.
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
NASA Technical Reports Server (NTRS)
Sayer, Andrew M.; Hsu, N. Christina; Hsiao, Ta-Chih; Pantina, Peter; Kuo, Ferret; Ou-Yang, Chang-Feng; Holben, Brent N.; Janjai, Serm; Chantara, Somporn; Wang, Sheng-Hsiang;
2016-01-01
The spring 2015 deployment of a suite of instrumentation at Doi Ang Khang (DAK) in northwestern Thailand enabled the characterization of air masses containing smoke aerosols from burning predominantly in Myanmar. Aerosol Robotic Network (AERONET) Sun photometer data were used to validate Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 "Deep Blue" aerosol optical depth (AOD) retrievals; MODIS Terra and Aqua provided results of similar quality, with correlation coefficients of 0.93-0.94 and similar agreement within expected uncertainties to global-average performance. Scattering and absorption measurements were used to compare surface and total column aerosol single scatter albedo (SSA); while the two were well-correlated, and showed consistent positive relationships with moisture (increasing SSA through the season as surface relative humidity and total columnar water vapor increased), in situ surface-level SSA was nevertheless significantly lower by 0.12-0.17. This could be related to vertical heterogeneity and/or instrumental issues. DAK is at approximately 1,500 meters above sea level in heterogeneous terrain, and the resulting strong diurnal variability in planetary boundary layer depth above the site leads to high temporal variability in both surface and column measurements, and acts as a controlling factor to the ratio between surface particulate matter (PM) levels and column AOD. In contrast, while some hygroscopic effects were observed relating to aerosol particle size and Angstrom exponent, relative humidity variations appear to be less important for this ratio here. As part of the Seven South-East Asian Studies (7-SEAS) project, the Biomass-burning Aerosols & Stratocumulus Environment: Lifecycles and Interactions Experiment (BASELInE) was intended to probe physicochemical processes, interactions, and feedbacks related to biomass burning aerosols and clouds during the spring burning season (February-April) in southeast Asia (SEA).
Yu, Dahong; Murdoch, Susan J; Parikh, Shamik J; Marcovina, Santica M; Cobitz, Alexander; Chen, Hongzi; Brunzell, John D
2006-12-01
A substantial number of individuals with type 2 diabetes mellitus (T2DM) demonstrate a predominance of small dense low-density lipoprotein (sdLDL), which is associated with an increased risk of cardiovascular disease (CVD). In some cases, sdLDL persists after treatment with a statin to reduce levels of LDL. The effect of the addition of a thiazolidinedione, rosiglitazone (RSG) (4 mg/day or 8 mg/day) to statin therapy on LDL phenotype and C reactive protein (CRP) levels was investigated in a 12- week, placebo-controlled study of 72 T2DM patients who were well controlled and on a statin, but who had persistently predominant sdLDL. Addition of RSG 8 mg to statin therapy significantly increased LDL buoyancy (relative flotation +0.014, p = 0.003) and LDL particle size (+4.2A, p = 0.001) from baseline and relative to the change with placebo (+0.014 and +3.8A; p = 0.03 and p = 0.04, respectively), and was associated with a non-significant decrease in sdLDL. RSG 8 mg moderately, but significantly, increased total cholesterol (by 12.2%, p = 0.004), LDL-cholesterol (11.2%, p = 0.02) and intermediate-density lipoprotein (IDL)-cholesterol from baseline but did not increase total or LDL apolipoprotein B. RSG 4 mg and 8 mg significantly reduced CRP compared with placebo (-44.9% and -48.0%; p = 0.008 and p = 0.004, respectively), and significantly reduced insulin resistance and fasting plasma glucose from baseline. Addition of RSG to statin therapy may further reduce cardiovascular risk by improving the LDL phenotype, as well as reducing insulin resistance and CRP levels. However, the increase in IDL may be proatherogenic and must be considered when assessing the benefits of rosiglitazone.
Increased blood 8-hydroxy-2-deoxyguanosine levels in methamphetamine users during early abstinence.
Huang, Ming-Chyi; Lai, Ying-Ching; Lin, Shih-Ku; Chen, Chun-Hsin
2018-01-01
Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p < 0.001). The 8-OHdG levels did not alter after 2 weeks of methamphetamine abstinence (0.32 ± 0.12 ng/mL, p = 0.051 compared to baseline measurement; p = 0.12 compared to healthy controls). No significant correlations were observed between baseline 8-OHdG levels in methamphetamine users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.
Urata, Satoko; Kitagawa, Yasuhide; Matsuyama, Satoko; Naito, Renato; Yasuda, Kenji; Mizokami, Atsushi; Namiki, Mikio
2017-04-01
To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.
Using PGFM (13,14-dihydro-15-keto-prostaglandin F2α) as a non-invasive pregnancy marker for felids.
Dehnhard, M; Finkenwirth, C; Crosier, A; Penfold, L; Ringleb, J; Jewgenow, K
2012-04-01
Understanding the complex endocrine interactions that control reproduction in felids is essential for captive breeding management. The most important demand is a quick and reliable pregnancy diagnosis. However, the occurrence of pseudopregnancies in felids complicates matters. We investigated whether the fecal prostaglandin metabolite (PGFM) recently suggested for pregnancy diagnosis in the lynx is suitable for all felid species. We found that increased levels of PGFM during the last trimester indicate pregnancy in seven of the eight main lineages of the carnivore family Felidae. PGFM levels in a sand cat (domestic cat lineage) were basal at mating and remained so until Day 40 post-mating. Day 41 marked the beginning of a distinct increase culminating in peak levels of 6.5 μg/g before parturition and decreasing again to baseline thereafter. Similar pregnancy profiles were obtained from the domestic cat, the leopard cat, the lynx, the ocelot and the caracal lineage, whereas in pseudopregnant individuals (sand cat, Iberian and Eurasian lynx) fecal PGFM remained at basal levels. In pregnant cheetahs (puma lineage) PGFM increased above basal following day ∼48 peaking before pregnancy but remained at baseline in pseudopregnant females. Discrepancies existed in the Panthera lineage. While Chinese leopard, Sumatran tiger, and the black panther showed marked increases of PGFM during the last weeks of pregnancy, only moderate increases in PGFM levels were found in the Indochinese tiger and the Persian leopard. Altogether, PGFM as tool for pregnancy diagnosis has been proven to be useful in breeding management of felids. Copyright © 2012 Elsevier Inc. All rights reserved.
The impact of Super Bowl parties on nutritional parameters among hemodialysis patients.
Ohlrich, Heather; Leon, Janeen B; Zimmerer, Jennifer; Sehgal, Ashwini R
2006-01-01
Little is known about the impact of holiday and other special-event meals on patients with chronic medical conditions. It is possible that patients are less adherent with dietary restrictions during such meals. We sought to determine the impact of Super Bowl parties on nutritional parameters among hemodialysis patients. To determine the relationship between attending a Super Bowl party and subsequent change in serum phosphorus level, serum potassium level, interdialytic weight gain, and blood pressure. Retrospective cohort study. Outpatient dialysis unit. One hundred twenty-two chronic hemodialysis patients. Patients were asked whether they had attended a Super Bowl party. Serum phosphorus level, serum potassium level, interdialytic weight gain, and predialysis blood pressure at the hemodialysis treatment after the Super Bowl and at the hemodialysis treatment 1 month previously were obtained by chart abstraction. The 15 patients who had attended a party had increased serum phosphorus levels (+0.5 mg/dL) and interdialytic weight gain (+1.1% of dry weight) from baseline. These increases were statistically significant (P values .005 and .02, respectively) compared with patients who did not attend a party. Attendees also had increased systolic blood pressure (+6 mm Hg) from baseline, but this was of marginal statistical significance compared with nonattendees (P = .14). Attending a party was not significantly associated with changes in serum potassium and diastolic blood pressure. Attending a Super Bowl party is associated with adverse changes in several nutritional parameters. Although patients should not be discouraged from attending holiday and special-event meals, management of hemodialysis patients should include increased dietary counseling before holidays and special events and increased monitoring afterward.
Guo, Suxia; Wang, Ruxing; Yang, Zhenyu; Li, Kulin; Wang, Qiang
2012-12-01
Statin treatment in patients with coronary heart disease is associated with a reduced incidence of short-term adverse events and endpoint cardiac events. However, the effects of statin treatment on atherosclerotic plaques, particularly stable plaques, remain poorly defined. In total, 228 consecutive patients with stable atherosclerotic plaques who had undergone coronary arteriography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to receive placebo (placebo group, n=54) or atorvastatin (ATOR) at a single daily dose of 10 mg (ATOR 10 mg group, n=47), 20 mg (ATOR 20 mg group, n=45), 40 mg (ATOR 40 mg group, n=43) or 80 mg (ATOR 80 mg group, n=39). Endpoints, including serum lipids, serum inflammation, plaque volume and percentage of plaque necrosis were assessed after 3-6 months. At baseline, mean low-density lipoprotein (LDL), high-density lipoprotein (HDL) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as plaque volumes and percentages of plaque necrosis, were similar between all groups. At 6 months of follow-up, the LDL levels in the ATOR groups were below those at their respective baselines (P<0.01). HDL levels in the ATOR 80 mg group following treatment were significantly higher compared with baseline (P=0.001). Additionally, they were significantly higher compared with those in the placebo, ATOR 10, 20 and 40 mg groups (P<0.01, P=0.001, P=0.048, P=0.047, respectively). Hs-CRP levels in the placebo group following treatment were higher compared with baseline levels (6.87±2.62 vs. 5.07±1.80, P<0.01), but hs-CRP levels in the ATOR 80 mg group following treatment were lower compared with baseline (3.59±1.07 vs. 6.10±2.12, P<0.01). According to the virtual histology (VH) of IVUS, the percentages of plaque necrosis following treatment in the placebo and ATOR 10 mg groups rose above baseline levels (15.51±12.56 vs. 7.69±1.31%, 13.54±11.76 vs. 7.83±1.43%, P<0.01) and conformed to the diagnostic criteria for unstable plaques (15.51±12.56, 13.54±11.76%). By contrast, in the ATOR 20, 40 and 80 mg groups, percentages of plaque necrosis remained stable following treatment compared with baseline (P=0.069, 0.846 and 0.643, respectively). Plaque volumes following treatment in the placebo, ATOR 10 and 20 mg groups were similar to baseline levels. However, in the ATOR 40 and 80 mg groups, plaque volumes decreased following treatment compared with baseline plaque volumes (30.69±8.12 vs. 37.09±12.01 mm(3), 24.99±1.01 vs. 36.47±14.68 mm(3), P=0.019, P<0.01, respectively). ATOR (20 mg/day) is able to lower LDL to standard levels while ATOR 40 mg/day was superior to 20 mg/day and had similar effects to 80 mg/day. Only ATOR 80 mg/day was able to increase HDL levels. Hs-CRP in patients without ATOR was higher and ATOR 80 mg/day decreased levels. ATOR ≥20 mg/day is able to stabilize plaques and ATOR 80 mg/day was superior to 20 and 40 mg/day. Thus, ATOR 40-80 mg/day reduces the volume of plaques.
GUO, SUXIA; WANG, RUXING; YANG, ZHENYU; LI, KULIN; WANG, QIANG
2012-01-01
Statin treatment in patients with coronary heart disease is associated with a reduced incidence of short-term adverse events and endpoint cardiac events. However, the effects of statin treatment on atherosclerotic plaques, particularly stable plaques, remain poorly defined. In total, 228 consecutive patients with stable atherosclerotic plaques who had undergone coronary arteriography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to receive placebo (placebo group, n=54) or atorvastatin (ATOR) at a single daily dose of 10 mg (ATOR 10 mg group, n=47), 20 mg (ATOR 20 mg group, n=45), 40 mg (ATOR 40 mg group, n=43) or 80 mg (ATOR 80 mg group, n=39). Endpoints, including serum lipids, serum inflammation, plaque volume and percentage of plaque necrosis were assessed after 3–6 months. At baseline, mean low-density lipoprotein (LDL), high-density lipoprotein (HDL) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as plaque volumes and percentages of plaque necrosis, were similar between all groups. At 6 months of follow-up, the LDL levels in the ATOR groups were below those at their respective baselines (P<0.01). HDL levels in the ATOR 80 mg group following treatment were significantly higher compared with baseline (P=0.001). Additionally, they were significantly higher compared with those in the placebo, ATOR 10, 20 and 40 mg groups (P<0.01, P=0.001, P=0.048, P=0.047, respectively). Hs-CRP levels in the placebo group following treatment were higher compared with baseline levels (6.87±2.62 vs. 5.07±1.80, P<0.01), but hs-CRP levels in the ATOR 80 mg group following treatment were lower compared with baseline (3.59±1.07 vs. 6.10±2.12, P<0.01). According to the virtual histology (VH) of IVUS, the percentages of plaque necrosis following treatment in the placebo and ATOR 10 mg groups rose above baseline levels (15.51±12.56 vs. 7.69±1.31%, 13.54±11.76 vs. 7.83±1.43%, P<0.01) and conformed to the diagnostic criteria for unstable plaques (15.51±12.56, 13.54±11.76%). By contrast, in the ATOR 20, 40 and 80 mg groups, percentages of plaque necrosis remained stable following treatment compared with baseline (P=0.069, 0.846 and 0.643, respectively). Plaque volumes following treatment in the placebo, ATOR 10 and 20 mg groups were similar to baseline levels. However, in the ATOR 40 and 80 mg groups, plaque volumes decreased following treatment compared with baseline plaque volumes (30.69±8.12 vs. 37.09±12.01 mm3, 24.99±1.01 vs. 36.47±14.68 mm3, P=0.019, P<0.01, respectively). ATOR (20 mg/day) is able to lower LDL to standard levels while ATOR 40 mg/day was superior to 20 mg/day and had similar effects to 80 mg/day. Only ATOR 80 mg/day was able to increase HDL levels. Hs-CRP in patients without ATOR was higher and ATOR 80 mg/day decreased levels. ATOR ≥20 mg/day is able to stabilize plaques and ATOR 80 mg/day was superior to 20 and 40 mg/day. Thus, ATOR 40–80 mg/day reduces the volume of plaques. PMID:23226776
DeBoer, Mark D; Lee, Arthur M; Herbert, Kirabo; Long, Jin; Thayu, Meena; Griffin, Lindsay M; Baldassano, Robert N; Denson, Lee A; Zemel, Babette S; Denburg, Michelle R; Herskovitz, Rita; Leonard, Mary B
2018-03-01
Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.
Schmidt, Morten; Mansfield, Kathryn E; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A
2017-01-09
To examine adherence to serum creatinine and potassium monitoring and discontinuation guidelines following initiation of treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs); and whether high-risk patients are monitored. A general practice-based cohort study using electronic health records from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. UK primary care, 2004-2014. 223 814 new ACEI/ARB users. Proportion of patients with renal function monitoring before and after ACEI/ARB initiation; creatinine increase ≥30% or potassium levels >6 mmol/L at first follow-up monitoring; and treatment discontinuation after such changes. Using logistic regression models, we also examined patient characteristics associated with these biochemical changes, and with follow-up monitoring within the guideline recommendation of 2 weeks after treatment initiation. 10% of patients had neither baseline nor follow-up monitoring of creatinine within 12 months before and 2 months after initiation of an ACEI/ARB, 28% had monitoring only at baseline, 15% only at follow-up, and 47% both at baseline and follow-up. The median period between the most recent baseline monitoring and drug initiation was 40 days (IQR 12-125 days). 34% of patients had baseline creatinine monitoring within 1 month before initiating therapy, but <10% also had the guideline-recommended follow-up test recorded within 2 weeks. Among patients experiencing a creatinine increase ≥30% (n=567, 1.2%) or potassium level >6 mmol/L (n=191, 0.4%), 80% continued treatment. Although patients with prior myocardial infarction, hypertension or baseline potassium >5 mmol/L were at high risk of ≥30% increase in creatinine after ACEI/ARB initiation, there was no evidence that they were more frequently monitored. Only one-tenth of patients initiating ACEI/ARB therapy receive the guideline-recommended creatinine monitoring. Moreover, the vast majority of the patients fulfilling postinitiation discontinuation criteria for creatinine and potassium increases continue on treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Hu, Yin; Niu, Yong; Wang, Dandan; Wang, Ying; Holden, Brien A; He, Mingguang
2015-01-22
Structural changes of retinal vasculature, such as altered retinal vascular calibers, are considered as early signs of systemic vascular damage. We examined the associations of 5-year mean level, longitudinal trend, and fluctuation in fasting plasma glucose (FPG) with retinal vascular caliber in people without established diabetes. A prospective study was conducted in a cohort of Chinese people age ≥40 years in Guangzhou, southern China. The FPG was measured at baseline in 2008 and annually until 2012. In 2012, retinal vascular caliber was assessed using standard fundus photographs and validated software. A total of 3645 baseline nondiabetic participants with baseline and follow-up data on FPG for 3 or more visits was included for statistical analysis. The associations of retinal vascular caliber with 5-year mean FPG level, longitudinal FPG trend (slope of linear regression-FPG), and fluctuation (standard deviation and root mean square error of FPG) were analyzed using multivariable linear regression analyses. Multivariate regression models adjusted for baseline FPG and other potential confounders showed that a 10% annual increase in FPG was associated independently with a 2.65-μm narrowing in retinal arterioles (P = 0.008) and a 3.47-μm widening in venules (P = 0. 0.004). Associations with mean FPG level and fluctuation were not statistically significant. Annual rising trend in FPG, but not its mean level or fluctuation, is associated with altered retinal vasculature in nondiabetic people. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
Gafni, Rachel I; Guthrie, Lori C; Kelly, Marilyn H; Brillante, Beth A; Christie, C Michele; Reynolds, James C; Yovetich, Nancy A; James, Robert; Collins, Michael T
2015-11-01
Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry bone syndrome. Further study and close monitoring is required to ensure safe transition to conventional therapy and to elucidate the physiological mechanism of this phenomenon. © 2015 American Society for Bone and Mineral Research.
Fong, Michelle C; Measelle, Jeffrey; Conradt, Elisabeth; Ablow, Jennifer C
2017-02-01
The purpose of the current study was to predict concurrent levels of problem behaviors from young children's baseline cortisol and attachment classification, a proxy for the quality of caregiving experienced. In a sample of 58 children living at or below the federal poverty threshold, children's baseline cortisol levels, attachment classification, and problem behaviors were assessed at 17 months of age. We hypothesized that an interaction between baseline cortisol and attachment classification would predict problem behaviors above and beyond any main effects of baseline cortisol and attachment. However, based on limited prior research, we did not predict whether or not this interaction would be more consistent with diathesis-stress or differential susceptibility models. Consistent with diathesis-stress theory, the results indicated no significant differences in problem behavior levels among children with high baseline cortisol. In contrast, children with low baseline cortisol had the highest level of problem behaviors in the context of a disorganized attachment relationship. However, in the context of a secure attachment relationship, children with low baseline cortisol looked no different, with respect to problem behavior levels, then children with high cortisol levels. These findings have substantive implications for the socioemotional development of children reared in poverty. Copyright © 2017 Elsevier Inc. All rights reserved.
A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.
Kimmel, M; Keller, D; Farmer, S; Warrino, D E
2010-03-01
GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.
Adelman, James Stephen; Moore, Ignacio Tomás; Hawley, Dana Michelle
2015-01-01
Aggression can alter infectious disease dynamics through two, non-exclusive mechanisms: 1) increasing direct contact among hosts and 2) altering hosts' physiological response to pathogens. Here we examined the latter mechanism in a social songbird by manipulating intraspecific aggression in the absence of direct physical contact. We asked whether the extent of aggression an individual experiences alters glucocorticoid levels, androgen levels, and individual responses to infection in an ecologically relevant disease model: house finches (Haemorhous mexicanus) infected with Mycoplasma gallisepticum (MG). Wild-caught male finches were housed in one of three settings, designed to produce increasing levels of aggression: 1) alone, with no neighbor ("no neighbor"), 2) next to a sham-implanted stimulus male ("sham neighbor"), or 3) next to a testosterone-implanted stimulus male ("testosterone neighbor"). Following one week of social treatment, focal males were experimentally infected with MG, which causes severe conjunctivitis and induces sickness behaviors such as lethargy and anorexia. While social treatment increased aggression as predicted, there were no differences among groups in baseline corticosterone levels, total circulating androgens, or responses to infection. Across all focal individuals regardless of social treatment, pre-infection baseline corticosterone levels were negatively associated with the severity of conjunctivitis and sickness behaviors, suggesting that corticosterone may dampen inflammatory responses in this host-pathogen system. However, because corticosterone levels differed based upon population of origin, caution must be taken in interpreting this result. Taken together, these results suggest that in captivity, although aggression does not alter individual responses to MG, corticosterone may play a role in this disease. © 2014 Wiley Periodicals, Inc.
Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants
Baack, Michelle L; Puumala, Susan E; Messier, Stephen E; Pritchett, Deborah K; Harris, William S
2016-01-01
Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother’s milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50mg/d) in addition to standard nutrition for preterm infants (24–34 weeks GA) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n=31) or placebo supplemented (n=29) preterm infants. Term peers (n=30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p<0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33% to 4.09%, p<0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35% to 3.32%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97%) at discharge (p=0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants. PMID:26846324
Oki, Ryo; Ito, Kazuto; Suzuki, Rie; Fujizuka, Yuji; Arai, Seiji; Miyazawa, Yoshiyuki; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro
2018-04-26
Japan has experienced a drastic increase in the incidence of prostate cancer (PC). To assess changes in the risk for PC, we investigated baseline prostate specific antigen (PSA) levels in first-time screened men, across a 25-year period. In total, 72,654 men, aged 50-79, underwent first-time PSA screening in Gunma prefecture between 1992 and 2016. Changes in the distribution of PSA levels were investigated, including the percentage of men with a PSA above cut-off values and linear regression analyses comparing log 10 PSA with age. The 'ultimate incidence' of PC and clinically significant PC (CSPC) were estimated using the PC risk calculator. Changes in the age-standardized incidence rate (AIR) during this period were analyzed. The calculated coefficients of linear regression for age versus log 10 PSA fluctuated during the 25-year period, but no trend was observed. In addition, the percentage of men with a PSA above cut-off values varied in each 5-year period, with no specific trend. The 'risk calculator (RC)-based AIR' of PC and CSPC were stable between 1992 and 2016. Therefore, the baseline risk for developing PC has remained unchanged in the past 25 years, in Japan. The drastic increase in the incidence of PC, beginning around 2000, may be primarily due to increased PSA screening in the country. © 2018 UICC.
Cunningham, Glenn R.; Stephens-Shields, Alisa J.; Rosen, Raymond C.; Wang, Christina; Ellenberg, Susan S.; Matsumoto, Alvin M.; Bhasin, Shalender; Molitch, Mark E.; Farrar, John T.; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A.; Cifelli, Denise; Crandall, Jill P.; Ensrud, Kristine E.; Fluharty, Laura; Gill, Thomas M.; Lewis, Cora E.; Pahor, Marco; Resnick, Susan M.; Storer, Thomas W.; Swerdloff, Ronald S.; Anton, Stephen; Basaria, Shehzad; Diem, Susan; Tabatabaie, Vafa; Hou, Xiaoling
2015-01-01
Context: The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear. Objective: To test the hypotheses that baseline serum TT, FT, estradiol (E2), and sex hormone-binding globulin (SHBG) levels are independently associated with sexual function, vitality, and physical function in older symptomatic men with low testosterone levels participating in the Testosterone Trials (TTrials). Design: Cross-sectional study of baseline measures in the TTrials. Setting: The study was conducted at 12 sites in the United States. Participants: The 788 TTrials participants were ≥ 65 years and had evidence of sexual dysfunction, diminished vitality, and/or mobility disability, and an average of two TT < 275 ng/dL. Interventions: None. Main Outcome Measures: Question 4 of Psychosocial Daily Questionnaire (PDQ-Q4), the FACIT-Fatigue Scale, and the 6-minute walk test. Results: Baseline serum TT and FT, but not E2 or SHBG levels had small, but statistically significant associations with validated measures of sexual desire, erectile function, and sexual activity. None of these hormones was significantly associated within or across trials with FACIT-Fatigue, PHQ-9 Depression or Physical Function-10 scores, or gait speed. Conclusions: FT and TT levels were consistently, independently, and positively associated, albeit to a small degree, with measures of sexual desire, erectile function, and sexual activity, but not with measures of vitality or physical function in symptomatic older men with low T who qualified for the TTrials. PMID:25548978
Cunningham, Glenn R; Stephens-Shields, Alisa J; Rosen, Raymond C; Wang, Christina; Ellenberg, Susan S; Matsumoto, Alvin M; Bhasin, Shalender; Molitch, Mark E; Farrar, John T; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A; Cifelli, Denise; Crandall, Jill P; Ensrud, Kristine E; Fluharty, Laura; Gill, Thomas M; Lewis, Cora E; Pahor, Marco; Resnick, Susan M; Storer, Thomas W; Swerdloff, Ronald S; Anton, Stephen; Basaria, Shehzad; Diem, Susan; Tabatabaie, Vafa; Hou, Xiaoling; Snyder, Peter J
2015-03-01
The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear. To test the hypotheses that baseline serum TT, FT, estradiol (E2), and sex hormone-binding globulin (SHBG) levels are independently associated with sexual function, vitality, and physical function in older symptomatic men with low testosterone levels participating in the Testosterone Trials (TTrials). Cross-sectional study of baseline measures in the TTrials. The study was conducted at 12 sites in the United States. The 788 TTrials participants were ≥ 65 years and had evidence of sexual dysfunction, diminished vitality, and/or mobility disability, and an average of two TT < 275 ng/dL. None. Question 4 of Psychosocial Daily Questionnaire (PDQ-Q4), the FACIT-Fatigue Scale, and the 6-minute walk test. Baseline serum TT and FT, but not E2 or SHBG levels had small, but statistically significant associations with validated measures of sexual desire, erectile function, and sexual activity. None of these hormones was significantly associated within or across trials with FACIT-Fatigue, PHQ-9 Depression or Physical Function-10 scores, or gait speed. FT and TT levels were consistently, independently, and positively associated, albeit to a small degree, with measures of sexual desire, erectile function, and sexual activity, but not with measures of vitality or physical function in symptomatic older men with low T who qualified for the TTrials.
Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Lind, Nina; Nordin, Steven; Brix, Susanne
2015-01-01
Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.
Malta, Daniela; Arcand, JoAnne; Ravindran, Anju; Floras, Vanessa; Allard, Johane P; Newton, Gary E
2016-10-01
Reduced potassium excretion caused by angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may increase the risk of hyperkalemia (serum potassium concentration >5 mmol/L) in the setting of increased potassium intake. The purpose of this study was to assess the effect of increasing dietary potassium on serum potassium concentration in hypertensive individuals with normal renal function treated with an ACEi or ARB. We hypothesized that an increase in dietary potassium would not provoke hyperkalemia in this population despite treatment with either an ACEi or ARB. We conducted a controlled, parallel-design clinical trial in 20 hypertensive subjects with normal renal function treated with an ACEi or ARB, with random assignment to a usual diet or a high-potassium diet (HKD). Fruit and vegetable intake was used to increase potassium intake. Serum potassium concentration, 3-d food records, and 24-h urine collections were completed at baseline and 4 wk. In the usual-diet group there were no statistically significant differences for potassium excretion, intake, or serum levels at end of study compared with baseline. The HKD group had significant differences in urinary potassium excretion (83 ± 26 mmol/d at baseline compared with 109 ± 35 mmol/d at 4 wk, P = 0.01) and dietary potassium intake (3775 ± 1189 mg/d at baseline compared with 5212 ± 1295 mg/d at 4 wk, P = 0.02). Despite increased potassium intake in the HKD group, serum potassium concentrations did not significantly increase from baseline at midpoint or end of study (4.1 ± 0.6, 4.3 ± 0.3, and 4.2 ± 0.4 mmol/L, respectively). This study demonstrates that an increase in dietary potassium over a 4-wk period is safe in hypertensive subjects who have normal renal function and are receiving ACEi and/or ARB therapy. This trial was registered at www.clinicaltrials.gov as NCT02759367. © 2016 American Society for Nutrition.
Javid, Patrick J; Oron, Assaf P; Duggan, Christopher; Squires, Robert H; Horslen, Simon P
2017-09-05
The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili<2 mg/dL, CBili 2-4 mg/dL, and CBili>4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili >4 mg/dL and CBili <2 mg/dL, respectively, at baseline. All-cause mortality was 23%. On univariate analysis, mortality was associated with CBili 2-4 mg/dL, CBili >4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2-4 mg/dL (HR 3.25 [1.07-9.92], p=0.04) and 4-fold for baseline CBili >4 mg/dL (HR 4.24 [1.51-11.92], p=0.006). On secondary analysis, CBili >4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged. Treatment Study, Level III. Copyright © 2017 Elsevier Inc. All rights reserved.
Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B
2009-07-01
To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.
Zeinomar, Nur; Moslehi, Roxana
2013-09-01
We determined the effectiveness of a community-based breast cancer education intervention among understudied populations in the New York State (NYS) Capital Region by assessing and comparing baseline and post-education breast cancer knowledge. Participants included 417 students recruited from five colleges/universities and 67 women from four community group organizations. Baseline and post-education knowledge was assessed via self-administered mostly multiple-choice questionnaires. An open-ended question soliciting opinions about public health prevention strategies against breast cancer was included on college/university students' questionnaires. Effectiveness of education intervention was estimated through a paired t test. Stratified analysis was done using demographic and descriptive variables. Answers to the open-ended questions were analyzed qualitatively. The mean percentage of correct answers increased from 39.9% at baseline to 80.8% post-education (P < 0.0001) among college/university students and from 43.5% to 77.8% (P < 0.0001) among community group members. Effectiveness remained statistically significant in all stratified analyses with similarly high percentage of correct answers achieved post-education irrespective of knowledge level at baseline. Stratified analysis also revealed similar patterns of improvement in overall knowledge and narrowing of the gap in post-education knowledge. Primary prevention emerged as the dominant theme post-education in students' responses to the open-ended question, signifying the effectiveness of our education in raising awareness about modifiable risk factors and inspiring proactive thinking about public health prevention strategies. This community-based education intervention was effective in increasing breast cancer knowledge among demographically diverse groups with low levels of baseline knowledge in the NYS Capital Region. Our findings provide leads for future public health prevention strategies.
Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination.
Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric
2017-09-02
Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT 50 ) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2-3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries.
Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination
Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric
2017-01-01
ABSTRACT Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT50) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2–3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries. PMID:28598256
An Analysis of Results of a High-Resolution World Ocean Circulation Model.
1988-03-01
Level Experiments ............... 16 a. Baseline (Laplacian Mixing) Integration ........ 16 b. Isopycnal Mixing Integration ................... 18 3...One-Half Degree, Twenty Level Experiments .......... 18 a. Baseline (Three Year Interior Restoring) Integration...TWENTY LEVEL EXPERIMENTS .................... 21 1. Baseline (Laplacian Mixing) Integration ............. 21 2. Isopycnal Mixing Integration
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.
Ida, Satoshi; Murata, Kazuya; Betou, Katunori; Kobayashi, Chiaki; Ishihara, Yuki; Imataka, Kanako; Uchida, Akihiro; Monguchi, Kou; Kaneko, Ryutaro; Fujiwara, Ryoko; Takahashi, Hiroka
2016-11-04
Trelagliptin, an oral DPP-4 inhibitor, which is administered once per week and characterized by a long half-life in blood. The effects of trelagliptin on vascular endothelial functions have not been clarified to date. The objective of the present study was to examine the effects of trelagliptin on vascular endothelial functions in patients with type 2 diabetes mellitus (DM) using flow-mediated dilatation (FMD), adiponectin, and asymmetric dimethylarginine (ADMA) as evaluation indicators. This study was a preliminary single-arm prospective pilot study. The subjects of this study were type 2 DM patients aged 20-74 years, who visited our outpatient department. The patients were treated with trelagliptin, and their FMD, adiponectin, and ADMA levels were measured at baseline and at 12 weeks after initial treatment to determine the changes during the study period. A total of 27 patients, excluding three dropouts, were included in the population for analysis. Trelagliptin treatment showed no significant changes in FMD (2.42 ± 2.7% at baseline vs. 2.66 ± 3.8% post-treatment, P = 0.785) and ADMA (0.41 ± 0.0 µg/mL at baseline vs. 0.40 ± 0.0 µg/mL post-treatment, P = 0.402). Trelagliptin treatment resulted in a significant increase of serum adiponectin level (7.72 ± 6.9 µg/mL at baseline vs. 8.82 ± 8.3 µg/mL post-treatment, P < 0.002). In this pilot study, trelagliptin treatment showed no significant changes in FMD. On the other hand, it was believed that trelagliptin treatment may increase serum adiponectin level. Trial Registration http://www.umin.ac.jp (Trial ID UMIN000018311).
Garimella, Pranav S; Ix, Joachim H; Katz, Ronit; Shlipak, Michael G; Criqui, Michael H; Siscovick, David S; Kramer, Holly; Sibley, Christopher T; Sarnak, Mark J
2015-01-01
Low ankle-brachial index (ABI) is a reflection of atherosclerotic disease, and high ABI is an indicator of calcified vessels. The associations of albuminuria and cystatin C level with incidence of either low or high ABI are unknown. Prospective longitudinal cohort study. MESA (Multi-Ethnic Study of Atherosclerosis) enrolled community-dwelling adults (N=6,814) aged 45-84 years who were free of clinical cardiovascular disease at baseline. Baseline albumin-creatinine ratio (ACR) and serum cystatin C level. Development of low (<0.90), and high (>1.40) ABI using multinomial regression among persons with ABI of 0.90-1.40 at baseline. During 9.8 years of follow-up, 221 and 89 participants progressed to low and high ABIs, respectively. Baseline ACR and cystatin C level were higher among progressors compared with nonprogressors. In multivariable analyses, doubling of ACR was associated with increased risk of progression to low (OR, 1.08; 95% CI, 0.99-1.20) and high (OR, 1.16; 95% CI, 1.01-1.32) ABIs. Compared to the lowest quintile, the highest quintile of ACR had a significantly increased risk of progression to low (OR, 1.79; 95% CI, 1.03-3.12) and high (OR, 2.76; 95% CI, 1.32-5.77) ABIs. Higher cystatin C levels were associated with progression to low (OR per 1-SD greater, 1.12; 95% CI, 1.00-1.26) but not high (OR per 1-SD greater, 1.01; 95% CI, 0.81-1.25) ABI, but the highest quintile of cystatin C was not associated independently with either outcome. Single measure of albuminuria and low number of progressors to high ABI. In adults free of clinical cardiovascular disease, albuminuria was a strong independent risk factor for the development of both high and low ABIs, important and different measures of peripheral artery disease. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Winn, Nathan C.; Grunewald, Zachary I.; Liu, Ying; Heden, Timothy D.; Nyhoff, Lauren M.; Kanaley, Jill A.
2017-01-01
Background and Purpose Irisin is an exercise-responsive myokine that has been proposed to exert anti-obesity benefits; yet its response during exercise in obese women is not described. This study characterized plasma irisin levels during a single bout of afternoon isocaloric-exercise of different intensities (moderate- vs high-intensity) in obese females. Methods Eleven obese females participated in 3 randomized study days beginning at 1600h: 1) no exercise (NoEx), 2) moderate exercise (ModEx; 55%VO2max) and 3) high intensity interval exercise (IntEx; 4 min (80%VO2max)/3 min (50% VO2max). Frequent blood samples were analyzed for glucose and lactate (whole-blood), and insulin, c-peptide, glucagon, and irisin (plasma) throughout 190 min of testing. Results Plasma irisin increased above baseline during ModEx and IntEx (P<0.05), but not NoEx (P>0.05). Peak irisin levels during ModEx and IntEx exercise were 11.9± 3.4% and 12.3 ± 4.1% relative to baseline (P<0.05), respectively, with no differences between exercise intensities (P>0.05). Irisin levels remained elevated above resting for 125 minutes post-exercise during ModEx, whereas levels returned to baseline within 15 minutes post-exercise during IntEx. Similarly, no associations were found between plasma irisin levels and circulating lactate, glucose, insulin, c-peptide, or glucagon among study days (P>0.05). However, there was an inverse association between basal irisin and lean mass (r = -0.70, P = 0.01). Conclusion A single bout of moderate and high intensity afternoon exercise induces modest increases in circulating irisin concentrations during exercise; however the regulation post-exercise appears to be dimorphic between exercise intensity in obese females. Future studies are needed to compare morning and afternoon exercise on irisin secretion. PMID:28125733
Luo, Xi; Hong, Haiyu; Tang, Jun; Wu, Xingmei; Lin, Zhibin; Ma, Renqiang; Fan, Yunping; Xu, Geng; Liu, Dabo; Li, Huabin
2016-03-01
MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10⁺CD4⁺ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.
Cheung, Tiffany C Y; Liu, Karen P Y; Wong, Janet Y H; Bae, Young-Hyeon; Hui, Stanley Sai-Chuen; Tsang, William W N; Cheng, Yoyo T Y; Fong, Shirley S M
2018-01-01
This study explored the immediate effects of Tai Chi (TC) training on attention and meditation, perceived stress level, heart rate, oxygen saturation level in blood, and palmar skin temperature in late middle-aged adults. Twenty TC practitioners and 20 nonpractitioners volunteered to join the study. After baseline measurements were taken, the TC group performed TC for 10 minutes while their cognitive states and cardiovascular responses were concurrently monitored. The control group rested for the same duration in a standing position. Both groups were then reassessed. The participants' attention and meditation levels were measured using electroencephalography; stress levels were measured using Perceived Stress Scale; heart rate and blood oxygenation were measured using an oximeter; and palmar skin temperature was measured using an infrared thermometer. Attention level tended to increase during TC and dropped immediately thereafter ( p < 0.001). Perceived stress level decreased from baseline to posttest in exclusively the TC group ( p = 0.005). Heart rate increased during TC ( p < 0.001) and decreased thereafter ( p = 0.001). No significant group, time, or group-by-time interaction effects were found in the meditation level, palmar skin temperature, and blood oxygenation outcomes. While a 10-minute TC training could temporarily improve attention and decrease perceived stress levels, it could not improve meditation, palmar skin temperature, or blood oxygenation among late middle-aged adults.
Cheung, Tiffany C. Y.; Bae, Young-Hyeon; Hui, Stanley Sai-Chuen; Cheng, Yoyo T. Y.
2018-01-01
This study explored the immediate effects of Tai Chi (TC) training on attention and meditation, perceived stress level, heart rate, oxygen saturation level in blood, and palmar skin temperature in late middle-aged adults. Twenty TC practitioners and 20 nonpractitioners volunteered to join the study. After baseline measurements were taken, the TC group performed TC for 10 minutes while their cognitive states and cardiovascular responses were concurrently monitored. The control group rested for the same duration in a standing position. Both groups were then reassessed. The participants' attention and meditation levels were measured using electroencephalography; stress levels were measured using Perceived Stress Scale; heart rate and blood oxygenation were measured using an oximeter; and palmar skin temperature was measured using an infrared thermometer. Attention level tended to increase during TC and dropped immediately thereafter (p < 0.001). Perceived stress level decreased from baseline to posttest in exclusively the TC group (p = 0.005). Heart rate increased during TC (p < 0.001) and decreased thereafter (p = 0.001). No significant group, time, or group-by-time interaction effects were found in the meditation level, palmar skin temperature, and blood oxygenation outcomes. While a 10-minute TC training could temporarily improve attention and decrease perceived stress levels, it could not improve meditation, palmar skin temperature, or blood oxygenation among late middle-aged adults. PMID:29636784
Zhang, Ming; Wang, Bingyuan; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Wang, Chongjian; Li, Linlin; Zhang, Lu; Ren, Yongcheng; Zhao, Yang; Zhou, Junmei; Han, Chengyi; Zhao, Jingzhi; Hu, Dongsheng
2017-03-01
Risk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China. We included data from 5706 people with normal body mass index (BMI) (18.5-23.9 kg/m 2 ) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure-response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2]. Risk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20-5.11], 3.77 [1.83-7.79], and 5.30 [2.21-12.71], P trend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22-6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index. Risk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.
Ungar, Nadine; Wiskemann, Joachim; Sieverding, Monika
2016-01-01
Background: Physical activity (PA) can support cancer patients during medical treatment by reducing side-effects and increasing quality of life. However, PA levels mostly decline after diagnosis. Which factors can explain if patients are able to remain or even increase their PA level? Self-efficacy is an important cognitive factor that has been linked to cancer patients' PA across many studies. In contrast, affective factors such as PA enjoyment have rarely been examined. We compare the influence of self-efficacy and PA enjoyment on cancer patients' PA levels after completion of an exercise or stress-management intervention. Methods: Outpatient cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34%, 15%)] were enrolled in the MOTIVACTION study, a 4-week intervention (1 h counseling followed by weekly phone calls), with pre-test (T1), post-test (T2), and a 10-week follow-up (T3). Participants were randomized to either an exercise intervention (emphasizing self-regulatory strategies for behavior change) or to a stress management intervention (coping and relaxation techniques). Sixty-seven patients remained in the study and completed the SQUASH assessment of PA, a measure of maintenance self-efficacy (7 items, Cronbach's α = 0.88) and PA enjoyment (2 items, Cronbach's α = 0.89). Regression analyses were calculated with PA level (at T2 and T3) as dependent variable and relative weight analyses were conducted. The study was registered at clinicalTrials.gov (unique identifier:NCT01576107; URL: https://clinicaltrials.gov/ct2/show/NCT01576107?term=motivaction&rank=1). Results: Baseline self-efficacy and change in PA enjoyment significantly predicted cancer patients' PA level at T2 adjusting for baseline PA and type of intervention. Relative weight (RW) analysis revealed that PA enjoyment (baseline and change together) explained 34.3% of the dependent variable, self-efficacy (baseline and change) explained 38.4%. At follow-up, self-efficacy was still a significant predictor of PA (RW = 74.6%), whereas PA enjoyment was no longer a relevant factor (RW = 5.2%). Conclusion: The affective factor PA enjoyment was equally important as self-efficacy for predicting cancer patient' PA level directly after completion of the intervention. Reasons for the reduced relevance at follow-up and a broader range of affective factors should be analyzed in future studies on cancer patients' PA level. PMID:27445882
Guo, Li; Feng, Ying; Guo, Hong-Gang; Liu, Bo-Wen; Zhang, Yang
2016-10-28
Malocclusion is a common disease of oral and maxillofacial region. The study was aimed to investigate levels changes of periodontal pathogens in malocclusion patients before, during and after orthodontic treatments, and to confirm the difference between adults and children. One hundred and eight malocclusion patients (46 adults and 62 children at the school-age) were randomly selected and received orthodontic treatment with fixed orthodontic appliances. Subgingival plaques were Porphyromonas gingivalis (P.gingivalis), Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia) and Tannerella forsythensis (T. forsythensis) collected from the observed regions before and after treatment. Clinical indexes, including plaque index (PLI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL) of observed teeth were examined. The detection rates of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis increased from baseline to the third month without significant difference, and then returned to pretreatment levels 12 month after applying fixed orthodontic appliances. Adults' percentage contents of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis were significantly higher than those of children at baseline and the first month, but not obvious at the third month. PLI and SBI were increased from baseline to the first and to the third month both in adults and children groups. Besides, PD were increased from baseline to first month, followed by a downward trend in the third month; however, all patients were failed to detect with AL. Periodontal and microbiological statuses of malocclusion patients may be influenced by fixed orthodontic appliances in both adults and children, more significant in children than in adults. Some microbiological indexes have synchronous trend with the clinical indexes. Long-term efficacy of fixed orthodontic appliances for malocclusion should be confirmed by future researches.
Steudte-Schmiedgen, Susann; Stalder, Tobias; Schönfeld, Sabine; Wittchen, Hans-Ulrich; Trautmann, Sebastian; Alexander, Nina; Miller, Robert; Kirschbaum, Clemens
2015-09-01
Previous evidence on endocrine risk markers for posttraumatic stress disorder (PTSD) has been inconclusive. Here, we report results of the first prospective study to investigate whether long-term hair cortisol levels and experimentally-induced cortisol stress reactivity are predictive of the development of PTSD symptomatology in response to trauma during military deployment. Male soldiers were examined before deployment to Afghanistan and at a 12-month post-deployment follow-up using dimensional measures for psychopathological symptoms. The predictive value of baseline (i) hair cortisol concentrations (HCC, N=90) and (ii) salivary cortisol stress reactivity (measured by the Trier Social Stress Test, N=80) for the development of PTSD symptomatology after being exposed to new-onset traumatic events was analyzed. Baseline cortisol activity significantly predicted PTSD symptom change from baseline to follow-up upon trauma exposure. Specifically, our results consistently revealed that lower HCC and lower cortisol stress reactivity were predictive of a greater increase in PTSD symptomatology in soldiers who had experienced new-onset traumatic events (explaining 5% and 10.3% of variance, respectively). Longitudinal analyses revealed an increase in HCC from baseline to follow-up and a trend for a negative relationship between HCC changes and the number of new-onset traumatic events. Additional pre-deployment analyses revealed that trauma history was reflected in lower HCC (at trend level) and that HCC were negatively related to stressful load. Our data indicate that attenuated cortisol secretion is a risk marker for subsequent development of PTSD symptomatology upon trauma exposure. Future studies are needed to confirm our findings in other samples. Copyright © 2015 Elsevier Ltd. All rights reserved.
Villa-Bellosta, Ricardo; Rodriguez-Osorio, Laura; Mas, Sebastian; Abadi, Younes; Rubert, Mercedes; de la Piedra, Concepción; Gracia-Iguacel, Carolina; Mahillo, Ignacio; Ortiz, Alberto; Egido, Jesús; González-Parra, Emilio
2017-01-01
Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice. PMID:28339474
Ghosal, Soutik; Trivedi, Jaimin; Chen, James; Rogers, Michael P; Cheng, Allen; Slaughter, Mark S; Kong, Maiying; Huang, Jiapeng
2018-06-01
Left ventricular assist device (LVAD) surgery is complex, high risk, and expensive. The authors' hypothesis is baseline regional cerebral oxygen saturation (rSO 2 ) might be a predictor of postoperative clinical outcomes. Retrospective review of 210 consecutive continuous flow LVAD patients between 2008 and 2014. The primary measure is 30-day mortality rate and secondary measures include modified major adverse cardiocerebral events (MACE), length of stay (LOS), and intensive care unit (ICU) stay. Multiple logistic regression models were applied to examine if a binary outcome variable, such as 30-day mortality and MACE, is associated with rSO 2 at baseline. Log-linear model was used to examine whether LOS or ICU stay hours is associated with rSO 2 at baseline. Single institution, academic hospital. Patients who received LVAD surgery at Jewish Hospital, Louisville, KY. All patients received LVAD surgery. Cerebral oximetry monitoring was used in both the preoperative and intraoperative periods. The authors found that higher rSO 2 at baseline is associated with lower 30-day mortality with an odds ratio of 0.94 and 95% confidence interval (0.888, 0.995) for every 1% increase of rSO 2 . For secondary outcomes, baseline rSO 2 was not significantly associated with MACE, requirement for postoperative renal failure/dialysis, reoperation for bleeding, and LOS or ICU hours. Regional cerebral oxygen saturation levels at baseline are significantly associated with 30-day mortality after LVAD surgeries. Copyright © 2017 Elsevier Inc. All rights reserved.
Serum uric acid levels and the risk of flares among gout patients in a US managed care setting.
Shiozawa, Aki; Buysman, Erin K; Korrer, Stephanie
2017-01-01
Serum uric acid (sUA) levels are causally associated with the risk of gout flares. Our aim was to assess the magnitude of the association and time to first flare among patients in a managed care setting. We conducted a retrospective cohort study using administrative claims data from a large US health plan. Patients were required to have evidence of gout based on medical and pharmacy claims between January 2009 and April 2012. The 12 months prior to the index gout claim were used to assess baseline sUA levels; risk of gout flares, stratified by baseline sUA levels, was examined for 2 years post-index. Risk of flare was modeled with Cox proportional hazards; time to first flare was assessed by Kaplan-Meier. We identified 18,008 patients with gout and available baseline SUA levels (mg/dL). The hazard ratios for the risk of gout flares compared with sUA <5.0 were: 1.17 for sUA 5.0 to <6.0; 1.69 for sUA 6.0 to <7.0; 2.16 for sUA 7.0 to <8.0; 2.87 for sUA 8.0 to <9.0; and 3.85 for sUA ≥9.0 (all p < .001 except for sUA 5.0 to <6.0 cohort). The time to first flare was shorter for cohorts with higher baseline sUA levels. These findings confirm that higher sUA levels are associated with an increased risk of gout flares in a dose-response manner over 2 years. This data supports the need to treat to sUA target levels as recommended by recent gout care guidelines. Claims-based algorithms were used to identify gout flares; although this would not be expected to influence estimates of risk by sUA level, there may have been over- or under-estimation of the incidence of flares.
Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L
2014-01-01
An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. © Society for the Experimental Analysis of Behavior.
Pre-treatment red blood cell distribution width provides prognostic information in multiple myeloma.
Zhou, Di; Xu, Peipei; Peng, Miaoxin; Shao, Xiaoyan; Wang, Miao; Ouyang, Jian; Chen, Bing
2018-06-01
The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure. The Kaplan-Meier product-limit method was used to determine OS and PFS, and the differences were assessed by the log-rank test. High RDW baseline was significantly associated with indexes including haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk stratification. After chemotherapy, the overall response rate (ORR) decreased as RDW baseline increased. In 24 patients with high RDW baseline, it was revealed RDW value decreased when patients achieved complete remission (CR), but increased when the disease progressed. The normal-RDW baseline group showed both longer overall survival (OS) and progression-free survival (PFS) than the high-RDW baseline group. Our study suggests pre-treatment RDW level is a prognostic factor in MM and should be regarded as an important parameter for assessment of therapeutic efficiency. Copyright © 2018. Published by Elsevier B.V.
Endocrine determinants of incident sarcopenia in middle-aged and elderly European men.
Gielen, Evelien; O'Neill, Terence W; Pye, Stephen R; Adams, Judith E; Wu, Frederick C; Laurent, Michaël R; Claessens, Frank; Ward, Kate A; Boonen, Steven; Bouillon, Roger; Vanderschueren, Dirk; Verschueren, Sabine
2015-09-01
In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia. In 518 men aged 40-79 years, recruited for participation in the European Male Ageing Study, total, free, and bioavailable testosterone (T), oestradiol (E), sex hormone-binding globulin, IGF-1, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone were assessed at baseline. Appendicular lean mass (aLM), gait speed, and grip strength were measured at baseline and after a mean follow-up of 4.3 years. Sarcopenia was defined by the definition of Baumgartner (relative aLM ≤7.26 kg/m(2)), the International Working Group on Sarcopenia (IWGS), and the European Working Group on Sarcopenia in Older People (EWGSOP). aLM significantly decreased from age 50 years, while gait speed and grip strength significantly decreased from age 70 years. The incidence of sarcopenia by the definitions of Baumgartner, IWGS, and EWGSOP was 8.1%, 3.0%, and 1.6%, respectively. After adjustment for age, centre, body mass index, smoking, and number of comorbidities at baseline, baseline levels of T and vitamin D metabolites were not associated with change in aLM, gait speed, and/or grip strength, while a high baseline level of total E2 was associated with a greater decrease in aLM. In men aged ≥70 years, low IGF-1 was associated with a greater decrease in gait speed. Baseline endocrine variables were not independently associated with an increased risk of incident sarcopenia by any definition. Low levels of T and 25OHD do not predict loss of muscle mass, gait speed, or grip strength in middle-aged and elderly community-dwelling European men. Low IGF-1 predicts change in gait speed in men aged ≥70 years.
2011-01-01
Background Several proteins that promote angiogenesis are overexpressed in hepatocellular carcinoma (HCC) and have been implicated in disease pathogenesis. Sunitinib has antiangiogenic activity and is an oral multitargeted inhibitor of vascular endothelial growth factor receptors (VEGFRs)-1, -2, and -3, platelet-derived growth factor receptors (PDGFRs)-α and -β, stem-cell factor receptor (KIT), and other tyrosine kinases. In a phase II study of sunitinib in advanced HCC, we evaluated the plasma pharmacodynamics of five proteins related to the mechanism of action of sunitinib and explored potential correlations with clinical outcome. Methods Patients with advanced HCC received a starting dose of sunitinib 50 mg/day administered orally for 4 weeks on treatment, followed by 2 weeks off treatment. Plasma samples from 37 patients were obtained at baseline and during treatment and were analyzed for vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGFR-2 (sVEGFR-2), soluble VEGFR-3 (sVEGFR-3), and soluble KIT (sKIT). Results At the end of the first sunitinib treatment cycle, plasma VEGF-A levels were significantly increased relative to baseline, while levels of plasma VEGF-C, sVEGFR-2, sVEGFR-3, and sKIT were significantly decreased. Changes from baseline in VEGF-A, sVEGFR-2, and sVEGFR-3, but not VEGF-C or sKIT, were partially or completely reversed during the first 2-week off-treatment period. High levels of VEGF-C at baseline were significantly associated with Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease control, prolonged time to tumor progression (TTP), and prolonged overall survival (OS). Baseline VEGF-C levels were an independent predictor of TTP by multivariate analysis. Changes from baseline in VEGF-A and sKIT at cycle 1 day 14 or cycle 2 day 28, and change in VEGF-C at the end of the first off-treatment period, were significantly associated with both TTP and OS, while change in sVEGFR-2 at cycle 1 day 28 was an independent predictor of OS. Conclusions Baseline plasma VEGF-C levels predicted disease control (based on RECIST) and were positively associated with both TTP and OS in this exploratory analysis, suggesting that this VEGF family member may have utility in predicting clinical outcome in patients with HCC who receive sunitinib. Trial registration ClinicalTrials.gov: NCT00247676 PMID:21787417
Endocrine determinants of incident sarcopenia in middle-aged and elderly European men
Gielen, Evelien; O'Neill, Terence W; Pye, Stephen R; Adams, Judith E; Wu, Frederick C; Laurent, Michaël R; Claessens, Frank; Ward, Kate A; Boonen, Steven; Bouillon, Roger; Vanderschueren, Dirk; Verschueren, Sabine
2015-01-01
Background In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia. Methods In 518 men aged 40–79 years, recruited for participation in the European Male Ageing Study, total, free, and bioavailable testosterone (T), oestradiol (E), sex hormone-binding globulin, IGF-1, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone were assessed at baseline. Appendicular lean mass (aLM), gait speed, and grip strength were measured at baseline and after a mean follow-up of 4.3 years. Sarcopenia was defined by the definition of Baumgartner (relative aLM ≤7.26 kg/m2), the International Working Group on Sarcopenia (IWGS), and the European Working Group on Sarcopenia in Older People (EWGSOP). Results aLM significantly decreased from age 50 years, while gait speed and grip strength significantly decreased from age 70 years. The incidence of sarcopenia by the definitions of Baumgartner, IWGS, and EWGSOP was 8.1%, 3.0%, and 1.6%, respectively. After adjustment for age, centre, body mass index, smoking, and number of comorbidities at baseline, baseline levels of T and vitamin D metabolites were not associated with change in aLM, gait speed, and/or grip strength, while a high baseline level of total E2 was associated with a greater decrease in aLM. In men aged ≥70 years, low IGF-1 was associated with a greater decrease in gait speed. Baseline endocrine variables were not independently associated with an increased risk of incident sarcopenia by any definition. Conclusions Low levels of T and 25OHD do not predict loss of muscle mass, gait speed, or grip strength in middle-aged and elderly community-dwelling European men. Low IGF-1 predicts change in gait speed in men aged ≥70 years. PMID:26401471
Five-year trajectories of social networks and social support in older adults with major depression.
Voils, Corrine I; Allaire, Jason C; Olsen, Maren K; Steffens, David C; Hoyle, Rick H; Bosworth, Hayden B
2007-12-01
Research with nondepressed adults suggests that social networks and social support are stable over the life course until very late age. This may not hold true for older adults with depression. We examined baseline status and trajectories of social networks and social support at the group and individual levels over five years. The sample consisted of 339 initially depressed adults aged 59 or older (M = 69 years) enrolled in a naturalistic study of depression. Measures of social ties, including social network size, frequency of interaction, instrumental support, and subjective support, were administered at baseline and yearly for five years. Latent growth curve models were estimated for each aspect of social ties. On average, social network size and frequency of interaction were low at baseline and remained stable over time, whereas subjective and instrumental support were high at baseline yet increased over time. There was significant variation in the direction and rate of change over time, which was not predicted by demographic or clinical factors. Because increasing social networks may be ineffective and may not be possible for a portion of people who already receive maximal support, interventions to increase social support may only work for a portion of older depressed adults.
Improving residents' oral health through staff education in nursing homes.
Le, Phu; Dempster, Laura; Limeback, Hardy; Locker, David
2012-01-01
This study assessed the efficacy of oral care education among nursing home staff members to improve the oral health of residents. Nursing home support staff members (NHSSMs) in the study group received oral care education at baseline between a pretest and posttest. NHSSMs' oral care knowledge was measured using a 20-item knowledge test at baseline, posteducation, and at a 6-month follow-up. Residents' oral health was assessed at baseline and again at a 6-month follow-up using the Modified Plaque Index (PI) and Modified Gingival Index (GI). Among staff members who received the oral care education (n = 32), posttest knowledge statistically significantly increased from the pretest level (p < .05). Thirty-nine control residents of the nursing homes and 41 study residents participated. Among residents in the study group, PI decreased at 6 months compared to baseline (p < .05), but there was no statistically significant difference in their GI measurements between baseline and 6-month follow-up (p= .07). © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.
The Effect of Pretest Exercise on Baseline Computerized Neurocognitive Test Scores.
Pawlukiewicz, Alec; Yengo-Kahn, Aaron M; Solomon, Gary
2017-10-01
Baseline neurocognitive assessment plays a critical role in return-to-play decision making following sport-related concussions. Prior studies have assessed the effect of a variety of modifying factors on neurocognitive baseline test scores. However, relatively little investigation has been conducted regarding the effect of pretest exercise on baseline testing. The aim of our investigation was to determine the effect of pretest exercise on baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores in adolescent and young adult athletes. We hypothesized that athletes undergoing self-reported strenuous exercise within 3 hours of baseline testing would perform more poorly on neurocognitive metrics and would report a greater number of symptoms than those who had not completed such exercise. Cross-sectional study; Level of evidence, 3. The ImPACT records of 18,245 adolescent and young adult athletes were retrospectively analyzed. After application of inclusion and exclusion criteria, participants were dichotomized into groups based on a positive (n = 664) or negative (n = 6609) self-reported history of strenuous exercise within 3 hours of the baseline test. Participants with a positive history of exercise were then randomly matched, based on age, sex, education level, concussion history, and hours of sleep prior to testing, on a 1:2 basis with individuals who had reported no pretest exercise. The baseline ImPACT composite scores of the 2 groups were then compared. Significant differences were observed for the ImPACT composite scores of verbal memory, visual memory, reaction time, and impulse control as well as for the total symptom score. No significant between-group difference was detected for the visual motor composite score. Furthermore, pretest exercise was associated with a significant increase in the overall frequency of invalid test results. Our results suggest a statistically significant difference in ImPACT composite scores between individuals who report strenuous exercise prior to baseline testing compared with those who do not. Since return-to-play decision making often involves documentation of return to neurocognitive baseline, the baseline test scores must be valid and accurate. As a result, we recommend standardization of baseline testing such that no strenuous exercise takes place 3 hours prior to test administration.
Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?
Kelsen, Jens; Dige, Anders; Schwindt, Heinrich; D'Amore, Francesco; Pedersen, Finn S.; Agnholt, Jørgen; Christensen, Lisbet A.; Dahlerup, Jens F.; Hvas, Christian L.
2011-01-01
Background Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. Methodology/Principal Findings We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n = 20) or adalimumab (Humira®; n = 26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5–15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. Conclusion/Significance CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents. PMID:21483853
Social Baseline Theory: The Social Regulation of Risk and Effort
Coan, James A.; Sbarra, David A.
2015-01-01
We describe Social Baseline Theory (SBT), a perspective that integrates the study of social relationships with principles of attachment, behavioral ecology, cognitive neuroscience, and perception science. SBT suggests the human brain expects access to social relationships that mitigate risk and diminish the level of effort needed to meet a variety of goals. This is accomplished in part by incorporating relational partners into neural representations of the self. By contrast, decreased access to relational partners increases cognitive and physiological effort. Relationship disruptions entail re-defining the self as independent, which implies greater risk, increased effort, and diminished well being. The ungrafting of the self and other may mediate recovery from relationship loss. PMID:25825706
Frisoli, Alberto; Chaves, Paulo H M; Pinheiro, Marcelo Medeiros; Szejnfeld, Vera Lucia
2005-05-01
In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily. Compared to baseline, ND increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05) and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years, respectively. The BMD of trochanter increased significantly only after the first year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group presented with significantly increased BMD of the trochanter and neck. ND significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; p < .05). ND showed a significant statistical increase in lean body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/- 29.2; p < .01). In addition, a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01). ND increased BMD, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.
Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.
Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj
2015-11-01
Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (β = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Withee, Eric D; Tippens, Kimberly M; Dehen, Regina; Tibbitts, Deanne; Hanes, Douglas; Zwickey, Heather
2017-01-01
Oxidative stress and muscle damage occur during exhaustive bouts of exercise, and many runners report pain and soreness as major influences on changes or breaks in training regimens, creating a barrier to training persistence. Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects. To investigate the effects of MSM in attenuating damage associated with physical exertion, this randomized, double-blind, placebo-controlled study evaluated the effects of MSM supplementation on exercise-induced pain, oxidative stress and muscle damage. Twenty-two healthy females ( n = 17) and males ( n = 5) (age 33.7 ± 6.9 yrs.) were recruited from the 2014 Portland Half-Marathon registrant pool. Participants were randomized to take either MSM (OptiMSM®) ( n = 11), or a placebo ( n = 11) at 3 g/day for 21 days prior to the race and for two days after (23 total). Participants provided blood samples for measurement of markers of oxidative stress, and completed VAS surveys for pain approximately one month prior to the race (T 0 ), and at 15 min (T 1 ), 90 min (T 2 ), 1 Day (T 3 ), and 2 days (T 4 ) after race finish. The primary outcome measure 8-hydroxy-2-deoxyguanine (8-OHdG) measured oxidative stress. Secondary outcomes included malondialdehyde (MDA) for oxidative stress, creatine kinase (CK) and lactate dehydrogenase (LDH) as measures of muscle damage, and muscle (MP) and joint pain (JP) recorded using a 100 mm Visual Analogue Scale (VAS). Data were analyzed using repeated and multivariate ANOVAs, and simple contrasts compared post-race time points to baseline, presented as mean (SD) or mean change (95% CI) where appropriate. Running a half-marathon induced significant increases in all outcome measures ( p < 0.001). From baseline, 8-OHdG increased significantly at T 1 by 1.53 ng/mL (0.86-2.20 ng/mL CI, p < 0.001) and T 2 by 1.19 ng/mL (0.37-2.01 ng/mL CI, p < 0.01), and fell below baseline levels at T 3 by -0.46 ng/mL (-1.18-0.26 CI, p > 0.05) and T 4 by -0.57 ng/mL (-1.27-0.13 CI, p > 0.05). MDA increased significantly at T 1 by 7.3 μM (3.9-10.7 CI, p < 0.001). Muscle damage markers CK and LDH saw significant increases from baseline at all time-points ( p < 0.01). Muscle and joint pain increased significantly from baseline at T 1 , T 2 , and T 3 ( p < 0.01) and returned to baseline levels at T 4 . Time-by-treatment results did not reach statistical significance for any outcome measure, however, the MSM group saw clinically significant (Δ > 10 mm) reductions in both muscle and joint pain. Participation in a half-marathon was associated with increased markers of oxidative stress, muscle damage, and pain. MSM supplementation was not associated with a decrease from pre-training levels of oxidative stress or muscle damage associated with an acute bout of exercise. MSM supplementation attenuated post-exercise muscle and joint pain at clinically, but not statistically significant levels.
NASA Technical Reports Server (NTRS)
Burnett, Jason; Hochschild, Ann; Smith, Scott M.; Diamond, Pam; Stotts, Angela; Dyer, Carmel
2011-01-01
Despite high mortality rates, elder self-neglect is characterized by refusal of medical and social interventions. To date there have been no tested clinical interventions in elders who self-neglect. Previous research from the TEAM Institute has shown significantly low vitamin D levels in this population. This study aimed to determine the feasibility of a clinical intervention. Replacement of vitamin D was chosen because of its ease of administration and favorable safety profile. Methods: A randomized clinical trial using directly observed therapy of vitamin D was conducted using 50 elders, >65 years of age, with Adult Protective Services (APS) validated self-neglect. A staggered intervention with waiting controls was used to maximize statistical power. One-third (n=17) of the group was administered 50,000 IU vitamin D2 (ergocalciferol) monthly and the remainder (n=33) were administered 400 IU monthly. Serum 25-OH vitamin D was assessed at baseline and 5-months. Results: 69% agreed to participate in the study and of those n=40 (80%) remained at 5-months. At baseline, 12% (n=7) were deficient in vitamin D (<30nmol/L) and approximately 38% (n=22) had inadequate vitamin D levels (<50nmol/L). The baseline 25-OH vitamin D level was 59 nmol/L +25 (mean SD), and increased significantly to 72nmol/L +21 nmol/L at 5-months. Conclusion: These data are the first to provide evidence that clinical interventions are feasible in elders who self-neglect. The increase in vitamin D levels confirmed that the study personnel were able to successfully intervene community-dwelling elders with self-neglect. This study sets the precedent for future intervention and prevention studies
Built Environment and Changes in Blood Pressure in Middle Aged and Older Adults
Li, Fuzhong; Harmer, Peter; Cardinal, Bradley J.; Vongjaturapat, Naruepon
2009-01-01
Objective Few studies have examined interaction effects between person and environment, especially for cardiovascular disease (CVD) risk. The purpose of this study was to examine built environment characteristics and resident health behaviors as they relate to change in blood pressure, an important component of CVD. Methods Participants (N=1,145, aged 50–75 at baseline) were recruited from 120 neighborhoods in Portland, Oregon. Using a longitudinal design, we assessed changes in participants’ systolic and diastolic blood pressure from baseline to 1-year follow-up (2006–2007 to 2007–2008). Independent variables included baseline neighborhood-level measures of GIS-constructed neighborhood walkability and density of fast-food restaurants, and resident-level measures of meeting physical activity recommendations and eating fruits and vegetables. Results There was a small but significant resident-level increase in both systolic and diastolic blood pressure (P<0.001) over the 1-year observation period. A similar trend was also observed at the neighborhood level (P<0.001). Significant differences in change in blood pressure, by neighborhood walkability, were observed, with decreases in systolic and diastolic blood pressure for those living in high walkable neighborhoods (P<0.001). Neighborhoods of low walkability but with a high density of fast-food outlets and residents making visits to fast-food restaurants were significantly associated with increases in blood pressure measures over time. The negative effect of fast-food restaurants on blood pressure was diminished among high-walkable neighborhoods, with benefits observed among residents meeting guidelines for physical activity and eating fruits and vegetables. Conclusions Neighborhoods with high walkability may ameliorate the risk of hypertension at the community level and promotion of neighborhood walkability could play a significant role in improving population health and reducing CVD risk. PMID:19297686
Tangpricha, Vin; Luo, Menghua; Fernández-Estívariz, Concepción; Gu, Li H; Bazargan, Niloofar; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Galloway, John R; Leader, Lorraine M; Ziegler, Thomas R
2006-01-01
Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.
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.
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
A longitudinal study of cotinine in long-term daily users of e-cigarettes.
Etter, Jean-François
2016-03-01
It is not clear whether, in established vapers, cotinine levels remain stable or change over time. We enrolled 98 exclusive users of e-cigarettes on websites and forums dedicated to smoking cessation and to e-cigarettes. We collected saliva vials by mail in 2013-2014 (baseline), and collected a second saliva vial eight months later (follow-up) in the same participants. Participants had not used any tobacco or nicotine medications in the previous five days. Cotinine in saliva was analyzed with liquid chromatography-mass spectrometry. Use of e-cigarettes, tobacco and nicotine medications was self-reported. All participants were former smokers, and 99% were using e-cigarettes daily. They had already been using e-cigarettes for nine months on average at baseline. The median cotinine level was 252ng/mL at baseline (quartiles: 124-421ng/mL) and 307ng/mL at follow-up (114-466ng/mL, W=0.9, p=0.4 for change over time). The median concentration of nicotine in refill liquids was 11mg/mL at baseline (quartiles: 6-15mg/mL) and 6mg/mL at follow-up (5-12mg/mL) (Wilcoxon signed rank test: W=5.2, p<0.001 for change over time). The median volume of e-liquid used per month was 80mL at baseline (quartiles: 50-130mL) and 100mL at follow-up (60-157mL, W=3.3, p=0.001 for change over time). In experienced e-cigarette users enrolled online, cotinine levels were similar to levels usually observed in cigarette smokers. Over time, these users decreased the concentration of nicotine in their e-liquids, but increased their consumption of e-liquid in order to maintain their cotinine levels constant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M
2017-05-01
Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Biester, Torben; Aschemeier, Baerbel; Fath, Maryam; Frey, Marcel; Scheerer, Markus F; Kordonouri, Olga; Danne, Thomas
2017-11-01
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. A total of 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into 3 baseline HbA1c categories (<7.5%, 7.5%-9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels at 160 to 220 mg/dL. DAPA reduced mean insulin dose by 13.6% ( P < .0001 by ANOVA) and increased urinary glucose excretion by 610% (143.4 vs 22.4 g/24 h; P < .0001), both irrespective of baseline HbA1c. Six independent episodes in 6 patients with plasma ß-hydroxybutyrate levels between ≥0.6 and <1.0 mmol/L were observed after liquid meal challenges, 5 episodes in the DAPA group and 1 in the placebo group. This study provides a proof-of-concept, irrespective of preexisting HbA1c levels, for adjunct SGLT2-inhibitor therapy in the paediatric age group by lowering insulin dose and increasing glucose excretion. © 2017 John Wiley & Sons Ltd.