Sample records for factors include increased

  1. Qualitative models of seat discomfort including static and dynamic factors.

    PubMed

    Ebe, K; Griffin, M J

    2000-06-01

    Judgements of overall seating comfort in dynamic conditions sometimes correlate better with the static characteristics of a seat than with measures of the dynamic environment. This study developed qualitative models of overall seat discomfort to include both static and dynamic seat characteristics. A dynamic factor that reflected how vibration discomfort increased as vibration magnitude increased was combined with a static seat factor which reflected seating comfort without vibration. The ability of the model to predict the relative and overall importance of dynamic and static seat characteristics on comfort was tested in two experiments. A paired comparison experiment, using four polyurethane foam cushions (50, 70, 100, 120 mm thick), provided different static and dynamic comfort when 12 subjects were exposed to one-third octave band random vertical vibration with centre frequencies of 2.5 and 5.5 Hz, at magnitudes of 0.00, 0.25 and 0.50 m x s(-2) rms measured beneath the foam samples. Subject judgements of the relative discomfort of the different conditions depended on both static and dynamic characteristics in a manner consistent with the model. The effect of static and dynamic seat factors on overall seat discomfort was investigated by magnitude estimation using three foam cushions (of different hardness) and a rigid wooden seat at six vibration magnitudes with 20 subjects. Static seat factors (i.e. cushion stiffness) affected the manner in which vibration influenced the overall discomfort: cushions with lower stiffness were more comfortable and more sensitive to changes in vibration magnitude than those with higher stiffness. The experiments confirm that judgements of overall seat discomfort can be affected by both the static and dynamic characteristics of a seat, with the effect depending on vibration magnitude: when vibration magnitude was low, discomfort was dominated by static seat factors; as the vibration magnitude increased, discomfort became dominated

  2. Possible risk factors for increased suicide following bariatric surgery.

    PubMed

    Mitchell, James E; Crosby, Ross; de Zwaan, Martina; Engel, Scott; Roerig, James; Steffen, Kristine; Gordon, Kathryn H; Karr, Trisha; Lavender, Jason; Wonderlich, Steve

    2013-04-01

    There is a growing research literature suggesting that there may be elevated risk of suicide following bariatric surgery. Most of the data reported thus far has been cross-sectional and observational, and very little is known about the possible specific causal variables involved. The purpose of this report is to review this literature and to review possible risk factors for increased suicidal risk following bariatric surgery, to delineate future research directions. First a variety of medical, biological, and genetic factors, including the persistence or recurrence of medical comorbidities after bariatric surgery, the disinhibition and impulsivity secondary to changes in the absorption of alcohol, hypoglycemia, as well as pharmacokinetic changes that may affect the absorption of various medications including antidepressant medications are reviewed. Also reviewed are possible mediating factors involving changes in various peptidergic systems such as GLP-1 and Ghrelin. A number of psychosocial issues that might be involved are discussed, including lack of improvement in quality of life after surgery, continued or recurrent physical mobility restrictions, persistence or recurrence of sexual dysfunction and relationship problems, low self-esteem, and a history of child maltreatment. Inadequate weight loss or weight regain are also discussed. A number of possible contributing factors have been identified. Possible theoretical models involved and directions for research are suggested. Copyright © 2012 The Obesity Society.

  3. The need to increase awareness of the risk factors of COPD.

    PubMed

    Roche, Nicolas

    2016-07-01

    COPD is a heterogeneous disease responsible for a major burden on public and individual health. A wide variety of intrinsic and environmental risk factors are involved, and exert their influence at various time points during the life span of individuals. Knowledge of these factors is of utmost importance to develop appropriate screening and prevention programs, and may help improving the pathophysiological knowledge of the disease. Accordingly, there are multiple targets of information and education on risk factors for COPD, including the general population and patients, workers and employers, doctors and other healthcare professionals, researchers, policy-makers, payers, etc. Gender and socioeconomic factors need to be specifically considered. Importantly, it is likely that increasing the specific knowledge of COPD risk factors among the above-mentioned targets cannot not be obtained without increasing the general knowledge of COPD in the population, which at present is dramatically low.

  4. AGU journals increase in importance according to 2010 Impact Factors

    NASA Astrophysics Data System (ADS)

    Cook, Bill

    2011-07-01

    AGU journals continue to rank highly in many categories in the 2010 Journal Citation Report (JCR), which was released by Thomson Reuters on 28 June. JCR reports on several measures of journal usage, including a journal's Eigenfactor score, its Article Influence score, its Impact Factor, and its rank within a cohort of similar journals. According to the 2010 statistics, AGU again has outperformed its larger competitors. Four different AGU titles are ranked in the top three journals in six different cohorts. The Impact Factor of several AGU journals increased significantly over the previous year.

  5. Proposed NOAA Budget Includes Hefty Increase for Satellites

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2010-03-01

    The Obama administration's proposed fiscal year (FY) 2011 budget for the U.S. National Oceanic and Atmospheric Administration (NOAA) would provide the agency with $5.55 billion, which represents a total increase of $806.1 million, or 17% above the FY 2010 budget enacted by Congress. At a February briefing about the budget, NOAA administrator Jane Lubchenco said the budget is a very good package for the agency and that it reflects the administration's commitment to the environment, science, public safety, and job creation. Noting that the agency's budget remained essentially flat between FY 2005 and FY 2008 during the George W. Bush administration, Lubchenco said, “the increasing demand for NOAA's services, coupled with a static budget, created a major challenge for NOAA in delivering on expectations.” She said the funding picture for the agency improved with the FY 2009 and FY 2010 enacted budgets. Lubchenco noted that the proposed budget would include $949 million for research and development, an $82 million increase, adding, “Our 2011 request for each line office [within NOAA] is higher than it was in 2010, and we are better aligned with congressional funding levels than in previous budgets.”

  6. Risk Factors for Breast Cancer, Including Occupational Exposures

    PubMed Central

    Meo, Margrethe; Vainio, Harri

    2011-01-01

    The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

  7. HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity.

    PubMed

    Trusolino, L; Cavassa, S; Angelini, P; Andó, M; Bertotti, A; Comoglio, P M; Boccaccio, C

    2000-08-01

    Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that this phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.

  8. Factors Increasing Vulnerability to Health Effects before, during and after Floods

    PubMed Central

    Lowe, Dianne; Ebi, Kristie L.; Forsberg, Bertil

    2013-01-01

    Identifying the risk factors for morbidity and mortality effects pre-, during and post-flood may aid the appropriate targeting of flood-related adverse health prevention strategies. We conducted a systematic PubMed search to identify studies examining risk factors for health effects of precipitation-related floods, among Organisation for Economic Co-Operation and Development (OECD) member countries. Research identifying flood-related morbidity and mortality risk factors is limited and primarily examines demographic characteristics such as age and gender. During floods, females, elderly and children appear to be at greater risk of psychological and physical health effects, while males between 10 to 29 years may be at greater risk of mortality. Post-flood, those over 65 years and males are at increased risk of physical health effects, while females appear at greater risk of psychological health effects. Other risk factors include previous flood experiences, greater flood depth or flood trauma, existing illnesses, medication interruption, and low education or socio-economic status. Tailoring messages to high-risk groups may increase their effectiveness. Target populations differ for morbidity and mortality effects, and differ pre-, during, and post-flood. Additional research is required to identify the risk factors associated with pre- and post-flood mortality and post-flood morbidity, preferably using prospective cohort studies. PMID:24336027

  9. Factors increasing vulnerability to health effects before, during and after floods.

    PubMed

    Lowe, Dianne; Ebi, Kristie L; Forsberg, Bertil

    2013-12-11

    Identifying the risk factors for morbidity and mortality effects pre-, during and post-flood may aid the appropriate targeting of flood-related adverse health prevention strategies. We conducted a systematic PubMed search to identify studies examining risk factors for health effects of precipitation-related floods, among Organisation for Economic Co-Operation and Development (OECD) member countries. Research identifying flood-related morbidity and mortality risk factors is limited and primarily examines demographic characteristics such as age and gender. During floods, females, elderly and children appear to be at greater risk of psychological and physical health effects, while males between 10 to 29 years may be at greater risk of mortality. Post-flood, those over 65 years and males are at increased risk of physical health effects, while females appear at greater risk of psychological health effects. Other risk factors include previous flood experiences, greater flood depth or flood trauma, existing illnesses, medication interruption, and low education or socio-economic status. Tailoring messages to high-risk groups may increase their effectiveness. Target populations differ for morbidity and mortality effects, and differ pre-, during, and post-flood. Additional research is required to identify the risk factors associated with pre- and post-flood mortality and post-flood morbidity, preferably using prospective cohort studies.

  10. Increasing Prevalence, Changes in Diagnostic Criteria, and Nutritional Risk Factors for Autism Spectrum Disorders

    PubMed Central

    Neggers, Yasmin H.

    2014-01-01

    The frequency of autism spectrum disorders (ASD) diagnoses has been increasing for decades, but researchers cannot agree on whether the trend is a result of increased awareness, improved detection, expanding definition, or an actual increase in incidence or a combination of these factors. Though both genetic and multiple environmental risk factors have been studied extensively, many potentially modifiable risk factors including nutritional and immune function related risk factors such as vitamin D, folic acid, and metabolic syndrome have not received sufficient attention. Several recent studies have put forward hypotheses to explain the mechanism of association between both folic acid and vitamin D and autism. A continuous rise in the prevalence of autism in the USA has coincided with a significant enhancement of maternal folate status with FDA mandated folic acid fortification of certain foods starting in 1998. There is also a growing body of research that suggests that vitamin D status either in utero or early in life may be a risk for autism. In this communication, controversies regarding increase in estimate of prevalence, implications of changes in definition, and possible association between some modifiable nutritional risk factors such as folic acid and vitamin D and ASD will be discussed. PMID:24967269

  11. Macroenvironmental factors including GDP per capita and physical activity in Europe.

    PubMed

    Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

    2013-02-01

    Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

  12. Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding.

    PubMed

    Lu, Mingliang; Sun, Gang; Zhang, Xiu-li; Zhang, Xiao-mei; Liu, Qing-sen; Huang, Qi-yang; Lau, James W Y; Yang, Yun-sheng

    2015-06-01

    To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p < 0.05 was considered statistically significant. The study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressure<100 mmHg, lack of endoscopic examination, comorbidities, blood transfusion, and rebleeding. Drug costs were higher in patients with rebleeding, blood transfusion, and prolonged hospital stay. In this patient cohort, re-bleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ-ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs.

  13. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  14. Circadian misalignment increases cardiovascular disease risk factors in humans

    PubMed Central

    Morris, Christopher J.; Purvis, Taylor E.; Hu, Kun; Scheer, Frank A. J. L.

    2016-01-01

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID:26858430

  15. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

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

    Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be; Van den Bergh, Laura; Al-Mamgani, Abrahim

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including themore » most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

  16. The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis.

    PubMed

    Welsh, Sarah J; Bellamy, William T; Briehl, Margaret M; Powis, Garth

    2002-09-01

    Hypoxia-inducible factor 1 (HIF-1), a heterodimer of HIF-1alpha and HIF-1beta subunits, is a transcriptional activator central to the cellular response to low oxygen that includes metabolic adaptation, angiogenesis, metastasis, and inhibited apoptosis. Thioredoxin-1 (Trx-1) is a small redox protein overexpressed in a number of human primary tumors. We have examined the effects of Trx-1 on HIF activity and the activation of downstream genes. Stable transfection of human breast carcinoma MCF-7 cells with human Trx-1 caused a significant increase in HIF-1alpha protein levels under both normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. Trx-1 increased hypoxia-induced HIF-1 transactivation activity measured using a luciferase reporter under the control of the hypoxia response element. Changes in HIF-1alpha mRNA levels did not account for the changes observed at the protein level, and HIF-1beta protein levels did not change. Trx-1 transfection also caused a significant increase in the protein products of hypoxia-responsive genes, including vascular endothelial growth factor (VEGF) and nitric oxide synthase 2 in a number of different cell lines (MCF-7 human breast and HT29 human colon carcinomas and WEHI7.2 mouse lymphoma cells) under both normoxic and hypoxic conditions. The pattern of expression of the different isoforms of VEGF was not changed by Trx-1. Transfection of a redox-inactive Trx-1 (C32S/C35S) markedly decreased levels of HIF-1alpha protein, HIF-1 transactivating activity, and VEGF protein in MCF-7 cells compared with empty vector controls. In vivo studies using WEHI7.2 cells transfected with Trx-1 showed significantly increased tumor VEGF and angiogenesis. The results suggest that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF production and tumor angiogenesis.

  17. Factors Associated with Increased Risk for Lethal Violence in Intimate Partner Relationships among Ethnically Diverse Black Women

    PubMed Central

    Sabri, Bushra; Stockman, Jamila K.; Campbell, Jacquelyn C.; O’Brien, Sharon; Campbell, Doris; Callwood, Gloria B.; Bertrand, Desiree; Sutton, Lorna W.; Hart-Hyndman, Greta

    2014-01-01

    The purpose of this study was to identify factors associated with increased risk for lethal violence among ethnically diverse Black women in Baltimore, Maryland (MD) and the US Virgin Islands (USVI). Women with abuse experiences (n=456) were recruited from primary care, prenatal or family planning clinics in Baltimore, MD and St. Thomas and St. Croix, USVI. Logistic regression was used to examine factors associated with the risk for lethal violence among abused women. Factors independently related to increased risk of lethal violence included fear of abusive partners, PTSD symptoms, and use of legal resources. These factors must be considered in assessing safety needs of Black women in abusive relationships. PMID:25429191

  18. Atrial natriuretic factor increases vascular permeability

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

    Lockette, W.; Brennaman, B.

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinationsmore » of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.« less

  19. Historical Increase in the Number of Factors Measured by Commercial Tests of Cognitive Ability: Are We Overfactoring?

    ERIC Educational Resources Information Center

    Frazier, Thomas W.; Youngstrom, Eric A.

    2007-01-01

    A historical increase in the number of factors purportedly measured by commercial tests of cognitive ability may result from four distinct pressures including: increasingly complex models of intelligence, test publishers' desires to provide clinically useful assessment instruments with greater interpretive value, test publishers' desires to…

  20. Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug-drug interactions.

    PubMed

    Eschmann, Emmanuel; Beeler, Patrick E; Kaplan, Vladimir; Schneemann, Markus; Zünd, Gregor; Blaser, Jürg

    2014-02-01

    Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia. The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring. The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p < 0.0001), impaired renal function (RR 2.7; p < 0.0001), diabetes mellitus (RR 1.6; p = 0.002) and female gender (RR 1.5; p = 0.007). Risk factors associated with medication were number of concurrently administered potassium-increasing drugs (RR 3.3 per additional drug; p < 0.0001) and longer duration of the DDI (RR 4.9 for duration ≥6 days; p < 0.0001). Physician-related factors associated with the development of hyperkalaemia were undetermined or elevated serum potassium level before treatment initiation (RR 2.2; p < 0.001) and infrequent monitoring of serum potassium during a DDI (interval >48 h: RR 1.6; p < 0.01). Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors.

  1. Robust Programming Problems Based on the Mean-Variance Model Including Uncertainty Factors

    NASA Astrophysics Data System (ADS)

    Hasuike, Takashi; Ishii, Hiroaki

    2009-01-01

    This paper considers robust programming problems based on the mean-variance model including uncertainty sets and fuzzy factors. Since these problems are not well-defined problems due to fuzzy factors, it is hard to solve them directly. Therefore, introducing chance constraints, fuzzy goals and possibility measures, the proposed models are transformed into the deterministic equivalent problems. Furthermore, in order to solve these equivalent problems efficiently, the solution method is constructed introducing the mean-absolute deviation and doing the equivalent transformations.

  2. Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells.

    PubMed Central

    Duncan, Roger F; Peterson, Hazel; Hagedorn, Curt H; Sevanian, Alex

    2003-01-01

    Dysregulated cell growth can be caused by increased activity of protein synthesis eukaryotic initiation factor (eIF) 4E. Dysregulated cell growth is also characteristic of atherosclerosis. It is postulated that exposure of vascular cells, such as endothelial cells, smooth muscle cells and monocytes/macrophages, to oxidants, such as oxidized low-density lipoprotein (oxLDL), leads to the elaboration of growth factors and cytokines, which in turn results in smooth muscle cell hyperproliferation. To investigate whether activation of eIF4E might play a role in this hyperproliferative response, vascular cells were treated with oxLDL, oxidized lipid components of oxLDL and several model oxidants, including H(2)O(2) and dimethyl naphthoquinone. Exposure to each of these compounds led to a dose- and time-dependent increase in eIF4E phosphorylation in all three types of vascular cells, correlated with a modest increase in overall translation rate. No changes in eIF4EBP, eIF2 or eIF4B modification state were observed. Increased eIF4E phosphorylation was paralleled by increased presence of eIF4E in high-molecular-mass protein complexes characteristic of its most active form. Anti-oxidants at concentrations typically employed to block oxidant-induced cell signalling likewise promoted eIF4E phosphorylation. The results of this study indicate that increased eIF4E activity may contribute to the pathophysiological events in early atherogenesis by increasing the expression of translationally inefficient mRNAs encoding growth-promoting proteins. PMID:12215171

  3. School-level factors associated with increased fruit and vegetable consumption among students in California middle and high schools.

    PubMed

    Gosliner, Wendi

    2014-09-01

    This study assessed associations between selective school-level factors and students' consumption of fruits and vegetables at school. Better understanding of school factors associated with increased produce consumption is especially important, as students are served more produce items at school. This cross-sectional study included 5439 seventh- and ninth-grade students from 31 schools in California in 2010. Multilevel regression models estimated whether the odds of consuming fruits or vegetables at school among students eating the school lunch were associated with the length of the lunch period, quality/variety of produce options, or other factors. A longer lunch period was associated with increased odds of a student eating fruits (odds ratio [OR] = 1.40) and vegetables (OR = 1.54) at school. Better fruit quality increased the odds of a student consuming fruit (OR = 1.44). Including a salad bar and involving students in food service decisions increased a student's odds of consuming vegetables (OR = 1.48 and OR = 1.34, respectively). This study suggests that institutional factors in schools are positively associated with middle and high school students' consumption of produce items at school. Additional efforts to structure school meal environments to enhance students' consumption of produce items can benefit students' nutrition and health. © 2014, American School Health Association.

  4. Risk Factors for Increased Severity of Paediatric Medication Administration Errors

    PubMed Central

    Sears, Kim; Goodman, William M.

    2012-01-01

    Patients' risks from medication errors are widely acknowledged. Yet not all errors, if they occur, have the same risks for severe consequences. Facing resource constraints, policy makers could prioritize factors having the greatest severe–outcome risks. This study assists such prioritization by identifying work-related risk factors most clearly associated with more severe consequences. Data from three Canadian paediatric centres were collected, without identifiers, on actual or potential errors that occurred. Three hundred seventy-two errors were reported, with outcome severities ranging from time delays up to fatalities. Four factors correlated significantly with increased risk for more severe outcomes: insufficient training; overtime; precepting a student; and off-service patient. Factors' impacts on severity also vary with error class: for wrong-time errors, the factors precepting a student or working overtime significantly increase severe-outcomes risk. For other types, caring for an off-service patient has greatest severity risk. To expand such research, better standardization is needed for categorizing outcome severities. PMID:23968607

  5. Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes

    PubMed Central

    Nagaishi, Kanna; Mizue, Yuka; Chikenji, Takako; Otani, Miho; Nakano, Masako; Konari, Naoto; Fujimiya, Mineko

    2016-01-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action. PMID:27721418

  6. Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

    PubMed Central

    Soliman, Ashraf; De Sanctis, Vincenzo; Elalaily, Rania; Bedair, Said

    2014-01-01

    Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS. PMID:25538878

  7. [Factors that increasing tendency to smoking cessation].

    PubMed

    Argüder, Emine; Hasanoğlu, H Canan; Karalezli, Ayşegül; Kılıç, Hatice

    2012-01-01

    Cigarette smoking is just important problem of public health. In the present study, our aim; was to determine to factors that increasing tendency to smoking cessation, the cases who are involved to policlinic of smoking cessation. Two hundred-forty five cigarette smokers were included in this study. It was recorded demographic signs, the novel of cigarette smoking, the degree of knowledge about the harmful of smoking in their opinion, the reason of starting to cigarette. It was evaluated that the principle reason to come to policlinic of smoking cessation and the other reasons. There were 53.9% male, 46.1% female in our study. Median (min-max) age was 45 (21-73) in females, 42 (20-75) in males. When evaluating the state of education; there was 35.9% primary school, 31.4% high school, 7.3% academy, 25.3% university graduates. 97.1% in all participants have used only cigarette smoking from tobacco products. Primarily reasons were 44% the fear of deterioration of health, 16.3% to be better model for their children, 9.8% to have disease at the time and 6.9% breathlessness for smoking cessation. Secondary reasons were of smoking harm to the environment, economic reasons, bad smell, being a good example of the environment and recommended by a physician. The most of cases are want to quit smoking because of smoking harm to their health. Specially, parents wish to quit smoking because of they don't want to be bad model for their children. As a result; it is given to necessary support to participants who are this awareness in policlinics of smoking cessation. However, we think that it was necessity that should be continue increase of the therapy to growing to these awareness for the smokers who couldn't be enough awareness and who didn't think of quit smoking.

  8. Increased Serum Levels of Epidermal Growth Factor in Children with Autism

    ERIC Educational Resources Information Center

    Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

    2011-01-01

    The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…

  9. Cost of bariatric surgery and factors associated with increased cost: an analysis of national inpatient sample.

    PubMed

    Khorgami, Zhamak; Aminian, Ali; Shoar, Saeed; Andalib, Amin; Saber, Alan A; Schauer, Philip R; Brethauer, Stacy A; Sclabas, Guido M

    2017-08-01

    In the current healthcare environment, bariatric surgery centers need to be cost-effective while maintaining quality. The aim of this study was to evaluate national cost of bariatric surgery to identify the factors associated with a higher cost. A retrospective analysis of 2012-2013 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS). We included all patients with a diagnosis of morbid obesity (ICD9 278.01) and a Diagnosis Related Group code related to procedures for obesity, who underwent Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or adjustable gastric banding (AGB) as their primary procedure. We converted "hospital charges" to "cost," using hospital specific cost-to-charge ratio. Inflation was adjusted using the annual consumer price index. Increased cost was defined as the top 20th percentile of the expenditure and its associated factors were analyzed using the logistic regression multivariate analysis. A total of 45,219 patients (20,966 RYGBs, 22,380 SGs, and 1,873 AGBs) were included. The median (interquartile range) calculated costs for RYGB, SG, and AGB were $12,543 ($9,970-$15,857), $10,531 ($8,248-$13,527), and $9,219 ($7,545-$12,106), respectively (P<.001). Robotic-assisted procedures had the highest impact on the cost (odds ratio 3.6, 95% confidence interval 3.2-4). Hospital cost of RYGB and SG increased linearly with the length of hospital stay and almost doubled after 7 days. Furthermore, multivariate analysis showed that certain co-morbidities and concurrent procedures were associated with an increased cost. Factors contributing to the cost variation of bariatric procedures include co-morbidities, robotic platform, complexity of surgery, and hospital length of stay. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  10. Factors Associated With Increases in US Health Care Spending, 1996-2013

    PubMed Central

    Squires, Ellen; Bui, Anthony L.; Campbell, Madeline; Chapin, Abigail; Hamavid, Hannah; Horst, Cody; Li, Zhiyin; Matyasz, Taylor; Reynolds, Alex; Sadat, Nafis; Schneider, Matthew T.; Murray, Christopher J. L.

    2017-01-01

    Importance Health care spending in the United States increased substantially from 1995 to 2015 and comprised 17.8% of the economy in 2015. Understanding the relationship between known factors and spending increases over time could inform policy efforts to contain future spending growth. Objective To quantify changes in spending associated with 5 fundamental factors related to health care spending in the United States: population size, population age structure, disease prevalence or incidence, service utilization, and service price and intensity. Design and Setting Data on the 5 factors from 1996 through 2013 were extracted for 155 health conditions, 36 age and sex groups, and 6 types of care from the Global Burden of Disease 2015 study and the Institute for Health Metrics and Evaluation’s US Disease Expenditure 2013 project. Decomposition analysis was performed to estimate the association between changes in these factors and changes in health care spending and to estimate the variability across health conditions and types of care. Exposures Change in population size, population aging, disease prevalence or incidence, service utilization, or service price and intensity. Main Outcomes and Measures Change in health care spending from 1996 through 2013. Results After adjustments for price inflation, annual health care spending on inpatient, ambulatory, retail pharmaceutical, nursing facility, emergency department, and dental care increased by $933.5 billion between 1996 and 2013, from $1.2 trillion to $2.1 trillion. Increases in US population size were associated with a 23.1% (uncertainty interval [UI], 23.1%-23.1%), or $269.5 (UI, $269.0-$270.0) billion, spending increase; aging of the population was associated with an 11.6% (UI, 11.4%-11.8%), or $135.7 (UI, $133.3-$137.7) billion, spending increase. Changes in disease prevalence or incidence were associated with spending reductions of 2.4% (UI, 0.9%-3.8%), or $28.2 (UI, $10.5-$44.4) billion, whereas changes in

  11. Hyponatremia and fractures: should hyponatremia be further studied as a potential biochemical risk factor to be included in FRAX algorithms?

    PubMed

    Ayus, J C; Bellido, T; Negri, A L

    2017-05-01

    The Fracture Risk Assessment Tool (FRAX®) was developed by the WHO Collaborating Centre for metabolic bone diseases to evaluate fracture risk of patients. It is based on patient models that integrate the risk associated with clinical variables and bone mineral density (BMD) at the femoral neck. The clinical risk factors included in FRAX were chosen to include only well-established and independent variables related to skeletal fracture risk. The FRAX tool has acquired worldwide acceptance despite having several limitations. FRAX models have not included biochemical derangements in estimation of fracture risk due to the lack of validation in large prospective studies. Recently, there has been an increasing number of studies showing a relationship between hyponatremia and the occurrence of fractures. Hyponatremia is the most frequent electrolyte abnormality measured in the clinic, and serum sodium concentration is a very reproducible, affordable, and readily obtainable measurement. Thus, we think that hyponatremia should be further studied as a biochemical risk factor for skeletal fractures prediction, particularly those at the hip which carries the greatest morbidity and mortality. To achieve this will require the collection of large patient cohorts from diverse geographical locations that include a measure of serum sodium in addition to the other FRAX variables in large numbers, in both sexes, over a wide age range and with wide geographical representation. It would also require the inclusion of data on duration and severity of hyponatremia. Information will be required both on the risk of fracture associated with the occurrence and length of exposure to hyponatremia and to the relationship with the other risk variables included in FRAX and also the independent effect on the occurrence of death which is increased by hyponatremia.

  12. Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

    PubMed Central

    Gorin, Caroline; Rochefort, Gael Y.; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Germain, Stéphane

    2016-01-01

    Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. Significance The results from the present study show that fibroblast growth factor-2 (FGF-2) priming is more

  13. A very-low-fat vegan diet increases intake of protective dietary factors and decreases intake of pathogenic dietary factors.

    PubMed

    Dewell, Antonella; Weidner, Gerdi; Sumner, Michael D; Chi, Christine S; Ornish, Dean

    2008-02-01

    There is increasing evidence that dietary factors in plant-based diets are important in the prevention of chronic disease. This study examined protective (eg, antioxidant vitamins, carotenoids, and fiber) and pathogenic (eg, saturated fatty acids and cholesterol) dietary factors in a very-low-fat vegan diet. Ninety-three early-stage prostate cancer patients participated in a randomized controlled trial and were assigned to a very-low-fat (10% fat) vegan diet supplemented with soy protein and lifestyle changes or to usual care. Three-day food records were collected at baseline (n=42 intervention, n=43 control) and after 1 year (n=37 in each group). Analyses of changes in dietary intake of macronutrients, vitamins, minerals, carotenoids, and isoflavones from baseline to 1 year showed significantly increased intake of most protective dietary factors (eg, fiber increased from a mean of 31 to 59 g/day, lycopene increased from 8,693 to 34,464 mug/day) and significantly decreased intake of most pathogenic dietary factors (eg, saturated fatty acids decreased from 20 to 5 g/day, cholesterol decreased from 200 to 10 mg/day) in the intervention group compared to controls. These results suggest that a very-low-fat vegan diet can be useful in increasing intake of protective nutrients and phytochemicals and minimizing intake of dietary factors implicated in several chronic diseases.

  14. Develop a PWL System for Dense Graded Hot Mix Asphalt Construction, Including Pay Factors

    DOT National Transportation Integrated Search

    2015-01-01

    This research project developed a PWL system that the Nevada DOT can effectively implement on the construction of dense graded HMA mixtures. The PWL system includes pay factors that are based on pavement performance indicators such as rutting and cra...

  15. Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.

    PubMed

    Self, Timothy H; Oliphant, Carrie S; Reaves, Anne B; Richardson, Amy M; Sands, Christopher W

    2015-01-01

    Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

    PubMed Central

    Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

    2010-01-01

    The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. PMID:20399528

  17. DNA Damage Response Factors from Diverse Pathways, Including DNA Crosslink Repair, Mediate Alternative End Joining

    PubMed Central

    Howard, Sean M.; Yanez, Diana A.; Stark, Jeremy M.

    2015-01-01

    Alternative end joining (Alt-EJ) chromosomal break repair involves bypassing classical non-homologous end joining (c-NHEJ), and such repair causes mutations often with microhomology at the repair junction. Since the mediators of Alt-EJ are not well understood, we have sought to identify DNA damage response (DDR) factors important for this repair event. Using chromosomal break reporter assays, we surveyed an RNAi library targeting known DDR factors for siRNAs that cause a specific decrease in Alt-EJ, relative to an EJ event that is a composite of Alt-EJ and c-NHEJ (Distal-EJ between two tandem breaks). From this analysis, we identified several DDR factors that are specifically important for Alt-EJ relative to Distal-EJ. While these factors are from diverse pathways, we also found that most of them also promote homologous recombination (HR), including factors important for DNA crosslink repair, such as the Fanconi Anemia factor, FANCA. Since bypass of c-NHEJ is likely important for both Alt-EJ and HR, we disrupted the c-NHEJ factor Ku70 in Fanca-deficient mouse cells and found that Ku70 loss significantly diminishes the influence of Fanca on Alt-EJ. In contrast, an inhibitor of poly ADP-ribose polymerase (PARP) causes a decrease in Alt-EJ that is enhanced by Ku70 loss. Additionally, the helicase/nuclease DNA2 appears to have distinct effects from FANCA and PARP on both Alt-EJ, as well as end resection. Finally, we found that the proteasome inhibitor Bortezomib, a cancer therapeutic that has been shown to disrupt FANC signaling, causes a significant reduction in both Alt-EJ and HR, relative to Distal-EJ, as well as a substantial loss of end resection. We suggest that several distinct DDR functions are important for Alt-EJ, which include promoting bypass of c-NHEJ and end resection. PMID:25629353

  18. Some Factors Being Overlooked as We Increase Tuition at Our Public Senior Institutions.

    ERIC Educational Resources Information Center

    Graziano, Anthony F.

    Tuition increases in Illinois public senior institutions are reviewed in light of factors being overlooked. These factors suggest the new emphasis on tuition could (1) spiral into higher tuition in the future, (2) create increased state response to provide financial support for students who would otherwise find higher charges a barrier to…

  19. Modifiable Risk Factors for Increased Arterial Stiffness in Outpatient Nephrology

    PubMed Central

    Elewa, Usama; Fernandez-Fernandez, Beatriz; Alegre, Raquel; Sanchez-Niño, Maria D.; Mahillo-Fernández, Ignacio; Perez-Gomez, Maria Vanessa; El-Fishawy, Hussein; Belal, Dawlat; Ortiz, Alberto

    2015-01-01

    Arterial stiffness, as measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5%) patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV) was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV) - (upper limit of the age-adjusted PWV values for the general population). Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients. PMID:25880081

  20. Structural factors that increase HIV/STI vulnerability among indigenous people in the Peruvian amazon.

    PubMed

    Orellana, E Roberto; Alva, Isaac E; Cárcamo, Cesar P; García, Patricia J

    2013-09-01

    We examined structural factors-social, political, economic, and environmental-that increase vulnerability to HIV among indigenous people in the Peruvian Amazon. Indigenous adults belonging to 12 different ethnic groups were purposively recruited in four Amazonian river ports and 16 indigenous villages. Qualitative data revealed a complex set of structural factors that give rise to environments of risk where health is constantly challenged. Ferryboats that cross Amazonian rivers are settings where unprotected sex-including transactional sex between passengers and boat crew and commercial sex work-often take place. Population mobility and mixing also occurs in settings like the river docks, mining sites, and other resource extraction camps, where heavy drinking and unprotected sex work are common. Multilevel, combination prevention strategies that integrate empirically based interventions with indigenous knowledge are urgently needed, not only to reduce vulnerability to HIV transmission, but also to eliminate the structural determinants of indigenous people's health.

  1. Analysis of vehicle classification data, including monthly and seasonal ADT factors, hourly distribution factors, and lane distribution factors

    DOT National Transportation Integrated Search

    1998-11-01

    This report documents the development of monthly and seasonal average daily traffic (ADT) factors for performing estimating AADTs. It appears that seasonal factors can estimate AADT as well as monthly factors, and it is recommended that seasonal fact...

  2. Factors associated with increasing nursing home closures.

    PubMed

    Castle, Nicholas G; Engberg, John; Lave, Judith; Fisher, Andrew

    2009-06-01

    We determine the rate of nursing home closures for 7 years (1999-2005) and examine internal (e.g., quality), organizational (e.g., chain membership), and external (e.g., competition) factors associated with these closures. The names of the closed facilities and dates of closure from state regulators in all 50 states were obtained. This information was linked to the Online Survey, Certification, and Reporting data, which contains information on internal, organizational, and market factors for almost all nursing homes in the United States. One thousand seven hundred and eighty-nine facilities closed over this time period (1999-2005). The average annual rate of closure was about 2 percent of facilities, but the rate of closure was found to be increasing. Nursing homes with higher rates of deficiency citations, hospital-based facilities, chain members, small bed size, and facilities located in markets with high levels of competition were more likely to close. High Medicaid occupancy rates were associated with a high likelihood of closure, especially for facilities with low Medicaid reimbursement rates. As states actively debate about how to redistribute long-term care services/dollars, our findings show that they should be cognizant of the potential these decisions have for facilitating nursing home closures.

  3. Adverse factors increase preeclampsia-like changes in pregnant mice with abnormal lipid metabolism.

    PubMed

    Ding, Xiaoyan; Yang, Zi; Han, Yiwei; Yu, Huan

    2014-01-01

    Preeclampsia (PE) is a multifactorial pregnancy complication. Maternal underlying condition and adverse factors both influence the pathogenesis of PE. Abnormal lipid metabolism as a maternal underlying disease may participate in the occurrence and development of PE. This study aimed to observe the effects of adverse factors on PE-like symptoms of pregnant mice with genetic abnormal lipid metabolism. Apolipoprotein C-III (ApoC3) transgenic mice with abnormal lipid metabolism were subcutaneously injected with L-arginine methyl ester (L-NAME) or normal saline (NS) daily starting at Day 7 or 16 of pregnancy (ApoC3+L-NA and ApoC3+NS groups), and wild-type (WT) mice served as a control (WT+L-NA and WT+NS groups). All mice were subdivided into early and late subgroups by injection time. The mean arterial pressure (MAP) and urinary protein were measured. Pregnancy outcomes, including fetal weight, placental weight, live birth rate, and fetal absorption rate, were analyzed. Pathologic changes in the placenta were observed by hematoxylin-eosin staining. One-way analysis of variance, t-test, and χ(2) test were used for statistical analysis. MAP significantly increased for ApoC3+NS groups compared with WT+NS groups (P < 0.05), without significant difference in urine protein. Following L-NAME injection, MAP and urinary protein significantly increased for ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), and the increase for ApoC3+L-NA was more obvious. Urinary protein levels in early ApoC3+L-NA and WT+L-NA significantly increased compared with the corresponding late groups (P < 0.05). Fetal absorption rate significantly increased and fetal and placental weights significantly decreased in early ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), without significant difference in late ApoC3+L-NA and WT+L-NA groups. Fetal weight in early ApoC3+L-NA was significantly lower than in early WT+L-NA group (P < 0.05). Morphologic

  4. Patient factors associated with increased acute care costs of hip fractures: a detailed analysis of 402 patients.

    PubMed

    Aigner, R; Meier Fedeler, T; Eschbach, D; Hack, J; Bliemel, C; Ruchholtz, S; Bücking, B

    2016-12-01

    The aim of the present study was to identify patient factors associated with higher costs in hip fracture patients. The mean costs of a prospectively observed sample of 402 patients were 8853 €. The ASA score, Charlson comorbidity index, and fracture location were associated with increased costs. Fractures of the proximal end of the femur (hip fractures) are of increasing incidence due to demographic changes. Relevant co-morbidities often present in these patients cause high complication rates and prolonged hospital stays, thus leading to high costs of acute care. The aim of this study was to perform a precise cost analysis of the actual hospital costs of hip fractures and to identify patient factors associated with increased costs. The basis of this analysis was a prospectively observed single-center trial, which included 402 patients with fractures of the proximal end of the femur. All potential cost factors were recorded as accurately as possible for each of the 402 patients individually, and statistical analysis was performed to identify associations between pre-existing patient factors and acute care costs. The mean total acute care costs per patient were 8853 ± 5676 € with ward costs (5828 ± 4294 €) and costs for surgical treatment (1972 ± 956 €) representing the major cost factors. The ASA score, Charlson comorbidity index, and fracture location were identified as influencing the costs of acute care for hip fracture treatment. Hip fractures are associated with high acute care costs. This study underlines the necessity of sophisticated risk-adjusted payment models based on specific patient factors. Economic aspects should be an integral part of future hip fracture research due to limited health care resources.

  5. Including dietary fiber and resistant starch to increase satiety and reduce aggression in gestating sows

    USDA-ARS?s Scientific Manuscript database

    The swine industry is under a great deal of pressure to return sows to group housing. However, aggression during mixing of pregnant sows impacts sow welfare and productivity. The aim of this study was to increase satiety and reduce aggression by including dietary fiber and fermentable carbohydrate. ...

  6. Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

    PubMed

    Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

    2014-05-09

    Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

  7. Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion.

    PubMed

    Gorin, Caroline; Rochefort, Gael Y; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Muller, Laurent; Chaussain, Catherine; Germain, Stéphane

    2016-03-01

    Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. ©AlphaMed Press.

  8. Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies.

    PubMed

    Roberson Ii, John D; McDonald, Andrew M; Baden, Craig J; Lin, Chee Paul; Jacob, Rojymon; Burnett Iii, Omer L

    2016-03-14

    To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 ((90)Y) microspheres. Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following (90)Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity. Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043). Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for (90)Y microsphere therapy.

  9. Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations.

    PubMed

    Celano, Marilena; Sponziello, Marialuisa; Tallini, Giovanni; Maggisano, Valentina; Bruno, Rocco; Dima, Mariavittoria; Di Oto, Enrico; Redler, Adriano; Durante, Cosimo; Sacco, Rosario; Filetti, Sebastiano; Russo, Diego

    2013-02-01

    Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors.

  10. Epidermal Growth Factor Increases LRF/Pokemon Expression in Human Prostate Cancer Cells

    PubMed Central

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K.

    2011-01-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. PMID:21640721

  11. The economic benefits of malaria elimination: do they include increases in tourism?

    PubMed

    Modrek, Sepideh; Liu, Jenny; Gosling, Roland; Feachem, Richard G A

    2012-07-28

    Policy makers have speculated that one of the economic benefits of malaria elimination includes increases in foreign direct investment, particularly tourism. This study examines the empirical relationship between the demand for travel and malaria cases in two countries with large tourism industries around the time in which they carried out malaria-elimination campaigns. In Mauritius, this analysis examines historical, yearly tourist arrivals and malaria cases from 1978-1999, accounting for the background secular trend of increasing international travel. In Dominican Republic, a country embarking upon malaria elimination, it employs a time-series analysis of the monthly, international tourist arrivals from 1998-2010 to determine whether the timing of significant deviations in tourist arrivals coincides with malaria outbreaks. While naïve relationships exist in both cases, the results show that the relationships between tourist arrivals and malaria cases are relatively weak and statistically insignificant once secular confounders are accounted for. This suggests that any economic benefits from tourism that may be derived from actively pursuing elimination in countries that have high tourism potential are likely to be small when measured at a national level. Rather, tourism benefits are likely to be experienced with greater impact in more concentrated tourist areas within countries, and future studies should seek to assess these relationships at a regional or local level.

  12. The economic benefits of malaria elimination: do they include increases in tourism?

    PubMed Central

    2012-01-01

    Background Policy makers have speculated that one of the economic benefits of malaria elimination includes increases in foreign direct investment, particularly tourism. Methods This study examines the empirical relationship between the demand for travel and malaria cases in two countries with large tourism industries around the time in which they carried out malaria-elimination campaigns. In Mauritius, this analysis examines historical, yearly tourist arrivals and malaria cases from 1978–1999, accounting for the background secular trend of increasing international travel. In Dominican Republic, a country embarking upon malaria elimination, it employs a time-series analysis of the monthly, international tourist arrivals from 1998–2010 to determine whether the timing of significant deviations in tourist arrivals coincides with malaria outbreaks. Results While naïve relationships exist in both cases, the results show that the relationships between tourist arrivals and malaria cases are relatively weak and statistically insignificant once secular confounders are accounted for. Conclusions This suggests that any economic benefits from tourism that may be derived from actively pursuing elimination in countries that have high tourism potential are likely to be small when measured at a national level. Rather, tourism benefits are likely to be experienced with greater impact in more concentrated tourist areas within countries, and future studies should seek to assess these relationships at a regional or local level. PMID:22839351

  13. Milk consumption during pregnancy increases birth weight, a risk factor for the development of diseases of civilization.

    PubMed

    Melnik, Bodo C; John, Swen Malte; Schmitz, Gerd

    2015-01-16

    Antenatal dietary lifestyle intervention and nutrition during pregnancy and early postnatal life are important for appropriate lifelong metabolic programming. Epidemiological evidence underlines the crucial role of increased birth weight as a risk factor for the development of chronic diseases of civilization such as obesity, diabetes and cancer. Obstetricians and general practitioners usually recommend milk consumption during pregnancy as a nutrient enriched in valuable proteins and calcium for bone growth. However, milk is not just a simple nutrient, but has been recognized to function as an endocrine signaling system promoting anabolism and postnatal growth by activating the nutrient-sensitive kinase mTORC1. Moreover, pasteurized cow's milk transfers biologically active exosomal microRNAs into the systemic circulation of the milk consumer apparently affecting more than 11,000 human genes including the mTORC1-signaling pathway. This review provides literature evidence and evidence derived from translational research that milk consumption during pregnancy increases gestational, placental, fetal and birth weight. Increased birth weight is a risk factor for the development of diseases of civilization thus involving key disciplines of medicine. With regard to the presented evidence we suggest that dietary recommendations promoting milk consumption during pregnancy have to be re-evaluated.

  14. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    PubMed

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Burkholderia Diffusible Signal Factor Signals to Francisella novicida To Disperse Biofilm and Increase Siderophore Production

    PubMed Central

    Dean, Scott N.; Chung, Myung-Chul

    2015-01-01

    In many bacteria, the ability to modulate biofilm production relies on specific signaling molecules that are either self-produced or made by neighboring microbes within the ecological niche. We analyzed the potential interspecies signaling effect of the Burkholderia diffusible signal factor (BDSF) on Francisella novicida, a model organism for Francisella tularensis, and demonstrated that BDSF both inhibits the formation and causes the dispersion of Francisella biofilm. Specificity was demonstrated for the cis versus the trans form of BDSF. Using transcriptome sequencing, quantitative reverse transcription-PCR, and activity assays, we found that BDSF altered the expression of many F. novicida genes, including genes involved in biofilm formation, such as chitinases. Using a chitinase inhibitor, the antibiofilm activity of BDSF was also shown to be chitinase dependent. In addition, BDSF caused an increase in RelA expression and increased levels of (p)ppGpp, leading to decreased biofilm production. These results support our observation that exposure of F. novicida to BDSF causes biofilm dispersal. Furthermore, BDSF upregulated the genes involved in iron acquisition (figABCD), increasing siderophore production. Thus, this study provides evidence for a potential role and mechanism of diffusible signal factor (DSF) signaling in the genus Francisella and suggests the possibility of interspecies signaling between Francisella and other bacteria. Overall, this study suggests that in response to the interspecies DSF signal, F. novicida can alter its gene expression and regulate its biofilm formation. PMID:26231649

  16. Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies.

    PubMed

    Shiri, Rahman; Euro, Ulla; Heliövaara, Markku; Hirvensalo, Mirja; Husgafvel-Pursiainen, Kirsti; Karppinen, Jaro; Lahti, Jouni; Rahkonen, Ossi; Raitakari, Olli T; Solovieva, Svetlana; Yang, Xiaolin; Viikari-Juntura, Eira; Lallukka, Tea

    2017-12-01

    The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica. We included 4 Finnish prospective cohort studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital discharge register data. We conducted a random-effects individual participant data meta-analysis. After adjustment for confounding factors, current smoking at baseline increased the risk of subsequent hospitalization for sciatica by 33% (95% confidence interval [CI], 13%-56%), whereas past smokers were no longer at increased risk. Obesity defined by body mass index increased the risk of hospitalization for sciatica by 36% (95% CI 7%-74%), and abdominal obesity defined by waist circumference increased the risk by 41% (95% CI 3%-93%). Walking or cycling to work reduced the risk of hospitalization for sciatica by 33% (95% CI 4%-53%), and the effect was independent of body weight and other leisure activities, while other types of leisure activities did not have a statistically significant effect. Smoking and obesity increase the risk of hospitalization for sciatica, whereas walking or cycling to work protects against hospitalization for sciatica. Walking and cycling can be recommended for the prevention of sciatica in the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Modifiable Risk Factors in Primary Joint Arthroplasty Increase 90-Day Cost of Care.

    PubMed

    Schroer, William C; Diesfeld, Paul J; LeMarr, Angela R; Morton, Diane J; Reedy, Mary E

    2018-04-19

    Risk factors in demographics and health status have been identified that increase the risk of complications after joint arthroplasty, necessitating additional care and incurring additional charges. The purpose of this study was to identify the number of patients in a hospital network database who had one or more predefined modifiable risk factors and determine their impact on average length of stay, need for additional care during the 90-day postoperative period, and the 90-day charges for care. An electronic hospital record query of 6968 lower extremity joint arthroplasty procedures under Diagnosis-Related Group 469/470 performed in 2014-2015 was reviewed, and total 90-day charges were calculated. The case mean was compared to charges for patients with modifiable risk factors: anemia (Hgb < 10 g/dL), malnutrition (albumin < 3.4 g/dL), obesity (body mass index > 45 kg/m 2 ), uncontrolled diabetes (random glucose >180 mg/dL or A1C > 8), narcotic use (prescription filled), and tobacco use (documented within 30 days before surgery). Length of stay, emergency room visits, and hospital readmission were compared. Mean 90-day charges for Diagnosis-Related Group 469/470 were $36,647. Risk factors were associated with a significant increase in 90-day charges: anemia (+$ 15,869/126 patients), malnutrition (+$9270/592), obesity (+$2048/445), diabetes (+$5074/291), narcotic use (+$1801/1943), and tobacco use (+$2034/1882). Intensive care unit admission rate, emergency department visits, and hospital readmission were significantly increased for patients with each risk factor. Length of stay was higher in patients with anemia, malnutrition, diabetes, and tobacco use. When separated by elective vs fracture admission, 90-day charges were significantly higher for each risk factor. Medical strategies to optimize patients before joint arthroplasty are warranted to improve postoperative outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Study of Factors Which Facilitate Increase of Effectiveness of University Education

    ERIC Educational Resources Information Center

    Albekov, Adam; Romanova, Tatyana; Vovchenko, Natalya; Epifanova, Tatyana

    2017-01-01

    Purpose: The purpose of this paper is to study the factors which facilitate the increase of effectiveness of university education and determination of perspectives of their management for provision of maximization of effectiveness of university education by the example of modern Russia. Design/methodology/approach: The authors define the notion…

  19. Risk Factor Analysis for AKI Including Laboratory Indicators: a Nationwide Multicenter Study of Hospitalized Patients.

    PubMed

    Nie, Sasa; Feng, Zhe; Tang, Li; Wang, Xiaolong; He, Yani; Fang, Jingai; Li, Suhua; Yang, Yibin; Mao, Huijuan; Jiao, Jundong; Liu, Wenhu; Cao, Ning; Wang, Wenge; Sun, Jifeng; Shao, Fengmin; Li, Wenge; He, Qiang; Jiang, Hongli; Lin, Hongli; Fu, Ping; Zhang, Xinzhou; Liu, Yinghong; Wu, Yonggui; Xi, ChunSheng; Liang, Meng; Qu, Zhijie; Zhu, Jun; Wu, Guangli; Zheng, Yali; Na, Yu; Li, Ying; Li, Wei; Cai, Guangyan; Chen, Xiangmei

    2017-01-01

    Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes' definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI. © 2017 The Author(s). Published by S. Karger AG, Basel.

  20. What factors are associated with increased risk for prolonged postoperative opioid usage after colorectal surgery?

    PubMed

    Stafford, Caitlin; Francone, Todd; Roberts, Patricia L; Ricciardi, Rocco

    2018-02-06

    Opioid-related deaths have increased substantially over the last 10 years placing clinician's prescription practices under intense scrutiny. Given the substantial risk of opioid dependency after colorectal surgery, we sought to analyze risk of postoperative prolonged opioid use after colorectal resections. Between 2008 and 2014, patients undergoing abdominopelvic procedure with intestinal resection at a tertiary care facility were retrospectively identified. Patient's postoperative narcotic usage including their prescriptions on discharge and their total opioid medication use was recorded. Patient variables such as demographics, surgical characteristics, and prescription use were evaluated. Finally, we developed multivariate models to identify risk factors for prolonged opioid use (> 30 days after incident surgical procedure). We identified 9423 recorded procedures of which 2173 consisted of abdominopelvic procedures with intestinal resection and survived > 1 year. Of these, 91% (n = 1981) were discharged on opioids, and 98% (n = 1955) of those patients filled only one prescription. A total of 92 (4%) patients remained on opioids beyond 30 days, and from this group, 25% (n = 23 patients) remained at 90 days. We found no association between postoperative complications, stoma formation, and patient's sex with risk of prolonged opioid use. However, younger age and history of chronic pain were associated with an increased risk of prolonged opioid use. The use of minimally invasive techniques also attenuated the risk of prolonged opioid use (Table 2). A small but considerable proportion of patients remain on opioids beyond 30 days. Predictors of opioid use for greater than 30 days include a history of chronic pain and younger age. The use of minimally invasive techniques reduced the risk of prolonged opioid use. We identified several immutable risk factors that predicted prolonged postoperative opioid use; however, surgeons may be able to attenuate

  1. Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.

    PubMed

    Labler, Ludwig; Rancan, Mario; Mica, Ladislav; Härter, Luc; Mihic-Probst, Daniela; Keel, Marius

    2009-03-01

    Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

  2. Increased expression of placental growth factor in high-grade endometrial carcinoma.

    PubMed

    Coenegrachts, Lieve; Schrauwen, Stefanie; Van Bree, Rita; Despierre, Evelyn; Luyten, Catherine; Jonckx, Bart; Stassen, Jean Marie; Vergote, Ignace; Amant, Frédéric

    2013-02-01

    Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer.

  3. Stepwise intervention including 1-on-1 counseling is highly effective in increasing influenza vaccination among health care workers.

    PubMed

    Jung, Younghee; Kwon, Mihye; Song, Jeongmi

    2017-06-01

    The influenza vaccination rate among health care workers (HCWs) remains suboptimal. We attempted to increase vaccine uptake in HCWs by nonmandatory measures, including 1-on-1 counseling. In 2015 we used a stepwise approach including (1) text messaging on the last day of the vaccination period, (2) extending the vaccination period by 3 days, (3) education for the low uptake group, and (4) 1-on-1 counseling for unvaccinated HCWs after the 3 interventions. There were 1,433 HCWs included. By the end of the initial 3 days, the uptake rate was 80.0% (1,146/1,433). During an extension for a further 3 days, 33 additional HCWs received the vaccine. One month after starting the vaccination, 90.1% (1,291/1,433) of the HCWs were vaccinated, but this included only 76.1% (210/276) of the doctors (lowest among HCWs). After 3 educational presentations targeted at the unvaccinated doctors, no additional individuals were vaccinated in the following 2 weeks. After 1-on-1 counseling for unvaccinated HCWs, the overall vaccination rate increased to 94.7% (1,357/1,433) in 2015, higher than in the previous year (82.5%, P < .001). Of the unvaccinated doctors, 63.2% (43/68) were vaccinated, therefore achieving 92.4% (255/276) compliance, higher than the 56.5% in the previous year (152/269, P < .001). Stepwise intervention including 1-on-1 counseling is effective in increasing influenza vaccination rates among HCWs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Increased Melanoma Growth and Metastasis Spreading in Mice Overexpressing Placenta Growth Factor

    PubMed Central

    Marcellini, Marcella; De Luca, Naomi; Riccioni, Teresa; Ciucci, Alessandro; Orecchia, Angela; Lacal, Pedro Miguel; Ruffini, Federica; Pesce, Maurizio; Cianfarani, Francesca; Zambruno, Giovanna; Orlandi, Augusto; Failla, Cristina Maria

    2006-01-01

    Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in adult pathological angiogenesis. To further investigate PlGF functions in tumor growth and metastasis formation, we used transgenic mice overexpressing PlGF in the skin under the control of the keratin 14 promoter. These animals showed a hypervascularized phenotype of the skin and increased levels of circulating PlGF with respect to their wild-type littermates. Transgenic mice and controls were inoculated intradermally with B16-BL6 melanoma cells. The tumor growth rate was fivefold increased in transgenic animals compared to wild-type mice, in the presence of a similar percentage of tumor necrotic tissue. Tumor vessel area was increased in transgenic mice as compared to controls. Augmented mobilization of endothelial and hematopoietic stem cells from the bone marrow was observed in transgenic animals, possibly contributing to tumor vascularization. The number and size of pulmonary metastases were significantly higher in transgenic mice compared to wild-type littermates. Finally, PlGF promoted tumor cell invasion of the extracellular matrix and increased the activity of selected matrix metalloproteinases. These findings indicate that PlGF, in addition to enhancing tumor angiogenesis and favoring tumor growth, may directly influence melanoma dissemination. PMID:16877362

  5. Increased hematocrit after applications of conducted energy weapons (including TASER(®) devices) to Sus scrofa.

    PubMed

    Jauchem, James R

    2011-01-01

    Conducted energy weapons (CEWs) are used by law enforcement personnel to incapacitate individuals quickly and effectively, without intending to cause lethality. CEWs have been deployed for relatively long or repeated exposures in some cases. In laboratory animal models, central venous hematocrit has increased significantly after CEW exposure. Even limited applications (e.g., three 5-sec applications) resulted in statistically significant increases in hematocrit. Preexposure hematocrit was significantly higher in nonsurvivors versus survivors after more extreme CEW applications. The purpose of this technical note is to address specific questions that may be generated when examining these results. Comparisons among results of CEW applications, other electrical muscle stimulation, and exercise/voluntary muscle contraction are included. The anesthetized swine appears to be an acceptable animal model for studying changes in hematocrit and associated red blood cell changes. Potential detrimental effects of increased hematocrit, and considerations during law enforcement use, are discussed. 2010 American Academy of Forensic Sciences. Published 2010. This article is a U.S. Government work and is in the public domain in the U.S.A.

  6. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    PubMed

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  7. Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

    PubMed Central

    Ji, Liang; Nazarali, Adil J.; Paterson, Phyllis G.

    2013-01-01

    Protein–energy malnutrition (PEM) exacerbates functional impairment caused by brain ischemia. This is correlated with reactive gliosis, which suggests an increased inflammatory response. The objective of the current study was to investigate if PEM increases hippocampal activation of nuclear factor κB (NFκB), a transcription factor that amplifies the inflammatory response involved in ischemic brain injury. Mongolian gerbils (11–12 weeks old) were randomly assigned to control diet (12.5% protein) or protein-deficient diet (2%) for 4 weeks. The 2% protein group had a 15% decrease in voluntary food intake (P<.001; unpaired t test), resulting in PEM. Body weight after 4 weeks was 20% lower in the PEM group (P<.001). Gerbils were then exposed to sham surgery or global ischemia induced by 5-min bilateral common carotid artery occlusion. PEM independently increased hippocampal NFκB activation detected by electrophoretic mobility shift assay at 6 h after surgery (P=.014; 2-factor ANOVA). Ischemia did not significantly affect NFκB activation nor was there interaction between diet and ischemia. Serum glucose and cortisol concentrations at 6 h postischemia were unaltered by diet or ischemia. A second experiment using gerbils of the same age and feeding paradigm demonstrated that PEM also increases hippocampal NFκB activation in the absence of surgery. These findings suggest that PEM, which exists in 16% of elderly patients at admission for stroke, may worsen outcome by increasing activation of NFκB. Since PEM increased NFκB activation independent of ischemia or surgery, the data also have implications for the inflammatory response of the many individuals affected globally by PEM. PMID:18430555

  8. Increased expression of placental growth factor in high-grade endometrial carcinoma

    PubMed Central

    COENEGRACHTS, LIEVE; SCHRAUWEN, STEFANIE; VAN BREE, RITA; DESPIERRE, EVELYN; LUYTEN, CATHERINE; JONCKX, BART; STASSEN, JEAN MARIE; VERGOTE, IGNACE; AMANT, FRÉDÉRIC

    2013-01-01

    Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer. PMID:23232836

  9. Resources–tasks imbalance: Experiences of nurses from factors influencing workload to increase

    PubMed Central

    Khademi, Mojgan; Mohammadi, Easa; Vanaki, Zohreh

    2015-01-01

    Background: While nursing workload is a worldwide challenge, less attention has been given to the determining factors. Understanding these factors is important and could help nursing managers to provide suitable working environment and to manage the adverse outcomes of nursing workload. The aim of this study was to discover nurses’ experiences of determinant factors of their workload. Materials and Methods: In this qualitative study, the participants included 15 nurses working in two hospitals in Tehran, Iran. The data were collected through 26 unstructured interviews and were analyzed using conventional content analysis. The rigor has been guaranteed with prolonged engagement, maximum variance sampling, member check, and audit trail. Results: Resource–task imbalance was the main theme of nurses’ experiences. It means that there was an imbalance between necessary elements to meet patients’ needs in comparison with expectation and responsibility. Resource–task imbalance included lack of resource, assignment without preparation, assigning non-care tasks, and patients’ and families’ needs/expectations. Conclusions: A deep and comprehensive imbalance between recourses and tasks and expectations has been perceived by the participants to be the main source of work overload. Paying more attention to resource allocation, education of quality workforce, and job description by managers is necessary. PMID:26257804

  10. High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients.

    PubMed

    Jean, Guillaume; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

    2009-09-01

    Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival. All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles. The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality. This study demonstrated a high level of circulating FGF-23 in LHD patients

  11. Mortality risk factor analysis in colonic perforation: would retroperitoneal contamination increase mortality in colonic perforation?

    PubMed

    Yoo, Ri Na; Kye, Bong-Hyeon; Kim, Gun; Kim, Hyung Jin; Cho, Hyeon-Min

    2017-10-01

    Colonic perforation is a lethal condition presenting high morbidity and mortality in spite of urgent surgical treatment. This study investigated the surgical outcome of patients with colonic perforation associated with retroperitoneal contamination. Retrospective analysis was performed for 30 patients diagnosed with colonic perforation caused by either inflammation or ischemia who underwent urgent surgical treatment in our facility from January 2005 to December 2014. Patient characteristics were analyzed to find risk factors correlated with increased postoperative mortality. Using the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) audit system, the mortality and morbidity rates were estimated to verify the surgical outcomes. Patients with retroperitoneal contamination, defined by the presence of retroperitoneal air in the preoperative abdominopelvic CT, were compared to those without retroperitoneal contamination. Eight out of 30 patients (26.7%) with colonic perforation had died after urgent surgical treatment. Factors associated with mortality included age, American Society of Anesthesiologists (ASA) physical status classification, and the ischemic cause of colonic perforation. Three out of 6 patients (50%) who presented retroperitoneal contamination were deceased. Although the patients with retroperitoneal contamination did not show significant increase in the mortality rate, they showed significantly higher ASA physical status classification than those without retroperitoneal contamination. The mortality rate predicted from Portsmouth POSSUM was higher in the patients with retroperitoneal contamination. Patients presenting colonic perforation along with retroperitoneal contamination demonstrated severe comorbidity. However, retroperitoneal contamination was not found to be correlated with the mortality rate.

  12. Risk factors and outcome of increased red blood cell transfusion in cardiac surgical patients aged 65 years and older.

    PubMed

    Isil, Canan Tulay; Yazici, Pinar; Bakir, Ihsan

    2015-02-01

    The use of blood products is not uncommon during cardiac surgery in elderly patients. We conducted this study to investigate the risk factors and adverse outcomes of increased red blood cell (RBC) transfusion in the patients aged ≥ 65 years undergoing cardiac surgery. During 1 year period, 288 patients (197 male/91 female) aged ≥ 65 years who underwent coronary and/or valvular surgery were retrospectively reviewed. Patients were stratified into groups on the basis of the number of transfusions received (< 4 and ≥ 4 U) which was classified as increased transfusion. Univariate analysis and multivariate logistic regression were used to identify risk factors for increased transfusion. The mean unit of RBC transfusion was 4.5 ± 3.1 and 55.9% (n = 161) of patients received ≥ 4 U RBC. The overall postoperative complication rate was 36% and significantly higher in those with ≥ 4 U) RBC transfusion (p < 0.01). Risk factors including age, EuroSCORE, and low body surface were significantly higher in patient with ≥ 4 U RBC transfusion. Besides, preoperative anemia, postoperative drainage volume, and fresh frozen plasma (FFP) transfusion during hospital stay were found to be significantly associated with increased transfusion requirements. No difference was observed in mortality (p = 0.13). These results suggest that improvement in blood transfusion policy in elderly patients undergoing cardiac surgery requires elimination of preoperative anemia, careful attention to surgical hemostasis, and FFP use. Georg Thieme Verlag KG Stuttgart · New York.

  13. Dynamic increase and decrease of photonic crystal nanocavity Q factors for optical pulse control.

    PubMed

    Upham, Jeremy; Tanaka, Yoshinori; Asano, Takashi; Noda, Susumu

    2008-12-22

    We introduce recent advances in dynamic control over the Q factor of a photonic crystal nanocavity system. By carefully timing a rapid increase of the Q factor from 3800 to 22,000, we succeed in capturing a 4ps signal pulse within the nanocavity with a photon lifetime of 18ps. By performing an additional transition of the Q factor within the photon lifetime, the held light is once again ejected from of the system on demand.

  14. Lack of supervision after residential cardiac rehabilitation increases cardiovascular risk factors.

    PubMed

    Berent, Robert; von Duvillard, Serge P; Auer, Johann; Sinzinger, Helmut; Schmid, Peter

    2010-06-01

    Cardiovascular rehabilitation (CR) is an important component of care for patients with cardiovascular disease (CVD) and has been well documented and promoted by various health organizations and position statements worldwide. The purpose of this study was to investigate whether patients readmitted to CR on average 16 months after their previous discharge, maintained the reduction in CVD risk factors, maintained or improved functional capacity, occurrence of adverse cardiovascular events, and possible modifications in prescribed medications. Five hundred and seventy patients (60+/-10 years) underwent cycle ergometry and blood sampling at the beginning, the end of 21+/-2 days of the previous CR, and again at readmission to CR. The CR consisted of cycling for 17+/-4 min at frequency of six times a week and daily walking for 45 min at 60-70% of the maximal individual heart rate. Blood total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and body mass index decreased significantly during CR. Resting blood pressure, maximal performance (watts), maximal oxygen uptake, and heart rate recovery improved significantly in 1 min (P<0.001). At readmission, all traditional CVD risk factors increased significantly, although medication was unchanged and angiotensin-converting enzyme inhibitors were partly replaced by angiotensin II receptor antagonists. Exercise performance remained unchanged. At readmission, we observed an increase in CVD risk factors, although, physical fitness remained stable. Thus, failure of lifestyle modification after CR indicates the cause for concern. Reinforcement of home setting sessions of CR patients or other strategies to enhance long-term compliance to lifestyle changes could reduce the observed attrition in CR benefits.

  15. Association Between the Duration of Periodontitis and Increased Cardiometabolic Risk Factors: A 9-Year Cohort Study.

    PubMed

    Morita, Toyoko; Yamazaki, Yoji; Fujiharu, Chika; Ishii, Takanori; Seto, Misae; Nishinoue, Norihide; Sasaki, Yoshiyuki; Nakai, Kumiko; Tanaka, Hideki; Kawato, Takayuki; Maeno, Masao

    2016-12-01

    Epidemiological studies have reported that periodontitis and cardiometabolic disease such as cardiovascular disease and type 2 diabetes are associated; however, there have been very few prospective cohort studies on this topic. Therefore, we conducted a 9-year follow-up study to examine the relationship between the duration of periodontitis and cardiometabolic risk factors, including hypertension, hyperglycemia, dyslipidemia, and obesity. The study participants comprised 572 adult industrial workers (417 men and 155 women; mean age, 37.4 years) who had undergone annual medical and dental health examinations from 2003 to 2012; the evaluation of the four cardiometabolic risk factors in 2003 revealed normal values in all the participants. We investigated the relationship between the cumulative duration of the presence of periodontal pockets, which is a major symptom of periodontitis, and the presence of cardiometabolic risk factors after 9 years using multiple logistic regression analysis. The odds ratio (OR) for the presence of ≥1 cardiometabolic risk factor in participants with a cumulative duration of periodontal pockets for ≥6 years was significantly higher than that in participants without pockets. The ORs for the onset of obesity, hypertension, dyslipidemia, and hyperglycemia were higher in participants with a cumulative duration of periodontal pockets for ≥6 years than those in participants without pockets or in participants with a cumulative duration of periodontal pockets for ≤5 years, and all the differences, except dyslipidemia, were significant. Chronic periodontitis was significantly associated with having cardiometabolic risk factors during the 9-year observation period, suggesting that the risk of cardiometabolic disease might increase in people who have untreated periodontitis.

  16. Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram

    PubMed Central

    Neigh, Gretchen N.; Nemeth, Christina L; Kelly, Sean D.; Hardy, Emily E.; Bourke, Chase; Stowe, Zachary N.; Owens, Michael J.

    2016-01-01

    Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function. PMID:27422674

  17. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

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

    Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp; Oda, Hideaki

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116more » and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.« less

  18. Children and adolescents' internal models of food-sharing behavior include complex evaluations of contextual factors.

    PubMed

    Markovits, Henry; Benenson, Joyce F; Kramer, Donald L

    2003-01-01

    This study examined internal representations of food sharing in 589 children and adolescents (8-19 years of age). Questionnaires, depicting a variety of contexts in which one person was asked to share a resource with another, were used to examine participants' expectations of food-sharing behavior. Factors that were varied included the value of the resource, the relation between the two depicted actors, the quality of this relation, and gender. Results indicate that internal models of food-sharing behavior showed systematic patterns of variation, demonstrating that individuals have complex contextually based internal models at all ages, including the youngest. Examination of developmental changes in use of individual patterns is consistent with the idea that internal models reflect age-specific patterns of interactions while undergoing a process of progressive consolidation.

  19. Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

    PubMed

    Singh, Savita; Soni, Ritu; Singh, K P; Tandon, O P

    2012-01-01

    Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (P<0.001) in Transfer factor of the lung for carbon monoxide (TLCO), forced vital capacity (FVC), forced expiratory volume in 1st sec (FEV1), peak expiratory flow rate (PEFR), maximum voluntary ventilation (MVV) and slow vital capacity (SVC) after yoga practice. Quality of life also increased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

  20. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone

    PubMed Central

    Culbertson, Christopher D.; Kyker-Snowman, Kelly; Bushinsky, David A.

    2012-01-01

    Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

  1. Utilizing a Human Factors Nursing Worksystem Improvement Framework to Increase Nurses' Time at the Bedside and Enhance Safety.

    PubMed

    Probst, C Adam; Carter, Megan; Cadigan, Caton; Dalcour, Cortney; Cassity, Cindy; Quinn, Penny; Williams, Tiana; Montgomery, Donna Cook; Wilder, Claudia; Xiao, Yan

    2017-02-01

    The aim of this study is to increase nurses' time for direct patient care and improve safety via a novel human factors framework for nursing worksystem improvement. Time available for direct patient care influences outcomes, yet worksystem barriers prevent nurses adequate time at the bedside. A novel human factors framework was developed for worksystem improvement in 3 units at 2 facilities. Objectives included improving nurse efficiency as measured by time-and-motion studies, reducing missing medications and subsequent trips to medication rooms and improving medication safety. Worksystem improvement resulted in time savings of 16% to 32% per nurse per 12-hour shift. Requests for missing medications dropped from 3.2 to 1.3 per day. Nurse medication room trips were reduced by 30% and nurse-reported medication errors fell from a range of 1.2 to 0.8 and 6.3 to 4.0 per month. An innovative human factors framework for nursing worksystem improvement provided practical and high priority targets for interventions that significantly improved the nursing worksystem.

  2. Factors associated with increased academic productivity among US academic radiation oncology faculty.

    PubMed

    Zhang, Catherine; Murata, Stephen; Murata, Mark; Fuller, Clifton David; Thomas, Charles R; Choi, Mehee; Holliday, Emma B

    Publication productivity metrics can help evaluate academic faculty for hiring, promotion, grants, and awards; however, limited benchmarking data exist, which makes intra- and interdepartmental comparisons difficult. Therefore, we sought to evaluate the scholarly activity of physician faculty at academic radiation oncology (RO) departments and establish factors associated with increased academic productivity. Citation database searches were performed for all physician-faculty in US residency-affiliated academic RO departments. Demographics, National Institutes of Health (NIH) funding, and bibliometrics (number of publications, Hirsch-[h]-index, and m-index [Hirsch index divided by the number of years since first publication]) were collected and stratified by academic rank. Senior academic rank was defined as full professor, professor, and/or chair. Junior academic rank was defined as all others. Logistic regression was performed to determine the association of academic rank and other factors with h- and m-indices. A total of 1191 academic RO physician faculty from 75 institutions were included in the analysis. The mean (standard deviation) number of publications and h- and m-indices were 48.2 (71.2), 14.5 (15), and 0.86 (0.83), respectively. The median (interquartile range) number of publications and h- and m-indices were 20 (6-61), 9 (4-20), and 0.69 (0.38-1.10), respectively. Recursive partitioning analysis revealed a statistically significant numeric h-index threshold of 21 between junior and senior faculty (LogWorth 114; receiver operating characteristic, 0.828). Senior faculty status, receipt of NIH funding, and a larger department size were associated with increased h- and m-indices. Current academic RO departments have relatively high objective metrics of scholastic productivity compared with prior benchmarking analyses of RO departments and compared with published metrics from other academic medicine subspecialties. An h-index of 21 or greater was

  3. M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

    PubMed Central

    2013-01-01

    Background Microglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation. Methods Using biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function. Results We found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide. Conclusions We show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit. PMID:23866312

  4. The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors

    PubMed Central

    Auger, Jean-Philippe; Chuzeville, Sarah; Roy, David; Mathieu-Denoncourt, Annabelle; Xu, Jianguo; Grenier, Daniel

    2017-01-01

    Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent mainly responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are genotypically and phenotypically heterogeneous. Though a multitude of virulence factors have been described for S. suis serotype 2, the lack of a clear definition regarding which ones are truly “critical” has created inconsistencies that have only recently been highlighted. Herein, the involvement of two factors previously described as being critical for S. suis serotype 2 virulence, whether the dipeptidyl peptidase IV and autolysin, were evaluated with regards to different ascribed functions using prototype strains belonging to important sequence types. Results demonstrate a lack of reproducibility with previously published data. In fact, the role of the dipeptidyl peptidase IV and autolysin as critical virulence factors could not be confirmed. Though certain in vitro functions may be ascribed to these factors, their roles are not unique for S. suis, probably due to compensation by other factors. As such, variations and discrepancies in experimental design, including in vitro assays, cell lines, and animal models, are an important source of differences between results. Moreover, the use of different sequence types in this study demonstrates that the role attributed to a virulence factor may vary according to the S. suis serotype 2 strain background. Consequently, it is necessary to establish standard experimental designs according to the experiment and purpose in order to facilitate comparison between laboratories. Alongside, studies should include strains of diverse origins in order to prevent erroneous and biased conclusions that could affect future studies. PMID:28753679

  5. Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.

    PubMed

    Bengualid, Victoria; Talari, Goutham; Rubin, David; Albaeni, Aiham; Ciubotaru, Ronald L; Berger, Judith

    2015-03-01

    The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients. ©2015 American Association of Critical-Care Nurses.

  6. Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

    PubMed

    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

  7. Increased nuclear factor-κB and loss of p53 are key mechanisms in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).

    PubMed

    Morris, Gerwyn; Maes, Michael

    2012-11-01

    Fukuda's criteria are adequate to make a distinction between Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and chronic fatigue (CF), but ME/CFS patients should be subdivided into those with (termed ME) and without (termed CFS) post exertional malaise [Maes et al. 2012]. ME/CFS is considered to be a neuro-immune disease. ME/CFS is characterized by activated immuno-inflammatory pathways, including increased levels of pro-inflammatory cytokines, nuclear factor κB (NF-κB) and aberrations in mitochondrial functions, including lowered ATP. These processes may explain typical symptoms of ME/CFS, e.g. fatigue, malaise, hyperalgesia, and neurologic and autonomic symptoms. Here we hypothesize that increased NF-κB together with a loss of p53 are key phenomena in ME/CFS that further explain ME/CFS symptoms, such as fatigue and neurocognitive dysfunction, and explain ME symptoms, such as post-exertional malaise following mental and physical activities. Inactivation of p53 impairs aerobic mitochondrial functions and causes greater dependence on anaerobic glycolysis, elevates lactate levels, reduces mitochondrial density in skeletal muscle and reduces endurance during physical exercise. Lowered p53 and increased NF-κB are associated with elevated reactive oxygen species. Increased NF-κB induces the production of pro-inflammatory cytokines, which increase glycolysis and further compromise mitochondrial functions. All these factors together may contribute to mitochondrial exhaustion and indicate that the demand for extra ATP upon the commencement of increased activity cannot be met. In conditions of chronic inflammation and oxidative stress, high NF-κB and low p53 may conspire to promote neuron and glial cell survival at a price of severely compromised metabolic brain function. Future research should examine p53 signaling in ME/CFS. Copyright © 2012. Published by Elsevier Ltd.

  8. Structural Factors That Increase HIV/STI Vulnerability Among Indigenous People in the Peruvian Amazon

    PubMed Central

    Orellana, E. Roberto; Alva, Isaac E.; Cárcamo, Cesar P.; García, Patricia J.

    2015-01-01

    We examined structural factors—social, political, economic, and environmental—that increase vulnerability to HIV among indigenous people in the Peruvian Amazon. Indigenous adults belonging to 12 different ethnic groups were purposively recruited in four Amazonian river ports and 16 indigenous villages. Qualitative data revealed a complex set of structural factors that give rise to environments of risk where health is constantly challenged. Ferryboats that cross Amazonian rivers are settings where unprotected sex—including transactional sex between passengers and boat crew and commercial sex work—often take place. Population mobility and mixing also occurs in settings like the river docks, mining sites, and other resource extraction camps, where heavy drinking and unprotected sex work are common. Multilevel, combination prevention strategies that integrate empirically based interventions with indigenous knowledge are urgently needed, not only to reduce vulnerability to HIV transmission, but also to eliminate the structural determinants of indigenous people’s health. PMID:23925407

  9. The increased concentration of macrophage migration inhibitory factor in serum and cerebrospinal fluid of patients with tick-borne encephalitis.

    PubMed

    Grygorczuk, Sambor; Parczewski, Miłosz; Świerzbińska, Renata; Czupryna, Piotr; Moniuszko, Anna; Dunaj, Justyna; Kondrusik, Maciej; Pancewicz, Sławomir

    2017-06-24

    Host factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1β). Concentrations of MIF, TNFα, and IL-1β were measured with commercial ELISA in serum and cerebrospinal fluid (CSF) from 36 hospitalized TBE patients, 7 patients with non-TBE meningitis, and 6 controls. The CSF albumin quotient (AQ) was used as a marker of blood-brain barrier permeability. Single nucleotide polymorphisms rs3775291, rs5743305 (associated with TLR3 expression), and rs755622 (associated with MIF expression) were assessed in blood samples from 108 TBE patients and 72 non-TBE controls. The data were analyzed with non-parametric tests, and p < 0.05 was considered significant. The median serum and CSF concentrations of MIF and IL-1β were significantly increased in TBE group compared to controls. MIF concentration in serum tended to correlate with AQ in TBE, but not in non-TBE meningitis. The serum concentration of TNFα was increased in TBE patients bearing a high-expression TLR3 rs5743305 TT genotype, which also associated with the increased risk of TBE. The low-expression rs3775291 TLR3 genotype TT associated with a prolonged increase of CSF protein concentration. The high-expression MIF rs755622 genotype CC tended to correlate with an increased risk of TBE, and within TBE group, it was associated with a mild presentation. The results point to the signaling route involving TLR3, MIF, and TNFα being active in TBE virus infection and contributing to the risk of an overt neuroinvasive disease. The same factors may play a protective role intrathecally contributing to the

  10. Factors predictive of increased influenza and pneumococcal vaccination coverage in long-term care facilities: the CMS-CDC standing orders program Project.

    PubMed

    Bardenheier, Barbara H; Shefer, Abigail; McKibben, Linda; Roberts, Henry; Rhew, David; Bratzler, Dale

    2005-01-01

    Between 1999 and 2002, a multistate demonstration project was conducted in long-term care facilities (LTCFs) to encourage implementation of standing orders programs (SOP) as evidence-based vaccine delivery strategies to increase influenza and pneumococcal vaccination coverage in LTCFs. Examine predictors of increase in influenza and pneumococcal vaccination coverage in LTCFs. Intervention study. Self-administered surveys of LTCFs merged with data from OSCAR (On-line Survey Certification and Reporting System) and immunization coverage was abstracted from residents' medical charts in LTCFs. Twenty LTCFs were sampled from 9 intervention and 5 control states in the 2000 to 2001 influenza season for baseline and during the 2001 to 2002 influenza season for postintervention. Each state's quality improvement organization (QIO) promoted the use of standing orders for immunizations as well as other strategies to increase immunization coverage among LTCF residents. Multivariate analysis included Poisson regression to determine independent predictors of at least a 10 percentage-point increase in facility influenza and pneumococcal vaccination coverage. Forty-two (20%) and 59 (28%) of the facilities had at least a 10 percentage-point increase in influenza and pneumococcal immunizations, respectively. In the multivariate analysis, predictors associated with increase in influenza vaccination coverage included adoption of requirement in written immunization protocol to document refusals, less-demanding consent requirements, lower baseline influenza coverage, and small facility size. Factors associated with increase in pneumococcal vaccination coverage included adoption of recording pneumococcal immunizations in a consistent place, affiliation with a multifacility chain, and provision of resource materials. To improve the health of LTCF residents, strategies should be considered that increase immunization coverage, including written protocol for immunizations and documentation of

  11. Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection.

    PubMed

    Axelsson, Lars; Nyman, Jan; Haugen-Cange, Hedda; Bove, Mogens; Johansson, Leif; De Lara, Shahin; Kovács, Anikó; Hammerlid, Eva

    2017-06-10

    Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Sixty-eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16-negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5-year survival rates, respectively. The overall and disease-free 5-year survival rates for all patients in the study were 82 and 74%. Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or

  12. Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

    PubMed Central

    Merrill, Liana; Malley, Susan

    2013-01-01

    Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

  13. Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

    PubMed

    Jalkanen, Juho; Hautero, Olli; Maksimow, Mikael; Jalkanen, Sirpa; Hakovirta, Harri

    2018-04-21

    The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end

  14. Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

    PubMed

    Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S

    2003-01-01

    Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

  15. Risk Factors for Increased ED Utilization in a Multinational Cohort of Children with Sickle Cell Disease

    PubMed Central

    Glassberg, Jeffrey A.; Wang, Jason; Cohen, Robyn; Richardson, Lynne D.; DeBaun, Michael R.

    2012-01-01

    Objectives To identify clinical, social, and environmental risk factors for increased emergency department (ED) use in children with sickle cell disease (SCD). Methods This study was a secondary analysis of ED utilization data from the international multicenter Silent Cerebral Infarct Transfusion (SIT) trial. Between December 2004 and June 2010, baseline demographic, clinical, and laboratory data were collected from children with SCD participating in the trial. The primary outcome was the frequency of ED visits for pain. A secondary outcome was the frequency of ED visits for acute chest syndrome. Results The sample included 985 children from the US, Canada, England, and France, for a total of 2,955 patient-years of data. There were 0.74 ED visits for pain per patient-year. A past medical history of asthma was associated with an increased risk of ED utilization for both pain (RR = 1.28, 95% CI = 1.04 to 1.58) and acute chest syndrome (RR = 1.60, 95% CI = 1.03 to 2.49). Exposure to environmental tobacco smoke in the home was associated with 73% more ED visits for acute chest syndrome (RR 1.73, 95% CI = 1.09 to 2.74). Each $10,000 increase in household income was associated with 5% fewer ED visits for pain (RR 0.95, 95% CI = 0.91 to 1.00, p = 0.05). The association between low income and ED utilization was not significantly different in the USA vs. countries with universal health care (p = 0.51). Conclusions Asthma and exposure to environmental tobacco smoke are potentially modifiable risk factors for greater ED use in children with SCD. Low income is associated with greater ED use for SCD pain in countries with and without universal health care. PMID:22687181

  16. Parenting Moderates a Genetic Vulnerability Factor in Longitudinal Increases in Youths' Substance Use

    ERIC Educational Resources Information Center

    Brody, Gene H.; Beach, Steven R. H.; Philibert, Robert A.; Chen, Yi-fu; Lei, Man-Kit; Murry, Velma McBride; Brown, Anita C.

    2009-01-01

    The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of "5HTT" (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive…

  17. Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization.

    PubMed

    Vialard, F; El Sirkasi, M; Tronchon, V; Boudjenah, R; Molina-Gomes, D; Bergere, M; Mauduit, C; Wainer, R; Selva, J; Benahmed, M

    2013-10-01

    Do TNF-308 and -238 polymorphisms impact the embryo implantation rate after in vitro fertilization (IVF) in women without female infertility factor? The presence of the TNF-308A allele is associated with high implantation and multiple pregnancy rates in women without known infertility factors after ovarian hyperstimulation with exogenous FSH. Multiple pregnancies are frequent after the use of Assisted Reproductive Technologies. Single embryo transfer (SET) has been proposed as a simple way to prevent these risks. However, the extension of SET indications to patients not selected based on specific criteria is controversial because of reduced pregnancy rates. To date, the predictive value of the parameters used for SET (age, gynecological history of the patient and uterine characteristics) allows a pregnancy rate of ~30%. The potential predictive value of TNF polymorphisms (-308, rs1800629 and -238, rs361525) on implantation rate was evaluated in 424 women requiring IVF due to male fertility factors. This cohort retrospective study was conducted over 4 years in University-affiliated hospitals. The entire patient group included 424 women undergoing intracytoplasmic sperm injection (ICSI) due to male fertility factors without the contribution of any female factor. From among this group, a selected patient group included 120 women with a normal karyotype, age under 38 years, serum follicle-stimulating hormone (Day-3 FSH) levels below 10 IU/l, a long agonist desensitization protocol associated with recombinant FSH treatment and a Caucasian background. The TNF-238 polymorphism was not associated with implantation rate. In contrast, the presence of the TNF-308A allele was associated with increased Day 3-E2 levels as well as higher implantation and multiple pregnancy rates after fresh embryo transfer in women from the entire and selected patient groups. Moreover, in the selected patient group, the presence of the TNF-308A allele was also associated with a decrease in the

  18. Impact Factors Show Increased Use of AGU Journals in 2008

    NASA Astrophysics Data System (ADS)

    Ford, Barbara Meyers

    2009-07-01

    The latest numbers released from Journal Citation Reports (JCR), published annually by Thomson Reuters, show large increases in the impact factor (IF) for several AGU journals. IFs are one way for publishers to know that readers have found their journals useful and of value in research. A journal's IF is calculated by taking the total number of citations to articles published by a given journal in the past 2 years and dividing it by the total number of papers published by the journal in the same time period. More generally, it can be seen as the frequency with which articles in a journal have been cited over the past year. The numbers speak for themselves (see Table 1).

  19. Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder.

    PubMed

    Kerling, A; Kück, M; Tegtbur, U; Grams, L; Weber-Spickschen, S; Hanke, A; Stubbs, B; Kahl, K G

    2017-06-01

    Brain derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depressive disorder (MDD). Existing data on exercise treatment in people with MDD are inconsistent concerning the effect of exercise on BDNF pointing either to increased or unaltered BDNF concentrations. However, studies in non-depressed persons demonstrated a significant effect on resting peripheral BDNF concentrations in aerobic training interventions. Given the lack of clarity mentioned above, the current study aimed at examining the effect of adjunctive exercise on serum BDNF levels in guideline based treated patients with MDD. 42 depressed inpatients were included, and randomized either to a 6 week structured and supervised exercise intervention plus treatment as usual (EXERCISE, n=22), or to treatment as usual (TAU, n=20). BDNF serum concentrations were assessed before and after the intervention in both study groups with established immunoassays. Serum BDNF slightly decreased in the TAU group, whilst there was an increase in BDNF levels in the exercise group. There was a significant time x group effect concerning sBDNF (p=0.030) with repeated ANOVA measures with age and BMI as covariates, suggesting an increase in BDNF concentrations in the EXERCISE group compared to TAU. Though there was no statistic difference in the antidepressant medication between EXERCISE and TAU potential interactions between exercise and medication on the effects of exercise in BDNF cannot be excluded. Gender was not considered as a covariate in ANOVA due to the small number of objects. Exercise training given as adjunct to standard guideline based treatment appears to have additional effects on BDNF serum concentrations in people with MDD. Our results add further evidence to the beneficial effects of exercise in the treatment of MDD. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  20. Accurate expressions for solar cell fill factors including series and shunt resistances

    NASA Astrophysics Data System (ADS)

    Green, Martin A.

    2016-02-01

    Together with open-circuit voltage and short-circuit current, fill factor is a key solar cell parameter. In their classic paper on limiting efficiency, Shockley and Queisser first investigated this factor's analytical properties showing, for ideal cells, it could be expressed implicitly in terms of the maximum power point voltage. Subsequently, fill factors usually have been calculated iteratively from such implicit expressions or from analytical approximations. In the absence of detrimental series and shunt resistances, analytical fill factor expressions have recently been published in terms of the Lambert W function available in most mathematical computing software. Using a recently identified perturbative relationship, exact expressions in terms of this function are derived in technically interesting cases when both series and shunt resistances are present but have limited impact, allowing a better understanding of their effect individually and in combination. Approximate expressions for arbitrary shunt and series resistances are then deduced, which are significantly more accurate than any previously published. A method based on the insights developed is also reported for deducing one-diode fits to experimental data.

  1. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

    PubMed

    Gianfrancesco, Milena A; Acuna, Brigid; Shen, Ling; Briggs, Farren B S; Quach, Hong; Bellesis, Kalliope H; Bernstein, Allan; Hedstrom, Anna K; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F

    2014-01-01

    To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  2. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors

    PubMed Central

    Gianfrancesco, Milena A.; Acuna, Brigid; Shen, Ling; Briggs, Farren B.S.; Quach, Hong; Bellesis, Kalliope H.; Bernstein, Allan; Hedstrom, Anna K.; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F.

    2014-01-01

    Objective To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Methods Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1,235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. Results In analyses stratified by gender, being overweight at age 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20’s demonstrated a linear relationship with MS (p-trend=9.60 × 10−4), and a twofold risk of MS for females with a BMI ≥ 30 kg/m2 was observed (OR = 2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20’s and MS in males were not observed. Multivariate modeling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Interpretation Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20’s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. PMID:25263833

  3. Recombinant factor concentrates may increase inhibitor development: a single centre cohort study.

    PubMed

    Strauss, T; Lubetsky, A; Ravid, B; Bashari, D; Luboshitz, J; Lalezari, S; Misgav, M; Martinowitz, U; Kenet, G

    2011-07-01

    Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety-two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min-max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or 'continuous infusion' and the family history of inhibitor development were investigated. During the follow-up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36-8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies. © 2011 Blackwell Publishing Ltd.

  4. Hydrogen Peroxide-Reducing Factor Released by PC12D Cells Increases Cell Tolerance against Oxidative Stress.

    PubMed

    Muraishi, Asami; Haneta, Emi; Saito, Yoshiro; Hitomi, Yutaka; Sano, Mamoru; Noguchi, Noriko

    2018-01-01

    PC12D cells, a subline of rat adrenal pheochromocytoma PC12 cells, extend neurites rapidly in response to differentiation stimuli and are used to investigate the molecular mechanisms of neurite extension. In the present study, we found significant tolerance of PC12D cells against Parkinson's disease-related stimuli such as dopamine and 6-hydroxydopamine; this tolerance was significantly decreased by a change in the medium. Conditioned medium from PC12D cells induced tolerance against oxidative stress, which suggests that cytoprotective factor may be released by PC12D cells into the culture medium. Conditioned medium-induced tolerance was not found for PC12 cells or human neuroblastoma SH-SY5Y cells. A cytoprotective factor generated by PC12D cells exhibited hydrogen peroxide-reducing activity. Chemical characterization showed that this cytoprotective factor is water soluble and has a molecular weight about 1000 Da, and that its activity is inhibited by sodium cyanide. Release of this cytoprotective factor was increased by differentiation stimuli and oxidative stress. Taken together, these results suggest that release of a hydrogen peroxide-reducing factor by PC12D cells increases cell tolerance against oxidative stress. This study provides new insights into the antioxidative properties of factors in extracellular fluid.

  5. Micro-level social and structural factors act synergistically to increase HIV risk among Nepalese female sex workers.

    PubMed

    Deuba, Keshab; Anderson, Sarah; Ekström, Anna Mia; Pandey, Satish Raj; Shrestha, Rachana; Karki, Deepak Kumar; Marrone, Gaetano

    2016-08-01

    Sex workers face stigma, discrimination, and violence across the globe and are almost 14 times more likely to be HIV-infected than other women in low- and middle-income countries. In Asia, condom campaigns at brothels have been effective in some settings, but for preventive interventions to be sustainable, it is important to understand micro-level social and structural factors that influence sexual behaviours of sex workers. This study assessed the syndemic effects of micro-level social and structural factors of unprotected sex and the prevalence of HIV among female sex workers (FSWs) in Nepal. This quantitative study included 610 FSWs who were recruited using two-stage cluster sampling from September to November 2012 in 22 Terai Highway districts of Nepal. Rapid HIV tests and face-to-face interviews were conducted to collect biological and behavioural information. A count of physical (sexual violence and other undesirable events), social (poor social support and condom negotiation skills), and economic (unprotected sex to make more money) factors that operate at the micro-level was calculated to test the additive relationship to unprotected sex. The HIV prevalence was 1%; this is presumably representative, with a large sample of FSWs in Nepal. The prevalence of unprotected sex with clients was high (24%). For each additional adverse physical, social, and economic condition, the probability of non-use of condoms with clients increased substantially: one problem = 12% (p<0.005), two problems = 19% (p<0.001), and three to five problems = 38% (p<0.001). Interactions between two or more adverse conditions linked to physical, social, and economic environments increased the risk of unprotected sex among Nepalese FSWs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Vaccine to fibroblast growth factor 23 peptides increases eggshell strength.

    PubMed

    Ren, Z Z; Piepenburg, A J; Bütz, D E; Claus, J R; Cook, M E

    2018-03-01

    Strategies that would increase eggshell quality could be of considerable value to egg producers. This research demonstrated the effective use of fibroblast growth factor 23 (FGF-23) peptide vaccines to increase eggshell quality of Single Comb White Leghorn laying hens (from 69 to 72 wk of age). Hens, fed a standard diet (containing 900 IU/kg vitamin D3), were intramuscularly injected (and boosted) with either a control vaccine (n = 14 hens) or one of 2 FGF-23 peptide vaccines (peptides NP1, GMNPPPYS; and NP7, YTSTERNSFH; n = 15 hens for each peptide). During peak antibody titer, eggs were collected for shell and internal quality analysis, hens were artificially inseminated, and the hatchability of fertilized eggs was determined. Laying hens vaccinated with either FGF-23 peptide NP1 or NP7 had increased (P < 0.05) plasma phosphate level (mmol/L; NP1 = 1.74, NP7 = 1.76, control = 1.47), egg specific gravity (NP1 = 1.083, NP7 = 1.083, control = 1.079), and eggshell strength (g of force; NP1 = 4002, NP7 = 4157, control = 3102) when compared to control vaccinated hens. FGF-23 peptide NP1 vaccinated hens also had increased eggshell thickness (mm, P < 0.001), shell weight (g, P = 0.032), and shell index (% of whole egg, P = 0.023) when compared to control vaccinated hens. FGF-23 peptide NP7 vaccinated hens tended to have decreased eggshell weight (P = 0.064) when compared to control vaccinated hens. Hatchability of fertilized eggs was not affected in incubations 1 and 3, but tended to be decreased (P = 0.097) by FGF-23 peptide NP1 vaccination in incubation 2. In conclusion, vaccines to FGF-23 peptides increased eggshell quality of laying hens with minimal adverse effects on egg internal quality. The effect of FGF-23 peptide vaccination on hatchability remains to be clarified.

  7. Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.

    PubMed

    Wykoff, Charles C

    2017-05-01

    Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.

  8. Anti-nerve growth factor therapy increases spontaneous day/night activity in mice with orthopedic surgery-induced pain.

    PubMed

    Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Ossipov, Michael H; Mantyh, Patrick W

    2017-04-01

    Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are 2 of the most common and successful surgical interventions to relieve osteoarthritis pain. Control of postoperative pain is critical for patients to fully participate in the required physical therapy which is the most influential factor in effective postoperative knee rehabilitation. Currently, opiates are a mainstay for managing postoperative orthopedic surgery pain including TKA or THA pain. Recently, issues including efficacy, dependence, overdose, and death from opiates have made clinicians and researchers more critical of use of opioids for treating nonmalignant skeletal pain. In the present report, a nonopiate therapy using a monoclonal antibody raised against nerve growth factor (anti-NGF) was assessed for its ability to increase the spontaneous activity of the operated knee joint in a mouse model of orthopedic surgery pain-induced by drilling and coring the trochlear groove of the mouse femur. Horizontal activity and velocity and vertical rearing were continually assessed over a 20 hours day/night period using automated activity boxes in an effort to reduce observer bias and capture night activity when the mice are most active. At days 1 and 3, after orthopedic surgery, there was a marked reduction in spontaneous activity and vertical rearing; anti-NGF significantly attenuated this decline. The present data suggest that anti-NGF improves limb use in a rodent model of joint/orthopedic surgery and as such anti-NGF may be useful in controlling pain after orthopedic surgeries such as TKA or THA.

  9. NZ-GMP Approved Serum Improve hDPSC Osteogenic Commitment and Increase Angiogenic Factor Expression.

    PubMed

    Spina, Anna; Montella, Roberta; Liccardo, Davide; De Rosa, Alfredo; Laino, Luigi; Mitsiadis, Thimios A; La Noce, Marcella

    2016-01-01

    Human dental pulp stem cells (hDPSCs), selected from the stromal-vascular fraction of dental pulp, are ecto-mesenchymal stem cells deriving from neural crests, successfully used in human bone tissue engineering. For their use in human therapy GMP procedures are required. For instance, the use of fetal bovine serum (FBS) is strongly discouraged in clinical practice due to its high risk of prions and other infections for human health. Alternatively, clinical grade sera have been suggested, including the New Zealand FBS (NZ-FBS). Therefore, the aim of this study was to evaluate the behavior of hDPSCs expanded in culture medium containing NZ-FBS. Since it was widely demonstrated hDPSCs display relevant capabilities to differentiate into osteogenic and angiogenic lineages, we performed a comparative study to assess if these features are also retained by cultivating the cells with a safer serum never tested on this cell line. hDPSCs were grown using NZ-FBS and conventional (C-FBS) for 7, 14, and 21 days, in both 2D and 3D cultures. Growth curves, expression of bone-related markers, calcification and angiogenesis were evaluated. NZ-FBS induced significant cell growth with respect to C-FBS and promoted an earlier increase expression of osteogenic markers, in particular of those involved in the formation of mineralized matrix (BSP and OPN) within 14 days. In addition, hDPSCs cultured in presence of NZ-FBS were found to produce higher mRNA levels of the angiogenic factors, such as VEGF and PDGFA. Taken together, our results highlight that hDPSCs proliferate, enhance their osteogenic commitment and increase angiogenic factors in NZ-FBS containing medium. These features have also been found when hDPSC were seeded on the clinical-grade collagen I scaffold (Bio-Gide®), leading to the conclusion that for human therapy some procedures and above all the use of GMP-approved materials have no negative impact.

  10. Increasing Risk Factors for Imported and Domestic Gnathostomiasis in the United States.

    PubMed

    Diaz, James H

    2015-01-01

    Gnathostomiasis is a foodborne zoonotic helminthic infection, commonly described in Asia and Latin America, which may follow the consumption of raw fish, eels, amphibians, and reptiles infected with muscle-encysted larvae of Gnathostoma species nematodes. After an inoculum of as little as one infective larva and an incubation period of months to years, most infections are characterized by intermittent migratory swellings due to subdermal larval migration. Less commonly, larval migration to the central nervous system may result in radiculomyelopathy or eosinophilic meningoencephalitis with high fatality rates; or larval migration to the eye with resulting blindness in untreated cases. Since the US now supports a zoonosis of Gnathostoma species with infective larvae encysted in imported and domestic fish and eels that may be consumed raw as exotic ethnic dishes, the objectives of this review were to describe the biology and life cycle of Gnathostoma nematodes and the behavioral risk factors for gnathostomiasis; and to describe the clinical manifestations, diagnosis, management, and prevention of human gnathostomiasis. Since the eradication of gnathostomiasis is very unlikely given the global distribution of Gnathostoma nematodes and the increasingly exotic culinary tastes of US residents and travelers to endemic regions, the only effective strategies for gnathostomiasis include: (1) educating citizens in the US and travelers abroad in endemic areas that fish, eels, frogs, snakes, and chicken must be cooked thoroughly first and not eaten raw or marinated; and (2) seeking medical care immediately for evaluation of migratory subcutaneous swellings. The combination of international travel and increased immigration from Asia and Latin America to the US has resulted in greater popularity of exotic ethnic cuisine, especially raw seafood dishes. The ethnic cuisine industry is supported by domestic aquaculture that produces fish-farmed tilapia and trout, and by increased

  11. [Study on the relationship between childhood obesity and various determinants, including socioeconomic factors, in an urban area].

    PubMed

    Kang, Hee-Tae; Ju, Young-Su; Park, Kyung-Hee; Kwon, Young-Jun; Im, Hyoung-June; Paek, Do-Myung; Lee, Hyun-Joo

    2006-09-01

    This study was conducted to investigate the prevalence of childhood obesity, the association between the undesirable lifestyles and socioeconomic factors, the association between childhood obesity and various risk factors, including socioeconomic factors, and the agreement between the body mass index (BMI) classification and the body fat percentage. The study subjects were all the 5th grade students from all the elementary schools in Gunpo City, Kyunggi Province, South Korea (4043 children at 22 schools). The subjects were measured for their height, weight and percent body fat etc. and they were also surveyed by questionnaire from March 18th to April 25th, 2005. To determine whether the children were within normal limits or not, standardized BMIs for each age group were used. The data was analyzed by logistic regression analysis using SAS 9.0 version. The prevalence of childhood obesity prevalence was 25.1%. Boys had a higher prevalence of obesity (27.5%) than did the girls (22.5%). Children had tendencies of having undesirable lifestyles and getting obese if they had a lower socioeconomic status. The risk factors for childhood obesity were low paternal education (OR: 1.17, 95% CI: 0.97-1.42) and non-parental caregivers (OR: 1.34, 95% CI: 0.98-1.82). Other risk factors for childhood obesity were a high birth-weight, longer TV/computer-using time, a lower fruit-eating frequency, short sleeping hours and parental obesity. The agreement rate between the BMI classification and the body fat percentage was 93.1%. This study showed the children had a higher prevalence of obesity: further, not only individual lifestyles, but also socioeconomic factors could influence childhood obesity. Childhood obesity was especially more problematic for children with a low socioeconomic status.

  12. Anisotropic Failure Strength of Shale with Increasing Confinement: Behaviors, Factors and Mechanism

    PubMed Central

    Cheng, Cheng; Li, Xiao; Qian, Haitao

    2017-01-01

    Some studies reported that the anisotropic failure strength of shale will be weakened by increasing confinement. In this paper, it is found that there are various types of anisotropic strength behaviors. Four types of anisotropic strength ratio (SA1) behaviors and three types of anisotropic strength difference (SA2) behaviors have been classified based on laboratory experiments on nine groups of different shale samples. The cohesion cw and friction angle ϕw of the weak planes are proven to be two dominant factors according to a series of bonded-particle discrete element modelling analyses. It is observed that shale is more prone to a slight increase of SA1 and significant increase of SA2 with increasing confinement for higher cohesion cw and lower to medium friction angle ϕw. This study also investigated the mechanism of the anisotropic strength behaviors with increasing confinement. Owing to different contributions of cw and ϕw under different confinements, different combinations of cw and ϕw may have various types of influences on the minimum failure strength with the increasing confinement; therefore, different types of anisotropic behaviors occur for different shale specimens as the confinement increases. These findings are very important to understand the stability of wellbore and underground tunneling in the shale rock mass, and should be helpful for further studies on hydraulic fracture propagations in the shale reservoir. PMID:29140292

  13. Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

    PubMed

    Biddinger, Jessica E; Fox, Edward A

    2014-07-30

    Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

  14. Factors affecting acceptability of an email-based intervention to increase fruit and vegetable consumption.

    PubMed

    Kothe, Emily J; Mullan, Barbara A

    2014-09-30

    Fresh Facts is a 30-day email-delivered intervention designed to increase the fruit and vegetable consumption of Australian young adults. This study investigated the extent to which the program was acceptable to members of the target audience and examined the relationships between participant and intervention characteristics, attrition, effectiveness, and acceptability ratings. Young adults were randomised to two levels of message frequency: high-frequency (n = 102), low-frequency (n = 173). Individuals in the high-frequency group received daily emails while individuals in the low-frequency group received an email every 3 days. Individuals in the high-frequency group were more likely to indicate that they received too many emails than individuals in the low-frequency group. No other differences in acceptability were observed. Baseline beliefs about fruit and vegetables were an important predictor of intervention acceptability. In turn, acceptability was associated with a number of indicators of intervention success, including change in fruit and vegetable consumption. The findings highlight the importance of considering the relationship between these intervention and participant factors and acceptability in intervention design and evaluation. Results support the ongoing use of email-based interventions to target fruit and vegetable consumption within young adults. However, the relationships between beliefs about fruit and vegetable consumption and acceptability suggest that this intervention may be differentially effective depending on individual's existing beliefs about fruit and vegetable consumption. As such, there is a pressing need to consider these factors in future research in order to minimize attrition and maximize intervention effectiveness when interventions are implemented outside of a research context.

  15. Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

    PubMed Central

    Sonestedt, Emily; Øverby, Nina Cecilie; Laaksonen, David E.; Birgisdottir, Bryndis Eva

    2012-01-01

    Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers), and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies), four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies were available

  16. Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia

    PubMed Central

    Choy, Fong Chan; Klarić, Thomas S; Leong, Wai Khay; Koblar, Simon A

    2015-01-01

    Stroke is the second leading cause of death and the most frequent cause of adult disability. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an activity-dependent transcription factor whose expression is induced in various brain insults, including cerebral ischaemia. Although previous studies have demonstrated that Npas4 plays a critical role in protecting neurons against neurodegenerative insults, the neuroprotective effect of Npas4 in response to ischaemic brain injury remains unknown. In this study, we used a loss-of-function approach to examine the neuroprotective potential of Npas4 in the context of ischaemic damage. Using oxygen and glucose deprivation, we demonstrated that the knockdown of Npas4 in mouse cortical neurons resulted in increased susceptibility to cell death. The protective effect of Npas4 was further investigated in vivo using a photochemically-induced stroke model in mice. We found a significantly larger lesion size and increased neurodegeneration in Npas4 knockout mice as compared to wild-type mice. Moreover, we also showed that ablation of Npas4 caused an increase in activated astrocytes and microglia, pro-inflammatory cytokines interleukin-6 and tumour necrosis factor alpha levels and a switch from apoptotic to necrotic cell death. Taken together, these data suggest that Npas4 plays a neuroprotective role in ischaemic stroke by limiting progressive neurodegeneration and neuroinflammation. PMID:26661154

  17. Anisotropic Failure Strength of Shale with Increasing Confinement: Behaviors, Factors and Mechanism.

    PubMed

    Cheng, Cheng; Li, Xiao; Qian, Haitao

    2017-11-15

    Some studies reported that the anisotropic failure strength of shale will be weakened by increasing confinement. In this paper, it is found that there are various types of anisotropic strength behaviors. Four types of anisotropic strength ratio ( S A 1 ) behaviors and three types of anisotropic strength difference ( S A 2 ) behaviors have been classified based on laboratory experiments on nine groups of different shale samples. The cohesion c w and friction angle ϕ w of the weak planes are proven to be two dominant factors according to a series of bonded-particle discrete element modelling analyses. It is observed that shale is more prone to a slight increase of S A 1 and significant increase of S A 2 with increasing confinement for higher cohesion c w and lower to medium friction angle ϕ w . This study also investigated the mechanism of the anisotropic strength behaviors with increasing confinement. Owing to different contributions of c w and ϕ w under different confinements, different combinations of c w and ϕ w may have various types of influences on the minimum failure strength with the increasing confinement; therefore, different types of anisotropic behaviors occur for different shale specimens as the confinement increases. These findings are very important to understand the stability of wellbore and underground tunneling in the shale rock mass, and should be helpful for further studies on hydraulic fracture propagations in the shale reservoir.

  18. An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

    PubMed

    Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

    2015-04-01

    Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders.

    PubMed

    Wong, Christine T; Wais, Joshua; Crawford, Dorota A

    2015-11-01

    The prevalence of autism spectrum disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes, and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity and calcium regulation. The previous review already described extrinsic factors, including deficient dietary supplementation, and exposure to oxidative stress, infections and inflammation that can disrupt signaling of the PGE2 pathway and contribute to ASDs. In this review, the structure and establishment of two key protective barriers for the brain during early development are described: the blood-brain barrier; and the placental barrier. Then, the first comprehensive summary of other environmental factors, such as exposure to chemicals in air pollution, pesticides and consumer products, which can also disturb PGE2 signaling and increase the risk for developing ASDs is provided. Also, how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed is described. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Insulin-Like Growth Factor Binding Proteins Increase Intracellular Calcium Levels in Two Different Cell Lines

    PubMed Central

    Seurin, Danielle; Lombet, Alain; Babajko, Sylvie; Godeau, François; Ricort, Jean-Marc

    2013-01-01

    Background Insulin-like growth factor binding proteins (IGFBPs) are six related secreted proteins that share IGF-dependent and -independent functions. If the former functions begin to be well described, the latter are somewhat more difficult to investigate and to characterize. At the cellular level, IGFBPs were shown to modulate numerous processes including cell growth, differentiation and apoptosis. However, the molecular mechanisms implicated remain largely unknown. We previously demonstrated that IGFBP-3, but not IGFBP-1 or IGFBP-5, increase intracellular calcium concentration in MCF-7 cells (Ricort J-M et al. (2002) FEBS lett 527: 293–297). Methodology/Principal Findings We perform a global analysis in which we studied, by two different approaches, the binding of each IGFBP isoform (i.e., IGFBP-1 to -6) to the surface of two different cellular models, MCF-7 breast adenocarcinoma cells and C2 myoblast proliferative cells, as well as the IGFBP-induced increase of intracellular calcium concentration. Using both confocal fluorescence microscopy and flow cytometry analysis, we showed that all IGFBPs bind to MCF-7 cell surface. By contrast, only four IGFBPs can bind to C2 cell surface since neither IGFBP-2 nor IGFBP-4 were detected. Among the six IGFBPs tested, only IGFBP-1 did not increased intracellular calcium concentration whatever the cellular model studied. By contrast, IGFBP-2, -3, -4 and -6, in MCF-7 cells, and IGFBP-3, -5 and -6, in C2 proliferative cells, induce a rapid and transient increase in intracellular free calcium concentration. Moreover, IGFBP-2 and -3 (in MCF-7 cells) and IGFBP-5 (in C2 cells) increase intracellular free calcium concentration by a pertussis toxin sensitive signaling pathway. Conclusions Our results demonstrate that IGFBPs are able to bind to cell surface and increase intracellular calcium concentration. By characterizing the IGFBPs-induced cell responses and intracellular couplings, we highlight the cellular specificity and

  1. Treatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations

    PubMed Central

    Imel, Erik A.; DiMeglio, Linda A.; Hui, Siu L.; Carpenter, Thomas O.; Econs, Michael J.

    2010-01-01

    Context: X-Linked hypophosphatemia (XLH) is characterized by renal phosphate wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D concentrations causing rickets and osteomalacia. Mutations in PHEX result in increased fibroblast growth factor 23 (FGF23) expression, elevating circulating FGF23 concentrations. Treating XLH with phosphate and calcitriol may further increase FGF23 concentrations, based on in vitro and in vivo models. Objective: The aim of the study was to investigate whether current standard XLH therapies increase circulating FGF23 concentrations. Design and Setting: We conducted a prospective observational study of XLH subjects during routine clinical management at two tertiary referral centers. Patients: The study included 10 XLH patients (seven children, three adults; age, 2–30 yr) initiating therapy and five XLH patients (age, 18–41 yr) electing not to undergo therapy. Intervention(s): Oral calcitriol and phosphate were administered. Main Outcome Measures: We measured circulating intact FGF23 concentrations. Results: Baseline circulating FGF23 concentrations were elevated in 14 of 15 subjects, increasing after treatment in most subjects. Follow-up was 14.4 ± 11.7 months (treatment cohort) and 25 ± 32 months (nontreatment cohort). FGF23 concentrations increased 132.7 ± 202.4% from pretreatment to peak during therapy but did not change significantly over time in the nontreatment cohort. FGF23 concentrations were related to phosphate doses (P = 0.04) and nonsignificantly to calcitriol doses (P = 0.06). Conclusions: Treating XLH with phosphate and calcitriol was associated with concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. Because it is unknown whether the degree of FGF23 elevation correlates with disease severity in XLH, further study is needed to determine whether adjusting therapy to minimize effects on FGF23 concentration is

  2. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy

    PubMed Central

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A.; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-01-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy. PMID:24398069

  3. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.

    PubMed

    Eriksson, Mikael; Hardell, Lennart; Carlberg, Michael; Akerman, Måns

    2008-10-01

    We report a population based case-control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to different agents was assessed by questionnaire. In total 910 (91 %) cases and 1016 (92%) controls participated. Exposure to herbicides gave odds ratio (OR) 1.72, 95% confidence interval (CI) 1.18-2.51. Regarding phenoxyacetic acids highest risk was calculated for MCPA; OR 2.81, 95% CI 1.27-6.22, all these cases had a latency period >10 years. Exposure to glyphosate gave OR 2.02, 95% CI 1.10-3.71 and with >10 years latency period OR 2.26, 95% CI 1.16-4.40. Insecticides overall gave OR 1.28, 95% CI 0.96-1.72 and impregnating agents OR 1.57, 95% CI 1.07-2.30. Results are also presented for different entities of NHL. In conclusion our study confirmed an association between exposure to phenoxyacetic acids and NHL and the association with glyphosate was considerably strengthened.

  4. Euglycemic Hyperinsulinemia Increases Blood Pressure in Pregnant Rats Independent of Placental Antiangiogenic and Inflammatory Factors

    PubMed Central

    2013-01-01

    BACKGROUND Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor α (TNF- α) levels and hypertension in pregnant rats. METHODS On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to pl acental sFlt-1 and TNF-α levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured. RESULTS MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-α concentrations between groups. CONCLUSIONS In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia. PMID:23955606

  5. Environmental and anthropogenic factors affecting the increasing occurrence of shark-human interactions around a fast-developing Indian Ocean island.

    PubMed

    Lagabrielle, Erwann; Allibert, Agathe; Kiszka, Jeremy J; Loiseau, Nicolas; Kilfoil, James P; Lemahieu, Anne

    2018-02-27

    Understanding the environmental drivers of interactions between predators and humans is critical for public safety and management purposes. In the marine environment, this issue is exemplified by shark-human interactions. The annual shark bite incidence rate (SBIR) in La Réunion (Indian Ocean) is among the highest in the world (up to 1 event per 24,000 hours of surfing) and has experienced a 23-fold increase over the 2005-2016 period. Since 1988, 86% of shark bite events on ocean-users involved surfers off the leeward coast, where 96% of surfing activities took place. We modeled the SBIR as a function of environmental variables, including benthic substrate, sea temperature and period of day. The SBIR peaked in winter, during the afternoon and dramatically increased on coral substrate since the mid-2000s. Seasonal patterns of increasing SBIR followed similar fluctuations of large coastal shark occurrences (particularly the bull shark Carcharhinus leucas), consistent with the hypothesis that higher shark presence may result in an increasing likelihood of shark bite events. Potential contributing factors and adaptation of ocean-users to the increasing shark bite hazard are discussed. This interdisciplinary research contributes to a better understanding of shark-human interactions. The modeling method is relevant for wildlife hazard management in general.

  6. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

    PubMed

    Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

    2016-02-01

    Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. 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/

  7. Antioxidative diet supplementation reverses high-fat diet-induced increases of cardiovascular risk factors in mice.

    PubMed

    Vargas-Robles, Hilda; Rios, Amelia; Arellano-Mendoza, Monica; Escalante, Bruno A; Schnoor, Michael

    2015-01-01

    Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion) would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD). Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  8. The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus.

    PubMed

    Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

    2018-02-01

    [Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45-3.85). Mother and father's history of T2D (HR=1.73; 95% CI=1.46-2.05; HR=1.83; 95% CI=1.40-2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08-1.40) smoking status (HR=1.62, CI=1.32-1.99), and drinking (HR=1.32, CI=1.13-1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D.

  9. Applying human factors principles to alert design increases efficiency and reduces prescribing errors in a scenario-based simulation

    PubMed Central

    Russ, Alissa L; Zillich, Alan J; Melton, Brittany L; Russell, Scott A; Chen, Siying; Spina, Jeffrey R; Weiner, Michael; Johnson, Elizabette G; Daggy, Joanne K; McManus, M Sue; Hawsey, Jason M; Puleo, Anthony G; Doebbeling, Bradley N; Saleem, Jason J

    2014-01-01

    Objective To apply human factors engineering principles to improve alert interface design. We hypothesized that incorporating human factors principles into alerts would improve usability, reduce workload for prescribers, and reduce prescribing errors. Materials and methods We performed a scenario-based simulation study using a counterbalanced, crossover design with 20 Veterans Affairs prescribers to compare original versus redesigned alerts. We redesigned drug–allergy, drug–drug interaction, and drug–disease alerts based upon human factors principles. We assessed usability (learnability of redesign, efficiency, satisfaction, and usability errors), perceived workload, and prescribing errors. Results Although prescribers received no training on the design changes, prescribers were able to resolve redesigned alerts more efficiently (median (IQR): 56 (47) s) compared to the original alerts (85 (71) s; p=0.015). In addition, prescribers rated redesigned alerts significantly higher than original alerts across several dimensions of satisfaction. Redesigned alerts led to a modest but significant reduction in workload (p=0.042) and significantly reduced the number of prescribing errors per prescriber (median (range): 2 (1–5) compared to original alerts: 4 (1–7); p=0.024). Discussion Aspects of the redesigned alerts that likely contributed to better prescribing include design modifications that reduced usability-related errors, providing clinical data closer to the point of decision, and displaying alert text in a tabular format. Displaying alert text in a tabular format may help prescribers extract information quickly and thereby increase responsiveness to alerts. Conclusions This simulation study provides evidence that applying human factors design principles to medication alerts can improve usability and prescribing outcomes. PMID:24668841

  10. Cardiovascular Risk Factors Increase the Risks of Diabetic Peripheral Neuropathy in Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Yang, Chun-Pai; Lin, Cheng-Chieh; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chen, Hsuan-Ju; Li, Tsai-Chung

    2015-01-01

    Abstract This study aimed to examine whether poor glycemic control, measured by glycated hemoglobin A1C (HbA1c) and other cardiovascular risk factors, can predict diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (DM). Patients aged ≥30 years with type 2 DM, enrolled in the National Diabetes Care Management Program, and free of DPN (n = 37,375) in the period 2002 to 2004 were included and followed up until 2011. The related factors were analyzed using Cox proportional hazards regression models. For an average follow-up of 7.00 years, 8379 cases of DPN were identified, with a crude incidence rate of 32.04/1000 person-years. After multivariate adjustment, patients with HbA1c levels 7 to 8%, 8 to 9%, 9 to 10%, and ≥10% exhibited higher risk of DPN (adjusted HR: 1.11 [1.04–1.20], 1.30 [1.21–1.40], 1.32 [1.22–1.43], and 1.62 [1.51–1.74], respectively) compared with patients with HbA1c level 6 to 7%. There was a significant linear trend in DPN incidence with increasing HbA1c (P < 0.001) and significant HRs of DPN for patients with HbA1c level ≥7%, blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL, high density of lipoprotein-cholesterol (HDL-C) <40 mg/dL in males and <50 mg/dL in females, low density of lipoprotein-cholesterol (LDL-C) ≥100 mg/dL, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Patients with type 2 DM and HbA1c ≥7.0% exhibit increased risk of DPN, demonstrating a linear relationship. The incidence of DPN is also associated with poor glucose control and cardiovascular risk factors like hypertension, hyper-triglyceridemia, low HDL-C, high LDL-C, and decreased eGFR. PMID:26496307

  11. What Factors Control the Trend of Increasing AAOD Over the United States in the Last Decade?

    NASA Technical Reports Server (NTRS)

    Zhang, Li; Henze, Daven K.; Grell, Georg A.; Torres, Omar; Jethva, Hiren; Lamsal, Lok N.

    2017-01-01

    We examine the spatial and temporal trends of absorbing aerosol optical depth (AAOD) in the last decade over the United States (U.S.) observed by the Ozone Monitoring Instrument (OMI). Monthly average OMI AAOD has increased over broad areas of the central U.S. from 2005 to 2015, by up to a factor of 4 in some grid cells (60 km resolution). The AAOD increases in all seasons, although the percentage increases are larger in summer (June-July-August) than in winter (December-January-February) by a factor of 3. Despite enhancements in AAOD, OMI AOD exhibits insignificant trend over most of the U.S. except parts of the central and western U.S., the latter which may partly be due to decreases in precipitation. Trends in AAOD contrast with declining trends in surface concentrations of black carbon (BC) aerosol. Interannual variability of local biomass burning emissions of BC may contribute to the positive trend in AAOD over the western U.S. Changes in both dust aerosol measured at the surface (in terms of concentration and size) and dust AAOD indicate distinct enhancements, especially over the central U.S. by 50-100%, which appears to be one of the major factors that impacts positive trends in AAOD.

  12. Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.

    PubMed

    Hussein, K; Stucki-Koch, A; Göhring, G; Kreipe, H; Suttorp, M

    2017-07-01

    Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.

  13. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    PubMed

    Blower, Sally; Go, Myong-Hyun

    2011-07-19

    Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability.

  14. Terrestrial ecosystems, increased solar ultraviolet radiation, and interactions with other climate change factors.

    PubMed

    Caldwell, M M; Bornman, J F; Ballaré, C L; Flint, S D; Kulandaivelu, G

    2007-03-01

    , such as diminished growth, acclimation responses of plants to UV-B radiation and interactions of plants with consumer organisms such as insects and plant pathogens. The response to UV-B radiation involves both the initial stimulus by solar radiation and transmission of signals within the plants. Resulting changes in gene expression induced by these signals may have elements in common with those elicited by other environmental factors, and generate overlapping functional (including acclimation) responses. Concurrent responses of terrestrial systems to the combination of enhanced UV-B radiation and other global change factors (increased temperature, CO2, available nitrogen and altered precipitation) are less well understood. Studies of individual plant responses to combinations of factors indicate that plant growth can be augmented by higher CO2 levels, yet many of the effects of UV-B radiation are usually not ameliorated by the elevated CO2. UV-B radiation often increases both plant frost tolerance and survival under extreme high temperature conditions. Conversely, extreme temperatures sometimes influence the UV-B radiation sensitivity of plants directly. Plants that endure water deficit stress effectively are also likely to be tolerant of high UV-B flux. Biologically available nitrogen is exceeding historical levels in many regions due to human activities. Studies show that plants well supplied with nitrogen are generally more sensitive to UV-B radiation. Technical issues concerning the use of biological spectral weighting functions (BSWFs) have been further elucidated. The BSWFs, which are multiplication factors assigned to different wavelengths giving an indication of their relative biological effectiveness, are critical to the proper conduct and interpretation of experiments in which organisms are exposed to UV radiation, both in the field and in controlled environment facilities. The characteristics of BSWFs vary considerably among different plant processes, such

  15. Granulocyte macrophage-colony stimulating factor and interleukin-3 increase expression of type II tumour necrosis factor receptor, increasing susceptibility to tumour necrosis factor-induced apoptosis. Control of leukaemia cell life/death switching.

    PubMed

    Rae, C; MacEwan, D J

    2004-12-01

    Tumour necrosis factor (TNF) induces apoptosis in a range of cell types via its two receptors, TNFR1 and TNFR2. Here, we demonstrate that proliferation and TNFR2 expression was increased in human leukaemic TF-1 cells by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), with TNFR1 expression unaffected. Consequently, they switch from a proliferative to a TNF-induced apoptotic phenotype. Raised TNFR2 expression and susceptibility to TNF-induced apoptosis was not a general effect of proliferation as IL-1beta and IFN-gamma both proliferated TF-1 cells with no effect on TNFR expression or apoptosis. Although raised TNFR2 expression correlated with the apoptotic phenotype, stimulation of apoptosis in GM-CSF-pretreated cells was mediated by TNFR1, with stimulation of TNFR2 alone insufficient to initiate cell death. However, TNFR2 did play a role in apoptotic and proliferative responses as they were blocked by the presence of an antagonistic TNFR2 antibody. Additionally, coincubation with cycloheximide blocked the mitotic effects of GM-CSF or IL-3, allowing only the apoptotic responses of TNF to persist. TNF life/death was also observed in K562, but not MOLT-4 and HL-60 human leukaemic cell types. These findings show a cooperative role of TNFR2 in the TNF life/death switching phenomenon.

  16. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    PubMed

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Brain-derived neurotrophic factor modulates angiotensin signaling in the hypothalamus to increase blood pressure in rats

    PubMed Central

    Backes, Iara; McCowan, Michael L.; Hayward, Linda F.; Scheuer, Deborah A.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli including stress and hyperosmolarity. However, it is unclear whether BDNF in the PVN contributes to increases in blood pressure (BP). We tested the hypothesis that increased BDNF levels within the PVN would elevate baseline BP and heart rate (HR) and cardiovascular stress responses by altering central angiotensin signaling. BP was recorded using radiotelemetry in male Sprague-Dawley rats after bilateral PVN injections of adeno-associated viral vectors expressing green fluorescent protein (GFP) or myc epitope-tagged BDNF fusion protein. Cardiovascular responses to acute stress were evaluated 3 to 4 wk after injections. Additional GFP and BDNF-treated animals were equipped with osmotic pumps for intracerebroventricular infusion of saline or the angiotensin type-1 receptor (AT1R) inhibitor losartan (15 μg·0.5 μl−1·h−1). BDNF treatment significantly increased baseline BP (121 ± 3 mmHg vs. 99 ± 2 mmHg in GFP), HR (394 ± 9 beats/min vs. 314 ± 4 beats/min in GFP), and sympathetic tone indicated by HR- and BP-variability analysis and adrenomedullary tyrosine hydroxylase protein expression. In contrast, body weight and BP elevations to acute stressors decreased. BDNF upregulated AT1R mRNA by ∼80% and downregulated Mas receptor mRNA by ∼50% in the PVN, and losartan infusion partially inhibited weight loss and increases in BP and HR in BDNF-treated animals without any effect in GFP rats. Our results demonstrate that BDNF overexpression in the PVN results in sympathoexcitation, BP and HR elevations, and weight loss that are mediated, at least in part, by modulating angiotensin signaling in the PVN. PMID:25576628

  18. [Case of cerebral venous thrombosis due to graves' disease with increased factor VIII activity].

    PubMed

    Kasuga, Kensaku; Naruse, Satoshi; Umeda, Maiko; Tanaka, Midori; Fujita, Nobuya

    2006-04-01

    A 39 year-old man was admitted to our hospital because of severe headache with fever continuing over two weeks. Three days after admission he developed aphasia and right hemiparesis, when his CT revealed subarachnoid hemorrhage at the left sylvian fissure. He was diagnosed as suffering from cerebral venous thrombosis because empty delta sign was positive on the enhanced brain CT. Suprasagittal sinus and bilateral transverse sinuses were not detected on the cerebral angiography. He was also diagnosed as having Graves' disease for the first time on the basis of free T3 13.56 pg/ml, free T4 4.65 ng/dl, TSH < 0.01 IU/ml, anti-TSH receptor antibody 4.3 IU/l, and thyroid stimulating antibody 224%. On the examination, homocystine and activities of antithrombin III, protein C, and protein S were normal. Antinculear, anti-DNA, anti-Sm, anticardiolipin beta2GP-I antibodies, and PR3ANCA were negative. Factor VIII activity, however, markedly increased over 300%, which has been known to increase in the cases of hyperthyroidism. He recovered well after the treatment with thiamazole in addition to warfarin followed by intravenous heparin. There are only six cases of cerebral venous thrombosis due to hyperthyroidism with increased factor VIII level. All of those cases were female, and 5 of them were taking oral contraceptives. This is a first Japanese male case.

  19. Does Including Public Health Students on Interprofessional Teams Increase Attainment of Interprofessional Practice Competencies?

    PubMed

    Duffy, Pamela Ann; Ronnebaum, Julie A; Stumbo, Teri A; Smith, Kari Nies; Reimer, Rachel A

    2017-04-01

    Interprofessional education (IPE) creates dynamic experiential learning that can address social determinants of health that influence health outcomes. To examine the effects of including public health students on IPE teams on the interprofessional practice domain constructs (values/ethics, roles/responsibilities, interprofessional communication, and teams and teamwork). This single-case, mixed-methods study was performed using a grounded theory approach. Students from 8 graduate health sciences programs participated in an asynchronous, 6-week, online IPE learning activity. Three of the 4 interprofessional practice domain constructs were examined as outcome variables: participants' biomedical vs biopsychosocial patient approach (values/ethics); reported change in attitudes, beliefs, or values about other health professions (roles/responsibilities); and anticipated changes in future professional behaviors/interactions/approaches (teams and teamwork). Predictor variables were having an MPH participant on the IPE team, participants' enrollment in a clinical or nonclinical program, and student perception of the online format (interprofessional communication). Three hundred nineteen students were included, 261 from clinical and 58 from nonclinical programs. A significant association was found between having an MPH participant on the IPE teams and participants' awareness of the influence of social determinants of health (OR, 2.04; 95% CI, 1.13-3.66; P<.05). Program type was also significantly associated with awareness of the influence of social determinants of health, such that participants in nonclinical programs were significantly more likely to report the importance of social determinants of health in the care plan (OR, 3.68; 95% CI, 1.38-9.84; P<.01). Participants were significantly less likely to report future behavior change if they were in clinical programs (OR, 0.44; 95% CI, 0.23-0.86; P<.05) or if they disliked the online format (OR, 0.25; 95% CI, 0.14-0.42; P

  20. The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus

    PubMed Central

    Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

    2018-01-01

    [Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45–3.85). Mother and father’s history of T2D (HR=1.73; 95% CI=1.46–2.05; HR=1.83; 95% CI=1.40–2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08–1.40) smoking status (HR=1.62, CI=1.32–1.99), and drinking (HR=1.32, CI=1.13–1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D. PMID:29545678

  1. Including dietary fiber and resistant starch to increase satiety and reduce aggression in gestating sows.

    PubMed

    Sapkota, A; Marchant-Forde, J N; Richert, B T; Lay, D C

    2016-05-01

    Aggression during mixing of pregnant sows impacts sow welfare and productivity. The aim of this study was to increase satiety and reduce aggression by including dietary fiber and fermentable carbohydrates. Sows were housed in individual stalls 7 to 14 d after breeding (moving day was considered d 0 of treatment) and were fed (at 0700 h) with a CONTROL (corn-soybean meal based with no additional fiber sources), RSTARCH (10.8% resistant starch), BEETPULP (27.2% sugar beet pulp), SOYHULLS (19.1% soybean hulls), or INCSOY (14.05% soybean hulls) for 21 d (5 sows/diet × 5 diets × 8 replications = 200 sows). The CONTROL diet was targeted to contain 185 g(d∙sow) NDF and the other diets were targeted to contain 350 g(d∙sow) NDF. The INCSOY diet was fed at 2.2 kg/(d∙sow) and the other diets were fed at 2 kg(d∙sow). On d 22, sows were mixed in groups of 5 (at 1200 h). Behaviors in stalls (on d 1, 7, 14, and 21) and after mixing (d 22 and 23), heart rate (on d 1, 7, 14, and 21), blood metabolites (on d 2, 8, 15, 22, and 25), and the effects of diets on production were collected and analyzed. Sows stood more ( < 0.01) and rested less ( < 0.001) over time irrespective of the diet. Sows on BEETPULP stood more ( < 0.01) and sows on SOYHULLS rested more ( < 0.01). Sham chewing increased over days irrespective of the diet. Chewing behavior (bar and feeder) increased with days on diet ( < 0.001) and was lowest in sows on the SOYHULLS diet ( = 0.045). When mixed, biting frequency in the first hour was highest for sows on the CONTROL diet (236.5 ± 62.6) and lowest for sows on the RSTARCH diet (90.5 ± 30.5). Skin lesions increased ( < 0.001) 24 h after mixing sows irrespective of diet. Blood urea nitrogen (BUN) concentration was lowest in sows fed BEETPULP and SOYHULLS ( < 0.001). Serum glucose concentration was highest in sows fed RSTARCH and BEETPULP ( = 0.04), but there was no day effect ( = 0.62) or diet × day interaction ( = 0.60). The NEFA was greatest in sows fed

  2. Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells.

    PubMed

    Gudasheva, T A; Koliasnikova, K N; Antipova, T A; Seredenin, S B

    2016-07-01

    It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.

  3. Definitive surgical closure of enterocutaneous fistula: outcome and factors predictive of increased postoperative morbidity.

    PubMed

    Ravindran, P; Ansari, N; Young, C J; Solomon, M J

    2014-03-01

    Enterocutaneous fistula (ECF) presents a complex management problem with significant mortality and morbidity. The aim of this study was to assess the outcome of patients undergoing surgical cure for ECF and to predict factors that might relate to increased postoperative morbidity. Medical records of all patients who underwent definitive surgery for cure of an ECF within our colorectal surgery unit between 2000 and 2010 were reviewed. Forty-one patients (18 male) were identified, in whom 44 definitive procedures were performed. The median age was 54 (17-81) years. The median postoperative length of stay in hospital was 14 (2-213) days. Half (50%) of the ECFs occurred as a postoperative complication followed by spontaneous fistulation in Crohn's disease (36%). The interval to definitive surgery was influenced by the aetiology of the fistula. The median time to surgery after formation of postoperative fistula was 240 days (7.9 months). There was no 30-day postoperative mortality. There were two (4.5%) recurrences at 3 months. Thirty-eight (86%) patients suffered postoperative morbidity as defined by the Clavien-Dindo classification. High-grade morbidity occurred in 32% of patients. On univariate analysis, factors identified as being significantly associated with high-grade morbidity included a fistula output of > 500 ml/day (P = 0.004) in patients with postoperative ECF, malnutrition at presentation (P = 0.04) and a serum albumin value of < 30 g/l (P = 0.02) in patients with spontaneous ECF due to Crohn's disease. The majority of persistent complex ECFs can be cured surgically with low mortality and recurrence in a multidisciplinary setting. Postoperative morbidity, however, remains a significant burden. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  4. PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

    PubMed

    Sherenian, M G; Cho, S H; Levin, A; Min, J-Y; Oh, S S; Hu, D; Galanter, J; Sen, S; Huntsman, S; Eng, C; Rodriguez-Santana, J R; Serebrisky, D; Avila, P C; Kalhan, R; Smith, L J; Borrell, L N; Seibold, M A; Keoki Williams, L; Burchard, E G; Kumar, R

    2017-09-01

    PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. There was an interaction between asthma status and the PAI-1 polymorphism on FEV 1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV 1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV 1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. The decrease in the FEV 1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation. © 2017

  5. Factors increasing the risk of inactivity among administrative, technical, and manual workers in Warszawa public institutions.

    PubMed

    Biernat, Elżbieta

    2015-01-01

    The research aims to assess the level of physical activity among administrative, technical, and manual workers employed in Warszawa public institutions and to analyze the factors that increase the risk of failing to meet World Health Organization (WHO) recommendations. The study comprised 373 employees of randomly selected institutions. A short version of International Physical Activity Questionnaire (IPAQ) was applied. The correlation between the mean values of duration, days, MET-min/week of efforts, gender, and type of work was analyzed using the Tukey's honest significant difference (HSD) test, while the correlation between the level of physical activity and the socio-demographic characteristics was assessed with the Chi2 test. The strength of the relationship between socio-demographic characteristics and fulfilment of WHO standards was expressed by the odds ratio (OR) and 95% confidence interval (95% CI). The significance level was p = 0.05. High levels of physical activity were declared by 41.8% of the manual workers, 14.7% of the administration staff, and 7.3% of the technicians; 19%, 31.5% and 54.5%, respectively, reported low levels of physical activity. Factors determining the fulfilment of the WHO recommendations include: the nature of work (p = 0.003), education (p = 0.004), and income (p = 0.003). The risk of being inactive nearly doubles in the case of administration staff (31.5%) and increases more than 4 times in the case of technicians (54.5%). Respondents with secondary school education (31.6%) are exposed to a 3-fold higher risk of inactivity, while in respondents with higher education (37.2%), the level of the risk is 4-fold higher. Compared to those in the highest income group (23.4%), people who earn less (34.1%) are inactive almost twice as often. Urgent intervention is necessary in all studied groups: increased energy expenditure for recreation and locomotion, educational offers of employers to promote healthy lifestyle

  6. Adaptive Upregulation of Clumping Factor A (ClfA) by Staphylococcus aureus in the Obese, Type 2 Diabetic Host Mediates Increased Virulence

    PubMed Central

    Farnsworth, Christopher W.; Schott, Eric M.; Jensen, Sarah E.; Zukoski, Jacob; Benvie, Abigail M.; Refaai, Majed A.; Kates, Stephen L.; Schwarz, Edward M.; Zuscik, Michael J.; Gill, Steven R.

    2017-01-01

    ABSTRACT Obesity and associated type 2 diabetes (T2D) are important risk factors for infection following orthopedic implant surgery. Staphylococcus aureus, the most common pathogen in bone infections, adapts to multiple environments to survive and evade host immune responses. Whether adaptation of S. aureus to the unique environment of the obese/T2D host accounts for its increased virulence and persistence in this population is unknown. Thus, we assessed implant-associated osteomyelitis in normal versus high-fat-diet obese/T2D mice and found that S. aureus infection was more severe, including increases in bone abscesses relative to nondiabetic controls. S. aureus isolated from bone of obese/T2D mice displayed marked upregulation of four adhesion genes (clfA, clfB, bbp, and sdrC), all with binding affinity for fibrin(ogen). Immunostaining of infected bone revealed increased fibrin deposition surrounding bacterial abscesses in obese/T2D mice. In vitro coagulation assays demonstrated a hypercoagulable state in obese/T2D mice that was comparable to that of diabetic patients. S. aureus with an inactivating mutation in clumping factor A (clfA) showed a reduction in bone infection severity that eliminated the effect of obesity/T2D, while infections in control mice were unchanged. In infected mice that overexpress plasminogen activator inhibitor-1 (PAI-1), S. aureus clfA expression and fibrin-encapsulated abscess communities in bone were also increased, further linking fibrin deposition to S. aureus expression of clfA and infection severity. Together, these results demonstrate an adaptation by S. aureus to obesity/T2D with increased expression of clfA that is associated with the hypercoagulable state of the host and increased virulence of S. aureus. PMID:28320836

  7. Telehealth among US hospitals: several factors, including state reimbursement and licensure policies, influence adoption.

    PubMed

    Adler-Milstein, Julia; Kvedar, Joseph; Bates, David W

    2014-02-01

    Telehealth is widely believed to hold great potential to improve access to, and increase the value of, health care. Gaining a better understanding of why some hospitals adopt telehealth technologies while others do not is critically important. We examined factors associated with telehealth adoption among US hospitals. Data from the Information Technology Supplement to the American Hospital Association's 2012 annual survey of acute care hospitals show that 42 percent of US hospitals have telehealth capabilities. Hospitals more likely to have telehealth capabilities are teaching hospitals, those equipped with additional advanced medical technology, those that are members of a larger system, and those that are nonprofit institutions. Rates of hospital telehealth adoption by state vary substantially and are associated with differences in state policy. Policies that promote private payer reimbursement for telehealth are associated with greater likelihood of telehealth adoption, while policies that require out-of-state providers to have a special license to provide telehealth services reduce the likelihood of adoption. Our findings suggest steps that policy makers can take to achieve greater adoption of telehealth by hospitals.

  8. School-Level Factors Associated with Increased Fruit and Vegetable Consumption among Students in California Middle and High Schools

    ERIC Educational Resources Information Center

    Gosliner, Wendi

    2014-01-01

    Background: This study assessed associations between selective school-level factors and students' consumption of fruits and vegetables at school. Better understanding of school factors associated with increased produce consumption is especially important, as students are served more produce items at school. Methods: This cross-sectional study…

  9. Vascular endothelial growth factor increases fenestral permeability in hepatic sinusoidal endothelial cells.

    PubMed

    Yokomori, Hiroaki; Oda, Masaya; Yoshimura, Kazunori; Nagai, Toshihiro; Ogi, Mariko; Nomura, Masahiko; Ishii, Hiromasa

    2003-12-01

    Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and vascular permeability. Hepatic sinusoidal endothelial cells (SECs) possess sieve-like pores that form an anastomosing labyrinth structure by the deeply invaginated plasma membrane. Caveolin is the principal structural protein in caveolae. In this study, we examined the role of VEGF on the fenestration and permeability of SECs and the relation with caveolin-1. SECs isolated from rat livers by collagenase infusion method were cultured for 24 h with (10 or 100 ng/ml) or without VEGF. The cells were then examined by transmission and scanning electron microscopy (EM). The expression of caveolin was investigated by confocal immunofluorescence, immunogold EM, and Western blot. Endocytosis and intracellular traffic was studied using horseradish peroxidase (HRP) reaction as a marker of fluid phase transport in SECs. Both transmission and scanning EM showed an increased number of sinusoidal endothelial fenestrae (SEF) in SECs cultured with VEGF. By confocal immunofluorescence, SECs cultured with VEGF displayed prominent caveolin-l-positive aggregates in the cytoplasm, especially surrounding the nucleus region. Immunogold EM depicted increased caveolin-1 reactivity on vesicles and vacuoles of VEGF-treated SECs compared with VEGF-nontreated cells. However, there was no change in the level of caveolin-1 protein expression on Western blot. After HRP injection, an increase of electron-dense tracer filled the SEF in cells treated with VEGF. Our results suggested that VEGF induced fenestration in SECs, accompanied by an increased number of caveolae-like vesicles. Increased caveolin-1 might be associated with vesicle formation but not with fenestration. Increased fenestration may augment hepatic sinusoidal permeability and transendothelial transport.

  10. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  11. Macrophage Control of Phagocytosed Mycobacteria Is Increased by Factors Secreted by Alveolar Epithelial Cells through Nitric Oxide Independent Mechanisms

    PubMed Central

    Freidl, Raphaela; Fernández, Carmen

    2014-01-01

    Tissue-resident macrophages are heterogeneous with tissue-specific and niche-specific functions. Thus, simplified models of macrophage activation do not explain the extent of heterogeneity seen in vivo. We focus here on the respiratory tract and ask whether factors secreted by alveolar epithelial cells (AEC) can influence the functionality of resident pulmonary macrophages (PuM). We have previously reported that factors secreted by AEC increase control of intracellular growth of BCG in macrophages. In the current study, we also aimed to investigate possible mechanisms by which AEC-derived factors increase intracellular control of BCG in both primary murine interstitial macrophages, and bone marrow-derived macrophages and characterize further the effect of these factors on macrophage differentiation. We show that; a) in contrast to other macrophage types, IFN-γ did not increase intracellular growth control of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG) by interstitial pulmonary macrophages although the same macrophages could be activated by factors secreted by AEC; b) the lack of response of pulmonary macrophages to IFN-γ was apparently regulated by suppressor of cytokine signaling (SOCS)1; c) AEC-derived factors did not induce pro-inflammatory pathways induced by IFN-γ e.g. expression of inducible nitric oxide synthase (iNOS), secretion of nitric oxide (NO), or IL-12, d) in contrast to IFN-γ, intracellular bacterial destruction induced by AEC-derived factors was not dependent on iNOS transcription and NO production. Collectively, our data show that PuM were restricted in inflammatory responses mediated by IFN-γ through SOCS1 and that factors secreted by AEC- enhanced the microbicidal capacities of macrophages by iNOS independent mechanisms. PMID:25089618

  12. Human factors dimensions in the evolution of increasingly automated control rooms for near-earth satellites

    NASA Technical Reports Server (NTRS)

    Mitchell, C. M.

    1982-01-01

    The NASA-Goddard Space Flight Center is responsible for the control and ground support for all of NASA's unmanned near-earth satellites. Traditionally, each satellite had its own dedicated mission operations room. In the mid-seventies, an integration of some of these dedicated facilities was begun with the primary objective to reduce costs. In this connection, the Multi-Satellite Operations Control Center (MSOCC) was designed. MSOCC represents currently a labor intensive operation. Recently, Goddard has become increasingly aware of human factors and human-machine interface issues. A summary is provided of some of the attempts to apply human factors considerations in the design of command and control environments. Current and future activities with respect to human factors and systems design are discussed, giving attention to the allocation of tasks between human and computer, and the interface for the human-computer dialogue.

  13. Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

    PubMed

    Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

    2014-08-20

    Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01). These data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This

  14. Factors associated with opioid dose increases: a chart review of patients’ first year on long-term opioids

    PubMed Central

    Bautista, Christopher A.; Iosif, Ana-Maria; Wilsey, Barth L.; Melnikow, Joy A.; Crichlow, Althea; Henry, Stephen G.

    2016-01-01

    OBJECTIVE To examine encounter-level factors associated with opioid dose increases during patients’ first year on opioid therapy for chronic pain. DESIGN Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type; opioid dose change; documented prescribing rationale; documentation of guideline-concordant opioid prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. RESULTS 674 encounters were coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with email encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared to face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95%CI 0.11 – 0.28) and email (OR 0.23, 95%CI 0.12 – 0.47) encounters; documentation of prescribing rationale was significantly more likely for email (OR 5.06, 95%CI 1.87–13.72) and less likely for telephone (OR 0.30, 95%CI 0.18–0.51) encounters. CONCLUSION Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation. PMID:27477581

  15. Slightly increased BMI at young age is a risk factor for future hypertension in Japanese men

    PubMed Central

    Tamura, Yoshifumi; Kohmura, Yoshimitsu; Aoki, Kazuhiro; Kawai, Sachio; Daida, Hiroyuki

    2018-01-01

    Background Hypertension is developed easily in Asian adults with normal body mass index (BMI) (~23 kg/m2), compared with other ethnicities with similar BMI. This study tested the hypothesis that slightly increased BMI at young age is a risk factor for future hypertension in Japanese men by historical cohort study. Methods The study participants were 636 male alumni of the physical education school. They had available data on their physical examination at college age and follow-up investigation between 2007 and 2011. The participants were categorized into six categories: BMI at college age of <20.0 kg/m2, 20.0–21.0kg/m2, 21.0–22.0kg/m2, 22.0–23.0kg/m2, 23.0–24.0kg/m2, and ≥24.0kg/m2, and the incidence of hypertension was compared. Results This study covered 27-year follow-up period (interquartile range: IQR: 23–31) which included 17,059 person-years of observation. Subjects were 22 (22–22) years old at graduated college, and 49 (45–53) years old at first follow-up investigation. During the period, 120 men developed hypertension. The prevalence rates of hypertension for lowest to highest BMI categories were 9.4%, 14.6%, 16.1%, 17.5%, 30.3%, and 29.3%, respectively (p<0.001 for trend), and their hazard ratios were 1.00 (reference), 1.80 (95%CI: 0.65–4.94), 2.17 (0.83–5.64), 2.29 (0.89–5.92), 3.60 (1.37–9.47) and 4.72 (1.78–12.48), respectively (p<0.001 for trend). This trend was similar after adjustment for age, year of graduation, smoking, current exercise status and current dietary intake. Conclusion Slightly increased BMI at young age is a risk factor for future hypertension in Japanese men. PMID:29324821

  16. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    NASA Technical Reports Server (NTRS)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  17. Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

    PubMed

    Antoniak, S; Tatsumi, K; Hisada, Y; Milner, J J; Neidich, S D; Shaver, C M; Pawlinski, R; Beck, M A; Bastarache, J A; Mackman, N

    2016-06-01

    Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection. © 2016 International Society on Thrombosis and Haemostasis.

  18. Analysis of factors that increase motorcycle rider risk compared to car driver risk.

    PubMed

    Keall, Michael D; Newstead, Stuart

    2012-11-01

    As in other parts of the Western world, there is concern in New Zealand about increasing popularity of motorcycles because of potential increases in road trauma. This study sought to identify important factors associated with increased risk for motorcyclists to inform potential policy approaches to reduce motorcyclist injury, such as changes to motorcyclist licensing, training and education. Using data extracted from a register of all New Zealand licensed motor vehicles that were matched to crash data, statistical models were fitted to examine patterns of motorcycle risk in comparison with small cars. These showed generally elevated risks for motorcyclists compared to cars, but particularly elevated risks for motorcycle owners aged in their 20s or who lived in more urbanised settings. In crashes, motorcyclists have little protection from injury, putting the motorcyclist at high risk of injury. When comparing new motorcycles with new cars, the odds of fatal or serious injury to a motorcycle rider involved in an injury crash were almost eight times the odds for a car driver. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Promoting CARE: including parents in youth suicide prevention.

    PubMed

    Hooven, Carole; Walsh, Elaine; Pike, Kenneth C; Herting, Jerald R

    2012-01-01

    This study evaluated the effectiveness of augmenting a youth suicide-preventive intervention with a brief, home-based parent program. A total of 615 high school youth and their parents participated. Three suicide prevention protocols, a youth intervention, a parent intervention, and a combination of youth and parent intervention, were compared with an "intervention as usual" (IAU) group. All groups experienced a decline in risk factors and an increase in protective factors during the intervention period, and sustained these improvements over 15 months. Results reveal that the youth intervention and combined youth and parent intervention produced significantly greater reductions in suicide risk factors and increases in protective factors than IAU comparison group.

  20. Structural factors associated with an increased risk of HIV and sexually transmitted infection transmission among street-involved youth

    PubMed Central

    Marshall, Brandon DL; Kerr, Thomas; Shoveller, Jean A; Montaner, Julio SG; Wood, Evan

    2009-01-01

    Background The prevalence of HIV and sexually transmitted infections (STIs) among street-involved youth greatly exceed that of the general adolescent population; however, little is known regarding the structural factors that influence disease transmission risk among this population. Methods Between September 2005 and October 2006, 529 street-involved youth were enroled in a prospective cohort known as the At Risk Youth Study (ARYS). We examined structural factors associated with number of sex partners using quasi-Poisson regression and consistent condom use using logistic regression. Results At baseline, 415 (78.4%) were sexually active, of whom 253 (61.0%) reported multiple sex partners and 288 (69.4%) reported inconsistent condom use in the past six months. In multivariate analysis, self-reported barriers to health services were inversely associated with consistent condom use (adjusted odds ratio [aOR] = 0.52, 95%CI: 0.25 – 1.07). Structural factors that were associated with greater numbers of sex partners included homelessness (adjusted incidence rate ratio [aIRR] = 1.54, 95%CI: 1.11 – 2.14) and having an area restriction that affects access to services (aIRR = 2.32, 95%CI: 1.28 – 4.18). Being searched or detained by the police was significant for males (aIRR = 1.36, 95%CI: 1.02 – 1.81). Conclusion Although limited by its cross-sectional design, our study found several structural factors amenable to policy-level interventions independently associated with sexual risk behaviours. These findings imply that the criminalization and displacement of street-involved youth may increase the likelihood that youth will engage in sexual risk behaviours and exacerbate the negative impact of resultant health outcomes. Moreover, our findings indicate that environmental-structural interventions may help to reduce the burden of these diseases among street youth in urban settings. PMID:19134203

  1. Applying human factors principles to alert design increases efficiency and reduces prescribing errors in a scenario-based simulation.

    PubMed

    Russ, Alissa L; Zillich, Alan J; Melton, Brittany L; Russell, Scott A; Chen, Siying; Spina, Jeffrey R; Weiner, Michael; Johnson, Elizabette G; Daggy, Joanne K; McManus, M Sue; Hawsey, Jason M; Puleo, Anthony G; Doebbeling, Bradley N; Saleem, Jason J

    2014-10-01

    To apply human factors engineering principles to improve alert interface design. We hypothesized that incorporating human factors principles into alerts would improve usability, reduce workload for prescribers, and reduce prescribing errors. We performed a scenario-based simulation study using a counterbalanced, crossover design with 20 Veterans Affairs prescribers to compare original versus redesigned alerts. We redesigned drug-allergy, drug-drug interaction, and drug-disease alerts based upon human factors principles. We assessed usability (learnability of redesign, efficiency, satisfaction, and usability errors), perceived workload, and prescribing errors. Although prescribers received no training on the design changes, prescribers were able to resolve redesigned alerts more efficiently (median (IQR): 56 (47) s) compared to the original alerts (85 (71) s; p=0.015). In addition, prescribers rated redesigned alerts significantly higher than original alerts across several dimensions of satisfaction. Redesigned alerts led to a modest but significant reduction in workload (p=0.042) and significantly reduced the number of prescribing errors per prescriber (median (range): 2 (1-5) compared to original alerts: 4 (1-7); p=0.024). Aspects of the redesigned alerts that likely contributed to better prescribing include design modifications that reduced usability-related errors, providing clinical data closer to the point of decision, and displaying alert text in a tabular format. Displaying alert text in a tabular format may help prescribers extract information quickly and thereby increase responsiveness to alerts. This simulation study provides evidence that applying human factors design principles to medication alerts can improve usability and prescribing outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Socioeconomic Disconnection as a Risk Factor for Increased HIV Infection in Young Men Who Have Sex with Men.

    PubMed

    Gayles, Travis A; Kuhns, Lisa M; Kwon, Soyang; Mustanski, Brian; Garofalo, Robert

    2016-06-01

    HIV disproportionately affects young men who have sex with men (YMSM), particularly black YMSM. Increasingly, researchers are turning to social, economic, and structural factors to explain these disproportionate rates. In this study, we explore the relationship between socioeconomic disconnection and HIV status and factors related to HIV infection, including drug use, condomless anal sex, and binge drinking. We operationalize socioeconomic disconnection in this young population as lack of engagement in educational and employment opportunities. Baseline data were analyzed from a longitudinal cohort study of YMSM aged 16-20 years recruited from the Chicago area (N = 450). Bivariate analyses of the association of socioeconomic disconnection and HIV-positive status, drug and alcohol use, and condomless anal sex were assessed using chi-square tests. The relationship of socioeconomic disconnection and HIV-positive status was then examined in multivariate logistic regression models, controlling for age and race/ethnicity and significant behavioral factors. Among study participants, 112 (25%) were not in school, 310 (69%) were not currently working, and 81 (18%) were neither in school nor working. Black MSM were more likely to be socioeconomically disconnected (neither in school nor working; n = 56, 23.3%). The results revealed that disconnected YMSM were more likely to binge drink (AOR = 2.34; 95% CI = 1.16, 4.74) and be HIV positive (AOR = 2.24; 95% CI = 1.04, 4.83). Subpopulation analysis for black participants revealed similar associations (AOR of binge drinking = 2.92; 95% CI = 1.07, 8.01; AOR of HIV positive = 2.38; 95% CI = 1.03, 5.51). Controlling for substance use, the association between disconnection and HIV-positive status remained significant (AOR = 2.37; 95% CI = 1.08, 5.20). Socioeconomic disconnection is significantly and positively associated with HIV status among YMSM, suggesting that the two factors are

  3. Factors associated with low vs increased perceived mastery of clinical work over ten years of practice: a prospective study of Norwegian doctors.

    PubMed

    Belfrage, Anna; Grotmol, Kjersti Støen; Tyssen, Reidar; Moum, Torbjørn; Lien, Lars

    2018-05-29

    A higher sense of mastery of doctors' clinical work could benefit not only their own mental health but also their work performance and patient care. However, we know little about factors associated with perceived mastery of clinical work among physicians. Our aim was therefore to study characteristics of those with stable low levels and of those with increased levels of mastery over a period of ten years of medical practice. N = 631 doctors were surveyed in their final year of medical school in 1993/94 (T1) and 10 (T2), 15 (T3) and 20 (T4) years later. Low and increased perceived mastery of clinical work were measured between T2, T3 and T4. Response rates for all items measuring low and increased mastery were 238/522 (46%) and 256/522 (49%) respectively. The following explanatory variables were included: demographics, medical school factors, personality and contextual work-related and non-work-related factors. N = 73 (31%) of the doctors reported stable low mastery from T2 to T4. The following variables were significantly associated with low mastery in the adjusted analyses: vulnerability (OR: 1.30, P < .000, CI: 1.12 to 1.50), drinking alcohol to cope with stress during medical school (OR: 2.66, P = .04, CI: 1.03 to 6.85) and social support (OR: 0.78, P = .002, CI: 0.66 to 0.91). N = 39 (15%) reported increased mastery during the ten-year period from T2 to T4. Perceived job demands (OR: 0.66, P = .02, CI: 0.45 to 0.98) and taking up a leading position (OR: 3.04, P = .01, CI: 1.31 to 7.07) were associated with increased mastery after adjustment. Stable low sense of mastery over time is associated with having a vulnerable personality, a history of having used alcohol to cope with stress during medical school and lack of contemporary social support. Conversely, increased sense of mastery is associated with taking up a leading position and having the perception that job demands are decreasing over time. These findings indicate that

  4. Molecular Imaging of Smoke-Induced Changes in Nuclear Factor-Kappa B Expression in Murine Tissues Including the Lung.

    PubMed

    Syrkina, Olga; Hales, Charles H; Bonab, Ali A; Hamrahi, Victoria; Paul, Kasie; Jung, Walter J; Tompkins, Ronald G; Fischman, Alan J; Carter, Edward A

    Many inflammatory responses are mediated by activation of the transcription factor, nuclear factor-kappa B (NF-κB), and a wide variety of human diseases involve abnormal regulation of its expression. In this investigation, we evaluated the effect of smoke inhalation injury on NF-κB expression in lung using two strains of NF-κB reporter mice. Groups of reporter mice with viral thymidine kinase (TK) or "fire fly" luciferase (Luc) genes under control by the NF-κB promoter (TK/NF-κB mice and Luc/NF-κB mice) were subjected to nonlethal smoke inhalation injury. Sham-treated animals served as controls. Twenty-four hours (each animal was injected intravenously with either 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (FHBG) (~ 1.0 mCi) or luciferin (1.0 mg). One hour later, the TK/NF-κB mice were studied by micro-positron emission tomography (µ-PET) imaging using a Concord P4 µ-PET camera, and the Luc/NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. The µ-PET data demonstrated that smoke injury produced massive increases in NF-κB expression (FHBG-standardized uptake value: 3.1 vs 0.0) 24 hours after smoke inhalation, which was reduced 48 hours after smoke inhalation, but still significantly different than the control. Qualitative analysis of the bioluminescence data revealed a remarkably similar effect of burn NF-κB luciferase expression in vivo. Biodistribution studies of FHBG uptake and luciferase activity in lung tissue demonstrated a similar increase 24 hours after injury, which was reduced 48 hours later, but still significantly higher than the sham. The present data with these models providing longitudinal imaging data on the same mouse may prove useful in the examination of the factors producing lung injury by smoke inhalation, as well as the treatment(s) for the damage produced with and without burn injury.

  5. A qualitative description of falls in a neuro-rehabilitation unit: the use of a standardised fall report including the International Classification of Functioning (ICF) to describe activities and environmental factors.

    PubMed

    Saverino, Alessia; Moriarty, Amy; Rantell, Khadija; Waller, Denise; Ayres, Rachael; Playford, Diane

    2015-01-01

    Falls are a recognised problem for people with long-term neurological conditions but less is known about fall risk in young adults. This study describes fallers' and falls' characteristics in adults less than 60 years old, in a neuro-rehabilitation unit. This single-centre, longitudinal, observational study included 114 consecutive admissions to a UK neuro-rehabilitation unit over 20 months. The demographic and clinical characteristics of eligible patients included age, sex, diagnosis, hospital length of stay and the Functional Independence Measure (FIM). Falls were recorded prospectively in a fall report, using the activities and environmental domains of the International Classification of Functioning (ICF). A total of 34 (30%) patients reported a fall, with 50% experiencing more than one fall. The majority of falls (60%) occurred during the first 2 weeks, during day-time (90%) and during mobile activities (70%). Overall, falls rate (95% confidence interval) was 1.33 (1.04 to 1.67) per 100 d of patient hospital stay. Factors associated with increased falls included becoming a walker during admission or being cognitively impaired. There were no serious fall-related injuries. The first 2 weeks of admission is a high risk time for fallers, in particular those who become walkers or are cognitively impaired. Prevention policies should be put in place based on fall characteristics. Implications for Rehabilitation The ICF is a valuable instrument for describing subject and environmental factors during a fall-event. Falls are frequent events but do not usually cause serious injuries during inpatient rehabilitation. There is an increased fall risk for subjects with cognitive impairments or those relearning how to walk.

  6. Global increasing of mean sea level and erroneous treatment of a role of thermal factors

    NASA Astrophysics Data System (ADS)

    Barkin, Yu. V.

    2009-04-01

    in the northern hemisphere. At averaging of measurements over all ocean surface (mainly located in a southern hemisphere where it occupies about 80 % of the areas) there will be an effect of apparent additional increase of the sea level. Therefore this ("apparent") velocity of increase of the sea level accepts the greater value (about 2.4 mm / year) in comparison with coastal determinations of this velocity that is rather close to the data of satellite observations. The additional effect in increase of the sea level is brought by deformation of the ocean bottom. The both mentioned phenomena: the secular drift of the center of mass of the Earth and the secular expansion of southern hemisphere of the Earth have been predicted by author [2], [3] and have obtained confirmations by space geodesy methods. The offered explanation has the extremely - important value for studying a possible role of thermal and climatic factors which can not apply any more for a big component attributed to it in change of the sea level. The account of fictitious component of this velocity results practically in real value of variation of the average sea level about 1.3-1.6 mm / yr, that completely coordinate positions of researchers of ocean by coastal and altimetry (satellite) methods. Moreover, the given work opens a direct opportunity for an explanation of increase of the sea level as result of deformation of the ocean bottom. This deformation is a major factor of change of the average sea level. Water superseded in a southern hemisphere gives the significant contribution to observably value of velocity of sea level rise up to 0.8-1.2 mm / yr [3, 4]. The work fulfilled at financial support of Russian projects of RFBR: N 07-05-00939 and N 06-02-16665. This abstract (without what or changes) has been accepted to EGU GA 2008 Session IS48 "75th Anniversary of the PSML"(Convener: Woodworth P.) but was not included in its program. References. [1] Nerem R.S., Leuliette E.W., Chambers D.P. (2005

  7. Factors Underlying the Temporal Increase in Maternal Mortality in the United States

    PubMed Central

    Joseph, K.S.; Lisonkova, Sarka; Muraca, Giulia M.; Razaz, Neda; Sabr, Yasser; Mehrabadi, Azar; Schisterman, Enrique F.

    2016-01-01

    OBJECTIVE To identify the factors underlying the recent increase in maternal mortality ratios (maternal deaths per 100,000 live births) in the United States. METHODS We carried out a retrospective study with data on maternal deaths and live births in the United States from 1993 to 2014 obtained from the birth and death files of the Centers for Disease Control and Prevention. Underlying causes of death were examined between 1999 and 2014 using International Classification of Diseases, Tenth Revision (ICD-10) codes. Poisson regression was used to estimate maternal mortality rate ratios (RR) and 95% confidence intervals (CI) after adjusting for the introduction of a separate pregnancy question and the standard pregnancy checkbox on death certificates, and adoption of ICD-10. RESULTS Maternal mortality ratios increased from 7.55 in 1993, to 9.88 in 1999 and to 21.5 per 100,000 live births in 2014 (RR 2014 vs 1993 2.84, 95% CI 2.49 to 3.24; RR 2014 vs 1999 2.17, 95% CI 1.93 to 2.45). The increase in maternal deaths from 1999 to 2014 was mainly due to increases in maternal deaths associated with two new ICD-10 codes (O26.8 i.e., primarily renal disease and O99 i.e., other maternal diseases classifiable elsewhere); exclusion of such deaths abolished the increase in mortality (RR 1.09, 95% CI 0.94 to 1.27). Regression adjustment for improvements in surveillance also abolished the temporal increase in maternal mortality ratios (adjusted maternal mortality ratios 7.55 in 1993, 8.00 per 100,000 live births in 2013; adjusted RR 2013 vs 1993 1.06, 95% CI 0.90 to 1.25). CONCLUSION Recent increases in maternal mortality ratios in the United States are likely an artifact of improvements in surveillance and highlight past underestimation of maternal death. Complete ascertainment of maternal death in populations remains a challenge even in countries with good systems for civil registration and vital statistics. PMID:27926651

  8. Risks for upper respiratory infections in infants during their first months in day care included environmental and child-related factors.

    PubMed

    Laursen, Rikke Pilmann; Larnkjaer, Anni; Ritz, Christian; Hojsak, Iva; Michaelsen, Kim; Mølgaard, Christian

    2018-03-14

    We examined the frequency and potential risk factors for respiratory infections, diarrhoea and absences in infants during their first months in day care. This prospective cohort study comprised 269 Danish infants aged eight months to 14 months and was part of a study that examined how probiotics affected absences from day care due to respiratory and gastrointestinal infections. The risk factors examined were the household, child characteristics and type of day care facility. Parents registered upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), diarrhoea and day care absences on web-based questionnaires. Over a mean of 5.6 months in day care, 36% and 20% of the infants had at least one URTI or LRTI, and 60% had diarrhoeal episodes. The risk of at least one URTI was increased by previous respiratory infections, with an odds ratio (OR) of 2.65, but was inversely associated with having a pet (OR: 0.43), being cared for by registered child minders compared to day care centres (OR: 0.36), birthweight (OR 0.40) and age at day care enrolment (OR: 0.64). No significant risk factors for LRTIs and diarrhoea were found. Infection risks were associated with environmental factors and factors related to the child. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  9. Factor V Leiden is associated with increased sperm count.

    PubMed

    van Mens, T E; Joensen, U N; Bochdanovits, Z; Takizawa, A; Peter, J; Jørgensen, N; Szecsi, P B; Meijers, J C M; Weiler, H; Rajpert-De Meyts, E; Repping, S; Middeldorp, S

    2017-11-01

    Is the thrombophilia mutation factor V Leiden (FVL) associated with an increased total sperm count? Carriers of FVL have a higher total sperm count than non-FVL-carriers, which could not be explained by genetic linkage or by observations in a FVL-mouse model. FVL has a high prevalence in Caucasians despite detrimental health effects. Carriers have been shown to have higher fecundity, which might partly explain this evolutionary paradox. We determined FVL status in two cohorts (Dutch, n = 627; Danish, n = 854) of consecutively included men without known causes for spermatogenic failure, and performed an individual patient data meta-analysis of these two cohorts together with one previously published (Dutch, n = 908) cohort. We explored possible biological underpinnings for the relation between sperm count and FVL, by use of a FVL-mouse model and investigations of genetic linkage. Participants were male partners of subfertile couples (two Dutch cohorts) and young men from the general population (Danish cohort): FVL carrier rate was 4.0%, 4.6% and 7.3%, respectively. There were differences in smoking, abstinence time and age between the cohorts. We corrected for these in the primary analysis, which consisted of a mixed linear effects model, also incorporating unobjectified population differences. In public haplotype data from subjects of European descent, we explored linkage disequilibrium of FVL with all known single nucleotide polymorphisms in a 1.5 MB region around the F5 gene with an R2 cutoff of 0.8. We sequenced exons of four candidate genes hypothesized to be linked to FVL in a subgroup of FVL carriers with extreme sperm count values. The animal studies consisted of never mated 15-18-week-old C57BL/J6 mice heterozygous and homozygous for FVL and wild-type mice. We compared spermatogenesis parameters (normalized internal genitalia weights, epididymis sperm content and sperm motility) between FVL and wild-type mice. Human FVL carriers have a higher total sperm

  10. Loss of epigenetic Kruppel-like factor 4 histone deacetylase (KLF-4-HDAC)-mediated transcriptional suppression is crucial in increasing vascular endothelial growth factor (VEGF) expression in breast cancer.

    PubMed

    Ray, Alpana; Alalem, Mohamed; Ray, Bimal K

    2013-09-20

    Vascular endothelial growth factor (VEGF) is recognized as an important angiogenic factor that promotes angiogenesis in a series of pathological conditions, including cancer, inflammation, and ischemic disorders. We have recently shown that the inflammatory transcription factor SAF-1 is, at least in part, responsible for the marked increase of VEGF levels in breast cancer. Here, we show that SAF-1-mediated induction of VEGF is repressed by KLF-4 transcription factor. KLF-4 is abundantly present in normal breast epithelial cells, but its level is considerably reduced in breast cancer cells and clinical cancer tissues. In the human VEGF promoter, SAF-1- and KLF-4-binding elements are overlapping, whereas SAF-1 induces and KLF-4 suppresses VEGF expression. Ectopic overexpression of KLF-4 and RNAi-mediated inhibition of endogenous KLF-4 supported the role of KLF-4 as a transcriptional repressor of VEGF and an inhibitor of angiogenesis in breast cancer cells. We show that KLF-4 recruits histone deacetylases (HDACs) -2 and -3 at the VEGF promoter. Chronological ChIP assays demonstrated the occupancy of KLF-4, HDAC2, and HDAC3 in the VEGF promoter in normal MCF-10A cells but not in MDA-MB-231 cancer cells. Co-transfection of KLF-4 and HDAC expression plasmids in breast cancer cells results in synergistic repression of VEGF expression and inhibition of angiogenic potential of these carcinoma cells. Together these results identify a new mechanism of VEGF up-regulation in cancer that involves concomitant loss of KLF-4-HDAC-mediated transcriptional repression and active recruitment of SAF-1-mediated transcriptional activation.

  11. Leptin Aggravates Reflux Esophagitis by Increasing Tissue Levels of Macrophage Migration Inhibitory Factor in Rats.

    PubMed

    Murata, Tsugihiro; Asanuma, Kiyotaka; Ara, Nobuyuki; Iijima, Katsunori; Hatta, Waku; Hamada, Shin; Asano, Naoki; Koike, Tomoyuki; Imatani, Akira; Masamune, Atsushi; Shimosegawa, Tooru

    2018-05-01

    Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). We therefore investigated the mechanism whereby leptin aggravates reflux esophagitis, by focusing on esophageal tissue levels of MIF and CD3+ T lymphocytes, both of which are crucial for the reflux-induced epithelial damage. Esophageal inflammation was surgically induced in male Wistar rats by ligating the forestomach and narrowing the duodenum to facilitate gastroesophageal reflux, followed by administration of leptin or vehicle with an osmotic pump system for 1 week. We demonstrated that the administration of leptin exacerbated the reflux esophagitis with the apparent infiltration of CD3+ T lymphocytes and caused the significant increase in the esophageal tissue levels of MIF. Moreover, the leptin caused increases in the esophageal tissue levels of TNF-α, IL-1β and IL-6, downstream targets of MIF. Importantly, the increases in these pro-inflammatory cytokines were accompanied by increased protein levels of phospho-STAT3 and phospho-AKT, pivotal molecules of leptin signaling pathways. In conclusion, through enhancing the MIF-induced inflammatory signaling, leptin could contribute to the development of gastroesophageal reflux disease.

  12. Increasing Children's Physical Activity: Individual, Social, and Environmental Factors Associated with Walking to and from School

    ERIC Educational Resources Information Center

    Trapp, Georgina S. A.; Giles-Corti, Billie; Christian, Hayley E.; Bulsara, Max; Timperio, Anna F.; McCormack, Gavin R.; Villaneuva, Karen P.

    2012-01-01

    Background. Efforts to increase the prevalence of children's active school transport require evidence to inform the development of comprehensive interventions. This study used a multilevel ecological framework to investigate individual, social, and environmental factors associated with walking to and from school among elementary school-aged…

  13. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    PubMed Central

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-01-01

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. Images PMID:1408831

  14. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    PubMed

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-10-11

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

  15. Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor.

    PubMed Central

    Høgåsen, A K; Abrahamsen, T G

    1993-01-01

    Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF. PMID:8478067

  16. Health risks of including alcohol and tobacco in PICTA free trade.

    PubMed

    Hill, Linda

    2004-03-01

    In April 2005 Pacific Forum leaders will decide whether to include alcohol and tobacco in the Pacific Island Countries Trade Agreement (PICTA). This article presents arguments for keeping alcohol out of regional free trade agreements. Inclusion will allow regional rationalisation of production, increased alcohol availability, competition and marketing, and lower prices. These trade goals are inappropriate for alcohol and tobacco. Pacific public health organisations are concerned that official advice has focused on fiscal impacts, not health and social impacts. The World Health Organization has identified alcohol as the leading factor in injury and disease for low-mortality developing countries. Effective policies to reduce alcohol related harm include restrictions on availability, as well as excise taxes affecting price. Under trade agreements elsewhere, national alcohol policies have been challenged as 'non-tariff barriers to trade'. Hazardous drinking is of increasingly concern in the Pacific and decisions about alcohol should not reflect commercial interests.

  17. Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa.

    PubMed

    Xie, Han; Qiao, Ping; Lu, Yi; Li, Ying; Tang, Yuping; Huang, Yiying; Bao, Yirong; Ying, Hao

    2017-12-01

    Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF.

  18. Genetic Factors That Increase Male Facial Masculinity Decrease Facial Attractiveness of Female Relatives

    PubMed Central

    Lee, Anthony J.; Mitchem, Dorian G.; Wright, Margaret J.; Martin, Nicholas G.; Keller, Matthew C.; Zietsch, Brendan P.

    2014-01-01

    For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework. PMID:24379153

  19. Genetic factors that increase male facial masculinity decrease facial attractiveness of female relatives.

    PubMed

    Lee, Anthony J; Mitchem, Dorian G; Wright, Margaret J; Martin, Nicholas G; Keller, Matthew C; Zietsch, Brendan P

    2014-02-01

    For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework.

  20. Hidden Risk Factors for Women

    MedlinePlus

    ... risk factors are present. History of Preeclampsia/Eclampsia: Women with a history of preeclampsia/eclampsia have an increased risk of ... can increase the risk of stroke. Clotting disorders: Women who’ve ... can include previous history of clots in the legs (deep vein thrombosis) ...

  1. Allele frequency distribution of 1691G >A F5 (which confers Factor V Leiden) across Europe, including Slavic populations.

    PubMed

    Clark, Jeremy S C; Adler, Grażyna; Salkic, Nermin N; Ciechanowicz, Andrzej

    2013-11-01

    The allele 1691A F5, conferring Factor V Leiden, is a common risk factor in venous thromboembolism. The frequency distribution for this allele in Western Europe has been well documented; but here data from Central, Eastern and South-Eastern Europe has been included. In order to assess the significance of the collated data, a chi-squared test was applied, and Tukey tests and z-tests with Bonferroni correction were compared. A distribution with a North-Southeast band of high frequency of the 1691A F5 allele was discovered with a pocket including some Southern Slavic populations with low frequency. European countries/regions can be arbitrarily delimited into low (group 1, <2.8 %, mean 1.9 % 1691A F5 allele) or high (group 2, ≥2.8 %, mean 4.0 %) frequency groups, with many significant differences between groups, but only one intra-group difference (the Tukey test is suggested to be superior to the z-tests). In Europe a North-Southeast band of 1691A F5 high frequency has been found, clarified by inclusion of data from Central, Eastern and South-Eastern Europe, which surrounds a pocket of low frequency in the Balkans which could possibly be explained by Slavic migration. There seem to be no indications of variation in environmental selection due to geographical location.

  2. Risk factors for exposure to influenza a viruses, including subtype H5 viruses, in Thai free-grazing ducks.

    PubMed

    Beaudoin, A L; Kitikoon, P; Schreiner, P J; Singer, R S; Sasipreeyajan, J; Amonsin, A; Gramer, M R; Pakinsee, S; Bender, J B

    2014-08-01

    Free-grazing ducks (FGD) have been associated with highly pathogenic avian influenza (HPAI) H5N1 outbreaks and may be a viral reservoir. In July-August 2010, we assessed influenza exposure of Thai FGD and risk factors thereof. Serum from 6254 ducks was analysed with enzyme-linked immunosorbent assay (ELISA) to detect antibodies to influenza A nucleoprotein (NP), and haemagglutinin H5 protein. Eighty-five per cent (5305 ducks) were seropositive for influenza A. Of the NP-seropositive sera tested with H5 assays (n = 1423), 553 (39%) were H5 ELISA positive and 57 (4%) suspect. Twelve per cent (74 of 610) of H5 ELISA-positive/suspect ducks had H5 titres ≥ 1 : 20 by haemagglutination inhibition. Risk factors for influenza A seropositivity include older age, poultry contact, flock visitors and older purchase age. Study flocks had H5 virus exposure as recently as March 2010, but no HPAI H5N1 outbreaks have been identified in Thailand since 2008, highlighting a need for rigorous FGD surveillance. © 2012 Blackwell Verlag GmbH.

  3. Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time

    PubMed Central

    Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

    2015-01-01

    Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro. PMID:26998384

  4. Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

    PubMed

    Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

    2015-12-01

    Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

  5. Clostridium difficile colitis: increasing incidence, risk factors, and outcomes in solid organ transplant recipients.

    PubMed

    Boutros, Marylise; Al-Shaibi, Maha; Chan, Gabriel; Cantarovich, Marcelo; Rahme, Elham; Paraskevas, Steven; Deschenes, Marc; Ghali, Peter; Wong, Philip; Fernandez, Myriam; Giannetti, Nadia; Cecere, Renzo; Hassanain, Mazen; Chaudhury, Prosanto; Metrakos, Peter; Tchervenkov, Jean; Barkun, Jeffrey S

    2012-05-27

    Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation. Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death. From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16-1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075-1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05-1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/μL (HR: 1.08, 95% CI=1.025-1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195-5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss. We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.

  6. Increased macrophage colony-stimulating factor levels in patients with Graves' disease.

    PubMed

    Morishita, Eriko; Sekiya, Akiko; Hayashi, Tomoe; Kadohira, Yasuko; Maekawa, Mio; Yamazaki, Masahide; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

    2008-10-01

    Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.

  7. [Early drop-outs and retentions in substance abuse outpatient clinics: a cross-sectional comparative study of factors that increase or decrease adherence].

    PubMed

    Calvo, Fran; Carbonell, Xavier; Valero, Ramón; Costa, Jordi; Turró, Oriol; Giralt, Cristina; Ramírez, Marissa

    2017-08-23

    The aim of this study is to define the risk factors associated with early discharge in out-patients clinics. Cross-sectional and observational study. Substance abuse clinics in Girona (Catalonia, Spain). A total of 264 individuals were included in the sample, and 34.8% of them abandoned the process within two months of starting the therapy (n=92). Clinical and socio-demographic variables of the clinical history were compared between participants with/without adherence. The Student t test was used to measure the comparison, and the chi-squared test was used for the analysis of qualitative variables. A binary logistic regression model was adjusted, with adherence as the dependent variable. The results indicated that attending the appointments unaccompanied (OR=3.13), being female (OR=2.44), having cocaine related issues (OR=1.14), and being younger (OR=0.89) are the factors which increase the risk early abandonment. Contrarily, being referred to specialists from a Primary Health Centre reduces the risk (OR=0.28). It is concluded that special attention must be devoted to the patients' families, women, and young patients. Moreover, the appropriate coordination between specialist services and basic services increases adherence to treatment among drug users. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Paternal postnatal depression in Japan: an investigation of correlated factors including relationship with a partner.

    PubMed

    Nishimura, Akiko; Fujita, Yuichi; Katsuta, Mayumi; Ishihara, Aya; Ohashi, Kazutomo

    2015-05-31

    A negative effect of paternal depression on child development has been revealed in several previous studies. The aims of this study were to examine the prevalence and relevant factors associated with paternal postnatal depression at four months postpartum, including age, part-time work or unemployment, experience of visiting a medical institution due to a mental health problem, economic anxiety, unexpected pregnancy, pregnancy with infertility treatment, first child, partner's depression, and lower marital relationship satisfaction. We distributed 2032 self-report questionnaires to couples (one mother and one father) with a 4-month old infant between January and April 2013. Data from 807 couples (39.7 %) were analyzed. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). In order to clarify the factors related with paternal depression, a logistic regression analysis was conducted. One hundred and ten fathers (13.6 %) and 83 mothers (10.3 %) were depressed. According to the logistic regression analysis, paternal depression was positively associated with partner's depression (adjusted odds ratio (AOR) 1.91, 95 % confidence interval (CI) 1.05-3.47), and negatively with marital relationship satisfaction (AOR 0.83, 95 % CI 0.77-0.89). History of infertility treatment (AOR 2.37, 95 % CI 1.32-4.24), experience of visiting a medical institution due to a mental health problem (AOR 4.56, 95 % CI 2.06-10.08), and economic anxiety (AOR 2.15, 95 % CI 1.34-3.45) were also correlated with paternal depression. This study showed that the prevalence of paternal depression at four months after childbirth was 13.6 % in Japan. The presence of partner's depression and low marital relationship satisfaction were significantly correlated with paternal postpartum depression, suggesting that health professionals need to pay attention to the mental status of both fathers and mothers, and to their relationship.

  9. Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

    PubMed

    Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

    2015-06-01

    Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Increased rate of endometriosis and spontaneous abortion in an in vitro fertilization program: no correlation with epidemiological factors.

    PubMed

    Matalliotakis, Ioannis; Cakmak, Hakan; Dermitzaki, Despina; Zervoudis, Stefanos; Goumenou, Anastasia; Fragouli, Yvoni

    2008-04-01

    There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB. The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the chi(2) test and odds ratios (OR) and 95% confidence intervals (CI). The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 - 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001). These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.

  11. Casein kinase 2 (CK2) increases survivin expression via enhanced β-catenin–T cell factor/lymphoid enhancer binding factor-dependent transcription

    PubMed Central

    Tapia, J. C.; Torres, V. A.; Rodriguez, D. A.; Leyton, L.; Quest, A. F. G.

    2006-01-01

    Increased expression of casein kinase 2 (CK2) is associated with hyperproliferation and suppression of apoptosis in cancer. Mutations in the tumor suppressor APC (adenomatous polyposis coli) are frequent in colon cancer and often augment β-catenin–T cell factor (Tcf)/lymphoid enhancer binding factor (Lef)-dependent transcription of genes such as c-myc and cyclin-D1. CK2 has also been implicated recently in the regulation of β-catenin stability. To identify mechanisms by which CK2 promotes survival, effects of the specific CK2 inhibitors 4,5,6,7-tetrabromobenzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole were assessed. TBB and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole significantly decreased proliferation and increased apoptosis of HT29(US) colon cancer cells. RT-PCR and immunoblot analysis revealed that both inhibitors decreased survivin mRNA and protein levels in HT29(US) cells. Similar effects were observed with TBB in human DLD-1 and SW-480 colorectal cells as well as ZR-75 breast cancer cells and HEK-293T embryonic kidney cells. Expression of GFP–CK2α in HEK-293T cells resulted in β-catenin–Tcf/Lef-dependent up-regulation of survivin and increased resistance to anticancer drugs. Augmented β-catenin–Tcf/Lef-dependent transcription and resistance to apoptosis observed upon GFP–CK2α expression were abolished by TBB. Alternatively, HEK-293T cells expressing GFP–survivin were resistant to TBB-induced apoptosis. Finally, siRNA-mediated down-regulation of CK2α in HEK-293T cells coincided with reduced β-catenin and survivin levels. Taken together, these results suggest that CK2 kinase activity promotes survival by increasing survivin expression via β-catenin–Tcf/Lef-mediated transcription. Hence, selective CK2 inhibition or down-regulation in tumors may provide an attractive opportunity for the development of novel cancer therapies. PMID:17005722

  12. Increased urinary excretion of platelet activating factor in mice with lupus nephritis

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

    Macconi, D.; Noris, M.; Benfenati, E.

    1991-01-01

    Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that:more » (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.« less

  13. Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS.

    PubMed

    Huang, Chu-Chun; Chou, Chia-Hung; Chen, Shee-Uan; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

    2018-05-17

    Abnormal folliculogenesis is one of the cardinal presentations of polycystic ovarian syndrome (PCOS) and permeability of follicular wall has been proposed to be involved in the normal follicular growth. However, whether or not there is a change in intrafollicular permeability underlies PCOS is unknown. This was a tertiary center-based case-control study. From 2014 to 2015, thirteen patients with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) were enrolled. Eleven normo-ovulatory patients who underwent IVF-ET due to male factor and/or tubal factor infertility were enrolled as the control group. The influence of ovarian follicular fluid (FF) on endothelial cell permeability was evaluated using a human umbilical vein endothelial cell monolayer permeability assay. The intrafollicular expression profiles of angiogenesis-related proteins were analyzed using a Human Angiogenesis Protein Array Kit. The FF from PCOS patients caused significantly poorer endothelial cell permeability comparing with the effect of FF from the control group (46% ± 12% vs. 58% ± 9%, P = 0.023). Among the 55 angiogenesis-related proteins tested, there was a significantly higher level of intrafollicular platelet factor 4 (PF4) and PF4/IL-8 complex in the PCOS group (p = 0.004). The anti-permeability effect of PF4 was related to the decrease in the intercellular gaps and antagonistic binding with IL-8. Our study provides the first evidence of the pathophysiologic contribution of the well-known angiostatic protein, PF4, on human reproductive biology. The increase of the intrafollicular PF4 and its anti-permeability effect might affect the formation of FF and folliculogenesis in PCOS. Copyright © 2018. Published by Elsevier B.V.

  14. Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

    PubMed

    Sprauten, M; Haugnes, H S; Brydøy, M; Kiserud, C; Tandstad, T; Bjøro, T; Bjerner, J; Cvancarova, M; Fosså, S D; Oldenburg, J

    2015-10-01

    Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Dietary L-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice.

    PubMed

    Ren, Wenkai; Liu, Shuping; Chen, Shuai; Zhang, Fengmei; Li, Nengzhang; Yin, Jie; Peng, Yuanyi; Wu, Li; Liu, Gang; Yin, Yulong; Wu, Guoyao

    2013-10-01

    This study was conducted to determine the effects of graded doses of L-glutamine supplementation on the replication and distribution of Pasteurella multocida, and the expression of its major virulence factors in mouse model. Mice were randomly assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0 % glutamine. Pasteurella multocida burden was detected in the heart, liver, spleen, lung and kidney after 12 h of P. multocida infection. The expression of major virulence factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5 % glutamine supplementation has little significant effect on these parameters, compared to those with basal diet. However, results showed that a high dose of glutamine supplementation increased the P. multocida burden (P < 0.001) and the expression of its major virulence factors (P < 0.05) as compared to those with a lower dose of supplementation. In the lung, high dose of glutamine supplementation inhibited the proinflammatory responses (P < 0.05) and TLRs signaling (P < 0.05). In the spleen, the effect of glutamine supplementation on different components in TLR signaling depends on glutamine concentration, and high dose of glutamine supplementation activated the proinflammatory response. In conclusion, glutamine supplementation increased P. multocida burden and the expression of its major virulence factors, while affecting the functions of the lung and spleen.

  16. Increasing Access and Relevance in Distance Education

    ERIC Educational Resources Information Center

    Mendenhall, Robert W.

    2009-01-01

    Access to higher education is subject to many factors including affordability, time and geography. Distance education can deliver education to those that live far from a campus. Some of that distance education may be synchronous, or live, requiring students to be available at certain times. Flexibility and access are increased when the instruction…

  17. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

    PubMed

    Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio; Ezquer, Fernando

    2017-01-01

    Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when

  18. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

    PubMed Central

    Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio

    2017-01-01

    Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when

  19. Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria.

    PubMed

    Rössing, K; Novak, N; Mommert, S; Pfab, F; Gehring, M; Wedi, B; Kapp, A; Raap, U

    2011-10-01

    Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non-allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Thus, we wanted to address the regulation of the neurotrophin brain-derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Fifty adult patients with chronic spontaneous urticaria and 23 skin-healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan-neurotrophin receptor p75(NTR) by immunohistochemistry. BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non-atopic skin-healthy controls (P<0.001). Furthermore, epidermal and dermal expression of BDNF and epidermal expression of p75(NTR) was significantly higher in patients with chronic spontaneous urticaria compared with controls (P<0.05-0.001). There was no difference with regard to the expression of trkB between chronic spontaneous urticaria and controls and no difference in BDNF serum levels between autologous serum skin test-positive (n=23) and -negative (n=27) patients with chronic spontaneous urticaria. This study shows that BDNF is increased in serum and diseased skin of patients with chronic spontaneous urticaria, suggesting a role for

  20. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines.

    PubMed

    Witta, Samir E; Gemmill, Robert M; Hirsch, Fred R; Coldren, Christopher D; Hedman, Karla; Ravdel, Larisa; Helfrich, Barbara; Dziadziuszko, Rafal; Chan, Daniel C; Sugita, Michio; Chan, Zeng; Baron, Anna; Franklin, Wilbur; Drabkin, Harry A; Girard, Luc; Gazdar, Adi F; Minna, John D; Bunn, Paul A

    2006-01-15

    The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer.

  1. Situational and contextual factors that increase the risk of harm when students drink: case-control and case-crossover investigation.

    PubMed

    Connor, Jennie; Cousins, Kimberly; Samaranayaka, Ari; Kypri, Kypros

    2014-07-01

    Better understanding of the circumstances of alcohol-related adverse events experienced by university students could identify opportunities for prevention. We aimed to identify situational and contextual factors associated with unintentional injury, assault, unsafe sex, sexual assault and drink-driving/riding amongst university students. We conducted a Web-based survey of full-time students aged 17-25 years at five New Zealand universities (n = 2683) and carried out between- and within-subjects comparisons (case-control and case-crossover, respectively) of situational and contextual characteristics of events in the last seven days and control drinking occasions. The response fraction was 49%. For the seven days preceding the survey, 4.9% of women and 7.4% of men reported at least one of the defined events while they were drinking or soon after. The number of drinking locations and getting drunker than expected were strongly associated with risk of an event in both case-control and case-crossover models, independent of consumption. Total number of drinks, drinking later and into the morning, and drinking with close friends were also associated with increased risk in the case-control analysis. No gender difference was seen after controlling for drinking and contextual factors. Strategies to reduce the duration and volume of alcohol consumption, including earlier closing of licensed premises, should be considered as countermeasures for alcohol-related adverse events. The use of two different comparison groups for the circumstances of adverse events when drinking can strengthen inferences about the contribution of contextual factors. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  2. Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?

    PubMed

    Büning, Carsten; Geissler, Nora; Prager, Matthias; Sturm, Andreas; Baumgart, Daniel C; Büttner, Janine; Bühner, Sabine; Haas, Verena; Lochs, Herbert

    2012-10-01

    A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

  3. Factors that affect the postnatal increase in superior mesenteric artery blood flow velocity in very low birth weight preterm infants.

    PubMed

    Havranek, Thomas; Miladinovic, Branko; Wadhawan, Rajan; Carver, Jane D

    2012-04-15

    To identify factors related to the postnatal increase in superior mesenteric artery blood flow velocity (SMA BFV). SMA BFV was measured in 35 infants (birth weight 1047±246 g) on day of life (DOL) 1, 3, 5, 7 10 and 14. Latent curve modeling (LCM) was used to measure the longitudinal change in BFV for each subject, and the correlation between changes in BFV and baseline values. Non-parametric correlations were calculated between BFV and variables previously reported to be related to SMA BFV. There was significant variability in SMA BFV on DOL 1, a significant increase from DOL 1-14, and significant variability in the postnatal increase. Infants with higher enteral feeding volumes had greater increases, while infants receiving positive pressure ventilation or hyperalimentation had lower increases. Several clinical factors affect the postnatal increase in SMA BFV. The use of LCM is useful in longitudinal studies of very low birth weight (VLBW) infants, who are clinically and demographically heterogeneous.

  4. Stroke Epidemiology and Risk Factor Management.

    PubMed

    Guzik, Amy; Bushnell, Cheryl

    2017-02-01

    Death from stroke has decreased over the past decade, with stroke now the fifth leading cause of death in the United States. In addition, the incidence of new and recurrent stroke is declining, likely because of the increased use of specific prevention medications, such as statins and antihypertensives. Despite these positive trends in incidence and mortality, many strokes remain preventable. The major modifiable risk factors are hypertension, diabetes mellitus, tobacco smoking, and hyperlipidemia, as well as lifestyle factors, such as obesity, poor diet/nutrition, and physical inactivity. This article reviews the current recommendations for the management of each of these modifiable risk factors. It has been documented that some blood pressure medications may increase variability of blood pressure and ultimately increase the risk for stroke. Stroke prevention typically includes antiplatelet therapy (unless an indication for anticoagulation exists), so the most recent evidence supporting use of these drugs is reviewed. In addition, emerging risk factors, such as obstructive sleep apnea, electronic cigarettes, and elevated lipoprotein (a), are discussed. Overall, secondary stroke prevention includes a multifactorial approach. This article incorporates evidence from guidelines and published studies and uses an illustrative case study throughout the article to provide examples of secondary prevention management of stroke risk factors.

  5. Linking climate and environmental factors to the recent and surprising growth increase of red spruce trees across the northeastern US

    NASA Astrophysics Data System (ADS)

    Kosiba, A. M.; Schaberg, P. G.; Rayback, S. A.; Hawley, G. J.

    2016-12-01

    Recent investigations have uncovered an unanticipated trend: red spruce (Picea rubens Sarg.) trees in the northeastern US are undergoing a marked surge in growth. This discovery stands in contrast to the declines in growth and vigor for red spruce that were documented in the second half of the 20th century and quantitatively attributed to acid deposition-induced calcium depletion. Further, predictions of potential habitat due to climate change depict red spruce habitat constricting from low elevations and latitudes. Considering these conflicting findings, we asked: what factors are most likely stimulating growth increases for red spruce trees? Here we use a uniquely large and both spatially- and temporally-explicit tree ring dataset to assess changes in red spruce growth over time. We compare patterns in growth to local weather data, atmospheric deposition rates, and other environmental and forest-stand metrics, including nutrient soil status and buffering capacity. These results allow us to model areas in the region where we predict similar growth increases for red spruce trees. Through this study, we suggest that this temperate conifer may be uniquely posed to benefit from a lengthened functional growing season, increased annual temperatures, particularly in winter, and decreased atmospheric pollution levels that proved problematic in the past.

  6. Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance.

    PubMed

    Bhat, Virunya S; Meek, M E Bette; Valcke, Mathieu; English, Caroline; Boobis, Alan; Brown, Richard

    2017-10-01

    The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.

  7. Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

    PubMed

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

    2008-12-01

    To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

  8. Comparing Factor, Class, and Mixture Models of Cannabis Initiation and DSM Cannabis Use Disorder Criteria, Including Craving, in the Brisbane Longitudinal Twin Study

    PubMed Central

    Kubarych, Thomas S.; Kendler, Kenneth S.; Aggen, Steven H.; Estabrook, Ryne; Edwards, Alexis C.; Clark, Shaunna L.; Martin, Nicholas G.; Hickie, Ian B.; Neale, Michael C.; Gillespie, Nathan A.

    2014-01-01

    Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use. PMID:24588857

  9. Metabolic syndrome is a significant and independent risk factor for increased arterial stiffness in Japanese subjects.

    PubMed

    Satoh, Hiroki; Kishi, Reiko; Tsutsui, Hiroyuki

    2009-12-01

    Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular disease; however, the impact of MetS on arterial stiffness has not been fully established in the general Japanese population. We analyzed the relationship between MetS and the severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 2744 male and 358 female subjects aged 38-62 years, adjusted for conventional risk factors and C-reactive protein. The prevalence rates of MetS identified by Japanese criteria were 22.7% (n=624) and 7.8% (n=28) in male and female subjects, respectively. The subjects with MetS had significantly greater mean values of baPWV than those without MetS among both male and female subjects (1444+/-209 vs. 1294+/-165 cm/s in male subjects, P<0.001; 1379+/-151 vs. 1220+/-171 cm/s in female subjects, P<0.001). After adjustment for atherosclerotic variables such as age, smoking habits, total cholesterol and C-reactive protein, the odds ratio (OR) of MetS for increased baPWV was 3.65 in male subjects (95% confidence interval (CI): 2.99-4.47, P<0.001) and 8.02 in female subjects (95% CI: 3.18-20.25 P<0.001). In conclusion, MetS was identified as a significant and independent risk factor for increased arterial stiffness in both the male and female general population in Japan.

  10. Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

    PubMed

    Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

    2006-03-01

    The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

  11. [Evaluation of the increasing serum lactate dehydrogenase caused by recombinant human granulocyte-colony stimulating factor].

    PubMed

    Sawa, Toshiyuki; Yoshida, Tsutomu; Ikoma, Tetsuroh; Toyoda, Miki; Ohno, Yasushi; Fujiwara, Hisayoshi

    2003-01-01

    Increasing serum lactate dehydrogenase (LDH) is often caused by granulocyte-colony stimulating factor (G-CSF) for leukopenia following chemotherapy in patients with lung cancer. To evaluate the increase in LDH, we investigated the significance of its elevation and LDH isozyme during chemotherapy supported by recombinant human G-CSF (rhG-CSF). To exclude effects of liver diseases and chemotherapy-induced liver dysfunction, only patients in whom laboratory findings concerning liver function were within normal range were entered in this study. If leukocyte or neutrophil counts were less than grade 3, subcutaneous injection of 50 micrograms/m2 of filgrastim was given daily until leukocyte counts increased to more than 10,000/mm3. Sixty patients with unresectable lung cancer were enrolled in this study and the LDH isozyme was evaluable in 54 patients. Increasing LDH was observed in 38 patients(70.4%), and LDH isozyme was measured in these 38 patients. Increases in granulocytes and LDH isozymes were found to have a positive correlation. LDH2, LDH3, LDH4 and LDH5 increased significantly after rhG-CSF administration, although LDH 1 did not increase. It was found that a rapid increase in leukocytes by rhG-CSF induced an increase in LDH, especially LDH 3.4. Considering the results of principal component analysis and the distribution ratio of LDH isozymes in neutrophils, it is thought that elevation of LDH is reflected in the rapid production and consumption of neutrophils.

  12. Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism.

    PubMed

    Maggio, R; Riva, M; Vaglini, F; Fornai, F; Racagni, G; Corsini, G U

    1997-01-01

    The repeated finding of an apparent protective effect of cigarette smoking on the risk of Parkinson's disease is one of the few consistent results in the epidemiology of this disorder. Among the innumerous substances that originate from tobacco smoke, nicotine is by far the most widely studied, and the most likely candidate for a protective effect against neuronal degeneration in Parkinson's disease. Nicotine is a natural alkaloid that has considerable stimulatory effects on the central nervous system (CNS). Its effects on the CNS are mediated by the activation of neuronal heteromeric acetylcholine-gated ion channel receptors (nAChR, also termed nicotinic acetylcholine receptors). In the present study, we describe the neuroprotective effects of (-)nicotine in two animal models of parkinsonism: the diethyldithiocarbamate (DDC)-induced enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice, and the methamphetamine-induced neurotoxicity in rats and mice. In parallel experiments, we found that (-)nicotine induces the basic fibroblast growth factor (FGF-2) and the brain-derived neurotrophic factor (BDNF) in rat striatum. As FGF-2 and BDNF have been reported to be neuroprotective for dopaminergic cells, our data indicate that the increase in neurotrophic factors is a possible mechanism by which (-)nicotine protects from experimental parkinsonisms. Moreover, they suggest that nAChR agonists could be of potential benefit in the progression of Parkinson's disease.

  13. Saxagliptin Induces β-Cell Proliferation through Increasing Stromal Cell-Derived Factor-1α In Vivo and In Vitro.

    PubMed

    Li, Chun-Jun; Sun, Bei; Fang, Qian-Hua; Ding, Min; Xing, Yun-Zhi; Chen, Li-Ming; Yu, De-Min

    2017-01-01

    Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the saxagliptin-treated diabetic rats, subsequently the key WNT-signaling regulators, β-catenin, and AKT were activated. However, the effect of saxagliptin inducing β-cell proliferation was attenuated when we silenced the SDF-1α receptor (CXCR4) with RNAi in INS cell lines. Collectively, our data indicate that SDF-1α mediates the protective effect of saxagliptin on β-cell proliferation, suggesting that DPP-4 inhibitors have the potential role on delaying β-cell failure and SDF-1α could be a therapeutic target of β-cell regeneration.

  14. Saxagliptin Induces β-Cell Proliferation through Increasing Stromal Cell-Derived Factor-1α In Vivo and In Vitro

    PubMed Central

    Li, Chun-Jun; Sun, Bei; Fang, Qian-Hua; Ding, Min; Xing, Yun-Zhi; Chen, Li-Ming; Yu, De-Min

    2017-01-01

    Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the saxagliptin-treated diabetic rats, subsequently the key WNT-signaling regulators, β-catenin, and AKT were activated. However, the effect of saxagliptin inducing β-cell proliferation was attenuated when we silenced the SDF-1α receptor (CXCR4) with RNAi in INS cell lines. Collectively, our data indicate that SDF-1α mediates the protective effect of saxagliptin on β-cell proliferation, suggesting that DPP-4 inhibitors have the potential role on delaying β-cell failure and SDF-1α could be a therapeutic target of β-cell regeneration. PMID:29230196

  15. Factors That Increase the Risk of Infection After Elbow Arthroscopy: Analysis of Patient Demographics, Medical Comorbidities, and Steroid Injections in 2,704 Medicare Patients.

    PubMed

    Camp, Christopher L; Cancienne, Jourdan M; Degen, Ryan M; Dines, Joshua S; Altchek, David W; Werner, Brian C

    2017-06-01

    To use a national database to determine (1) the incidence of joint infection after elbow arthroscopy, (2) identify independent patient-related risk factors for infection, and (3) determine the influence of concomitant intra-articular corticosteroid injection on infection risk. The 100% Medicare Standard Analytic Files were queried to identify patients who underwent elbow arthroscopy from 2005 to 2012. Postoperative elbow infections occurring within 6 months of surgery were identified using both International Classification of Diseases, 9th Revision codes for postoperative infection and Current Procedural Terminology codes for the surgical treatment of a postoperative infection. Patients were excluded if their initial arthroscopic procedure was performed for infection. A multivariate binomial logistic regression analysis was then used to evaluate patient-related risk factors for postoperative infection. Of the 2,704 elbow arthroscopy cases identified, 42 (1.55%) developed a postoperative infection. The annual incidence of infections did not increase significantly over the course of the study (P = .374). A number of patient demographics and medical comorbidities significantly increased the risk of infection. The most notable factors included age ≥ 65 years (odds ratio [OR] 2.38, P = .006), body mass index > 40 (OR 1.97, P = .024), tobacco usage (OR 1.80, P = .046), alcohol usage (OR 4.01, P < .001), diabetes mellitus (OR 2.10, P = .015), inflammatory arthritis (OR 2.81, P < .001), hypercoagulable disorder (OR 2.51, P = .015), and intra-articular corticosteroid injection at the time of arthroscopy (OR 2.79, P = .006). The annual number of elbow arthroscopies performed in the United States has increased steadily; however, the postoperative infection rate remained consistently low at 1.55%. There are a number of patient-specific risk factors that increase this risk with OR ranging from 1.97 to 4.01. Similarly, patients who receive an intra

  16. Tumor necrosis factor-{alpha} enhances IL-15-induced natural killer cell differentiation

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

    Lee, Jiwon; Lee, Suk Hyung; Korea University of Science and Technology, Yusong, Daejeon 305-333

    2009-09-04

    The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-{alpha} (TNF-{alpha}) is a positive regulator of NK cell differentiation. TNF-{alpha} augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-{alpha} alone also induced NK cell maturation as well as IL-15. TNF-{alpha} also increased IFN-{gamma} production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-{alpha} and IL-15. In addition, TNF-{alpha} increased nuclear factor-kappamore » B (NF-{kappa}B) activity in NK cells and inhibition of NF-{kappa}B impeded TNF-{alpha}-enhanced NK cell maturation. Overall, these data suggest that TNF-{alpha} significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-{kappa}B activity.« less

  17. Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1.

    PubMed Central

    Ellis, Peter D; Martin, Karen M; Rickman, Colin; Metcalfe, James C; Kemp, Paul R

    2002-01-01

    Recent evidence has implicated CC(A/T(richG))GG (CArG) boxes, binding sites for serum response factor (SRF), in the regulation of expression of a number of genes in response to changes in the actin cytoskeleton. In many cases, the activity of SRF at CArG boxes is modulated by transcription factors binding to overlapping (e.g. Yin Yang 1, YY1) or adjacent (e.g. ets) binding sites. However, the mechanisms by which SRF activity is regulated by the cytoskeleton have not been determined. To investigate these mechanisms, we screened for cells that did or did not increase the activity of a fragment of the promoter for a smooth-muscle (SM)-specific gene SM22alpha, in response to changes in actin cytoskeletal polymerization induced by LIM kinase. These experiments showed that vascular SM cells (VSMCs) and C2C12 cells increased the activity of promoters containing at least one of the SM22alpha CArG boxes (CArG near) in response to LIM kinase, whereas P19 cells did not. Bandshift assays using a probe to CArG near showed that P19 cells lacked detectable YY1 DNA binding to the CArG box in contrast with the other two cell types. Expression of YY1 in P19 cells inhibited SM22alpha promoter activity and conferred responsiveness to LIM kinase. Mutation of the CArG box to inhibit YY1 or SRF binding indicated that both factors were required for the LIM kinase response in VSMCs and C2C12 cells. The data indicate that changes in the actin cytoskeletal organization modify SRF activity at CArG boxes by modulating YY1-dependent inhibition. PMID:12023898

  18. Clinical and Surgical Factors Associated With Increased Epilepsy Risk in Children With Hydrocephalus.

    PubMed

    Tully, Hannah M; Kukull, Walter A; Mueller, Beth A

    2016-06-01

    Children with hydrocephalus are at risk for epilepsy both due to their underlying condition and as a consequence of surgical treatment; however, the relative contributions of these factors remain unknown. The authors sought to characterize epilepsy among children with infancy-onset hydrocephalus and to examine the risks of epilepsy associated with hydrocephalus subtype and with factors related to surgical treatment. We conducted a longitudinal cohort study of all children with infancy-onset hydrocephalus treated at a major regional children's hospital during 2002 to 2012, with follow-up to ascertain risk factors and epilepsy outcome through April 2015. Poisson regression was used to calculate adjusted risk ratios and 95% confidence intervals for associations. Among 379 children with hydrocephalus, 86 (23%) developed epilepsy (mean onset age = 2.7 years), almost one fifth of whom had a history of infantile spasms. Relative to spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes had fourfold higher risks of developing epilepsy. Among children who underwent surgery, surgical infection doubled the risk of epilepsy (risk ratio = 2.0, 95% confidence interval = 1.4 to 3.0). Epilepsy was associated with surgical failure for intracranial reasons but not extracranial reasons (risk ratio = 1.7, 95% confidence interval = 1.1 to 2.7; risk ratio = 1.1, 95% confidence interval = 0.7 to 1.9, respectively). Epilepsy is common among children with hydrocephalus. Compared with children with spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes have a markedly increased risk of epilepsy. Surgical infection doubles the risk of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. ICSI does not increase the cumulative live birth rate in non-male factor infertility.

    PubMed

    Li, Z; Wang, A Y; Bowman, M; Hammarberg, K; Farquhar, C; Johnson, L; Safi, N; Sullivan, E A

    2018-06-12

    What is the cumulative live birth rate following ICSI cycles compared with IVF cycles for couples with non-male factor infertility? ICSI resulted in a similar cumulative live birth rate compared with IVF for couples with non-male factor infertility. The ICSI procedure was developed for couples with male factor infertility. There has been an increased use of ICSI regardless of the cause of infertility. Cycle-based statistics show that there is no difference in pregnancy rates between ICSI and IVF in couples with non-male factor infertility. However, evidence indicates that ICSI is associated with an increased risk of adverse perinatal outcomes. A population-based cohort of 14 693 women, who had their first ever stimulated cycle with fertilization performed for at least one oocyte by either IVF or ICSI between July 2009 and June 2014 in Victoria, Australia was evaluated retrospectively. The pregnancy and birth outcomes following IVF or ICSI were recorded for the first oocyte retrieval (fresh stimulated cycle and associated thaw cycles) until 30 June 2016, or until a live birth was achieved, or until all embryos from the first oocyte retrieval had been used. Demographic, treatment characteristics and resulting outcome data were obtained from the Victorian Assisted Reproductive Treatment Authority. Data items in the VARTA dataset were collected from all fertility clinics in Victoria. Women were grouped by whether they had undergone IVF or ICSI. The primary outcome was the cumulative live birth rate, which was defined as live deliveries (at least one live birth) per woman after the first oocyte retrieval. A discrete-time survival model was used to evaluate the cumulative live birth rate following IVF and ICSI. The adjustment was made for year of treatment in which fertilization occurred, the woman's and male partner's age at first stimulated cycle, parity and the number of oocytes retrieved in the first stimulated cycle. A total of 4993 women undergoing IVF and 8470

  20. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.

    PubMed

    Tomlinson, Elizabeth; Fu, Ling; John, Linu; Hultgren, Bruce; Huang, Xiaojian; Renz, Mark; Stephan, Jean Philippe; Tsai, Saio Ping; Powell-Braxton, Lyn; French, Dorothy; Stewart, Timothy A

    2002-05-01

    The fibroblast growth factors (FGFs), and the corresponding receptors, are implicated in more than just the regulation of epithelial cell proliferation and differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism. The recently described FGF19 is unusual in that it is nonmitogenic and appears to interact only with FGF receptor-4. Here, we report that FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure. Further, the FGF19 transgenic mice did not become obese or diabetic on a high fat diet. The FGF19 transgenic mice had increased brown adipose tissue mass and decreased liver expression of acetyl coenzyme A carboxylase 2, providing two mechanisms by which FGF19 may increase energy expenditure. Consistent with the reduction in expression of acetyl CoA carboxylase 2, liver triglyceride levels were reduced.

  1. Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

    PubMed

    Anderson, D

    2001-09-01

    It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which

  2. Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment

    PubMed Central

    Chihara, Yuichi; Akamizu, Takashi; Azuma, Masanori; Murase, Kimihiko; Harada, Yuka; Tanizawa, Kiminobu; Handa, Tomohiro; Oga, Toru; Mishima, Michiaki; Chin, Kazuo

    2015-01-01

    Study Objectives: There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Methods: Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Results: Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. Conclusions: Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in

  3. Bisphenol A exposure induces increased microglia and microglial related factors in the murine embryonic dorsal telencephalon and hypothalamus.

    PubMed

    Takahashi, Mifumi; Komada, Munekazu; Miyazawa, Ken; Goto, Shigemi; Ikeda, Yayoi

    2018-03-01

    Bisphenol A (BPA) is a widely used compound in the food packaging industry. Prenatal exposure to BPA induces histological abnormalities in the neocortex and hypothalamus in association with abnormal behaviors. Yet, the molecular and cellular neurodevelopmental toxicological mechanisms of BPA are incompletely characterized on neuroinflammatory-related endopoints. To evaluate the neurodevelopmental effects of BPA exposure in mouse embryos, we examined microglial numbers as well as the expression of microglial-related factors in the E15.5 embryonic brain. BPA-exposed embryos exhibited significant increases in Iba1-immunoreactive microglial numbers in the dorsal telencephalon and the hypothalamus compared to control embryos. Further, the expression levels of microglial markers (Iba1, CD16, iNOS, and CD206), inflammatory factors (TNFα and IL4), signal transducing molecules (Cx3Cr1 and Cx3Cl1), and neurotrophic factor (IGF1) were altered in BPA-exposed embryos. These findings suggest that BPA exposure increases microglial numbers in the brain and alters the neuroinflammatory status at a transcriptional level. Together, these changes may represent a novel target for neurodevelopmental toxicity assessment after BPA exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    EPA Science Inventory

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  5. Modeling genetic and environmental factors to increase heritability and ease the identification of candidate genes for birth weight: a twin study.

    PubMed

    Gielen, M; Lindsey, P J; Derom, C; Smeets, H J M; Souren, N Y; Paulussen, A D C; Derom, R; Nijhuis, J G

    2008-01-01

    Heritability estimates of birth weight have been inconsistent. Possible explanations are heritability changes during gestational age or the influence of covariates (e.g. chorionicity). The aim of this study was to model birth weights of twins across gestational age and to quantify the genetic and environmental components. We intended to reduce the common environmental variance to increase heritability and thereby the chance of identifying candidate genes influencing the genetic variance of birth weight. Perinatal data were obtained from 4232 live-born twin pairs from the East Flanders Prospective Twin Survey, Belgium. Heritability of birth weights across gestational ages was estimated using a non-linear multivariate Gaussian regression with covariates in the means model and in covariance structure. Maternal, twin-specific, and placental factors were considered as covariates. Heritability of birth weight decreased during gestation from 25 to 42 weeks. However, adjusting for covariates increased the heritability over this time period, with the highest heritability for first-born twins of multipara with separate placentas, who were staying alive (from 52% at 25 weeks to 30% at 42 weeks). Twin-specific factors revealed latent genetic components, whereas placental factors explained common and unique environmental factors. The number of placentas and site of the insertion of the umbilical cord masked the effect of chorionicity. Modeling genetic and environmental factors leads to a better estimate of their role in growth during gestation. For birth weight, mainly environmental factors were explained, resulting in an increase of the heritability and thereby the chance of finding genes influencing birth weight in linkage and association studies.

  6. Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain.

    PubMed

    Nishio, T; Sunohara, N; Furukawa, S; Akiguchi, I; Kudo, Y

    1998-03-01

    We studied whether nicergoline, clinically active in chronic cerebrovascular insufficiency, influences nerve growth factor (NGF) levels in the rat brain. In young Fischer rats, repeated intraperitoneal injections of nicergoline (0.3 and 1.0 mg/kg body weight) did not show any effects on frontal NGF contents determined by a highly sensitive enzyme immunoassay. In aged rats, 22-month-old, however, repeated injections of nicergoline (1.0 mg/kg body weight) induced a significant increase in the NGF level in the frontal region.

  7. Does antiperspirant use increase the risk of aluminium-related disease, including Alzheimer's disease?

    PubMed

    Exley, C

    1998-03-01

    Aluminium salts are the major constituent of many widely used antiperspirant products. The use of such antiperspirants has been linked with the systemic accumulation of aluminium and an increased risk of Alzheimer's disease. But can the frequent use of aluminium-based antiperspirants lead to the accumulation of toxic levels of aluminium? And are there measures that we can take to reduce such accumulation without reducing the effectiveness of antiperspirants?

  8. Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

    PubMed

    Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

    2007-10-01

    A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

  9. Expression of virulence factors by Staphylococcus aureus grown in serum.

    PubMed

    Oogai, Yuichi; Matsuo, Miki; Hashimoto, Masahito; Kato, Fuminori; Sugai, Motoyuki; Komatsuzawa, Hitoshi

    2011-11-01

    Staphylococcus aureus produces many virulence factors, including toxins, immune-modulatory factors, and exoenzymes. Previous studies involving the analysis of virulence expression were mainly performed by in vitro experiments using bacterial medium. However, when S. aureus infects a host, the bacterial growth conditions are quite different from those in a medium, which may be related to the different expression of virulence factors in the host. In this study, we investigated the expression of virulence factors in S. aureus grown in calf serum. The expression of many virulence factors, including hemolysins, enterotoxins, proteases, and iron acquisition factors, was significantly increased compared with that in bacterial medium. In addition, the expression of RNA III, a global regulon for virulence expression, was significantly increased. This effect was partially restored by the addition of 300 μM FeCl₃ into serum, suggesting that iron depletion is associated with the increased expression of virulence factors in serum. In chemically defined medium without iron, a similar effect was observed. In a mutant with agr inactivated grown in serum, the expression of RNA III, psm, and sec4 was not increased, while other factors were still induced in the mutant, suggesting that another regulatory factor(s) is involved. In addition, we found that serum albumin is a major factor for the capture of free iron to prevent the supply of iron to bacteria grown in serum. These results indicate that S. aureus expresses virulence factors in adaptation to the host environment.

  10. Vitamin D Supplementation increases fibroblast growth factor-23 in HIV-infected youth treated with tenofovir disoproxil fumarate

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biologic...

  11. Risk factor management in a contemporary Australian population at increased cardiovascular disease risk.

    PubMed

    Campbell, D J; Coller, J M; Gong, F F; McGrady, M; Prior, D L; Boffa, U; Shiel, L; Liew, D; Wolfe, R; Owen, A J; Krum, H; Reid, C M

    2017-11-14

    Effective management of cardiovascular and chronic kidney disease risk factors offers longer, healthier lives and savings in health care. We examined risk factor management in participants of the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. Medical history, clinical examination, full blood examination and biochemistry (without lipids and HbA1c) were performed for 3847 participants on enrolment, and blood pressure, lipids and HbA1c were measured 1-2 years after enrolment for 3202 participants. Despite 99% of 3294 participants with hypertension receiving antihypertensive medication, half had blood pressures >140/90 mmHg. Approximately 77% of participants were overweight or obese, with one third obese. Additionally, 74% of participants at high cardiovascular disease risk had low density lipoprotein cholesterol levels ≥2 mmol/l, one third of diabetic participants had HbA1c >7%, 22% had estimated glomerular filtration rate <60 ml/min/1.73m 2 , and substantial proportions had under-utilisation of antiplatelet therapy, anticoagulation for atrial fibrillation, and were physically inactive. This population demonstrated substantial potential to reduce cardiovascular and renal morbidity and mortality and health care costs through more effective management of modifiable risk factors. This article is protected by copyright. All rights reserved.

  12. Asymmetric dimethylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease.

    PubMed

    Liu, Xiaohong; Xu, Xin; Shang, Ruru; Chen, Yingjie

    2018-06-19

    Patients with chronic kidney disease have an increased cardiovascular morbidity and mortality. It has been recognized that the traditional cardiovascular risk factors could only partially explain the increased cardiovascular morbidity and mortality in patients with chronic kidney disease. Asymmetric dimethylarginine (ADMA) and N-monomethy l-arginine (L-NMMA) are endogenous inhibitors of nitric oxide synthases that attenuate nitric oxide production and enhance reactive oxidative specie generation. Increased plasma ADMA and/or L-NMMA are strong and independent risk factor for chronic kidney disease, and various cardiovascular diseases such as hypertension, coronary artery disease, atherosclerosis, diabetes, and heart failure. Both ADMA and L-NMMA are also eliminated from the body through either degradation by dimethylarginine dimethylaminohydrolase-1 (DDAH1) or urine excretion. This short review will exam the literature of ADMA and L-NMMA degradation and urine excretion, and the role of chronic kidney diseases in ADMA and L-NMMA accumulation and the increased cardiovascular disease risk. Based on all available data, it appears that the increased cardiovascular morbidity in chronic kidney disease may relate to the dramatic increase of systemic ADMA and L-NMMA after kidney failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

    PubMed

    Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

    2015-01-01

    For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

  14. Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

    PubMed Central

    Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

    2015-01-01

    For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection. PMID:26413188

  15. Increasing numbers of nonaneurysmal subarachnoid hemorrhage in the last 15 years: antithrombotic medication as reason and prognostic factor?

    PubMed

    Konczalla, Juergen; Kashefiolasl, Sepide; Brawanski, Nina; Senft, Christian; Seifert, Volker; Platz, Johannes

    2016-06-01

    OBJECT Subarachnoid hemorrhage (SAH) is usually caused by a ruptured intracranial aneurysm, but in some patients no source of hemorrhage can be detected. More recent data showed increasing numbers of cases of spontaneous nonaneurysmal SAH (NASAH). The aim of this study was to analyze factors, especially the use of antithrombotic medications such as systemic anticoagulation or antiplatelet agents (aCPs), influencing the increasing numbers of cases of NASAH and the clinical outcome. METHODS Between 1999 and 2013, 214 patients who were admitted to the authors' institution suffered from NASAH, 14% of all patients with SAH. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Risk factors were identified based on the outcome. RESULTS The number of patients with NASAH increased significantly in the last 15 years of the study period. There was a statistically significant increase in the rate of nonperimesencephalic (NPM)-SAH occurrence and aCP use, while the proportion of elderly patients remained stable. Favorable outcome (mRS 0-2) was achieved in 85% of cases, but patients treated with aCPs had a significantly higher risk for an unfavorable outcome. Further analysis showed that elderly patients, and especially the subgroup with a Fisher Grade 3 bleeding pattern, had a high risk for an unfavorable outcome, whereas the subgroup of NPM-SAH without a Fisher Grade 3 bleeding pattern had a favorable outcome, similar to perimesencephalic (PM)-SAH. CONCLUSIONS Over the years, a significant increase in the number of patients with NASAH has been observed. Also, the rate of aCP use has increased significantly. Risk factors for an unfavorable outcome were age > 65 years, Fisher Grade 3 bleeding pattern, and aCP use. Both "PM-SAH" and "NPM-SAH without a Fisher Grade 3 bleeding pattern" had excellent outcomes. Patients with NASAH and a Fisher Grade 3 bleeding pattern had a significantly higher risk for an unfavorable outcome and death. Therefore, for further

  16. Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

    PubMed

    Oberle, Doris; Pavel, Jutta; Mayer, Geert; Geisler, Peter; Keller-Stanislawski, Brigitte

    2017-06-01

    Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Survey indicated that core outcome set development is increasingly including patients, being conducted internationally and using Delphi surveys.

    PubMed

    Biggane, Alice M; Brading, Lucy; Ravaud, Philippe; Young, Bridget; Williamson, Paula R

    2018-02-17

    There are numerous challenges in including patients in a core outcome set (COS) study, these can vary depending on the patient group. This study describes current efforts to include patients in the development of COS, with the aim of identifying areas for further improvement and study. Using the COMET database, corresponding authors of COS projects registered or published from 1 January 2013 to 2 February 2017 were invited via a personalised email to participate in a short online survey. The survey and emails were constructed to maximise the response rate by following the academic literature on enhancing survey responses. Personalised reminder emails were sent to non-responders. This survey explored the frequency of patient input in COS studies, who was involved, what methods were used and whether or not the COS development was international. One hundred and ninety-two COS developers were sent the survey. Responses were collected from 21 February 2017 until 7 May 2017. One hundred and forty-six unique developers responded, yielding a 76% response rate and data in relation to 195 unique COSs (as some developers had worked on multiple COSs). Of focus here are their responses regarding 162 COSs at the published, completed or ongoing stages of development. Inclusion of patient participants was indicated in 87% (141/162) of COSs in the published completed or ongoing stages and over 94% (65/69) of ongoing COS projects. Nearly half (65/135) of COSs included patient participants from two or more countries and 22% (30/135) included patient participants from five or more countries. The Delphi survey was reported as being used singularly or in combination with other methods in 85% (119/140) of projects. Almost a quarter (16/65) of ongoing studies reported using a combination of qualitative interviews, Delphi survey and consensus meeting. These findings indicated that the Delphi survey is the most popular method of facilitating patient participation, while the combination of

  18. Cuprophane but not synthetic membrane induces increases in serum tumor necrosis factor-alpha levels during hemodialysis.

    PubMed

    Canivet, E; Lavaud, S; Wong, T; Guenounou, M; Willemin, J C; Potron, G; Chanard, J

    1994-01-01

    Cytokine synthesis and secretion by blood mononuclear cells is a well-documented phenomenon in hemodialyzed patients. The present study was conducted in 17 chronically hemodialyzed patients to test the relative effect of uremic toxicity, membrane biocompatibility, dialysate composition, and the risk of endotoxinemia on the serum level of tumor necrosis factor-alpha (TNF-alpha). The only significant parameter that influenced circulating TNF-alpha was the chemical characteristics of the dialyzer membrane. Tumor necrosis factor-alpha levels significantly increased during the session with cuprophane, whereas they decreased with AN69. The TNF-alpha increase was documented whatever the dialysate buffer and the presence or absence (negative Limulus amoebocyte lysate test) of endotoxin in the dialysate. In the subgroup of patients treated with a contaminated dialysate and AN69, none had clinical symptoms and the central body temperature remained constant throughout the session. In these patients, serum TNF-alpha levels did not change after priming the dialyzer with sterile saline. In conclusion, the serum TNF-alpha level during hemodialysis appears to be modulated by biocompatibility, permeability, and binding properties of dialysis membrane rather than dialysate composition. Endotoxin in the dialysate did not result in positive TNF-alpha balance no matter what its possible priming effect on mononucleated blood cells.

  19. Increasing the marketability and recognition of provider network joint ventures.

    PubMed

    Sjobeck, S J

    1998-08-01

    Physicians have been developing provider network joint ventures to market their services jointly to managed care plans, employers, and other purchasers. Over the past few years, external market factors have produced a growing impact on these joint ventures. These external market factors include the Federal government's revised antitrust guidelines, National Committee for Quality Assurance activities, and state and Federal consumer protection laws. Simply responding to these forces may not increase a provider network's marketability unless the network can demonstrate its value in the terms and measurements accepted by the consumer, managed care plans, and provider networks. By doing so, a provider network can not only increase its marketability, but also increase its recognition in the market, improve its competitive advantage, and enhance its return on investment.

  20. Is increased antidepressant exposure a contributory factor to the obesity pandemic?

    PubMed Central

    Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

    2016-01-01

    of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalating use of antidepressants, resulting in high rates of antidepressant exposure, might be a contributory factor to the obesity epidemic. PMID:26978741

  1. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.

    PubMed

    Fu, Ling; John, Linu M; Adams, Sean H; Yu, Xing Xian; Tomlinson, Elizabeth; Renz, Mark; Williams, P Mickey; Soriano, Robert; Corpuz, Racquel; Moffat, Barbara; Vandlen, Richard; Simmons, Laura; Foster, Jessica; Stephan, Jean-Philippe; Tsai, Siao Ping; Stewart, Timothy A

    2004-06-01

    Hormonal control of metabolic rate can be important in regulating the imbalance between energy intake and expenditure that underlies the development of obesity. In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05 liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant change in food intake. Furthermore, in addition to a reduction in weight gain, treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin. To explore the mechanisms underlying the FGF19-mediated increase in metabolic rate, we profiled the FGF19-induced gene expression changes in the liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a gene expression profile that is consistent with activation of this tissue. We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent with the experimentally determined increase in fat oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation.

  2. Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment.

    PubMed

    Chihara, Yuichi; Akamizu, Takashi; Azuma, Masanori; Murase, Kimihiko; Harada, Yuka; Tanizawa, Kiminobu; Handa, Tomohiro; Oga, Toru; Mishima, Michiaki; Chin, Kazuo

    2015-08-15

    There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of

  3. Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

    PubMed Central

    Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M.; Kim, Sharon; Noble-Haeusslein, Linda J.

    2011-01-01

    Abstract The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits. PMID:21175261

  4. Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat.

    PubMed

    Sultanian, R; Deng, Y; Kaufman, S

    2001-05-15

    The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

  5. Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System

    PubMed Central

    Taylor, Shannon L.; Wahl-Jensen, Victoria; Copeland, Anna Maria; Jahrling, Peter B.; Schmaljohn, Connie S.

    2013-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during

  6. Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex.

    PubMed

    Croll, S D; Suri, C; Compton, D L; Simmons, M V; Yancopoulos, G D; Lindsay, R M; Wiegand, S J; Rudge, J S; Scharfman, H E

    1999-01-01

    Transgenic mice overexpressing brain-derived neurotrophic factor from the beta-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a significant passive avoidance deficit. This deficit was dependent on continued overexpression, and resolved with age as brain-derived neurotrophic factor transcripts decreased. In addition, the brain-derived neurotrophic factor transgenic mice showed increased seizure severity in response to kainic acid. Hippocampal slices from brain-derived neurotrophic factor transgenic mice showed hyperexcitability in area CA3 and entorhinal cortex, but not in dentate gyrus. Finally, area CA1 long-term potentiation was disrupted, indicating abnormal plasticity. Our data suggest that overexpression of brain-derived neurotrophic factor in the brain can interfere with normal brain function by causing learning impairments and increased excitability. The results also support the hypothesis that excess brain-derived neurotrophic factor could be pro-convulsant in the limbic system.

  7. PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

    PubMed

    Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

    2013-01-01

    Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

  8. Health Promotion Behavior of Chinese International Students in Korea Including Acculturation Factors: A Structural Equation Model.

    PubMed

    Kim, Sun Jung; Yoo, Il Young

    2016-03-01

    The purpose of this study was to explain the health promotion behavior of Chinese international students in Korea using a structural equation model including acculturation factors. A survey using self-administered questionnaires was employed. Data were collected from 272 Chinese students who have resided in Korea for longer than 6 months. The data were analyzed using structural equation modeling. The p value of final model is .31. The fitness parameters of the final model such as goodness of fit index, adjusted goodness of fit index, normed fit index, non-normed fit index, and comparative fit index were more than .95. Root mean square of residual and root mean square error of approximation also met the criteria. Self-esteem, perceived health status, acculturative stress and acculturation level had direct effects on health promotion behavior of the participants and the model explained 30.0% of variance. The Chinese students in Korea with higher self-esteem, perceived health status, acculturation level, and lower acculturative stress reported higher health promotion behavior. The findings can be applied to develop health promotion strategies for this population. Copyright © 2016. Published by Elsevier B.V.

  9. The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

    PubMed

    Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

    2017-08-18

    Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

  10. Effective Factors in Enhancing School Manager's Job Motivation

    PubMed Central

    Mirzamani, S. Mahmoud; Esfahani, Hamideh Darb

    2011-01-01

    Objective This study examines the effective factors in enhancing school manager's job motivation from viewpoint of school mangers, teachers, education department managerial and staff experts in teaching, and also identifies and prioritizes each of these factors and indicators. Method For selecting a representative sample and increasing measurement precision, 587 people were selected using classified random sampling. The measurement tool was a 79-questionnaire made by the researcher. The questionnaire was collected using motivation theories and observing the findings of previous researches. Then, according to the three-stage Delphi technique, the questionnaire was sent to experts in education. The reliability of instruments was measured by calculating Cronbach's Alpha coefficient, and total reliability of the test was 0.99; the validity of the instrument was assessed by factor analysis (Construct Validity) and its load factor was 0.4 which was high. Results The results from factor analysis shows that the effective factors in enhancing manager's job motivation are as follows: self- actualization (51%) including 28 indices; social factor (7/9%) including 22 indices; self-esteem (3.2%) including 17 indices; job desirable features (2.2%) including 4 indices; physiologic (1.8%) including 4 indices; and job richness (1.6%) including 4 indices. Conclusions The results show that the six mentioned factors determine 68% of the total variance of manager's motivation. PMID:22952541

  11. Is Fibroblast growth factor 23 the leading cause of increased mortality among chronic kidney disease patients? A narrative review.

    PubMed

    Sharaf El Din, Usama A; Salem, Mona M; Abdulazim, Dina O

    2017-05-01

    The death rate among chronic kidney disease patients is the highest compared to other chronic diseases. 60% of these fatalities are cardiovascular. Cardiovascular calcifications and chronic inflammation affect almost all chronic kidney disease patients and are associated with cardiovascular mortality. Fibroblast growth factor 23 is associated with vascular calcification. Systemic inflammation in chronic kidney disease patients is multifactorial. The role of systemic inflammation in the pathogenesis of vascular calcification was recently reappraised. Fibroblast growth factor 23 was accused as a direct stimulus of left ventricular hypertrophy, uremic inflammation, and impaired neutrophil function. This review will discuss the underlying mechanisms that underlie the link between Fibroblast growth factor 23 and increased mortality encountered among chronic kidney disease patients.

  12. The Environmental Factors Influencing Attrition.

    ERIC Educational Resources Information Center

    Villella, Edward F.

    1986-01-01

    Offers an economics/business-management perspective on student attrition, focusing on the external macro-environment (including such factors as government funding of education, changing enrollment patterns, and the increased number of postsecondary institutions) and the internal micro-environment (exhibiting characteristics of intangibility,…

  13. Causes and risk factors for male-factor infertility in Nigeria: a review.

    PubMed

    Abarikwu, Sunny O

    2013-12-01

    In recent times there has been a decline in the semen quality of young healthy men worldwide, with similar findings being reported in Nigeria. Although little is known about what is responsible for the decline in male sperm count worldwide, significant associations have been reported between impaired semen quality including sperm count, motility as well as morphology and exposures to heavy metals such as cadmium and lead, mycotoxins such as aflatoxins, pesticides, industrial chemicals and endocrine factors. In Nigeria, the problem is further compounded by a variety of factors such as sexually transmitted infections, genito-urinary tract infections/inflammations and deficiencies of dietary antioxidant nutrients, thereby increasing male-factor contribution to infertility in the population. In this article, we analyze data from different sources and present evidence of the possible etiology and risk factors for male-factor infertility in Nigeria.

  14. Recombinant human granulocyte colony-stimulating factor administration in a case of neutropenia due to increased neutrophil sequestration.

    PubMed

    Carulli, G; Lazzeri, E; Lagomarsini, G; Zucca, A; Cannizzo, E; Riccioni, R; Petrini, M

    2007-01-01

    A 55-year-old female was admitted with fever which followed an episode of pseudomembranous colitis. Despite an accurate clinical investigation, there was no evidence for specific sites of infection. Remission of fever was not obtained with antibiotic therapy (gentamycin plus carbepenem) and progressive neutropenia was observed. Neutrophils fell to 0.3 x 10(9)/1. The diagnostic approach, including a bone marrow aspirate, excluded mechanisms leading to impaired neutrophil production, and in the suspect of increased neutrophil sequestration/destruction, whole-body scintigraphy with (99m)technetium-hexamethylpropyleneamineoxime ((99m)Tc-HMPAO)-labeled autologous leukocytes was performed. As a result, a site of leukocyte sequestration localized at the medium lobe of the right lung was detected. In an attempt to enhance neutrophil functions and achieve remission of infection, recombinant human granulocyte colony-stimulating factor (Filgrastim, Granulokine 30, Roche) at the dosage of 300 microg/day, subcutaneously, was added. As a results, fever disappeared in three days, but neutrophil recovery was slower, and normalization of the absolute neutrophil count (ANC) was obtained on day +7. The results obtained in this peculiar case of neutropenia, and the kinetics of both fever and ANC, suggest the possible combination of neutrophil function enhancement and an anti-inflammatory effect of rhG-CSF.

  15. Predictors, Including Blood, Urine, Anthropometry, and Nutritional Indices, of All-Cause Mortality among Institutionalized Individuals with Intellectual Disability

    ERIC Educational Resources Information Center

    Ohwada, Hiroko; Nakayama, Takeo; Tomono, Yuji; Yamanaka, Keiko

    2013-01-01

    As the life expectancy of people with intellectual disability (ID) increases, it is becoming necessary to understand factors affecting survival. However, predictors that are typically assessed among healthy people have not been examined. Predictors of all-cause mortality, including blood, urine, anthropometry, and nutritional indices, were…

  16. Systematic review of factors affecting pharmaceutical expenditures.

    PubMed

    Mousnad, Mohamed Awad; Shafie, Asrul Akmal; Ibrahim, Mohamed Izham

    2014-06-01

    To systematically identify the main factors contributing to the increase in pharmaceutical expenditures. A systematic search of published studies was conducted utilising major widely used electronic databases using the search terms 'factors,' 'financing,' 'pharmaceutical,' and 'expenditures.' To be included, the studies needed to: (1) measure at least one of the following outcomes: total growth in pharmaceutical expenditures, price growth or quantity growth; (2) mention a clear method for analysing the impact of factors affecting the increases in drug expenditures; (3) be written in English. Nonprimary articles that were published only as an abstract, a review, a commentary or a letter were excluded. From a total of 2039 studies, only 25 were included in the full review. The main determinant categories that were identified in the review were factors related to price, utilisation, therapeutic choice, demand and health care system. The major cost drivers were found to be changes in drug quantities and therapies as well as new drugs. It is important for policymakers to understand pharmaceutical spending trends and the factors that influence them in order to formulate effective cost containment strategies and design optimum drug policy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice.

    PubMed

    Maekawa, Ryuya; Seino, Yusuke; Ogata, Hidetada; Murase, Masatoshi; Iida, Atsushi; Hosokawa, Kaori; Joo, Erina; Harada, Norio; Tsunekawa, Shin; Hamada, Yoji; Oiso, Yutaka; Inagaki, Nobuya; Hayashi, Yoshitaka; Arima, Hiroshi

    2017-11-01

    Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks. Mice fed a high-sucrose diet showed resistance to body weight gain, in comparison with mice fed a high-starch diet or control diet, due to increased energy expenditure. Plasma FGF21 levels were highest among the three groups in mice fed a high-sucrose diet, whereas no significant difference in GLP-1 levels was observed. Expression levels of uncoupling protein 1 (UCP-1), FGF receptor 1c (FGFR1c) and β-klotho (KLB) mRNA in brown adipose tissue were significantly increased in high sucrose-fed mice, suggesting increases in FGF21 sensitivity and energy expenditure. Expression of carbohydrate responsive element binding protein (ChREBP) mRNA in liver and brown adipose tissue was also increased in high sucrose-fed mice. These results indicate that FGF21 production in liver and brown adipose tissue is increased in high-sucrose diet and participates in resistance to weight gain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Towards a Four-Dimensional Model of Burnout: A Multigroup Factor-Analytic Study Including Depersonalization and Cynicism

    ERIC Educational Resources Information Center

    Salanova, Marisa; Llorens, Susana; Garcia-Renedo, Monica; Burriel, Raul; Breso, Edgar; Schaufeli, Wilmar B.

    2005-01-01

    This article investigated whether cynicism and depersonalization are two different dimensions of burnout or whether they may be collapsed into one construct of mental distance. Using confirmatory factor analyses in two samples of teachers (n = 483) and blue-collar workers (n = 474), a superior fit was found for the four-factor model that contained…

  19. Increased postural sway during quiet stance as a risk factor for prospective falls in community-dwelling elderly individuals.

    PubMed

    Johansson, Jonas; Nordström, Anna; Gustafson, Yngve; Westling, Göran; Nordström, Peter

    2017-11-01

    fall-related injuries constitute major health risks in older individuals, and these risks are projected to increase in parallel with increasing human longevity. Impaired postural stability is a potential risk factor related to falls, although the evidence is inconclusive, partly due to the lack of prospective studies. This study aimed to investigate how objective measures of postural sway predict incident falls. this prospectively observational study included 1,877 community-dwelling individuals aged 70 years who participated in the Healthy Ageing Initiative between June 2012 and December 2015. postural sway was measured during eyes-open (EO) and eyes-closed (EC) trials using the Wii Balance Board. Functional mobility, muscle strength, objective physical activity and cognitive performance were also measured. Participants reported incident falls 6 and 12 months after the examination. during follow-up, 255 (14%) prospective fallers were identified. Division of centre of pressure (COP) sway lengths into quintiles revealed a nonlinear distribution of falls for EO trial data, but not EC trial data. After adjustment for multiple confounders, fall risk was increased by 75% for participants with COP sway lengths ≥400 mm during the EO trial (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.09-2.79), and approximately doubled for sway lengths ≥920 mm during the EC trial (OR 1.90, 95% CI 1.12-3.22). objective measures of postural sway independently predict incident falls in older community-dwelling men and women. Further studies are needed to evaluate whether postural sway length is of interest for the prediction of incident falls in clinical settings. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

  20. Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

    PubMed

    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. Clinical

  1. Perinatal risk factors increase the risk of being affected by both type 1 diabetes and coeliac disease.

    PubMed

    Adlercreutz, Emma H; Wingren, Carl Johan; Vincente, Raquel P; Merlo, Juan; Agardh, Daniel

    2015-02-01

    This study investigated whether perinatal factors influenced the risk of a double diagnosis of type 1 diabetes and coeliac disease. We used multinomial logistic regression models to study the associations between perinatal factors, gender, mode of delivery, season of birth and the risk of type 1 diabetes, coeliac disease or both, in Swedish-born singleton children. We found that 4327 of the 768 395 children (0.6%) had been diagnosed with type 1 diabetes, 3817 (0.5%) had been diagnosed with coeliac disease and 191 (0.02%) were affected by both diseases. If the children already had type 1 diabetes (n = 4518), the absolute risk of being affected by coeliac disease increased to 4.2% (n = 191). Children with both type 1 diabetes and coeliac disease were more likely to be female (OR = 1.48, 95% CI = 1.01-1.97), delivered by Caesarean section (OR = 1.60, 95% CI = 1.07-2.39), have native-born Swedish mothers (OR = 4.84, 95% CI = 1.96-11.97) or be born during the summer months (OR = 1.43, 95% CI = 1.07-1.92). The increased risk of being affected by a double diagnosis of type 1 diabetes and coeliac disease was modulated by perinatal risk factors. This suggests that early life events are important when it comes to children with type 1 diabetes also developing coeliac disease. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  2. Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

    2012-01-01

    Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

  3. Poststroke Fatigue: Who Is at Risk for an Increase in Fatigue?

    PubMed Central

    van Eijsden, Hanna Maria; van de Port, Ingrid Gerrie Lambert; Visser-Meily, Johanna Maria August; Kwakkel, Gert

    2012-01-01

    Background. Several studies have examined determinants related to post-stroke fatigue. However, it is unclear which determinants can predict an increase in poststroke fatigue over time. Aim. This prospective cohort study aimed to identify determinants which predict an increase in post-stroke fatigue. Methods. A total of 250 patients with stroke were examined at inpatient rehabilitation discharge (T0) and 24 weeks later (T1). Fatigue was measured using the Fatigue Severity Scale (FSS). An increase in post-stroke fatigue was defined as an increase in the FSS score beyond the 95% limits of the standard error of measurement of the FSS (i.e., 1.41 points) between T0 and T1. Candidate determinants included personal factors, stroke characteristics, physical, cognitive, and emotional functions, and activities and participation and were assessed at T0. Factors predicting an increase in fatigue were identified using forward multivariate logistic regression analysis. Results. The only independent predictor of an increase in post-stroke fatigue was FSS (OR 0.50; 0.38–0.64, P < 0.001). The model including FSS at baseline correctly predicted 7.9% of the patients who showed increased fatigue at T1. Conclusion. The prognostic model to predict an increase in fatigue after stroke has limited predictive value, but baseline fatigue is the most important independent predictor. Overall, fatigue levels remained stable over time. PMID:22028989

  4. A wheat CCAAT box-binding transcription factor increases the grain yield of wheat with less fertilizer input.

    PubMed

    Qu, Baoyuan; He, Xue; Wang, Jing; Zhao, Yanyan; Teng, Wan; Shao, An; Zhao, Xueqiang; Ma, Wenying; Wang, Junyi; Li, Bin; Li, Zhensheng; Tong, Yiping

    2015-02-01

    Increasing fertilizer consumption has led to low fertilizer use efficiency and environmental problems. Identifying nutrient-efficient genes will facilitate the breeding of crops with improved fertilizer use efficiency. This research performed a genome-wide sequence analysis of the A (NFYA), B (NFYB), and C (NFYC) subunits of Nuclear Factor Y (NF-Y) in wheat (Triticum aestivum) and further investigated their responses to nitrogen and phosphorus availability in wheat seedlings. Sequence mining together with gene cloning identified 18 NFYAs, 34 NFYBs, and 28 NFYCs. The expression of most NFYAs positively responded to low nitrogen and phosphorus availability. In contrast, microRNA169 negatively responded to low nitrogen and phosphorus availability and degraded NFYAs. Overexpressing TaNFYA-B1, a low-nitrogen- and low-phosphorus-inducible NFYA transcript factor on chromosome 6B, significantly increased both nitrogen and phosphorus uptake and grain yield under differing nitrogen and phosphorus supply levels in a field experiment. The increased nitrogen and phosphorus uptake may have resulted from the fact that that overexpressing TaNFYA-B1 stimulated root development and up-regulated the expression of both nitrate and phosphate transporters in roots. Our results suggest that TaNFYA-B1 plays essential roles in root development and in nitrogen and phosphorus usage in wheat. Furthermore, our results provide new knowledge and valuable gene resources that should be useful in efforts to breed crops targeting high yield with less fertilizer input. © 2015 American Society of Plant Biologists. All Rights Reserved.

  5. Retention strategies and factors associated with missed visits among low income women at increased risk of HIV acquisition in the US (HPTN 064).

    PubMed

    Haley, Danielle F; Lucas, Jonathan; Golin, Carol E; Wang, Jing; Hughes, James P; Emel, Lynda; El-Sadr, Wafaa; Frew, Paula M; Justman, Jessica; Adimora, Adaora A; Watson, Christopher Chauncey; Mannheimer, Sharon; Rompalo, Anne; Soto-Torres, Lydia; Tims-Cook, Zandraetta; Carter, Yvonne; Hodder, Sally L

    2014-04-01

    Women at high-risk for HIV acquisition often face challenges that hinder their retention in HIV prevention trials. These same challenges may contribute to missed clinical care visits among HIV-infected women. This article, informed by the Gelberg-Andersen Behavioral Model for Vulnerable Populations, identifies factors associated with missed study visits and describes the multifaceted retention strategies used by study sites. HPTN 064 was a multisite, longitudinal HIV seroincidence study in 10 US communities. Eligible women were aged 18-44 years, resided in a census tract/zipcode with high poverty and HIV prevalence, and self-reported ≥1 personal or sex partner behavior related to HIV acquisition. Multivariate analyses of predisposing (e.g., substance use) and enabling (e.g., unmet health care needs) characteristics, and study attributes (i.e., recruitment venue, time of enrollment) identified factors associated with missed study visits. Retention strategies included: community engagement; interpersonal relationship building; reduction of external barriers; staff capacity building; and external tracing. Visit completion was 93% and 94% at 6 and 12 months. Unstable housing and later date of enrollment were associated with increased likelihood of missed study visits. Black race, recruitment from an outdoor venue, and financial responsibility for children were associated with greater likelihood of attendance. Multifaceted retention strategies may reduce missed study visits. Knowledge of factors associated with missed visits may help to focus efforts.

  6. Retention Strategies and Factors Associated with Missed Visits Among Low Income Women at Increased Risk of HIV Acquisition in the US (HPTN 064)

    PubMed Central

    Lucas, Jonathan; Golin, Carol E.; Wang, Jing; Hughes, James P.; Emel, Lynda; El-Sadr, Wafaa; Frew, Paula M.; Justman, Jessica; Adimora, Adaora A.; Watson, Christopher Chauncey; Mannheimer, Sharon; Rompalo, Anne; Soto-Torres, Lydia; Tims-Cook, Zandraetta; Carter, Yvonne; Hodder, Sally L.

    2014-01-01

    Abstract Women at high-risk for HIV acquisition often face challenges that hinder their retention in HIV prevention trials. These same challenges may contribute to missed clinical care visits among HIV-infected women. This article, informed by the Gelberg-Andersen Behavioral Model for Vulnerable Populations, identifies factors associated with missed study visits and describes the multifaceted retention strategies used by study sites. HPTN 064 was a multisite, longitudinal HIV seroincidence study in 10 US communities. Eligible women were aged 18–44 years, resided in a census tract/zipcode with high poverty and HIV prevalence, and self-reported ≥1 personal or sex partner behavior related to HIV acquisition. Multivariate analyses of predisposing (e.g., substance use) and enabling (e.g., unmet health care needs) characteristics, and study attributes (i.e., recruitment venue, time of enrollment) identified factors associated with missed study visits. Retention strategies included: community engagement; interpersonal relationship building; reduction of external barriers; staff capacity building; and external tracing. Visit completion was 93% and 94% at 6 and 12 months. Unstable housing and later date of enrollment were associated with increased likelihood of missed study visits. Black race, recruitment from an outdoor venue, and financial responsibility for children were associated with greater likelihood of attendance. Multifaceted retention strategies may reduce missed study visits. Knowledge of factors associated with missed visits may help to focus efforts. PMID:24697160

  7. Unhealthy lifestyle and sleep problems as risk factors for increased direct employers' cost of short-term sickness absence.

    PubMed

    Kanerva, Noora; Pietiläinen, Olli; Lallukka, Tea; Rahkonen, Ossi; Lahti, Jouni

    2018-03-01

    Objectives Unhealthy lifestyle (eg, smoking) as well as sleep problems are associated with increased risk of sickness absence, but the financial impact of these associations beyond risk ratios is not well known. We aimed to estimate the additive contribution of lifestyle and sleep problems (risk factors) to direct costs of short-term (<15 days) sickness absence. Methods The Helsinki Health Study is a longitudinal cohort of employees of the City of Helsinki, Finland (N=8960, response rate 67%). During 2000-2002 the participants were mailed a survey questionnaire that gathered information on their lifestyle and sleep. A sum of the risk factors was calculated: participants received one point for being a smoker; high alcohol user (>7 servings/week for women and >14 servings/week for men); physically inactive [<14 metabolic equivalents (MET) hours/week]; having low fruit and vegetable consumption (<1 times/day); or suffering from frequent insomnia symptoms. Sickness absence, salary, and time of employment were followed through the employer's register between 2002-2016. Individual salary data were used to calculate the direct costs of short-term sickness absence. Data were analyzed using a two-part model. Results Direct costs of short-term sickness absences were on average €9057 (standard deviation €11 858) per employee over the follow-up. Those with ≥3 risk factors had €3266 [95% confidence interval (95% CI) €2114-4417] higher direct costs for the employer over the follow-up compared to those without any risk factors. Conclusions Unhealthy lifestyle and sleep problems may increase the costs of short-term sickness absence to the employer by 10-30%. Consequently, programs addressing lifestyle and sleep may yield to significant savings.

  8. Psychosocial factors and theory in physical activity studies in minorities.

    PubMed

    Mama, Scherezade K; McNeill, Lorna H; McCurdy, Sheryl A; Evans, Alexandra E; Diamond, Pamela M; Adamus-Leach, Heather J; Lee, Rebecca E

    2015-01-01

    To summarize the effectiveness of interventions targeting psychosocial factors to increase physical activity (PA) among ethnic minority adults and explore theory use in PA interventions. Studies (N = 11) were identified through a systematic review and targeted African American/Hispanic adults, specific psychosocial factors, and PA. Data were extracted using a standard code sheet and the Theory Coding Scheme. Social support was the most common psychosocial factor reported, followed by motivational readiness, and self-efficacy, as being associated with increased PA. Only 7 studies explicitly reported using a theoretical framework. Future efforts should explore theory use in PA interventions and how integration of theoretical constructs, including psychosocial factors, increases PA.

  9. The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility: A meta-analysis including FPRP test of 8710 participants.

    PubMed

    Tong, Xiang; Ma, Yao; Niu, Xundong; Yan, Zhipeng; Liu, Sitong; Peng, Bo; Peng, Shifeng; Fan, Hong

    2016-07-01

    with sarcoidosis susceptibility (A vs G, FPRP < 0.001). Additionally, the FPRP test confirmed that the BTNL2 G16071A gene polymorphism was associated only with granulomatous disease susceptibility among Caucasians (A vs G, FPRP < 0.001) at the level of a prior probability, which was 0.001. The meta-analysis indicated that BTNL2 G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians.

  10. Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youth treated with tenofovir disoproxil fumarate

    USDA-ARS?s Scientific Manuscript database

    Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor-23 causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding proetin (VDBP) binds to 1,25-OH(2)D, decreasing biologic activity, and is elevated...

  11. Risk Factors for Pressure Ulcers Including Suspected Deep Tissue Injury in Nursing Home Facility Residents: Analysis of National Minimum Data Set 3.0.

    PubMed

    Ahn, Hyochol; Cowan, Linda; Garvan, Cynthia; Lyon, Debra; Stechmiller, Joyce

    2016-04-01

    To provide information on risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home residents in the United States. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Examine the literature related to risk factors for the development of PrUs.2. Compare risk factors associated with the prevalence of PrUs and sDTI from the revised Minimum Data Set 3.0 2012 using a modified Defloor's conceptual model of PrUs as a theoretical framework. This study aims to characterize and compare risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home (NH) residents in the United States. Secondary analysis of the 2012 Minimum Data Set (MDS 3.0). Medicare- or Medicaid-certified NHs in the United States. Nursing home residents (n = 2,936,146) 18 years or older with complete PrU data, who received comprehensive assessments from January to December 2012. Pressure ulcer by stage was the outcome variable. Explanatory variables (age, gender, race and ethnicity, body mass index, skin integrity, system failure, disease, infection, mobility, and cognition) from the MDS 3.0 were aligned with the 4 elements of Defloor's conceptual model: compressive forces, shearing forces, tissue tolerance for pressure, and tissue tolerance for oxygen. Of 2,936,146 NH residents who had complete data for PrU, 89.9% had no PrU; 8.4% had a Stage 2, 3, or 4 or unstagable PrU; and 1.7% had an sDTI. The MDS variables corresponding to the 4 elements of Defloor's model were significantly predictive of both PrU and sDTI. Black residents had the highest risk of any-stage PrU, and Hispanic residents had the highest risk of sDTI. Skin integrity, system failure, infection, and disease risk factors had larger effect sizes for sDTI than for other PrU stages

  12. Bayesian methods including nonrandomized study data increased the efficiency of postlaunch RCTs.

    PubMed

    Schmidt, Amand F; Klugkist, Irene; Klungel, Olaf H; Nielen, Mirjam; de Boer, Anthonius; Hoes, Arno W; Groenwold, Rolf H H

    2015-04-01

    Findings from nonrandomized studies on safety or efficacy of treatment in patient subgroups may trigger postlaunch randomized clinical trials (RCTs). In the analysis of such RCTs, results from nonrandomized studies are typically ignored. This study explores the trade-off between bias and power of Bayesian RCT analysis incorporating information from nonrandomized studies. A simulation study was conducted to compare frequentist with Bayesian analyses using noninformative and informative priors in their ability to detect interaction effects. In simulated subgroups, the effect of a hypothetical treatment differed between subgroups (odds ratio 1.00 vs. 2.33). Simulations varied in sample size, proportions of the subgroups, and specification of the priors. As expected, the results for the informative Bayesian analyses were more biased than those from the noninformative Bayesian analysis or frequentist analysis. However, because of a reduction in posterior variance, informative Bayesian analyses were generally more powerful to detect an effect. In scenarios where the informative priors were in the opposite direction of the RCT data, type 1 error rates could be 100% and power 0%. Bayesian methods incorporating data from nonrandomized studies can meaningfully increase power of interaction tests in postlaunch RCTs. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

    PubMed Central

    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

  14. Factors related to increasing safety belt use in states with safety belt use laws : second annual report to Congress

    DOT National Transportation Integrated Search

    1989-01-01

    This report is the second in a series of four annual reports to the Congress on provisions of state safety belt use laws and other programmatic factors related to increasing safety belt use levels. The first Congressional Report reviewed what was kno...

  15. Factors associated with increased felt stigma among individuals with epilepsy.

    PubMed

    Bautista, Ramon Edmundo D; Shapovalov, Denys; Shoraka, Ali Reza

    2015-08-01

    The aim of the study is to determine whether certain demographic, clinical, and psychosocial traits are associated with higher levels of felt stigma among persons with epilepsy (PWE) patients followed at a level 4 epilepsy center. We performed a direct survey of 182 consenting patients that included the Epilepsy Stigma Scale. On univariate analysis, higher levels of perceived stigma were associated with age, marital status, race, driving, work status, seizure etiology, Quality of Life in Epilepsy-10 (QOLIE-10) scores, and health literacy. Among coping reactions, the use of denial, behavioral disengagement and venting were also associated with higher degrees of felt stigma. Using multiple linear regression, being single, poorer QOLIE-10 scores, difficulties understanding written information, and the use of behavioral disengagement were independently associated with poorer scores on the Epilepsy Stigma Scale. Our study paints a compelling profile of a PWE who has greater perceived stigma. Programs that increase the level of social support, improve health literacy, and enhance quality of life may also help decrease the amount of felt stigma among PWE. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators.

    PubMed

    Norambuena-Soto, Ignacio; Núñez-Soto, Constanza; Sanhueza-Olivares, Fernanda; Cancino-Arenas, Nicole; Mondaca-Ruff, David; Vivar, Raul; Díaz-Araya, Guillermo; Mellado, Rosemarie; Chiong, Mario

    2017-05-23

    Fibroblasts play several homeostatic roles, including electrical coupling, paracrine signaling and tissue repair after injury. Fibroblasts have low secretory activity. However, in response to injury, they differentiate to myofibroblasts. These cells have an increased extracellular matrix synthesis and secretion, including collagen fibers, providing stiffness to the tissue. In pathological conditions myofibroblasts became resistant to apoptosis, remaining in the tissue, causing excessive extracellular matrix secretion and deposition, which contributes to the progressive tissue remodeling. Therefore, increased myofibroblast content within damaged tissue is a characteristic hallmark of heart, lung, kidney and liver fibrosis. Recently, it was described that cardiac fibroblast to myofibroblast differentiation is triggered by the transforming growth factor β1 (TGF-β1) through a Smad-independent activation of Forkhead box O (FoxO). FoxO proteins are a transcription factor family that includes FoxO1, FoxO3, FoxO4 and FoxO6. In several cells types, they play an important role in cell cycle arrest, oxidative stress resistance, cell survival, energy metabolism, and cell death. Here, we review the role of FoxO family members on the regulation of cardiac fibroblast proliferation and differentiation.

  17. Spatial and Temporal Factors Associated with an Increased Prevalence of Listeria monocytogenes in Spinach Fields in New York State

    PubMed Central

    Weller, Daniel; Wiedmann, Martin

    2015-01-01

    While rain and irrigation events have been associated with an increased prevalence of foodborne pathogens in produce production environments, quantitative data are needed to determine the effects of various spatial and temporal factors on the risk of produce contamination following these events. This study was performed to quantify these effects and to determine the impact of rain and irrigation events on the detection frequency and diversity of Listeria species (including L. monocytogenes) and L. monocytogenes in produce fields. Two spinach fields, with high and low predicted risks of L. monocytogenes isolation, were sampled 24, 48, 72, and 144 to 192 h following irrigation and rain events. Predicted risk was a function of the field's proximity to water and roads. Factors were evaluated for their association with Listeria species and L. monocytogenes isolation by using generalized linear mixed models (GLMMs). In total, 1,492 (1,092 soil, 334 leaf, 14 fecal, and 52 water) samples were collected. According to the GLMM, the likelihood of Listeria species and L. monocytogenes isolation from soil samples was highest during the 24 h immediately following an event (odds ratios [ORs] of 7.7 and 25, respectively). Additionally, Listeria species and L. monocytogenes isolates associated with irrigation events showed significantly lower sigB allele type diversity than did isolates associated with precipitation events (P = <0.001), suggesting that irrigation water may be a point source of L. monocytogenes contamination. Small changes in management practices (e.g., not irrigating fields before harvest) may therefore reduce the risk of L. monocytogenes contamination of fresh produce. PMID:26116668

  18. Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells.

    PubMed

    Su, Y-S; Fan, Z-X; Xiao, S-E; Lin, B-J; Miao, Y; Hu, Z-Q; Liu, H

    2017-04-01

    Icariin is a major flavonoid isolated from Epimedium spp. leaves (Epimedium Herba), and has multiple pharmacological functions, including anti-angiogenesis, anti-oxidant, anti-inflammatory and immunoprotective effects. To investigate whether icariin can stimulate growth of hair follicles in mice and the underlying mechanism. In vitro, the effect of icariin on hair growth was assessed by using a vibrissae hair follicle (VHF) organ-culture model. The proliferation of hair matrix keratinocytes and the expression of insulin-like growth factor (IGF)-1 in follicles were examined by double immunostaining for 5-bromo-2'-deoxyuridine and IGF-1, in the presence or absence of icariin. Dermal papilla cells (DPCs) were cultured and IGF-1 level was measured by reverse transcription-PCR and ELISA after icariin treatment. In vivo, the effect of icariin on hair growth was examined by gavage feeding of icariin to mice whose backs had been depilated, and the conversion of telogen to anagen hair was observed. Treatment with icariin promoted hair shaft elongation, prolonged the hair cycle growth phase (anagen) in cultured VHFs, and accelerated transition of hair cycle from telogen to anagen phase in the dorsal skin of mice. There was significant proliferation of matrix keratinocytes and an increased level of IGF-1 in cultured VHFs. Moreover, icariin treatment upregulated IGF-1 mRNA expression in DPCs and increased IGF-1 protein content in the conditioned medium of DPCs. These results suggest that icariin can promote mouse hair follicle growth via stimulation of IGF-1 expression in DPCs. © 2017 British Association of Dermatologists.

  19. A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins

    PubMed Central

    de Wilde, Adriaan H.; Wannee, Kazimier F.; Scholte, Florine E. M.; Goeman, Jelle J.; ten Dijke, Peter; Snijder, Eric J.

    2015-01-01

    ABSTRACT To identify host factors relevant for severe acute respiratory syndrome-coronavirus (SARS-CoV) replication, we performed a small interfering RNA (siRNA) library screen targeting the human kinome. Protein kinases are key regulators of many cellular functions, and the systematic knockdown of their expression should provide a broad perspective on factors and pathways promoting or antagonizing coronavirus replication. In addition to 40 proteins that promote SARS-CoV replication, our study identified 90 factors exhibiting an antiviral effect. Pathway analysis grouped subsets of these factors in specific cellular processes, including the innate immune response and the metabolism of complex lipids, which appear to play a role in SARS-CoV infection. Several factors were selected for in-depth validation in follow-up experiments. In cells depleted for the β2 subunit of the coatomer protein complex (COPB2), the strongest proviral hit, we observed reduced SARS-CoV protein expression and a >2-log reduction in virus yield. Knockdown of the COPB2-related proteins COPB1 and Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) also suggested that COPI-coated vesicles and/or the early secretory pathway are important for SARS-CoV replication. Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) enhanced virus replication in the primary screen, and validation experiments confirmed increased SARS-CoV protein expression and virus production upon PKR depletion. In addition, cyclin-dependent kinase 6 (CDK6) was identified as a novel antiviral host factor in SARS-CoV replication. The inventory of pro- and antiviral host factors and pathways described here substantiates and expands our understanding of SARS-CoV replication and may contribute to the identification of novel targets for antiviral therapy. IMPORTANCE Replication of all viruses, including SARS-CoV, depends on and is influenced by cellular pathways. Although

  20. Identifying Factors That Increase the Likelihood for Alcohol-Induced Blackouts in the Prepartying Context

    PubMed Central

    LaBrie, Joseph W.; Hummer, Justin; Kenney, Shannon; Lac, Andrew; Pedersen, Eric

    2015-01-01

    The present study examined risk factors related to “blacking out” (e.g., temporary periods of memory loss during drinking) during preparty drinking events (i.e., pregaming, predrinking). Participants were students from two universities on the West Coast who reported past month prepartying (N = 2,546) in online surveys administered in the fall of 2008. Among these students, 25% (n = 636) reported blacking out during at least one occasion in which they prepartied in the past month. A logistic regression model underscored that Greek student affiliation, family history of alcohol abuse, frequency of prepartying, and both playing drinking games and consuming shots of liquor while prepartying increased the likelihood of blacking out. Limitations and implications for future research and collegiate prevention strategies are discussed. PMID:21222521

  1. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    PubMed

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

  2. An increase in serum tumour necrosis factor-α during anti-tumour necrosis factor-α therapy for Crohn's disease - A paradox or a predictive index?

    PubMed

    Eder, Piotr; Korybalska, Katarzyna; Łykowska-Szuber, Liliana; Stawczyk-Eder, Kamila; Krela-Kaźmierczak, Iwona; Łuczak, Joanna; Czepulis, Natasza; Linke, Krzysztof; Witowski, Janusz

    2016-10-01

    Soluble tumour necrosis factor-α (sTNF-α) has been reported to increase in the course of anti-TNF-α therapy for rheumatoid and skin diseases. To assess changes in sTNF-α and clinical efficacy of anti-TNF-α agents in Crohn's disease (CD). Sixty-four patients on infliximab or adalimumab were analyzed. Clinical outcomes were assessed by using CD Activity Index after the induction therapy and at week 52. sTNF-α was measured before and after the induction therapy with high-sensitivity immunoassay. In the majority of patients, sTNF-α increased significantly. Those with the greatest increase were more likely to experience long-term response, were more often treated with infliximab, had less frequently isolated small bowel CD, and tended to have sTNF-α levels at baseline that correlated with C-reactive protein. Neutralization of sTNF-α does not seem to be critical for the efficacy of anti-TNF-α therapy in CD. Paradoxically - an increase in sTNF-α may reflect an ongoing process that is beneficial for the clinical outcome. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Risk factors for amyotrophic lateral sclerosis

    PubMed Central

    Ingre, Caroline; Roos, Per M; Piehl, Fredrik; Kamel, Freya; Fang, Fang

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence during the last decades has been suggested. Although recent genetic studies have substantially improved our understanding of the causes of ALS, especially familial ALS, an important role of non-genetic factors in ALS is recognized and needs further study. In this review, we briefly discuss several major genetic contributors to ALS identified to date, followed by a more focused discussion on the most commonly examined non-genetic risk factors for ALS. We first review factors related to lifestyle choices, including smoking, intake of antioxidants, physical fitness, body mass index, and physical exercise, followed by factors related to occupational and environmental exposures, including electromagnetic fields, metals, pesticides, β-methylamino-L-alanine, and viral infection. Potential links between ALS and other medical conditions, including head trauma, metabolic diseases, cancer, and inflammatory diseases, are also discussed. Finally, we outline several future directions aiming to more efficiently examine the role of non-genetic risk factors in ALS. PMID:25709501

  4. Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

    PubMed

    Suikkari, A M; Tiitinen, A; Stenman, U H; Seppälä, M; Laatikainen, T

    1991-05-01

    Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. Seven women with PCOD and five healthy control subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.

  5. batman Interacts with polycomb and trithorax group genes and encodes a BTB/POZ protein that is included in a complex containing GAGA factor.

    PubMed

    Faucheux, M; Roignant, J-Y; Netter, S; Charollais, J; Antoniewski, C; Théodore, L

    2003-02-01

    Polycomb and trithorax group genes maintain the appropriate repressed or activated state of homeotic gene expression throughout Drosophila melanogaster development. We have previously identified the batman gene as a Polycomb group candidate since its function is necessary for the repression of Sex combs reduced. However, our present genetic analysis indicates functions of batman in both activation and repression of homeotic genes. The 127-amino-acid Batman protein is almost reduced to a BTB/POZ domain, an evolutionary conserved protein-protein interaction domain found in a large protein family. We show that this domain is involved in the interaction between Batman and the DNA binding GAGA factor encoded by the Trithorax-like gene. The GAGA factor and Batman codistribute on polytene chromosomes, coimmunoprecipitate from nuclear embryonic and larval extracts, and interact in the yeast two-hybrid assay. Batman, together with the GAGA factor, binds to MHS-70, a 70-bp fragment of the bithoraxoid Polycomb response element. This binding, like that of the GAGA factor, requires the presence of d(GA)n sequences. Together, our results suggest that batman belongs to a subset of the Polycomb/trithorax group of genes that includes Trithorax-like, whose products are involved in both activation and repression of homeotic genes.

  6. batman Interacts with Polycomb and trithorax Group Genes and Encodes a BTB/POZ Protein That Is Included in a Complex Containing GAGA Factor

    PubMed Central

    Faucheux, M.; Roignant, J.-Y.; Netter, S.; Charollais, J.; Antoniewski, C.; Théodore, L.

    2003-01-01

    Polycomb and trithorax group genes maintain the appropriate repressed or activated state of homeotic gene expression throughout Drosophila melanogaster development. We have previously identified the batman gene as a Polycomb group candidate since its function is necessary for the repression of Sex combs reduced. However, our present genetic analysis indicates functions of batman in both activation and repression of homeotic genes. The 127-amino-acid Batman protein is almost reduced to a BTB/POZ domain, an evolutionary conserved protein-protein interaction domain found in a large protein family. We show that this domain is involved in the interaction between Batman and the DNA binding GAGA factor encoded by the Trithorax-like gene. The GAGA factor and Batman codistribute on polytene chromosomes, coimmunoprecipitate from nuclear embryonic and larval extracts, and interact in the yeast two-hybrid assay. Batman, together with the GAGA factor, binds to MHS-70, a 70-bp fragment of the bithoraxoid Polycomb response element. This binding, like that of the GAGA factor, requires the presence of d(GA)n sequences. Together, our results suggest that batman belongs to a subset of the Polycomb/trithorax group of genes that includes Trithorax-like, whose products are involved in both activation and repression of homeotic genes. PMID:12556479

  7. Technology advancement: a factor in increasing resource use

    USGS Publications Warehouse

    Wilburn, David R.; Goonan, Thomas G.; Bleiwas, Donald I.

    2001-01-01

    The specter of mineral resource scarcity has been repeatedly raised as a concern because ever-growing populations with seemingly insatiable appetites for minerals place claims against a finite resource endowment. This report analyzes how technology has helped to ease resource constraints, and uses case studies of aluminum, copper, potash, and sulfur minerals to identify the effects of technology on resource supply. In spite of heightened demand for and increased loss of resources to environmental policy and urbanization, mineral producers historically have been able to continually expand production and lower costs. Specific production increases for the years 1900-98 were: aluminum (3,250 percent), copper (2,465 percent), potash (3,770 percent), and sulfur (6,000 percent). For the same period, constant-dollar (1998) prices decreased: aluminum (90 percent), copper (75 percent), potash (94 percent), and sulfur (89 percent). The application of technology has made available mineral deposits that were previously overlooked or considered non-viable. Using technology, producers can meet the demand for stronger, energy-efficient, more environmentally safe products with less physical material. Technologies have been developed to increase the amount of materials recycled and remanufactured. Technology development can occur in breakthroughs, but most often advances incrementally. Technological development is driven by the profit motive.

  8. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    PubMed

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  9. Risk factors for retained placenta.

    PubMed

    Coviello, Elizabeth M; Grantz, Katherine L; Huang, Chun-Chih; Kelly, Tara E; Landy, Helain J

    2015-12-01

    Retained placenta complicates 2-3% of vaginal deliveries and is a known cause of postpartum hemorrhage. Treatment includes manual or operative placental extraction, potentially increasing risks of hemorrhage, infections, and prolonged hospital stays. We sought to evaluate risk factors for retained placenta, defined as more than 30 minutes between the delivery of the fetus and placenta, in a large US obstetrical cohort. We included singleton, vaginal deliveries ≥24 weeks (n = 91,291) from the Consortium of Safe Labor from 12 US institutions (2002-2008). Multivariable logistic regression analyses estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) for potential risk factors for retained placenta stratified by parity, adjusting for relevant confounding factors. Characteristics such as stillbirth, maternal age, race, and admission body mass index were examined. Retained placenta complicated 1047 vaginal deliveries (1.12%). Regardless of parity, significant predictors of retained placenta included stillbirth (nulliparous adjusted OR, 5.67; 95% CI, 3.10-10.37; multiparous adjusted OR, 4.56; 95% CI, 2.08-9.94), maternal age ≥30 years, delivery at 24 0/7 to 27 6/7 compared with 34 weeks or later and delivery in a teaching hospital. In nulliparous women, additional risk factors were identified: longer first- or second-stage labor duration, whereas non-Hispanic black compared with non-Hispanic white race was found to be protective. Body mass index was not associated with an increased risk. Multiple risk factors for retained placenta were identified, particularly the strong association with stillbirth. It is plausible that there could be something intrinsic about stillbirth that causes a retained placenta, or perhaps there are shared pathways of certain etiologies of stillbirth and a risk of retained placenta. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Life stories of people with rheumatoid arthritis who retired early: how gender and other contextual factors shaped their everyday activities, including paid work.

    PubMed

    Stamm, T A; Machold, K P; Smolen, J; Prodinger, B

    2010-06-01

    The aim of the present study was to explore how contextual factors affect the everyday activities of women and men with rheumatoid arthritis (RA), as evident in their life stories. Fifteen people with RA, who had retired early due to the disease, were interviewed up to three times, according to a narrative biographic interview style. The life stories of the participants, which were reconstructed from the biographical data and from the transcribed 'told story' were analysed from the perspective of contextual factors, including personal and environmental factors. The rigour and accuracy of the analysis were enhanced by reflexivity and peer-review of the results. The life stories of the participants in this study reflected how contextual factors (such as gender, the healthcare system, the support of families and social and cultural values) shaped their everyday activities. In a society such as in Austria, which is based on traditional patriarchal values, men were presented with difficulties in developing a non-paid-work-related role. For women, if paid work had to be given up, they were more likely to engage in alternative challenging activities which enabled them to develop reflective skills, which in turn contributed to a positive and enriching perspective on their life stories. Health professionals may thus use some of the women's strategies to help men. Interventions by health professionals in people with RA may benefit from an approach sensitive to personal and environmental factors.

  11. Does sports participation (including level of performance and previous injury) increase risk of osteoarthritis? A systematic review and meta-analysis

    PubMed Central

    Tran, Gui; Smith, Toby O; Grice, Adam; Kingsbury, Sarah R; McCrory, Paul; Conaghan, Philip G

    2016-01-01

    Background To assess the relationship between sport and osteoarthritis (OA), and specifically to determine whether previous participation, in terms of level (elite or non-elite), type of sport, intensity or previous injury, was associated with OA. Methods This systematic review was developed using PRISMA guidelines. Databases were searched (to May 2016). Narrative review and meta-analysis (with risk ratio (RR) and 95% CIs) approaches were undertaken where appropriate. Study quality was assessed using GRADE. Results 46 studies were included. Narratively, 31 studies reported an increased risk of OA, with 19 demonstrating an increased risk in elite athletes. There was an increased risk after sports exposure (irrespective of type; RR 1.37; 95% CI 1.14 to 1.64; 21 studies). It remained uncertain whether there was a difference in risk of OA between elite and non-elite athletes (RR 1.37; 95% CI 0.84 to 2.22; 17 studies). The risk was higher in soccer (RR 1.42; 95% CI 1.14 to 1.77; 15 studies) but lower in runners (RR 0.86; 95% CI 0.53 to 1.41; 12 studies). 9 studies showed an association with the intensity of sport undertaken and OA. 5 studies demonstrated a higher prevalence of OA following meniscectomies and anterior cruciate ligament tears. Overall, the evidence was of GRADE ‘very low’ quality. Conclusions There was very low-quality evidence to support an increased relationship between sports participation and OA in elite participants. It is unclear whether there is a difference in risk between elite and non-elite participants with further prospective studies needed to evaluate this. Pooled findings suggested that significant injuries were associated with OA in soccer players. PMID:27683348

  12. Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women.

    PubMed

    Coelho, F M; Pereira, D S; Lustosa, L P; Silva, J P; Dias, J M D; Dias, R C D; Queiroz, B Z; Teixeira, A L; Teixeira, M M; Pereira, L S M

    2012-01-01

    Biomarkers are important factors in the identification of the frail elderly (higher risk of developing disease) and in assessing the impact of PTI. On the other hand, BDNF has been related to neuroprotection in a series of central nervous system diseases in older age. The levels of BDNF in groups of elderly women classified according to Fried phenotype (non-frail and pre-frail) were compared. We assessed the impact of a PTI on BDNF levels. A convenience sample of 48 elderly women was randomly selected. The PTI group was composed by 20 elderly women selected from this group. Plasma neurotrophic factors, such as BDNF, glial-derived neutrophic factor (GDNF), and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay (ELISA). Timed-up-and-go (TUG) test, hand-grip and work/body weight were evaluated before and after the intervention. Plasma concentrations of BDNF were significantly higher in non-frail in comparison to pre-frail elderly women. After the PTI, higher levels of BDNF were found in elderly women (before 351±68 pg/ml and after 593±79 pg/ml; p<0.001). Both groups had an increase in BDNF levels after the PTI. The low levels of BDNF in pre-frail elderly women suggest that this neurotrophic factor may be a key pathophysiological mediator in the syndrome of frailty. The fact that PTI increased BDNF levels in both groups suggests that it may be possible to modify this phenotype. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Factors influencing success of marine protected areas in the Visayas, Philippines as related to increasing protected area coverage.

    PubMed

    Pollnac, Richard; Seara, Tarsila

    2011-04-01

    Throughout the world there is a general consensus among environmentalists that there should be an increase in the amount of marine area that should be reserved in marine protected areas (MPAs). In fact, the 1998 Philippines Fishery Code indicates a need for designation of at least 15% of municipal waters for fish refuges or sanctuaries. Such an increase in area would take productive fishing areas away from fishing communities that can ill-afford the loss. The larger the protected area, there will be a greater number of people impacted. This article examines the relationship between factors that influence the success of Community Based MPA (CBMPA) performance in the Visayas, Philippines and their significance in efforts to increase the size of protected areas.

  14. Psychosocial Factors and Theory in Physical Activity Studies in Minorities

    PubMed Central

    Mama, Scherezade K.; McNeill, Lorna H.; McCurdy, Sheryl A.; Evans, Alexandra E.; Diamond, Pamela M.; Adamus-Leach, Heather J.; Lee, Rebecca E.

    2015-01-01

    Objectives To summarize the effectiveness of interventions targeting psychosocial factors to increase physical activity (PA) among ethnic minority adults and explore theory use in PA interventions. Methods Studies (N = 11) were identified through a systematic review and targeted African American/Hispanic adults, specific psychosocial factors, and PA. Data were extracted using a standard code sheet and the Theory Coding Scheme. Results Social support was the most common psychosocial factor reported, followed by motivational readiness, and self-efficacy, as being associated with increased PA. Only 7 studies explicitly reported using a theoretical framework. Conclusions Future efforts should explore theory use in PA interventions and how integration of theoretical constructs, including psychosocial factors, increases PA. PMID:25290599

  15. Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions

    PubMed Central

    Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki

    2015-01-01

    Summary Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. PMID:26626177

  16. Increase in the circulating level of hepatocyte growth factor in pancreatic cancer patients.

    PubMed

    Kemik, Ozgur; Purisa, Sevim; Kemik, Ahu Sarbay; Tuzun, Sefa

    2009-01-01

    Hepatocyte growth factor (HGF) has been reported the cause of many biological events, including cell proliferation, invasiveness, morphogenesis, and angiogenesis. Elevated HGF content in tumor tissue was reported to predict a more aggressive biology in breast and gastric cancer patients. Eighty patients with invasive pancreatic cancer investigated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group created from healthy individuals. Serum concentrations of soluble HGF were measured by the quantitative sandwich enzyme immunoassay technique. The mean value of serum soluble HGF in patients with invasive pancreatic cancer was 497.2 +/- 53.8 pg/ml and that of control group was 53.6 +/- 7.5 pg/ml and the difference was significant (p < 0.001). The serum levels of soluble HGF might reflect the severity of invasive pancreatic cancer and deserve further evaluation (Tab. 2, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

  17. Factor structure of the happiness-increasing strategies scales (H-ISS): activities and coping strategies in relation to positive and negative affect.

    PubMed

    Al Nima, Ali; Garcia, Danilo

    2015-01-01

    Background. Previous research (Tkach & Lyubomirsky, 2006) shows that there are eight general happiness-increasing strategies: social affiliation, partying, mental control, goal pursuit, passive leisure, active leisure, religion, and direct attempts. The present study investigates the factor structure of the happiness-increasing strategies scales (H-ISS) and their relationship to positive and negative affect. Method. The present study used participants' (N = 1,050 and age mean = 34.21 sd = 12.73) responses to the H-ISS in structural equation modeling analyses. Affect was measured using the Positive Affect Negative Affect Schedule. Results. After small modifications we obtained a good model that contains the original eight factors/scales. Moreover, we found that women tend to use social affiliation, mental control, passive leisure, religion, and direct attempts more than men, while men preferred to engage in partying and clubbing more than women. The H-ISS explained significantly the variance of positive affect (R (2) = .41) and the variance of negative affect (R (2) = .27). Conclusions. Our study is an addition to previous research showing that the factor structure of the happiness-increasing strategies is valid and reliable. However, due to the model fitting issues that arise in the present study, we give some suggestions for improving the instrument.

  18. Evaluation of ways and procedures to reduce construction cost and increase competition.

    DOT National Transportation Integrated Search

    2009-01-01

    Construction cost inflation is affecting many state highway agencies including the Texas Department of : Transportation While some of this increase can be attributed to factors such as soaring cost of energy, : reports of large variations in cost of ...

  19. Increased circulating procoagulant and anticoagulant factors as TF and TFPI according to severity or infecting serotypes in human dengue infection.

    PubMed

    Leal de Azeredo, Elzinandes; Solórzano, Victor Edgar Fiestas; de Oliveira, Débora Batista; Marinho, Cintia Ferreira; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de-Oliveira-Pinto, Luzia Maria

    2017-01-01

    Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    EPA Science Inventory


    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  1. Including the biogeochemical impacts of deforestation increases projected warming of climate

    NASA Astrophysics Data System (ADS)

    Scott, Catherine; Monks, Sarah; Spracklen, Dominick; Arnold, Stephen; Forster, Piers; Rap, Alexandru; Carslaw, Kenneth; Chipperfield, Martyn; Reddington, Carly; Wilson, Christopher

    2016-04-01

    Forests cover almost one third of the Earth's land area and their distribution is changing as a result of human activities. The presence, and removal, of forests affects the climate in many ways, with the net climate impact of deforestation dependent upon the relative strength of these effects (Betts, 2000; Bala et al., 2007; Davin and de Noblet-Ducoudré, 2010). In addition to controlling the surface albedo and exchanging carbon dioxide (CO2) and moisture with the atmosphere, vegetation emits biogenic volatile organic compounds (BVOCs), which lead to the formation of biogenic secondary organic aerosol (SOA) and alter the oxidative capacity of the atmosphere, affecting ozone (O3) and methane (CH4) concentrations. In this work, we combine a land-surface model with a chemical transport model, a global aerosol model, and a radiative transfer model to compare several radiative impacts of idealised deforestation scenarios in the present day. We find that the simulated reduction in biogenic SOA production, due to complete global deforestation, exerts a positive combined aerosol radiative forcing (RF) of between +308.0 and +362.7 mW m-2; comprised of a direct radiative effect of between +116.5 and +165.0 mW m-2, and a first aerosol indirect effect of between +191.5 and +197.7 mW m-2. We find that the reduction in O3 exerts a negative RF of -150.7 mW m-2 and the reduction in CH4 results in a negative RF of -76.2 mWm-2. When the impacts on biogenic SOA, O3 and CH4 are combined, global deforestation exerts an overall positive RF of between +81.1 and +135.9 mW m-2 through changes to short-lived climate forcers (SLCF). Taking these additional biogeochemical impacts into account increases the net positive RF of complete global deforestation, due to changes in CO2 and surface albedo, by 7-11%. Overall, our work suggests that deforestation has a stronger warming impact on climate than previously thought. References: Bala, G. et al., 2007. Combined climate and carbon-cycle effects

  2. TauFactor: An open-source application for calculating tortuosity factors from tomographic data

    NASA Astrophysics Data System (ADS)

    Cooper, S. J.; Bertei, A.; Shearing, P. R.; Kilner, J. A.; Brandon, N. P.

    TauFactor is a MatLab application for efficiently calculating the tortuosity factor, as well as volume fractions, surface areas and triple phase boundary densities, from image based microstructural data. The tortuosity factor quantifies the apparent decrease in diffusive transport resulting from convolutions of the flow paths through porous media. TauFactor was originally developed to improve the understanding of electrode microstructures for batteries and fuel cells; however, the tortuosity factor has been of interest to a wide range of disciplines for over a century, including geoscience, biology and optics. It is still common practice to use correlations, such as that developed by Bruggeman, to approximate the tortuosity factor, but in recent years the increasing availability of 3D imaging techniques has spurred interest in calculating this quantity more directly. This tool provides a fast and accurate computational platform applicable to the big datasets (>108 voxels) typical of modern tomography, without requiring high computational power.

  3. Hypoxia Increases Sirtuin 1 Expression in a Hypoxia-inducible Factor-dependent Manner*

    PubMed Central

    Chen, Rui; Dioum, Elhadji M.; Hogg, Richard T.; Gerard, Robert D.; Garcia, Joseph A.

    2011-01-01

    Hypoxia-inducible factors (HIFs) are stress-responsive transcriptional regulators of cellular and physiological processes involved in oxygen metabolism. Although much is understood about the molecular machinery that confers HIF responsiveness to oxygen, far less is known about HIF isoform-specific mechanisms of regulation, despite the fact that HIF-1 and HIF-2 exhibit distinct biological roles. We recently determined that the stress-responsive genetic regulator sirtuin 1 (Sirt1) selectively augments HIF-2 signaling during hypoxia. However, the mechanism by which Sirt1 maintains activity during hypoxia is unknown. In this report, we demonstrate that Sirt1 gene expression increases in a HIF-dependent manner during hypoxia in Hep3B and in HT1080 cells. Impairment of HIF signaling affects Sirt1 deacetylase activity as decreased HIF-1 signaling results in the appearance of acetylated HIF-2α, which is detected without pharmacological inhibition of Sirt1. We also find that Sirt1 augments HIF-2 mediated, but not HIF-1 mediated, transcriptional activation of the isolated Sirt1 promoter. These data in summary reveal a bidirectional link of HIF and Sirt1 signaling during hypoxia. PMID:21345792

  4. Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

    PubMed Central

    Riesle, E; Friess, H; Zhao, L; Wagner, M; Uhl, W; Baczako, K; Gold, L I; Korc, M; Büchler, M W

    1997-01-01

    BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the

  5. The Unhealthy Lifestyle Factors Associated with an Increased Risk of Poor Nutrition among the Elderly Population in China.

    PubMed

    Lin, W-Q; Wang, H H X; Yuan, L-X; Li, B; Jing, M-J; Luo, J-L; Tang, J; Ye, B-K; Wang, P-X

    2017-01-01

    The associations between nutritional status and lifestyle factors have not been well established. This study aimed to investigate the prevalence of poor nutrition and to examine the relationships between nutritional status and unhealthy lifestyle and other related factors among the elderly. This cross-sectional study was conducted in Liaobu Town, Dongguan city, China. A total of 708 community-dwelling older adults aged ≥60 years were recruited by stratified random sampling. Data on sociodemographic characteristics, health and lifestyle factors, and the Mini Nutritional Assessment (MNA) scores were collected using structured questionnaires via face-to-face interviews. A multivariate logistic regression model was constructed to identify the risk factors of poor nutrition. The prevalence of malnutrition among the elderly adults in this study was 1.3%, and 24.4% were at risk of malnutrition (RM). Poor nutrition was significantly associated with female gender, older age, lower education, a high number of self-reported chronic diseases, and hospitalization in the last year. Unhealthy lifestyle factors associated with poor nutrition included current smoking status, higher alcohol consumption, lack of physical activity, longer duration of sitting, negative attitude towards life, and a poor family relationship. While the prevalence of malnutrition was low, RM was high in the elderly population in China. The determinants of malnutrition were explored and the relationships between nutritional status and unhealthy lifestyle factors were examined. The results of this study provide information for future longitudinal studies with multi-factorial interventional design in order to determine the effects of the causal relationships.

  6. Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions.

    PubMed

    Michel, Laurent; Des Jarlais, Don C; Duong Thi, Huong; Khuat Thi Hai, Oanh; Pham Minh, Khuê; Peries, Marianne; Vallo, Roselyne; Nham Thi Tuyet, Thanh; Hoang Thi, Giang; Le Sao, Mai; Feelemyer, Jonathan; Vu Hai, Vinh; Moles, Jean-Pierre; Laureillard, Didier; Nagot, Nicolas

    2017-10-01

    The aim of this study was to describe patterns among people who inject drugs (PWID), risk-related behaviours and access to methadone treatment, in order to design a large-scale intervention aiming to end the HIV epidemic in Haiphong, Vietnam. A respondent-driven sampling (RDS) survey was first conducted to identify profiles of drug use and HIV risk-related behaviour among PWID. A sample of PWID was then included in a one-year cohort study to describe access to methadone treatment and associated factors. Among the 603 patients enrolled in the RDS survey, 10% were female, all were injecting heroin and 24% were using methamphetamine, including 3 (0.5%) through injection. Different profiles of risk-related behaviours were identified, including one entailing high-risk sexual behaviour (n=37) and another involving drug-related high-risk practices (n=22). High-risk sexual activity was related to binge drinking and methamphetamine use. Among subjects with low sexual risk, sexual intercourse with a main partner with unknown serostatus was often unprotected. Among the 250 PWID included in the cohort, 55.2% initiated methadone treatment during the follow-up (versus 4.4% at RDS); methamphetamine use significantly increased. The factors associated with not being treated with methadone after 52 weeks were fewer injections per month and being a methamphetamine user at RDS. Heroin is still the main drug injected in Haiphong. Methamphetamine use is increasing markedly and is associated with delay in methadone initiation. Drug-related risks are low but sexual risk behaviours are still present. Comprehensive approaches are needed in the short term. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit.

    PubMed

    Garmann, D; McLeay, S; Shah, A; Vis, P; Maas Enriquez, M; Ploeger, B A

    2017-07-01

    The pharmacokinetics (PK), safety and efficacy of BAY 81-8973, a full-length, unmodified, recombinant human factor VIII (FVIII), were evaluated in the LEOPOLD trials. The aim of this study was to develop a population PK model based on pooled data from the LEOPOLD trials and to investigate the importance of including samples with FVIII levels below the limit of quantitation (BLQ) to estimate half-life. The analysis included 1535 PK observations (measured by the chromogenic assay) from 183 male patients with haemophilia A aged 1-61 years from the 3 LEOPOLD trials. The limit of quantitation was 1.5 IU dL -1 for the majority of samples. Population PK models that included or excluded BLQ samples were used for FVIII half-life estimations, and simulations were performed using both estimates to explore the influence on the time below a determined FVIII threshold. In the data set used, approximately 16.5% of samples were BLQ, which is not uncommon for FVIII PK data sets. The structural model to describe the PK of BAY 81-8973 was a two-compartment model similar to that seen for other FVIII products. If BLQ samples were excluded from the model, FVIII half-life estimations were longer compared with a model that included BLQ samples. It is essential to assess the importance of BLQ samples when performing population PK estimates of half-life for any FVIII product. Exclusion of BLQ data from half-life estimations based on population PK models may result in an overestimation of half-life and underestimation of time under a predetermined FVIII threshold, resulting in potential underdosing of patients. © 2017 Bayer AG. Haemophilia Published by John Wiley & Sons Ltd.

  8. Factors influencing the crystallization of monosodium urate: a systematic literature review.

    PubMed

    Chhana, Ashika; Lee, Gerald; Dalbeth, Nicola

    2015-10-14

    Gout is a chronic disease of monosodium urate (MSU) crystal deposition. Although hyperuricaemia is the central risk factor for development of gout, not all people with hyperuricaemia have subclinical MSU crystal deposition or indeed, symptomatic disease. The aim of this systematic literature review was to identify factors that contribute to MSU crystallization. A search was conducted of the electronic databases PubMed, Science Direct and Scopus. Articles were included if they contained original data related to MSU crystallization. The methods and results were summarized and categorized into articles describing at least one of the three key steps in MSU crystallization (reduced urate solubility, nucleation and growth). A total of 2175 articles were initially identified in our systematic search with 35 of these articles included in the final analysis. Elevated urate concentration was identified as a central factor driving all three stages of MSU crystallization. Factors that were found to consistently reduce urate solubility were reduced temperatures, pH 7-9 and various ions including sodium ions. Connective tissue factors including bovine cartilage homogenates and healthy human synovial fluid and serum all enhanced urate solubility. MSU nucleation was found to be increased by a number of factors, including sodium ions, uric acid binding antibodies, and synovial fluid or serum from patients with gout. Other than elevated urate concentrations, no other specific factors were identified as promoters of MSU crystal growth. Increased urate concentration is the key factor required at each stage of MSU crystallization. Different proteins and factors within connective tissues may promote MSU crystallization and may be important for determining the sites at which MSU crystallization occurs in the presence of elevated urate concentrations.

  9. Increasing colorectal cancer screening among individuals in the carpentry trade: test of risk communication interventions.

    PubMed

    Lipkus, Isaac M; Skinner, Celette Sugg; Dement, John; Pompeii, Lisa; Moser, Barry; Samsa, Gregory P; Ransohoff, David

    2005-05-01

    Individuals in the carpentry trade, due to lifestyle habits and occupational exposures, may be at above-average risk for colorectal cancer (CRC). Based on the literature which suggests that increasing perceived risk motivates behavior change, we report on the effectiveness of four risk-communication interventions targeted to increase initial, yearly and repeat fecal occult screening (FOBT) among carpenters (N = 860) over a 3-year period. Our 2 x 2 factorial design intervention study varied two dimensions of providing CRC risk factor information: (1) type of risk factor-one set of interventions emphasized three basic risk factors (age, family history and polyps); the other set emphasized a comprehensive set of risk factors including basic, lifestyle, and occupational factors, and (2) tailoring/not tailoring risk factor information. Participants were provided FOBTs. Outcomes were the proportion of returned FOBTs. Varying the amount and intensity of delivering CRC risk factors information affected neither risk perceptions nor initial, yearly, or repeat screening. However, yearly and repeat screening rates were greater among participants who received interventions addressing comprehensive set of risk factors, especially with increasing age. Tailoring on several CRC risk factors appears insufficient to increase and sustain elevated perceptions of CRC risks to promote screening.

  10. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    PubMed

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. Copyright © 2012 Wiley Periodicals, Inc.

  11. [Risk factors for infection in total knee artrhoplasty, including previously unreported intraoperative fracture and deep venous thrombosis].

    PubMed

    de Dios, M; Cordero-Ampuero, J

    2015-01-01

    To carry out a statistical analysis on the significant risk factors for deep late infection (prosthetic joint infection, PJI) in patients with a knee arthroplasty (TKA). A retrospective observational case-control study was conducted on a case series of 32 consecutive knee infections, using an analysis of all the risk factors reported in the literature. A control series of 100 randomly selected patients operated in the same Department of a University General Hospital during the same period of time, with no sign of deep infection in their knee arthroplasty during follow-up. Statistical comparisons were made using Pearson for qualitative and ANOVA for quantitative variables. The significant (p>0.05) factors found in the series were: Preoperative previous knee surgery, glucocorticoids, immunosuppressants, inflammatory arthritis. prolonged surgical time, inadequate antibiotic prophylaxis, intraoperative fractures. Postoperative secretion of the wound longer than 10 days, deep palpable haematoma, need for a new surgery, and deep venous thrombosis in lower limbs. Distant infections cutaneous, generalized sepsis, urinary tract, pneumonia, abdominal. This is the first report of intraoperative fractures and deep venous thrombosis as significantly more frequent factors in infected TKAs. Other previously described risk factors for TKA PJI are also confirmed. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  12. Computational Prediction and Experimental Verification of New MAP Kinase Docking Sites and Substrates Including Gli Transcription Factors

    PubMed Central

    Whisenant, Thomas C.; Ho, David T.; Benz, Ryan W.; Rogers, Jeffrey S.; Kaake, Robyn M.; Gordon, Elizabeth A.; Huang, Lan; Baldi, Pierre; Bardwell, Lee

    2010-01-01

    In order to fully understand protein kinase networks, new methods are needed to identify regulators and substrates of kinases, especially for weakly expressed proteins. Here we have developed a hybrid computational search algorithm that combines machine learning and expert knowledge to identify kinase docking sites, and used this algorithm to search the human genome for novel MAP kinase substrates and regulators focused on the JNK family of MAP kinases. Predictions were tested by peptide array followed by rigorous biochemical verification with in vitro binding and kinase assays on wild-type and mutant proteins. Using this procedure, we found new ‘D-site’ class docking sites in previously known JNK substrates (hnRNP-K, PPM1J/PP2Czeta), as well as new JNK-interacting proteins (MLL4, NEIL1). Finally, we identified new D-site-dependent MAPK substrates, including the hedgehog-regulated transcription factors Gli1 and Gli3, suggesting that a direct connection between MAP kinase and hedgehog signaling may occur at the level of these key regulators. These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates. PMID:20865152

  13. Factors related to increasing safety belt use in states with safety belt use laws : second annual report to Congress, 1988.

    DOT National Transportation Integrated Search

    1989-01-01

    This report. is the second in a series of four annual reports to the : Congress on provisions of state safety belt use laws and other : programmatic factors related to increasing safety belt use levels. : The first Congressional Report reviewed what ...

  14. Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2).

    PubMed

    Schneider, Kevin; Valdez, Joshua; Nguyen, Janice; Vawter, Marquis; Galke, Brandi; Kurtz, Theodore W; Chan, Jefferson Y

    2016-04-01

    The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/-)white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. De-novo discovery of differentially abundant transcription factor binding sites including their positional preference.

    PubMed

    Keilwagen, Jens; Grau, Jan; Paponov, Ivan A; Posch, Stefan; Strickert, Marc; Grosse, Ivo

    2011-02-10

    Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters. The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not been fully solved yet. Here, we present a de-novo motif discovery tool called Dispom for finding differentially abundant transcription factor binding sites that models existing positional preferences of binding sites and adjusts the length of the motif in the learning process. Evaluating Dispom, we find that its prediction performance is superior to existing tools for de-novo motif discovery for 18 benchmark data sets with planted binding sites, and for a metazoan compendium based on experimental data from micro-array, ChIP-chip, ChIP-DSL, and DamID as well as Gene Ontology data. Finally, we apply Dispom to find binding sites differentially abundant in promoters of auxin-responsive genes extracted from Arabidopsis thaliana microarray data, and we find a motif that can be interpreted as a refined auxin responsive element predominately positioned in the 250-bp region upstream of the transcription start site. Using an independent data set of auxin-responsive genes, we find in genome-wide predictions that the refined motif is more specific for auxin-responsive genes than the canonical auxin-responsive element. In general, Dispom can be used to find differentially abundant motifs in sequences of any origin. However, the positional distribution learned by Dispom is especially beneficial if all sequences are aligned to some anchor point like the transcription start site in case of promoter sequences. We demonstrate that the combination of searching for differentially abundant motifs and inferring a position distribution from the data is beneficial for de-novo motif discovery. Hence, we make the tool freely available as a component of the open

  16. Risk Factors and Prodromal Eating Pathology

    ERIC Educational Resources Information Center

    Stice, Eric; Ng, Janet; Shaw, Heather

    2010-01-01

    Prospective studies have identified factors that increase risk for eating pathology onset, including perceived pressure for thinness, thin-ideal internalization, body dissatisfaction, dietary restraint, and negative affect. Research also suggests that body dissatisfaction and dietary restraint may constitute prodromal stages of the development of…

  17. Comprehensive Geriatric Assessment (CGA) based risk factors for increased caregiver burden among elderly Asian patients with cancer.

    PubMed

    Rajasekaran, Tanujaa; Tan, Tira; Ong, Whee Sze; Koo, Khai Nee; Chan, Lili; Poon, Donald; Roy Chowdhury, Anupama; Krishna, Lalit; Kanesvaran, Ravindran

    2016-05-01

    This study aims to identify Comprehensive Geriatric Assessment (CGA) based risk factors to help predict caregiver burden among elderly patients with cancer. The study evaluated 249 patients newly diagnosed with cancer, aged 70years and above, who attended the geriatric oncology clinic at the National Cancer Centre Singapore between 2007 and 2010. Out of 249 patients, 244 patients had information available on family caregiver burden and were analysed. On univariate analysis, ADL dependence, lower IADL scores, ECOG performance status of 3-4, higher fall risk, lower scores in dominant hand grip strength test and mini mental state examination, polypharmacy, higher nutritional risk, haemoglobin <12g/dL and presence of geriatric syndromes were significantly associated with mild to severe caregiver burden. On multivariate analysis, only ECOG performance status of 3-4 (odds ratio [OR], 4.47; 95% confidence interval [CI], 2.27-8.80) and haemoglobin <12g/dL (OR, 2.38; 95% CI, 1.14-4.99) were associated with an increased probability of mild to severe caregiver burden. The model achieved a good fit (Hosmer-Lemeshow's p=0.196) and discrimination (area under the curve [AUC]=0.742; bias-corrected AUC=0.737). Based on this, patients were stratified into 3 risk groups with different proportion of patients with increased caregiver burden (low risk: 3.9% vs intermediate risk: 18.8% vs high risk: 39.6%; p<0.001). ECOG performance status and haemoglobin were associated with increased caregiver burden among elderly patients with cancer. Using these two factors in the clinic may help clinicians identify caregivers at risk and take preventive action to mitigate that. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene.

    PubMed

    Nakayama, Youhei; Nakajima, Yu; Kato, Naoko; Takai, Hideki; Kim, Dong-Soon; Arai, Masato; Mezawa, Masaru; Araki, Shouta; Sodek, Jaro; Ogata, Yorimasa

    2006-08-01

    Insulin-like growth factor-I (IGF-I) promotes bone formation by stimulating proliferation and differentiation of osteoblasts. Bone sialoprotein (BSP), is thought to function in the initial mineralization of bone, is selectively expressed by differentiated osteoblast. To determine the molecular mechanism of IGF-I regulation of osteogenesis, we analyzed the effects of IGF-I on the expression of BSP in osteoblast-like Saos2 and in rat stromal bone marrow (RBMC-D8) cells. IGF-I (50 ng/ml) increased BSP mRNA levels at 12 h in Saos2 cells. In RBMC-D8 cells, IGF-I increased BSP mRNA levels at 3 h. From transient transfection assays, a twofold increase in transcription by IGF-I was observed at 12 h in pLUC3 construct that included the promoter sequence from -116 to +60. Effect of IGF-I was abrogated by 2-bp mutations in either the FGF2 response element (FRE) or homeodomain protein-binding site (HOX). Gel shift analyses showed that IGF-I increased binding of nuclear proteins to the FRE and HOX elements. Notably, the HOX-protein complex was supershifted by Smad1 antibody, while the FRE-protein complex was shifted by Smad1 and Cbfa1 antibodies. Dlx2 and Dlx5 antibodies disrupted the formation of the FRE- and HOX-protein complexes. The IGF-I effects on the formation of FRE-protein complexes were abolished by tyrosine kinase inhibitor herbimycin A (HA), PI3-kinase/Akt inhibitor LY249002, and MAP kinase kinase inhibitor U0126, while IGF-I effects on HOX-protein complexes were abolished by HA and LY249002. These studies demonstrate that IGF-I stimulates BSP transcription by targeting the FRE and HOX elements in the proximal promoter of BSP gene.

  19. Arsenite induces endothelial cell permeability increase through a reactive oxygen species-vascular endothelial growth factor pathway.

    PubMed

    Bao, Lingzhi; Shi, Honglian

    2010-11-15

    As a potent environmental oxidative stressor, arsenic exposure has been reported to exacerbate cardiovascular diseases and increase vascular endothelial cell monolayer permeability. However, the underlying mechanism of this effect is not well understood. In this paper, we test our hypothesis that reactive oxygen species (ROS)-induced vascular endothelial growth factor (VEGF) expression may play an important role in an arsenic-caused increase of endothelial cell monolayer permeability. The mouse brain vascular endothelial cell bEnd3 monolayer was exposed to arsenite for 1, 3, and 6 days. The monolayer permeability, VEGF protein release, and ROS generation were determined. In addition, VE-cadherin and zonula occludens-1 (ZO-1), two membrane structure proteins, were immunostained to elucidate the effects of arsenite on the cell-cell junction. The roles of ROS and VEGF in arsenite-induced permeability was determined by inhibiting ROS with antioxidants and immuno-depleting VEGF with a VEGF antibody. We observed that arsenite increased bEnd3 monolayer permeability, elevated the production of cellular ROS, and increased VEGF release. VE-cadherin and ZO-1 disruptions were also found in cells treated with arsenite. Furthermore, both antioxidant (N-acetyl cysteine and tempol) and the VEGF antibody treatments significantly lowered the arsenite-induced permeability of the bEnd3 monolayer as well as VEGF expression. VE-cadherin and ZO-1 disruptions were also diminished by N-acetyl cysteine and the VEGF antibody. Our data suggest that the increase in VEGF expression caused by ROS may play an important role in the arsenite-induced increase in endothelial cell permeability.

  20. A Wheat CCAAT Box-Binding Transcription Factor Increases the Grain Yield of Wheat with Less Fertilizer Input1

    PubMed Central

    Qu, Baoyuan; He, Xue; Wang, Jing; Zhao, Yanyan; Teng, Wan; Shao, An; Zhao, Xueqiang; Ma, Wenying; Wang, Junyi; Li, Bin; Li, Zhensheng; Tong, Yiping

    2015-01-01

    Increasing fertilizer consumption has led to low fertilizer use efficiency and environmental problems. Identifying nutrient-efficient genes will facilitate the breeding of crops with improved fertilizer use efficiency. This research performed a genome-wide sequence analysis of the A (NFYA), B (NFYB), and C (NFYC) subunits of Nuclear Factor Y (NF-Y) in wheat (Triticum aestivum) and further investigated their responses to nitrogen and phosphorus availability in wheat seedlings. Sequence mining together with gene cloning identified 18 NFYAs, 34 NFYBs, and 28 NFYCs. The expression of most NFYAs positively responded to low nitrogen and phosphorus availability. In contrast, microRNA169 negatively responded to low nitrogen and phosphorus availability and degraded NFYAs. Overexpressing TaNFYA-B1, a low-nitrogen- and low-phosphorus-inducible NFYA transcript factor on chromosome 6B, significantly increased both nitrogen and phosphorus uptake and grain yield under differing nitrogen and phosphorus supply levels in a field experiment. The increased nitrogen and phosphorus uptake may have resulted from the fact that that overexpressing TaNFYA-B1 stimulated root development and up-regulated the expression of both nitrate and phosphate transporters in roots. Our results suggest that TaNFYA-B1 plays essential roles in root development and in nitrogen and phosphorus usage in wheat. Furthermore, our results provide new knowledge and valuable gene resources that should be useful in efforts to breed crops targeting high yield with less fertilizer input. PMID:25489021

  1. Increased fructose intake as a risk factor for dementia.

    PubMed

    Stephan, B C M; Wells, J C K; Brayne, C; Albanese, E; Siervo, M

    2010-08-01

    The transition in the world age demographic toward older age is associated with an increased risk of neurodegenerative diseases, such as Alzheimer's disease. Risk profiles for dementia may also be changing. Obesity and type 2 diabetes have increased in prevalence in the last half-century and have been associated with increased dementia risk. Specific changes in nutrition may also represent a direct risk. A diet transition in the United States has occurred in the intake of refined sugar, particularly high-fructose corn syrup (HFCS) from a yearly estimate of 8.1 kg/person at the beginning of the XIX century to a current estimate of 65 kg/person. This article considers the association between refined sugar intake, markers of cardiovascular disease risk, and the possible promotion of the development of dementia.

  2. Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro.

    PubMed

    Syal, Ashu; Schiavi, Susan; Chakravarty, Sumana; Dwarakanath, Vangipuram; Quigley, Raymond; Baum, Michel

    2006-02-01

    Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in X-linked hypophosphatemia, tumor-induced osteomalacia, and autosomal dominant hypophosphatemic rickets. Recently, we demonstrated that Hyp mice have greater urinary PGE2 levels compared with C57/B6 mice and that indomethacin administration in vivo and in vitro ameliorates the phosphate transport defect in Hyp mice. To determine further whether altered prostaglandin metabolism plays a role in the renal phosphate transport defect in Hyp mice, we incubated renal proximal tubules with arachidonic acid. We find that PGE2 production was higher in Hyp mice than in C57/B6 mice. Incubation of C57/B6 mouse renal proximal tubules with FGF-23R176Q, an active mutant form of FGR23, increased tubular PGE2 production, an effect that was inhibited by 50 microM PD-98059 and 10 microM SB-203580, inhibitors of the MAP kinase pathway. C57/B6 mice injected with FGF-23R176Q had a approximately 10-fold increase in PGE2 excretion 24 h after intraperitoneal injection of FGF-23R176Q compared with vehicle-treated controls. Finally, we show that PGE2 inhibited both phosphate and volume absorption in mouse proximal convoluted tubules perfused in vitro and reduced brush-border membrane vesicle NaPi-2a protein abundance from renal cortex incubated in vitro with PGE2. In conclusion, FGF-23 increases urinary and renal tubular PGE2 production via the MAP kinase pathway and PGE2 inhibits proximal tubule phosphate transport.

  3. Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro

    PubMed Central

    Syal, Ashu; Schiavi, Susan; Chakravarty, Sumana; Dwarakanath, Vangipuram; Quigley, Raymond; Baum, Michel

    2014-01-01

    Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in X-linked hypophosphatemia, tumor-induced osteomalacia, and autosomal dominant hypophosphatemic rickets. Recently, we demonstrated that Hyp mice have greater urinary PGE2 levels compared with C57/B6 mice and that indomethacin administration in vivo and in vitro ameliorates the phosphate transport defect in Hyp mice. To determine further whether altered prostaglandin metabolism plays a role in the renal phosphate transport defect in Hyp mice, we incubated renal proximal tubules with arachidonic acid. We find that PGE2 production was higher in Hyp mice than in C57/B6 mice. Incubation of C57/B6 mouse renal proximal tubules with FGF-23R176Q, an active mutant form of FGR23, increased tubular PGE2 production, an effect that was inhibited by 50 μM PD-98059 and 10 μM SB-203580, inhibitors of the MAP kinase pathway. C57/B6 mice injected with FGF-23R176Q had a ~10-fold increase in PGE2 excretion 24 h after intraperitoneal injection of FGF-23R176Q compared with vehicle-treated controls. Finally, we show that PGE2 inhibited both phosphate and volume absorption in mouse proximal convoluted tubules perfused in vitro and reduced brush-border membrane vesicle NaPi-2a protein abundance from renal cortex incubated in vitro with PGE2. In conclusion, FGF-23 increases urinary and renal tubular PGE2 production via the MAP kinase pathway and PGE2 inhibits proximal tubule phosphate transport. PMID:16144964

  4. Solar radiation increases suicide rate after adjusting for other climate factors in South Korea.

    PubMed

    Jee, Hee-Jung; Cho, Chul-Hyun; Lee, Yu Jin; Choi, Nari; An, Hyonggin; Lee, Heon-Jeong

    2017-03-01

    Previous studies have indicated that suicide rates have significant seasonal variations. There is seasonal discordance between temperature and solar radiation due to the monsoon season in South Korea. We investigated the seasonality of suicide and assessed its association with climate variables in South Korea. Suicide rates were obtained from the National Statistical Office of South Korea, and climatic data were obtained from the Korea Meteorological Administration for the period of 1992-2010. We conducted analyses using a generalized additive model (GAM). First, we explored the seasonality of suicide and climate variables such as mean temperature, daily temperature range, solar radiation, and relative humidity. Next, we identified confounding climate variables associated with suicide rate. To estimate the adjusted effect of solar radiation on the suicide rate, we investigated the confounding variables using a multivariable GAM. Suicide rate showed seasonality with a pattern similar to that of solar radiation. We found that the suicide rate increased 1.008 times when solar radiation increased by 1 MJ/m 2 after adjusting for other confounding climate factors (P < 0.001). Solar radiation has a significant linear relationship with suicide after adjusting for region, other climate variables, and time trends. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Clinical and epidemiological profiles including meteorological factors of low respiratory tract infection due to human rhinovirus in hospitalized children.

    PubMed

    Yan, Yongdong; Huang, Li; Wang, Meijuan; Wang, Yuqing; Ji, Wei; Zhu, Canhong; Chen, Zhengrong

    2017-03-07

    Lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality in children. Human rhinovirus (HRV) is confirmed to be associated with pediatric lower respiratory tract infection. Seasonal and meteorological factors may play a key role in the epidemiology of HRV. The purposes of this study were to investigate the frequency, seasonal distribution, and clinical characteristics of hospitalized children with LRTI caused by HRVs. In addition, associations between incidence of HRVs and meteorological factors in a subtropical region of China were discussed. Hospitalized children <14 years old admitted to the Respiratory Department of the Children's Hospital, which is affiliated to Soochow University, between January 1, 2013 and December 31, 2015, were enrolled in this study. Multi-pathogens were detected in nasopharyngeal aspirate samples. Meanwhile, meteorological factors were recorded. The average incidence of HRVs infection was 11.4% (707/6194) and 240 cases of which were co-infection cases with other pathogens. Children with co-infection presented more frequent fever and tachypnea compared to children infected with HRVs only (both P < 0.05). Among 707 HRV positive children, the mean age was 23.2 months (range 1 to 140 months). Among all respiratory infections, the highest incidence of HRVs cases occurred in children age 13-36 months old (15.1%, 203/1341). Of all 228 HRV cases in 2014, 85 cases (37.3%) were HRV-C positive. HRVs and HRV-C infection occurred throughout the year during the study period, although a higher incidence was observed in summer and autumn seasons. HRVs or HRV-C incidence in hospitalized children with LRTI was associated with the monthly mean temperature (both P < 0.05). HRV was one of the most common viral pathogen detected in hospitalized children with LRTI at the Children's Hospital of Suzhou, China, and had its own seasonal distribution including HRV-C, which was partly caused by temperature.

  6. Exploring Risk Factors for Follicular Lymphoma

    PubMed Central

    Ambinder, Alexander J.; Shenoy, Pareen J.; Malik, Neha; Maggioncalda, Alison; Nastoupil, Loretta J.; Flowers, Christopher R.

    2012-01-01

    Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair gene XRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment. PMID:23028387

  7. trans-Resveratrol Protects Ischemic PC12 Cells by Inhibiting the Hypoxia Associated Transcription Factors and Increasing the Levels of Antioxidant Defense Enzymes

    PubMed Central

    2012-01-01

    An in vitro model of ischemic cerebral stroke [oxygen-glucose deprivation (OGD) for 6 h followed by 24 h reoxygenation (R)] with PC12 cells increases Ca2+ influx by upregulating native L-type Ca2+ channels and reactive oxygen species (ROS) generation. This reactive oxygen species generation and increase in intracellular Ca2+ triggers the expression of hypoxic homeostasis transcription factors such as hypoxia induced factor-1 alpha (HIF-1α), Cav-beta 3 (Cav β3), signal transducer and activator of transcription 3 (STAT3), heat shock protein 27 (hsp-27), and cationic channel transient receptor potential melastatin 7 (TRPM7). OGD insulted PC12 cells were subjected to biologically safe doses (5, 10, and 25 μM) of trans-resveratrol in three different treatment groups: 24 h prior to OGD (pre-treatment); 24 h post OGD (post-treatment); and from 24 h before OGD to end of reoxygenation period (whole-treatment). Here, we demonstrated that OGD-R-induced neuronal injury/death is by reactive oxygen species generation, increase in intracellular calcium levels, and decrease in antioxidant defense enzymes. trans-Resveratrol increases the viability of OGD-R insulted PC12 cells, which was assessed by using MTT, NRU, and LDH release assay. In addition, trans-resveratrol significantly decreases reactive oxygen species generation, intracellular Ca2+ levels, and hypoxia associated transcription factors and also increases the level of antioxidant defense enzymes. Our data shows that the whole-treatment group of trans-resveratrol is most efficient in decreasing hypoxia induced cell death through its antioxidant properties. PMID:23421680

  8. Increasing prevalence of diabetes mellitus in a developing country and its related factors.

    PubMed

    Animaw, Worku; Seyoum, Yeshaneh

    2017-01-01

    All countries, irrespective of their developmental stage, face an increasing burden of non-communicable diseases including diabetes mellitus. There is substantial evidence of the existence of the gap in the level of diabetes mellitus and its complications prevention and control measures in developing countries. This study aimed to assess the prevalence of diabetes mellitus in urban and rural dwellers in a low-income country from both younger and older population and to identify factors related. This is a community based comparative cross-sectional study conducted in a low-income country, Ethiopia. The sample size was determined by EPI-Info for two populations; the WHO's STEP-wise approach for non-communicable diseases surveillance in developing countries was employed for sampling, study variable selection and data collection procedures. Fasting blood glucose levels were measured by finger pricking after overnight fasting. Data entry was done by EPI-data computer program version 3.1 and then processed by SPSS version 20. Bivariate and multivariate logistic regression tests were used to assess the associations between diabetes status of individuals and its potential predictor variables. P-value < 0.05 was considered as statistically significant level. The study was conducted on 1405 individuals with age range of 18-97 years old. The mean fasting blood glucose level for study participants was 91.16mg/dl; while it was 94.73mg/dl for urban and 87.71mg/dl for rural dwellers. The prevalence of diabetes mellitus was 3.3%; while it was 2.0% for rural and (4.6%) for urban dwellers. Both the mean blood glucose level and the prevalence of diabetes mellitus were significantly higher for urban residents than rural. More than three-fourths of diabetic cases were newly diagnosed by this study. Urban dwellers, centrally obese, overweight, and hypertensive individuals have higher odds of getting diabetes mellitus. High prevalence of diabetes mellitus involving both old and young

  9. Increased serum bicarbonate in critically ill patients: a retrospective analysis.

    PubMed

    Libório, Alexandre Braga; Noritomi, Danilo Teixeira; Leite, Tacyano Tavares; de Melo Bezerra, Candice Torres; de Faria, Evandro Rodrigues; Kellum, John A

    2015-03-01

    Although metabolic alkalosis is a common occurrence, no study has evaluated its prevalence, associated factors or outcomes in critically ill patients. This is a retrospective study from the Multiparameter Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient records, 18,982 patients met the inclusion criteria. Serum bicarbonate levels demonstrated a U-shaped association with mortality with knots at 25 and 30 mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple factors that are classically associated with metabolic alkalosis (mainly diuretic use, hypernatremia, hypokalemia and high gastric output). Patients with increased serum bicarbonate exhibited increased ICU LOS, more days on mechanical ventilation and higher hospital mortality. After multivariate adjustment, each 5-mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with an odds ratio of 1.21 for hospital mortality. The association between increased serum bicarbonate levels and mortality occurs independently of its possible etiologies. An increased serum bicarbonate level is common in critically ill patients; this can be attributed to multiple factors in the majority of cases, and its presence and duration negatively influence patient outcomes.

  10. Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior.

    PubMed

    Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L

    2008-06-01

    Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.

  11. Chronic pre-operative opioid use is a risk factor for increased complications, resource use and costs after cervical fusion.

    PubMed

    Jain, Nikhil; Brock, John L; Phillips, Frank M; Weaver, Tristan; Khan, Safdar N

    2018-04-27

    As healthcare transitions to value-based models, there has been an increased focus on patient factors that can influence peri- and post-operative adverse events, resource use, and costs. Many studies have reported risk factors for systemic complications after cervical fusion, but none have studied chronic opioid therapy (COT) as a risk factor. To answer the following questions from a large cohort of patients who underwent primary cervical fusion for degenerative pathology: (1) What is the patient profile associated with pre-operative COT? (2) Is pre-operative COT a risk factor for 90-day systemic complications, emergency department (ED) visits, readmission, and one-year adverse events? (3) What are the risk factors and one-year adverse events related to long-term post-operative opioid use? and (4) How much did payers reimburse for management of complications and adverse events? Retrospective review of Humana commercial insurance data (2007-Q3 2015). 29,101 patients undergoing primary cervical fusion for degenerative pathology. Patients and procedures of interest were included using International Classification of Diseases (ICD) coding. Patients with opioid prescriptions for >6 months before surgery were considered as having pre-operative COT. Patients with continued opioid use till one-year after surgery were considered as long-term users. Descriptive analysis of patient cohorts has been done. Multiple-variable logistic regression analyses adjusting for approach, number of levels of surgery, discharge disposition, and comorbidities were done to answer first three study questions. Reimbursement data from insurers has been reported to answer our fourth study question. Of the entire cohort, 6,643 (22.8%) had pre-operative COT. Pre-operative COT was associated with a higher risk of 90-day wound complications (OR 1.39, 95% CI:1.16-1.66), all-cause 90-day ED visits (adjusted OR 1.22, 95% CI:1.13-1.32), and pain-related ED visits (adjusted OR 1.39, 95% CI:1

  12. Relationship between sleep duration and childhood obesity: Systematic review including the potential underlying mechanisms.

    PubMed

    Felső, R; Lohner, S; Hollódy, K; Erhardt, É; Molnár, D

    2017-09-01

    The prevalence of obesity is continually increasing worldwide. Determining risk factors for obesity may facilitate effective preventive programs. The present review focuses on sleep duration as a potential risk factor for childhood obesity. The aim is to summarize the evidence on the association of sleep duration and obesity and to discuss the underlying potential physiological and/or pathophysiological mechanisms. The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers using text words with appropriate truncation and relevant indexing terms. All studies objectively measuring sleep duration and investigating the association between sleep duration and obesity or factors (lifestyle and hormonal) possibly associated with obesity were included, without making restrictions based on study design or language. Data from eligible studies were extracted in tabular form and summarized narratively. After removing duplicates, 3540 articles were obtained. Finally, 33 studies (including 3 randomized controlled trials and 30 observational studies) were included in the review. Sleep duration seems to influence weight gain in children, however, the underlying explanatory mechanisms are still uncertain. In our review only the link between short sleep duration and the development of insulin resistance, sedentarism and unhealthy dietary patterns could be verified, while the role of other mediators, such as physical activity, screen time, change in ghrelin and leptin levels, remained uncertain. There are numerous evidence gaps. To answer the remaining questions, there is a need for studies meeting high methodological standards and including a large number of children. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All

  13. Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

    PubMed Central

    Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

    2014-01-01

    Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

  14. Artemin growth factor increases nicotinic cholinergic receptor subunit expression and activity in nociceptive sensory neurons.

    PubMed

    Albers, Kathryn M; Zhang, Xiu Lin; Diges, Charlotte M; Schwartz, Erica S; Yang, Charles I; Davis, Brian M; Gold, Michael S

    2014-05-22

    Artemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity. Reverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund's adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice. These findings suggest that Artn

  15. Factors Which Increase Acid Production in Milk by Lactobacilli

    PubMed Central

    Huhtanen, C. N.; Williams, W. L.

    1963-01-01

    The stimulation by yeast extract of acid production in milk by various lactobacilli was studied. It was found that supplementing milk with purine and pyrimidine bases and amino acids allowed nearly maximal acid production by Lactobacillus bulgaricus strain 7994, L. acidophilus 4796, 4356, and 4357, and L. leichmannii 326 and 327. Further supplementation with deoxyribotides allowed maximal acid production by L. acidophilus 204, but L. acidophilus 207 required adenosine or adenylic acid. L. casei strain 7469 showed no appreciable response to the amino acids or purine and pyrimidine bases, and is presumed to require an unidentified factor in corn steep liquor. PMID:13955610

  16. Parental concern about vaccine safety in Canadian children partially immunized at age 2: a multivariable model including system level factors.

    PubMed

    MacDonald, Shannon E; Schopflocher, Donald P; Vaudry, Wendy

    2014-01-01

    Children who begin but do not fully complete the recommended series of childhood vaccines by 2 y of age are a much larger group than those who receive no vaccines. While parents who refuse all vaccines typically express concern about vaccine safety, it is critical to determine what influences parents of 'partially' immunized children. This case-control study examined whether parental concern about vaccine safety was responsible for partial immunization, and whether other personal or system-level factors played an important role. A random sample of parents of partially and completely immunized 2 y old children were selected from a Canadian regional immunization registry and completed a postal survey assessing various personal and system-level factors. Unadjusted odds ratios (OR) and adjusted ORs (aOR) were calculated with logistic regression. While vaccine safety concern was associated with partial immunization (OR 7.338, 95% CI 4.138-13.012), other variables were more strongly associated and reduced the strength of the relationship between concern and partial immunization in multivariable analysis (aOR 2.829, 95% CI 1.151-6.957). Other important factors included perceived disease susceptibility and severity (aOR 4.629, 95% CI 2.017-10.625), residential mobility (aOR 3.908, 95% CI 2.075-7.358), daycare use (aOR 0.310, 95% CI 0.144-0.671), number of needles administered at each visit (aOR 7.734, 95% CI 2.598-23.025) and access to a regular physician (aOR 0.219, 95% CI 0.057-0.846). While concern about vaccine safety may be addressed through educational strategies, this study suggests that additional program and policy-level strategies may positively impact immunization uptake.

  17. Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

    PubMed

    Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

    2016-01-28

    In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Risk factors for stress fractures.

    PubMed

    Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

    1999-08-01

    Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

  19. Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions.

    PubMed

    Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki

    2015-12-08

    Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

    PubMed Central

    Noble, Emily E.; Mavanji, Vijayakumar; Little, Morgan R.; Billington, Charles J.; Kotz, Catherine M.; Wang, ChuanFeng

    2014-01-01

    Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. PMID:24755094

  1. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

    PubMed

    Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

    2014-10-01

    Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

  2. Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

    NASA Technical Reports Server (NTRS)

    Adams, G. R.

    1998-01-01

    Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

  3. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer's Disease.

    PubMed

    Brewer, George J

    2015-12-02

    It has become clear that copper toxicity is playing a major role in Alzheimer's disease; but why is the brain copper toxicity with cognition loss in Alzheimer's disease so much different clinically than brain copper toxicity in Wilson's disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer's is at least in part, a copper-2 toxicity disease, while Wilson's is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer's epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.

  4. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea

    PubMed Central

    Ayas, Najib T.

    2018-01-01

    increased glomerular area (by 1.13 fold, p< 0.001) and expansion of mesangial matrix (by 1.8 fold, p< 0.01). Moreover, the glomerular expressions of TGF-β1, CTGF and VEGF-A proteins were 2.7, 2.2 and 3.8-fold higher in mice exposed to IH (p< 0.05 for all). Furthermore, western blotting protein analysis demonstrates that IH-exposed mice express higher levels of TGF-β1, CTGF and VEGF-A proteins by 1.9, 4.0 and 1.6-fold (p< 0.05 for all) respectively. Renal cellular apoptosis was greater in the IH group as shown by an increased cortical Bax/Bcl-2 protein ratio (p< 0.01) and higher fluorometric TUNEL staining (p< 0.001). Finally, 24-hr urinary albumin levels were higher in mice exposed to IH (43.4 μg vs 9.7 μg, p< 0.01), while there were no differences in serum creatinine levels between the two groups. We conclude that IH causes kidney injury that is accompanied by glomerular hypertrophy, mesangial matrix expansion, increased expression of glomerular growth factors and an increased cellular apoptosis. PMID:29389945

  5. Bio-environmental factors associated with myopia: An updated review.

    PubMed

    Galvis, V; Tello, A; Camacho, P A; Parra, M M; Merayo-Lloves, J

    2017-07-01

    Experimental studies in animals, as well as observational and intervention studies in humans, seem to support the premise that the development of juvenile myopia is promoted by a combination of the effect of genetic and environmental factors, with a complex interaction between them. The very rapid increase in myopia rates in some parts of the world, such as Southeast Asia, supports a significant environmental effect. Several lines of evidence suggest that humans might respond to various external factors, such as increased activity in near vision, increased educational pressure, decreased exposure to sunlight outdoors, dietary changes (including increased intake of carbohydrates), as well as low light levels indoors. All these factors could be associated with a higher prevalence of myopia. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Increasing diversity in radiologic technology.

    PubMed

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

  7. Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

    PubMed

    Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K

    2013-07-01

    The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P < .001) and IGFBP-3 (P = .01) and the LF diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.

  8. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

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

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp; Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522; Ota, Hiroyo

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned mediummore » significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell.

  9. Increasing maternal percentage body fat in early second trimester: a risk factor for preeclampsia.

    PubMed

    Wang, Yanxia; Qiu, Jie; Zhou, Min; Wang, Youjie; Du, Yukai

    2015-02-01

    To determine if maternal percentage body fat (PBF) or fat free mass (FFM) in the early second trimester of pregnancy influenced the development of preeclampsia. A matched nested case-control study was conducted from a cohort study of 1668 women at Gansu provincial maternal and child care hospital from July 2007 to August 2011 in China. Maternal PBF and FFM were assessed by bioelectrical impedance analysis during 12th-16th gestational week. The demographic characteristics were all chart abstracted. After childbirth, 70 cases of preeclampsia were matched by race/age with 140 uncomplicated pregnancies women. Multivariate logistic regression analysis was performed to determine the associated risk factors. Pre-pregnancy body mass index were higher in women who subsequently developed preeclampsia compared with controls (p < 0.001). During 12th-16th gestational week, there were nearly 7-fold increase in the odds of preeclampsia (adjusted OR: 6.84, 95% CI: 4.15-41.60) among women with PBF ≥ 40% versus women with PBF < 40%. But FFM were not at further increased risk of the development of preeclampsia (adjusted OR, 1.02; 95% CI, 0.6-3.6). Maternal PBF but not FFM is a predictor of preeclampsia in the early second trimester. Excessive adipose tissue possibly played an important role in developing of preeclampsia.

  10. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

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

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  11. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    DOE PAGES

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; ...

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  12. Porcine granulocyte-colony stimulating factor (G-CSF) delivered via replication-defective adenovirus induces a sustained increase in circulating peripheral blood neutrophils

    USDA-ARS?s Scientific Manuscript database

    The use of immunomodulators is a promising area for biotherapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease, particularly during periods of peak disease incidence. Cytokines, including granulocyte colony-stimulating factor (G-CSF), are one class of compounds that...

  13. Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

    PubMed

    da Silva, Tatiana Pereira; Giacoia-Gripp, Carmem Beatriz Wagner; Schmaltz, Carolina A; Sant'Anna, Flavia Marinho; Saad, Maria Helena; Matos, Juliana Arruda de; de Lima E Silva, Julio Castro Alves; Rolla, Valeria Cavalcanti; Morgado, Mariza Gonçalves

    2017-09-06

    Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4 + T cell counts <200 cells/mm 3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4 + T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4 + T cell counts at follow-up visits of ≥200 cells/mm 3 . These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens

  14. Increasing influenza vaccination rates via low cost messaging interventions.

    PubMed

    Baskin, Ernest

    2018-01-01

    This article tests low cost interventions to increase influenza vaccination rates. By changing an email announcement sent out to employees in 2014 (n > 30,000), the following interventions are tested: incentives, attention to the negative impacts of not get vaccinated, and showing a map to the vaccination centers at the end of the email announcement. Only the map condition helped increase influenza vaccination rates. The use of low-cost interventions can improve influenza vaccination rates though not all interventions work as well as others in the field. In particular, while including maps helped increase vaccination rates, other factors such as negative impact reminders and incentives, which previous studies have found to be successful in the laboratory, did not.

  15. Increased DNA double-strand break was associated with downregulation of repair and upregulation of apoptotic factors in rat hippocampus after alcohol exposure.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; N'Gouemo, Prosper; Datta, Kamal

    2016-08-01

    Binge drinking is known to cause damage in critical areas of the brain, including the hippocampus, which is important for relational memory and is reported to be sensitive to alcohol toxicity. However, the roles of DNA double-strand break (DSB) and its repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) in alcohol-induced hippocampal injury remain to be elucidated. The purpose of this first study was to assess alcohol-induced DNA DSB and the mechanism by which alcohol affects DSB repair pathways in rat hippocampus. Male Sprague-Dawley rats (8-10 weeks old) were put on a 4-day binge ethanol treatment regimen. Control animals were maintained under similar conditions but were given the vehicle without ethanol. All animals were humanely euthanized 24 h after the last dose of ethanol administration and the hippocampi were dissected for immunoblot and immunohistochemistry analysis. Ethanol exposure caused increased 4-hydroxynonenal (4-HNE) staining as well as elevated γH2AX and 53BP1 foci in hippocampal cells. Immunoblot analysis showed decreased Mre11, Rad51, Rad50, and Ku86 as well as increased Bax and p21 in samples from ethanol-treated rats. Additionally, we also observed increased activated caspase3 staining in hippocampal cells 24 h after ethanol withdrawal. Taken together, our data demonstrated that ethanol concurrently induced DNA DSB, downregulated DSB repair pathway proteins, and increased apoptotic factors in hippocampal cells. We believe these findings will provide the impetus for further research on DNA DSB and its repair pathways in relation to alcohol toxicity in brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Should visceral fat be reduced to increase longevity?

    PubMed

    Finelli, Carmine; Sommella, Luigi; Gioia, Saverio; La Sala, Nicolina; Tarantino, Giovanni

    2013-09-01

    Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The use of an electric field in increasing the resistance of plants to the action of unfavorable space flight factors

    NASA Astrophysics Data System (ADS)

    Nechitailo, G.; Gordeev, A.

    The key role in increasing the resistance of plants to unfavorable space flight factors is assigned to biomembranes of root cells. It is these biomembranes on which numerous biochemical and biophysical processes determining the adaptive capacity of plant organisms occur. In the initial period of exposure to unfavorable space flight factors the adaptational reactions of the plant organism undoubtedly increase its resistance. But the intensification of removal of H+ ions through the plasmalemma with an increase of the external influence sharply raises the quantity of cations leaving the cell, which leads to the accumu lation of a considerable quantity of intracellular negative charges. These charges together with negative charges built in the membrane force protons to concentrate on the external surface of the membrane. Since protons have a very strong electric field, they form such a charge of which the electric field is about from several to hundreds of V/cm. The concentration of positive charges of protons entails the formation of a double electric field which extremely impedes the diffusion of other ions. Thus, a proton barrier is formed. Its length can be very considerable due to which the whole process of transmembrane energy and mass-transfer is disturbed. The proton barrier is easily destroyed by a weak electric field created in the root zone. In experiment on electrostimulation of different plants under space flight conditions at the orbital station MIR the absorption of nutrient elements by the root system increased to the optimal level, the ratio of physiologically active substances in the rhizosphere was normalized, the content of chlorophyll, carotin, and ascorbic acid in leaves corresponded to the ground-based control. Understanding of the mechanism of formation of a proton barrier on the plasmalemma of root cells as a result of the response of plants to the negative action of external factors (microgravity) is of great importance. It allows the

  18. The use of an electric field in increasing the resistance of plants to the action of unfavorable space flight factors

    NASA Astrophysics Data System (ADS)

    Nechitailo, G.; Gordeev, A.

    2004-01-01

    The key role in increasing the resistance of plants to unfavorable space flight factors is assigned to biomembranes of root cells. It is these biomembranes in which numerous biochemical and biophysical processes determining the adaptive capacity of plant organisms occur. In the initial period of exposure to unfavorable space flight factors the adaptation reactions of the plant organism undoubtedly increase its resistance. But the intensification of removal of H + ions through the plasmalemma with an increase of the external influence sharply raises the quantity of cations leaving the cell, which leads to the accumulation of a considerable quantity of intracellular negative charges. These charges together with negative charges built in the membrane force protons to concentrate on the external surface of the membrane. Since protons have a very strong electric field, they form such a charge of which the electric field is about from several to hundreds of V/cm. The concentration of positive charges of protons entails the formation of a double electric field which extremely impedes the diffusion of other ions. Thus, a proton barrier is formed. Its length can be very considerable due to which the whole process of transmembrane energy and mass-transfer is disturbed. The proton barrier is easily destroyed by a weak electric field created in the root zone. In experiments on electrostimulation of different plants under space flight conditions at the orbital station MIR the absorption of nutrient elements by the root system increased to the optimal level, the ratio of physiologically active substances in the rhizosphere was normalized, the content of chlorophyll, carotin, and ascorbic acid in leaves corresponded to the ground-based control. Understanding of the mechanism of formation of a proton barrier on the plasmalemma of root cells as a result of the response of plants to the negative action of external factors (microgravity) is of great importance. It allows the

  19. Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis.

    PubMed

    Chien, Wenwen; O'Kelly, James; Lu, Daning; Leiter, Amanda; Sohn, Julia; Yin, Dong; Karlan, Beth; Vadgama, Jay; Lyons, Karen M; Koeffler, H Phillip

    2011-06-01

    Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis.

  20. Presupernova Evolution of Differentially Rotating Massive Stars Including Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Heger, A.; Woosley, S. E.; Spruit, H. C.

    2005-06-01

    As a massive star evolves through multiple stages of nuclear burning on its way to becoming a supernova, a complex, differentially rotating structure is set up. Angular momentum is transported by a variety of classic instabilities and also by magnetic torques from fields generated by the differential rotation. We present the first stellar evolution calculations to follow the evolution of rotating massive stars including, at least approximately, all these effects, magnetic and nonmagnetic, from the zero-age main sequence until the onset of iron-core collapse. The evolution and action of the magnetic fields is as described by Spruit in 2002, and a range of uncertain parameters is explored. In general, we find that magnetic torques decrease the final rotation rate of the collapsing iron core by about a factor of 30-50 when compared with the nonmagnetic counterparts. Angular momentum in that part of the presupernova star destined to become a neutron star is an increasing function of main-sequence mass. That is, pulsars derived from more massive stars rotate faster and rotation plays a more important role in the star's explosion. The final angular momentum of the core has been determined-to within a factor of 2-by the time the star ignites carbon burning. For the lighter stars studied, around 15 Msolar, we predict pulsar periods at birth near 15 ms, though a factor of 2 range is easily tolerated by the uncertainties. Several mechanisms for additional braking in a young neutron star, especially by fallback, are explored.

  1. An Analysis of Factor Extraction Strategies: A Comparison of the Relative Strengths of Principal Axis, Ordinary Least Squares, and Maximum Likelihood in Research Contexts That Include Both Categorical and Continuous Variables

    ERIC Educational Resources Information Center

    Coughlin, Kevin B.

    2013-01-01

    This study is intended to provide researchers with empirically derived guidelines for conducting factor analytic studies in research contexts that include dichotomous and continuous levels of measurement. This study is based on the hypotheses that ordinary least squares (OLS) factor analysis will yield more accurate parameter estimates than…

  2. Using Dynamic Walking Models to Identify Factors that Contribute to Increased Risk of Falling in Older Adults

    PubMed Central

    Roos, Paulien E.; Dingwell, Jonathan B.

    2013-01-01

    Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of

  3. Using dynamic walking models to identify factors that contribute to increased risk of falling in older adults.

    PubMed

    Roos, Paulien E; Dingwell, Jonathan B

    2013-10-01

    Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of

  4. Risk factors in neuroleptic malignant syndrome.

    PubMed

    Gupta, Vinay; Magon, Rakesh; Mishra, B P; Sidhu, G B S; Mahajan, Ranjiv

    2003-01-01

    Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important.

  5. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

    PubMed

    Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

    2010-11-01

    Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

  6. 12 CFR 1225.4 - Standards and factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... § 1225.4 Standards and factors. (a) Standard for imposing a temporary increase. In making a determination... ability to access liquidity and funding; (2) Credit (including counterparty), market, operational and... market conditions; (6) Level of reserves or retained earnings; (7) Initiatives, operations, products, or...

  7. 12 CFR 1225.4 - Standards and factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... § 1225.4 Standards and factors. (a) Standard for imposing a temporary increase. In making a determination... ability to access liquidity and funding; (2) Credit (including counterparty), market, operational and... market conditions; (6) Level of reserves or retained earnings; (7) Initiatives, operations, products, or...

  8. 12 CFR 1225.4 - Standards and factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... § 1225.4 Standards and factors. (a) Standard for imposing a temporary increase. In making a determination... ability to access liquidity and funding; (2) Credit (including counterparty), market, operational and... market conditions; (6) Level of reserves or retained earnings; (7) Initiatives, operations, products, or...

  9. Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

    PubMed

    Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

    2000-07-01

    To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

  10. Microparticles released by vascular endothelial cells increase hypoxia inducible factor expression in human proximal tubular HK-2 cells.

    PubMed

    Fernandez-Martínez, Ana Belen; Torija, Ana Valdehita; Carracedo, Julia; Ramirez, Rafael; de Lucio-Cazaña, Francisco Javier

    2014-08-01

    Microparticles are produced by vesiculation of the cell plasma membrane and serve as vectors of cell-to-cell communication. Co-culture experiments have shown that hypoxia-inducible factor-α (HIF-α)-regulated-genes are up-regulated in human renal proximal tubular HK-2 cells by endothelial cell factors which might be transported inside endothelial microparticles (EMP). Here we aimed to study in HK-2 cells the effect of EMP, produced by activated endothelial cells, on HIF-α and HIF-α-regulated vascular endothelial growth factor-A (VEGF-A). EMP, at a concentration much lower than that found in plasma, increased the expression of HIF-α/VEGF-A in a COX-2/EP2 receptor dependent manner. Since the EMP/cells ratio was ∼1/1000, we hypothesized that paracrine mediators produced by HK-2 cells amplified the initial signal. This hypothesis was confirmed by two facts which also suggested that the mediators were conveyed by particles released by HK-2 cells: (i) HIF-α was up-regulated in HK-2 cells treated with the pellet obtained from the conditioned medium of the EMP-treated HK-2 cells. (ii) In transwell experiments, EMP-treated cells increased the expression of HIF-α in untreated HK-2 cells. Interestingly, we detected these cells, particles that were released by EMP-treated HK-2 cells. Depending on the pathological context, activation of HIF-α and VEGF-A signaling in renal tissue/cells may have either beneficial or harmful effects. Therefore, our results suggest that their presence in the urinary space of EMP produced by activated endothelial cells may influence the outcome of a number of renal diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

    PubMed

    Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

    2017-06-07

    The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

  12. The prevalence and associated factors for prehypertension and hypertension in Cambodia

    PubMed Central

    Gupta, Vinay; LoGerfo, James P; Raingsey, Prak Piseth; Fitzpatrick, Annette L

    2013-01-01

    Background Hypertension is strongly associated with adverse cardiovascular outcomes and was the leading modifiable associated factor for global disease burden in 2010. Analysis of modifiable associated factors will be important to those concerned with mitigating the adverse effects of hypertension. We studied factors associated with hypertension in adults aged 25–64 years of age in Cambodia in order to help develop strategies for planned new initiatives for prevention and control of hypertension. Methods Using data from a nationwide survey in Cambodia assessing the prevalence of associated factors for non-communicable disease in 2010 (WHO STEPs survey), 5017 participants between the ages of 25 and 64 years were included in a secondary analysis of the prevalence and predictors of hypertension. Results The prevalence of prehypertension in this sample was approximately double that of overall hypertension (27.9% vs 15.3%). Male sex, increasing age and known cardiovascular associated factors, including higher Body Mass Index (BMI), dyslipidaemia, impaired fasting glycaemia, and abdominal obesity were all associated with an increased prevalence of hypertension. In multivariate models, increasing age was the strongest associated factor for hypertension (OR 8.79, 95% CI (5.43 to 14.2)), whereas, higher BMI was the primary associated factor associated with prehypertension (OR 3.27, 95% CI 2.21 to 4.82). Conclusions Modifiable cardiovascular-associated factors are strongly correlated with prehypertension and hypertension in Cambodia, and may be a focus of public health and primary care strategies to mitigate subsequent ischaemic heart disease and stroke. A national strategy aimed at increased screening and adherence to medical therapy is a necessary first step to reduce burden of disease and related morbidities. PMID:27326148

  13. Factors Related to Urinary Incontinence among the Malaysian Elderly.

    PubMed

    Eshkoor, S A; Hamid, T A; Shahar, S; Mun, C Y

    2017-01-01

    Urinary incontinence is a prevalent condition in the elderly that is the spontaneous leakage of urine. It is an age-related problem and increases especially in people aged above 65 years. It can cause many psychological, behavioral, biological, economic and social effects. The treatment of urinary incontinence can reduce morbidity and mortality. Thus, this study aimed to determine the effects of variables including age, ethnicity, gender, education, marital status, body weight, blood elements and nutritional parameters on urinary incontinence among the Malaysian elderly. The study was on 2322 non-institutionalized Malaysian elderly. The hierarchy logistic regression analysis was applied to estimate the risk of independent variables for urinary incontinence among respondents. The findings indicated that approximately 3.80% of subjects had urinary incontinence. In addition, constipation was found a significant factor that increased the risk of urinary incontinence in samples (p=0.006; OR=3.77). The increase in dietary monounsaturated fat (p=0.038; OR=0.59) and plasma triglyceride levels (p=0.029; OR=0.56) significantly reduced the risk of incontinence in subjects. Many of suspected variables including socio-demographic factors, diseases, nutritional minerals, blood components and body weight were non-relevant factors to urinary incontinence in respondents. Constipation increased the risk of urinary incontinence in subjects, and increase in dietary monounsaturated fat and plasma triglyceride levels decreased the risk.

  14. [New populations at increased cardiovascular risk: Cardiovascular disease in dermatological diseases].

    PubMed

    Godoy-Gijón, Elena; Meseguer-Yebra, Carmen; Palacio-Aller, Lucía; Godoy-Rocati, Diego Vicente; Lahoz-Rallo, Carlos

    2016-01-01

    The increased cardiovascular risk in some dermatological diseases has been demonstrated in recent decades. Diseases such as psoriasis and systemic lupus erythematosus are currently included in the guidelines for prevention of cardiovascular disease. Other diseases such as androgenic alopecia, polycystic ovary syndrome, hidradenitis suppurativa or lichen planus have numerous studies that point to an increased risk, however, they have not been included in these guidelines. In this article we review the evidence supporting this association, in order to alert the clinician to the need for greater control in cardiovascular risk factors in these patients. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  15. Evaluation of factors that affect hip moment impulse during gait: A systematic review.

    PubMed

    Inai, Takuma; Takabayashi, Tomoya; Edama, Mutsuaki; Kubo, Masayoshi

    2018-03-01

    Decreasing the daily cumulative hip moments in the frontal and sagittal planes may lower the risk of hip osteoarthritis. Therefore, it may be important to evaluate factors that affect hip moment impulse during gait. It is unclear what factors affect hip moment impulse during gait. This systematic review aimed to evaluate different factors that affect hip moment impulse during gait in healthy adults and patients with hip osteoarthritis. Four databases (Scopus, ScienceDirect, PubMed, and PEDro) were searched up to August 2017 to identify studies that examined hip moment impulse during gait. Data extracted for analysis included the sample size, age, height, body mass, type of intervention, and main findings. After screening, 10 of the 975 studies identified were included in our analysis. Several factors, including a rocker bottom shoe, FitFlop™ sandals, ankle push-off, posture, stride length, body-weight unloading, a rollator, walking poles, and a knee brace, were reviewed. The main findings were as follows: increasing ankle push-off decreased both the hip flexion and extension moment impulses; body-weight unloading decreased both the hip extension and adduction moment impulses; the FitFlop™ sandal increased the sum of the hip flexion and extension moment impulses; long strides increased the hip extension moment impulse; and the use of a knee brace increased hip flexion moment impulse. Of note, none of the eligible studies included patients with hip osteoarthritis. The hip moment impulses can be modified by person-specific factors (ankle push-off and long strides) and external factors (body-weight unloading and use of the FitFlop™ sandals and a knee brace). Effects on the progression of hip osteoarthritis remain to be evaluated. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study.

    PubMed

    Tanuma, Yasushi; Tanaka, Yoshinori; Takeyama, Ko; Okamoto, Tomoshi

    2017-01-01

    We evaluated the predictive factors which affect the efficacy of naftopidil 50 mg/day therapy and dose increase therapy to administration of 75 mg/day after an initial dose of 50 mg/day. A total of 92 patients with male lower urinary tract symptoms/benign prostatic hyperplasia were administrated naftopidil 50 mg/day for 4 weeks (50 mg therapy). At week 4, the patients were divided into an effective and an ineffective group (Group E and Group I, respectively). For further 4 weeks, the dosage of naftopidil was increased to 75 mg/day in all patients. At week 8, the patients of Group E and Group I were divided into an effective and an ineffective group (Group EE, Group EI, Group IE, and Group II, respectively). Postvoid residual (PVR) urine volume at baseline was a predictive factor for efficacy of 50 mg therapy. In Group E, change in International Prostate Symptom Score storage symptoms subscore from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. In Group I, change in maximum flow rate from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. The short term of naftopidil 50 mg therapy was ineffective for the patients who had large PVR. The predictive factor of this dose increase therapy might be a dynamic variable in 50 mg/day of dose period, but not a baseline variable at the time of 75 mg/day dosage starts.

  17. Effect of Increased Endometrial Thickness and Implantation Rate by Granulocyte Colony-Stimulating Factor on Unresponsive Thin Endometrium in Fresh In Vitro Fertilization Cycles: A Randomized Clinical Trial

    PubMed Central

    Sarvi, Fatemeh; Arabahmadi, Marjan; Alleyassin, Ashraf; Aghahosseini, Marzieh

    2017-01-01

    Background The correlation between endometrial thickness and receptivity has been mentioned in various studies. This study investigated the effect of granulocyte colony-stimulating factor in treating thin endometrium of infertile women who were chosen for in vitro fertilization in our infertility clinic in 2014 and 2015. Methods In this randomized clinical trial, 28 women who were chosen for in vitro fertilization and had endometrial thickness of less than 6 mm on the day of human chorionic gonadotropin (hCG) injection were included in the study. They were randomly divided into two groups: investigation and control groups. In investigation group (n = 13) one granulocyte colony-stimulating factor vial (300 micrograms in 1 mL) was infused into the uterus within five minutes by embryo transfer catheter. In control group (n = 15) 1 mL of saline was injected into the uterus with the same catheter. Results There were significant differences between the two groups in terms of means of endometrial thickness on oocyte retrieval day (P = 0.001), embryo transfer day (P = 0.001), hCG injections (P = 0.001), and implantation rates (P = 0.001). Conclusion Granulocyte colony-stimulating factor can increase endometrial thickness in women treated with in vitro fertilization. RCT Code is 201406046063N2. PMID:28791050

  18. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

    PubMed

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  19. High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury.

    PubMed

    Leech, Kristan A; Hornby, T George

    2017-03-15

    High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.

  20. High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury

    PubMed Central

    Leech, Kristan A.

    2017-01-01

    Abstract High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity–dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury. PMID:27526567

  1. Explaining the Rapid Increase in Nigeria's Sex Ratio at Birth: Factors and Implications.

    PubMed

    Kaba, Amadu J

    2015-06-01

    This paper examines the rapid increase in Nigeria's sex ratio at birth from 1.03 boys born for every 1 girl born in each year from 1996-2008 to 1.06 in each year from 2009-2014, second only to Tunisia in Africa at 1.07. The average sex ratio at birth in the world in 2014 was 1.07. In most Black African nations or Black majority nations, it is 1.03 or less. Among the factors presented for this development are: historical fluctuations of sex ratio at birth; geography and ethnicity; male preference/chasing a son; Age of parents; high death rates of male infants and males in general; and wealth/socioeconomic status. Among the potential implications are: young and poor men in Nigeria may not be able to find brides and form families due to a potential shortage of females; emigration of young and poor Nigerian men to West (Africa) and elsewhere to seek brides and form families; immigration of marriage age women from West (Africa) and around the world to Nigeria to seek husbands; and low contraceptive use and high fertility rates in Nigeria.

  2. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.

    PubMed

    Schanberg, Laura E; Sandborg, Christy; Barnhart, Huiman X; Ardoin, Stacy P; Yow, Eric; Evans, Gregory W; Mieszkalski, Kelly L; Ilowite, Norman T; Eberhard, Anne; Levy, Deborah M; Kimura, Yukiko; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L; Punaro, Lynn; Singer, Nora G; Sherry, David D; McCurdy, Deborah; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard; Wagner-Weiner, Linda; Higgins, Gloria C; Brunner, Hermine I; Jung, Lawrence; Soep, Jennifer B; Reed, Ann

    2009-05-01

    To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE). In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling. Based on the mean-mean common or the mean-max CIMT as the dependent variable, univariable analysis showed significant associations of the following variables with increased CIMT: increasing age, longer SLE duration, minority status, higher body mass index (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level, proteinuria, azathioprine treatment, and prednisone dose. In multivariable modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for the mean-max model) and male sex (P<0.001) were associated with increases in the mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low-dose prednisone were associated with increases in the mean-mean common CIMT (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031) remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level (P=0.005) were associated with increased mean-max CIMT. Traditional as well as nontraditional risk factors were associated with increased CIMT in this cohort of patients in the APPLE trial. Azathioprine treatment was associated with

  3. Consumption of ready-made meals and increased risk of obesity: findings from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study.

    PubMed

    Alkerwi, Ala'a; Crichton, Georgina E; Hébert, James R

    2015-01-28

    The consumption of ready-made meals, such as pre-packaged dishes, available at grocery stores and fast-food restaurants, is a habit related to our modern fast-paced lives. No study has examined the association of daily ready-made meal consumption with diet quality or health-related outcomes. The present study aimed to investigate the association between self-reported ready-made meal consumption and diet quality, as measured by compliance with dietary recommendations and with a set of adiposity measures, in a nationally representative sample of 1352 subjects, aged 18-69 years, participating in the nationwide population-based ORISCAV-LUX (Observation of Cardiovascular Risk Factors in Luxembourg) survey. The daily consumption of ready-made meals was calculated as follows: frequency of consumption × portion size × number of portions consumed. The sum of the daily consumption values of the eleven pre-packaged dishes included in the FFQ represented the total daily consumption of ready-made meals (g/d) for each participant. About 97% of the participants reported daily consumption of ready-made meals. The intake was highly prevalent in men living alone and varied according to education level. Ready-made meal consumption provided >7% of total daily energy. The fractions (%) of macro- and micronutrients derived from daily consumption of ready-made meals varied from 10% for total cholesterol to 0.65% for total fibre. Increased consumption of ready-made meals was found to be independently associated with abdominal obesity. On controlling for age, sex, socio-economic status and lifestyle factors, daily consumption of ready-made meals was found to be associated with higher energy intake and with poor compliance with national nutritional recommendations, and hence it could plausibly increase the risk of central obesity and fat deposition.

  4. Factors Associated with Increased Rates of Post-procedural Stroke or Death following Carotid Artery Stent Placement: A Systematic Review.

    PubMed Central

    Khan, Muhib; Qureshi, Adnan I

    2014-01-01

    Background and Purpose We provide an assessment of clinical, angiographic, and procedure related risk factors associated with stroke and/or death in patients undergoing carotid artery stent placement which will assist in patient stratification and identification of high-stent risk patients. Methods A comprehensive search of Medline from January 1st 1996 to December 31st 2011 was performed with key words “carotid artery stenosis”, “ carotid artery stenting”, “carotid artery stent placement”, “death” , ” mortality”, “stroke”, “outcome”, “clinical predictors”, “angiographic predictors”, was performed in various combinations. We independently abstracted data and assessed the quality of the studies. This analysis led to the selection of 71 articles for review. Results Clinical factors including age≥80 years, symptomatic status, procedure within 2 weeks of symptoms, chronic renal failure, diabetes mellitus, and hemispheric TIA were associated with stroke (ischemic or hemorrhagic) and death within 1 month after carotid artery stent placement. Angiographic factors including left carotid artery intervention, stenosis > 90%, ulcerated and calcified plaques, lesion length > 10mm, thrombus at the site, ostial involvement, predilation without EPD, ICA-CCA angulation > 60%, aortic arch type III, and aortic arch calcification were also associated with 1 month stroke and/or death. Intra-procedural platelet GP IIb/IIIa inhibitors, protamine use, multiple stents, predilatation prior to stent placement were associated with stroke (ischemic or hemorrhagic) and death after carotid artery stent placement. Intraprocedural use of embolic protection devices and stent design (open versus closed cell design) did not demonstrate a consistent relationship with 1 month stroke and/or death. Procedural statin use, and operator and center experience of more than 50 procedures per year were protective for 1 month stroke and/or death. Conclusions Our review

  5. Technologies to Increase PV Hosting Capacity in Distribution Feeders

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

    Ding, Fei; Mather, Barry; Gotseff, Peter

    This paper studies the distributed photovoltaic (PV) hosting capacity in distribution feeders by using the stochastic analysis approach. Multiple scenario simulations are conducted to analyze several factors that affect PV hosting capacity, including the existence of voltage regulator, PV location, the power factor of PV inverter and Volt/VAR control. Based on the conclusions obtained from simulation results, three approaches are then proposed to increase distributed PV hosting capacity, which can be formulated as the optimization problem to obtain the optimal solution. All technologies investigated in this paper utilize only existing assets in the feeder and therefore are implementable for amore » low cost. Additionally, the tool developed for these studies is described.« less

  6. Better consenting for thyroidectomy: who has an increased risk of postoperative hypocalcaemia?

    PubMed

    Harris, Andrew S; Prades, Eduardo; Tkachuk, Olena; Zeitoun, Hisham

    2016-12-01

    Hypocalcaemia is the most common complication following thyroidectomy. This study aimed to establish the factors associated with increased risk of hypocalcaemia on day 1 following thyroidectomy. All patients who underwent thyroidectomy under a single consultant during a 5-year period were included. A multivariate analysis was undertaken to ascertain which variables had the most effect on the risk of hypocalcaemia. A prognosis table was constructed to allow risk to be predicted for individual patients based on these factors. Included in the analysis were 210 procedures and 194 patients. Eighty-two percent of patients had no calcium derangement postoperatively. Fourteen point nine percent were categorised as early hypocalcaemia, 1 % had protracted hypocalcaemia and 2.1 % had permanent hypocalcaemia. For hemi-thyroidectomies 2.8 % had postoperative hypocalcaemia and 0.9 % had permanent hypocalcaemia. The multivariate analysis revealed total thyroidectomy (risk ratio 26.5, p < 0.0001), diabetes (risk ratio 4.8, p = 0.07) and thyrotoxicosis (risk ratio 3.1, p = 0.04) as statistically significant variables for early postoperative hypocalcaemia. Gender as an isolated factor did not reach significance but was included in the model. The p value for the model was p < 1 × 10 -12 . Total thyroidectomy increases risk of early hypocalcaemia when compared to hemithyroidectomy. Gender, diabetes and thyrotoxicosis were also been found to influence the risk. All of these factors are available pre-operatively and can therefore be used to predict a more specific risk for individual patients. It is hoped that this can lead to better informed consent, prevention and better resource allocation.

  7. Confirmatory Factor Analysis of the Minnesota Nicotine Withdrawal Scale

    PubMed Central

    Toll, Benjamin A.; O’Malley, Stephanie S.; McKee, Sherry A.; Salovey, Peter; Krishnan-Sarin, Suchitra

    2008-01-01

    The authors examined the factor structure of the Minnesota Nicotine Withdrawal Scale (MNWS) using confirmatory factor analysis in clinical research samples of smokers trying to quit (n = 723). Three confirmatory factor analytic models, based on previous research, were tested with each of the 3 study samples at multiple points in time. A unidimensional model including all 8 MNWS items was found to be the best explanation of the data. This model produced fair to good internal consistency estimates. Additionally, these data revealed that craving should be included in the total score of the MNWS. Factor scores derived from this single-factor, 8-item model showed that increases in withdrawal were associated with poor smoking outcome for 2 of the clinical studies. Confirmatory factor analyses of change scores showed that the MNWS symptoms cohere as a syndrome over time. Future investigators should report a total score using all of the items from the MNWS. PMID:17563141

  8. Factors influencing increased expertise for a sustainable workforce at a research centre in South Africa

    PubMed Central

    Draper, H. R.; Enarson, D. A.; Beyers, N.; Claassens, M.

    2014-01-01

    Setting: The Desmond Tutu Tuberculosis (TB) Centre (DTTC), Stellenbosch University, South Africa. Objectives: 1) To determine whether access to designated funding is associated with the development of expertise in employees, and 2) which other factors are associated with the development of expertise in employees. Design: This was a retrospective study. The target population consisted of all employees at the DTTC during the period 1 January 2004 to 31 December 2011. Improvement in expertise during employment was the primary outcome; the secondary outcome was an increase in educational level linked to the National Qualifications Framework. Results: There was no association between access to funding and expertise development, but an association between the number of months employed and improvement of expertise during employment was observed (OR 1.03, 95%CI 1.02–1.04, P < 0.001), controlling for age at appointment, sex, access to designated funding and education level. Conclusion: The study shows that almost a third of employees increased their expertise, more than 90% had access to designated funding and personnel employed for a longer duration were more likely to experience improvements in expertise. We encourage research organisations in low- and middle-income countries to implement strategies to retain employees in order to build their expertise. PMID:26400709

  9. Melanogenesis-inducing effect of cirsimaritin through increases in microphthalmia-associated transcription factor and tyrosinase expression.

    PubMed

    Kim, Hyo Jung; Kim, Il Soon; Dong, Yin; Lee, Ik-Soo; Kim, Jin Sook; Kim, Jong-Sang; Woo, Je-Tae; Cha, Byung-Yoon

    2015-04-20

    The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.

  10. Risk Factors in Neuroleptic Malignant Syndrome

    PubMed Central

    Gupta, Vinay; Magon, Rakesh; Mishra, B.P.; Sidhu, G.B.S.; Mahajan, Ranjiv

    2003-01-01

    Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important. PMID:21206810

  11. Menopause, obesity and inflammation: interactive risk factors for Alzheimer’s disease

    PubMed Central

    Christensen, Amy; Pike, Christian J.

    2015-01-01

    Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, the development of which is regulated by several environmental and genetic risk factors. Two factors theorized to contribute to the initiation and/or progression of AD pathogenesis are age-related increases in inflammation and obesity. These factors may be particularly problematic in women. The onset of menopause in mid-life elevates the vulnerability of women to AD, an increased risk that is likely associated with the depletion of estrogens. Menopause is also linked with an abundance of additional changes, including increased central adiposity and inflammation. Here, we review the current literature to explore the interactions between obesity, inflammation, menopause and AD. PMID:26217222

  12. Analysis of factors influencing safety management for metro construction in China.

    PubMed

    Yu, Q Z; Ding, L Y; Zhou, C; Luo, H B

    2014-07-01

    With the rapid development of urbanization in China, the number and size of metro construction projects are increasing quickly. At the same time, and increasing number of accidents in metro construction make it a disturbing focus of social attention. In order to improve safety management in metro construction, an investigation of the participants' perspectives on safety factors in China metro construction has been conducted to identify the key safety factors, and their ranking consistency among the main participants, including clients, consultants, designers, contractors and supervisors. The result of factor analysis indicates that there are five key factors which influence the safety of metro construction including safety attitude, construction site safety, government supervision, market restrictions and task unpredictability. In addition, ANOVA and Spearman rank correlation coefficients were performed to test the consistency of the means rating and the ranking of safety factors. The results indicated that the main participants have significant disagreement about the importance of safety factors on more than half of the items. Suggestions and recommendations on practical countermeasures to improve metro construction safety management in China are proposed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Polycystic Ovary Syndrome and Increased Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis Levels Are Independent Predictors of Dyslipidemia in Youth.

    PubMed

    Erkenekli, Kudret; Oztas, Efser; Kuscu, Elif; Keskin, Uğur; Kurt, Yasemin Gulcan; Tas, Ahmet; Yilmaz, Nafiye

    2017-01-01

    Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth. © 2016 S. Karger AG, Basel.

  14. Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study.

    PubMed

    Roberts, Christine L; Algert, Charles S; Morris, Jonathan M; Ford, Jane B

    2015-10-05

    Since the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia. Population-based record linkage study utilising linked birth and hospital records. A cohort of 1,076,122 deliveries in New South Wales, Australia, 2001-2012. Pregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome. From 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.9-18.4%) and labour inductions by 10% (24.8-27.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ≥35 years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20 years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38 weeks gestation and were steepest from 41 weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery. It appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk factors for hypertension were relatively more likely to be selected for early delivery

  15. Genetics and risk factors for basal cell carcinoma.

    PubMed

    Madan, V; Hoban, P; Strange, R C; Fryer, A A; Lear, J T

    2006-05-01

    Nonmelanoma skin cancer (NMSC) is the commonest cancer in whites and its incidence is increasing worldwide. The prevalence of this cancer is predicted to equal that of all others combined and it was estimated that there were over 2 million cases diagnosed in the U.S.A. in 2004. Patients exhibit marked differences in clinical phenotype with variations in tumour numbers, rate of tumour accrual, site and histological subtype. Furthermore, patients are at increased risk of other cutaneous and noncutaneous cancers. The factors accounting for this variation are complex and still not completely understood. Clearly, ultraviolet light (UV) exposure is a major influence but its relationship to clinical phenotype is not yet clear. In addition, immunosuppression is a significant risk factor. Our group has identified high-risk groups for the development of further basal cell carcinoma (BCC), namely patients with truncal BCC and those presenting with tumour clusters. This presentation will concentrate on these clinical subgroups as well as immunosuppressed patients. These groups represent significant management challenges and are areas where novel, nonsurgical treatment options may make a significant clinical impact in patient care. The risk factors predisposing to these clinical phenotypes will be discussed, including genetic factors and UV exposure. Potential clinical applications, including predictive indices, will be considered.

  16. Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes.

    PubMed

    Sert, Tuba; Kırzıoğlu, F Yeşim; Fentoğlu, Ozlem; Aylak, Firdevs; Mungan, Tamer

    2011-12-01

    The aim of this study is the evaluation of levels of serum interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and soluble VEGF receptor (sVEGFR)-1 and -2 in the association between periodontal disease and adverse pregnancy outcomes. One hundred and nine mothers, who recently gave birth, and 51 women who were not recently pregnant, aged 18 to 35 years, were included in this study. The mothers were classified as term birth, preterm birth (PTB), and preterm low birth weight (PLBW) in respect to their gestational age and baby's birth weight. The birth mothers were grouped as having gingivitis or periodontitis. The non-pregnant group also included periodontally healthy patients. Venous blood samples were collected to evaluate serum IL-1β, IL-6, IL-10, TNF-α, VEGF, PIGF, and sVEGFR-1 and -2 levels. Mother's weight, education, and income level were significantly associated with pregnancy outcomes. Serum levels of IL-1β, TNF-α, IL-6, VEGF, and sVEGFR-1 and -2 showed an increase in significance when related to pregnancy. Whereas in the PLBW group IL-1β, VEGF, and sVEGFR-2 levels were increased, in the PTB group sVEGFR-1 levels were increased. Additionally, the patients in the PLBW group with periodontitis had higher serum levels of IL-1β, VEGF, sVEGFR-2, and IL-1β/IL-10. The serum levels of IL-1β, VEGF, and sVEGFR-1 and -2 may have a potential effect on the mechanism of the association between periodontal disease and adverse pregnancy outcomes.

  17. Pregnancy-induced hypertension is associated with an increase in the prevalence of cardiovascular disease risk factors in Japanese women.

    PubMed

    Watanabe, Kazushi; Kimura, Chiharu; Iwasaki, Ai; Mori, Toshitaka; Matsushita, Hiroshi; Shinohara, Koichi; Wakatsuki, Akihiko; Gosho, Masahiko; Miyano, Ichiro

    2015-06-01

    This study assessed whether pregnancy-induced hypertension (PIH) affects the prevalence of cardiovascular disease (CVD) risk factors in later life among Japanese women. Study participants were 1,185 women (mean [SD] age, 46.5 [5.6] y; range, 38-73 y) aged 40 years or older who underwent a health checkup at a periodic health examination facility between January 2012 and December 2013 and had experienced giving birth. Questionnaires were sent to potential participants, and they were encouraged to provide their Maternal and Child Health Handbook (handbook). We recruited 101 women with a history of PIH (PIH group) and 1,084 women with uncomplicated pregnancy at delivery (control group). Groupings were based on information from the handbook. We assessed the association between PIH and CVD in later life among Japanese women by focusing on hypertension, diabetes mellitus, and dyslipidemia as risk factors for CVD. Odds ratios (ORs) for the use of antihypertensive, diabetes mellitus, and dyslipidemic medications in the PIH group were determined. Women with PIH had increased risk of antihypertensive medication use compared with women without PIH (2.9% vs 13.9%; OR, 4.28; 95% CI, 2.14-8.57). Triglycerides were significantly higher and high-density lipoprotein cholesterol was significantly lower in the PIH group than in the control group. The OR for dyslipidemic medication use in the PIH group relative to the control group was 3.20 (95% CI, 1.42-7.22). Our findings suggest that a history of PIH may be associated with an increased risk of hypertension (a risk factor for CVD) in later life among Japanese women.

  18. A single factor underlies the metabolic syndrome: a confirmatory factor analysis.

    PubMed

    Pladevall, Manel; Singal, Bonita; Williams, L Keoki; Brotons, Carlos; Guyer, Heidi; Sadurni, Josep; Falces, Carles; Serrano-Rios, Manuel; Gabriel, Rafael; Shaw, Jonathan E; Zimmet, Paul Z; Haffner, Steven

    2006-01-01

    Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.

  19. Risk Factors for Drug-Resistant Cap in Immunocompetent Patients.

    PubMed

    Arancibia, Francisco; Ruiz, Mauricio

    2017-03-01

    The increase in drug-resistant community-acquired pneumonia (CAP) is an important problem all over the world. This article explores the current state of antimicrobial resistance of different bacteria that cause CAP and also assesses risk factors to identify those pathogens. In the last two decades, it has been documented that there is a significant increase in drug-resistant Streptococcus pneumoniae and other bacteria causing CAP. The most important risk factors are overuse of antibiotics, prior hospitalization, and lung comorbidities. The direct consequences can be severe, including prolonged stays in hospital, increased costs, and morbi-mortality. However, drug-resistant CAP declined after the introduction of the pneumococcal conjugate vaccine. This review found an increase in resistance to the antibiotics used in CAP, and the risk factor can be used for identifying patients with drug-resistant CAP and initiate appropriate treatment. Judicious use of antibiotics and the development of effective new vaccines are needed.

  20. Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs.

    PubMed

    You, Jinyoung; Lee, Joohyeong; Kim, Jinyoung; Park, Junhong; Lee, Eunsong

    2010-02-01

    The objective of this study was to examine the effect of post-fusion treatment of somatic cell nuclear transfer (SCNT) oocytes with the proteasomal inhibitor MG132 on maturation promoting factor (MPF) activity, nuclear remodeling, embryonic development, and gene expression of cloned pig embryos. Immediately after electrofusion, SCNT oocytes were treated with MG132 and/or caffeine for 2 hr, vanadate for 0.5 hr, or vanadate for 0.5 hr followed by MG132 for 1.5 hr. Of the MG132 concentrations tested (0-5 microM), the 1 microM concentration showed a higher rate of blastocyst formation (25.9%) than 0 (14.2%), 0.5 (16.9%), and 5 microM (16.9%). Post-fusion treatment with MG132, caffeine, and both MG132 and caffeine improved blastocyst formation (22.1%, 21.4%, and 24.4%, respectively), whereas vanadate treatment inhibited blastocyst formation (6.5%) compared to the control (11.1%). When examined 2 hr after fusion and 1 hr after activation, MPF activity remained at a higher (P < 0.05) level in SCNT oocytes that were treated post-fusion with caffeine and/or MG132, but it was decreased by vanadate. The rate of oocytes showing premature chromosome condensation was not altered by MG132 but was decreased by vanadate treatment. In addition, formation of single pronuclei was increased by MG132 compared to control and vanadate treatment. MG132-treated embryos showed increased expression of POU5F1, DPPA2, DPPA3, DPPA5, and NDP52l1 genes compared to control embryos. Our results demonstrate that post-fusion treatment of SCNT oocytes with MG132 prevents MPF degradation and increases expression of transcription factors in SCNT embryos, which are necessary for normal development of SCNT embryos. (c) 2009 Wiley-Liss, Inc.

  1. Implementation considerations when expanding health worker roles to include safe abortion care: a five-country case study synthesis.

    PubMed

    Glenton, Claire; Sorhaindo, Annik M; Ganatra, Bela; Lewin, Simon

    2017-09-21

    Allowing a broader range of trained health workers to deliver services can be an important way of improving access to safe abortion care. However, the expansion of health worker roles may be challenging to implement. This study aimed to explore factors influencing the implementation of role expansion strategies for non-physician providers to include the delivery of abortion care. We conducted a multi-country case study synthesis in Bangladesh, Ethiopia, Nepal, South Africa and Uruguay, where the roles of non-physician providers have been formally expanded to include the provision of abortion care. We searched for documentation from each country related to non-physician providers, abortion care services and role expansion through general internet searches, Google Scholar and PubMed, and gathered feedback from 12 key informants. We carried out a thematic analysis of the data, drawing on categories from the SURE Framework of factors affecting the implementation of policy options. Several factors appeared to affect the successful implementation of including non-physician providers to provide abortion care services. These included health workers' knowledge about abortion legislation and services; and health workers' willingness to provide abortion care. Health workers' willingness appeared to be influenced by their personal views about abortion, the method of abortion and stage of pregnancy and their perceptions of their professional roles. While managers' and co-workers' attitudes towards the use of non-physician providers varied, the synthesis suggests that female clients focused less on the type of health worker and more on factors such as trust, privacy, cost, and closeness to home. Health systems factors also played a role, including workloads and incentives, training, supervision and support, supplies, referral systems, and monitoring and evaluation. Strategies used, with varying success, to address some of these issues in the study countries included values

  2. Meta-analyses including data from observational studies.

    PubMed

    O'Connor, Annette M; Sargeant, Jan M

    2014-02-15

    Observational studies represent a wide group of studies where the disease or condition of interest is naturally occurring and the investigator does not control allocation to interventions or exposures. Observational studies are used to test hypotheses about the efficacy of interventions or about exposure-disease relationships, to estimate incidence or prevalence of conditions, and to assess the sensitivity and specificity of diagnostic assays. Experimental-study designs and randomized controlled trials (RCTs) can also contribute to the body of evidence about such questions. Meta-analyses (either with or without systematic reviews) aim to combine information from primary research studies to better describe the entire body of work. The aim of meta-analyses may be to obtain a summary effect size, or to understand factors that affect effect sizes. In this paper, we discuss the role of observational studies in meta-analysis questions and some factors to consider when deciding whether a meta-analysis should include results from such studies. Our suggestion is that one should only include studies that are not at high risk of inherent bias when calculating a summary effect size. Study design however can be a meaningful variable in assessment of outcome heterogeneity. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Nutrition, metabolic factors and cancer risk.

    PubMed

    Dossus, Laure; Kaaks, Rudolf

    2008-08-01

    Excess body weight (adiposity) and physical inactivity are increasingly being recognized as major nutritional risk factors for cancer, and especially for many of those cancer types that have increased incidence rates in affluent, industrialized parts of the world. In this review, an overview is presented of some key biological mechanisms that may provide important metabolic links between nutrition, physical activity and cancer, including insulin resistance and reduced glucose tolerance, increased activation of the growth hormone/IGF-I axis, alterations in sex-steroid synthesis and/or bioavailability, and low-grade chronic inflammation through the effects of adipokines and cytokines.

  4. Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006.

    PubMed

    Rastam, Samer; Al Ali, Radwan; Maziak, Wasim; Mzayek, Fawaz; Fouad, Fouad M; O'Flaherty, Martin; Capewell, Simon

    2012-09-09

    Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD.

  5. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia.

    PubMed

    Bonaccorso, Stefania; Sodhi, Monsheel; Li, Jiang; Bobo, William V; Chen, Yuejin; Tumuklu, Mevhibe; Theleritis, Christos; Jayathilake, Karuna; Meltzer, Herbert Y

    2015-08-01

    We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested. This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76). BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01). The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Association of a Behaviorally Based High School Health Education Curriculum with Increased Exercise

    ERIC Educational Resources Information Center

    Annesi, James J.; Trinity, John; Mareno, Nicole; Walsh, Stephanie M.

    2015-01-01

    Increasing exercise in children and adolescents through academic classes is an understudied area. Potential benefits include associated improvements in health, psychosocial, and quality-of-life factors. A sample of 98 students (M[subscript age] = 14.3) from high school health education classes received six, 40-min lessons incorporating…

  7. The space station: Human factors and productivity

    NASA Technical Reports Server (NTRS)

    Gillan, D. J.; Burns, M. J.; Nicodemus, C. L.; Smith, R. L.

    1986-01-01

    Human factor researchers and engineers are making inputs into the early stages of the design of the Space Station to improve both the quality of life and work on-orbit. Effective integration of the human factors information related to various Intravehicular Activity (IVA), Extravehicular Activity (EVA), and teletobotics systems during the Space Station design will result in increased productivity, increased flexibility of the Space Stations systems, lower cost of operations, improved reliability, and increased safety for the crew onboard the Space Station. The major features of productivity examined include the cognitive and physical effort involved in work, the accuracy of worker output and ability to maintain performance at a high level of accuracy, the speed and temporal efficiency with which a worker performs, crewmember satisfaction with their work environment, and the relation between performance and cost.

  8. Increasing risk of prosthetic joint infection after total hip arthroplasty

    PubMed Central

    2012-01-01

    Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods The study was based on the Nordic Arthroplasty Register Association (NARA) dataset. 432,168 primary THAs from 1995 to 2009 were included (Denmark: 83,853, Finland 78,106, Norway 88,455, and Sweden 181,754). Adjusted survival analyses were performed using Cox regression models with revision due to infection as the endpoint. The effect of risk factors such as the year of surgery, age, sex, diagnosis, type of prosthesis, and fixation were assessed. Results 2,778 (0.6%) of the primary THAs were revised due to infection. Compared to the period 1995–1999, the relative risk (with 95% CI) of revision due to infection was 1.1 (1.0–1.2) in 2000–2004 and 1.6 (1.4–1.7) in 2005–2009. Adjusted cumulative 5–year revision rates due to infection were 0.46% (0.42–0.50) in 1995–1999, 0.54% (0.50–0.58) in 2000–2004, and 0.71% (0.66–0.76) in 2005–2009. The entire increase in risk of revision due to infection was within 1 year of primary surgery, and most notably in the first 3 months. The risk of revision due to infection increased in all 4 countries. Risk factors for revision due to infection were male sex, hybrid fixation, cement without antibiotics, and THA performed due to inflammatory disease, hip fracture, or femoral head necrosis. None of these risk factors increased in incidence during the study period. Interpretation We found increased relative risk of revision and increased cumulative 5–year revision rates due to infection after primary THA during the period 1995–2009. No change in risk factors in the NARA dataset could explain this increase. We believe that there has been an actual increase in the incidence of prosthetic joint infections after THA. PMID

  9. [Maternal and perinatal risk factors for neonatal morbidity: a narrative literature review].

    PubMed

    Hernández Núñez, Jónathan; Valdés Yong, Magel; Suñol Vázquez, Yoanca de la Caridad; López Quintana, Marelene de la Caridad

    2015-07-14

    Newborn diseases increase neonatal mortality rates, so a literature review was conducted to establish the risk factors related to maternal and peripartum morbidity affecting the newborn. We searched the following electronic databases: Cumed, EBSCO, LILACS, IBECS and PubMed/MEDLINE. We used specific terms and Boolean operators in Spanish, Portuguese and English. We included longitudinal and cross-sectional descriptive studies, as well as case-control and cohort studies, systematic reviews and meta-analysis, spanning from 2010 to 2015 that responded the topic of interest. The included studies show that multiple maternal and perinatal conditions are risk factors for significant increase of neonatal morbidity, which are described in this narrative review.

  10. Bone cell communication factors and Semaphorins

    PubMed Central

    Negishi-Koga, Takako; Takayanagi, Hiroshi

    2012-01-01

    Bone tissue is continuously renewed throughout adult life by a process called 'remodeling', which involves a dynamic interplay among bone cells including osteoclasts, osteoblasts and osteocytes. For example, a tight coupling between bone resorption and formation is essential for the homeostasis of the skeletal system. Studies on the coupling mechanism in physiological and pathological settings have revealed that osteoclasts or osteoclastic bone resorption promote bone formation through the production of diverse coupling factors. The classical coupling factors are the molecules that promote bone formation after resorption, but there may be distinct mechanisms at work in various phases of bone remodeling. A recent study revealed that the Semaphorin 4D expressed by osteoclasts inhibits bone formation, which represents a mechanism by which coupling is dissociated. Furthermore, it has been demonstrated that osteoblastic expression of Semaphorin 3A exerts an osteoprotective effect by both suppressing bone resorption and increasing bone formation. Thus, recent advances have made it increasingly clear that bone remodeling is regulated by not only classical coupling factors, but also molecules that mediate cell–cell communication among bone cells. We propose that such factors be called bone cell communication factors, which control the delicate balance of the interaction of bone cells so as to maintain bone homeostasis. PMID:24171101

  11. Cognitive, personality, and social factors associated with adolescents' online personal information disclosure.

    PubMed

    Liu, Cong; Ang, Rebecca P; Lwin, May O

    2013-08-01

    The current study aims to understand the factors that influence adolescents' disclosure of personally identifiable information (PII) on social networking sites (SNSs). A survey was conducted among 780 adolescent participants (between 13 and 18) who were Facebook users. Structural equation modeling was used for analyzing the data and obtaining an overarching model that include cognitive, personality, and social factors that influence adolescents' PII disclosure. Results showed privacy concern as the cognitive factor reduces adolescents' PII disclosure and it serves as a potential mediator for personality and social factors. Amongst personality factors, narcissism was found to directly increase PII disclosure, and social anxiety indirectly decreases PII disclosure by increasing privacy concern. Amongst social factors, active parental mediation decreases PII disclosure directly and indirectly by increasing privacy concern. Restrictive parental mediation decreases PII disclosure only indirectly by increasing privacy concern. Implications of the findings to parents, educators, and policy makers were discussed. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  12. Satellite Cell Functional Alterations Following Cutaneous Burn in rats Include an Increase in Their Osteogenic Potential

    DTIC Science & Technology

    2013-10-07

    response to local injury [3]. They have also been recognized as having a role in diseases, including cachexia and sarcopenia, where muscle mass may be...1961;9:493. [4] Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle 2012;3:225. [5] Glass DJ. Signaling pathways that mediate

  13. The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.

    PubMed

    Dankovic, D A; Naumann, B D; Maier, A; Dourson, M L; Levy, L S

    2015-01-01

    The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation from shorter duration studies to a full life-time exposure, and other insufficiencies in the overall health effects database indicating that the most sensitive adverse effect may not have been evaluated. In addition, a modifying factor is used by some organizations to account for other remaining uncertainties-typically related to exposure scenarios or accounting for the interplay among the five areas noted above. Consideration of uncertainties in occupational exposure limit derivation is a systematic process whereby the factors applied are not arbitrary, although they are mathematically imprecise. As the scientific basis for uncertainty factor application has improved, default uncertainty factors are now used only in the absence of chemical-specific data, and the trend is to replace them with chemical-specific adjustment factors whenever possible. The increased application of scientific data in the development of uncertainty factors for individual chemicals also has

  14. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease

    PubMed Central

    Brewer, George J.

    2015-01-01

    It has become clear that copper toxicity is playing a major role in Alzheimer’s disease; but why is the brain copper toxicity with cognition loss in Alzheimer’s disease so much different clinically than brain copper toxicity in Wilson’s disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer’s is at least in part, a copper-2 toxicity disease, while Wilson’s is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer’s epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure. PMID:26633489

  15. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

    PubMed Central

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

  16. Benefits of Group Living Include Increased Feeding Efficiency and Lower Mass Loss during Desiccation in the Social and Inbreeding Spider Stegodyphus dumicola

    PubMed Central

    Vanthournout, Bram; Greve, Michelle; Bruun, Anne; Bechsgaard, Jesper; Overgaard, Johannes; Bilde, Trine

    2016-01-01

    Group living carries a price: it inherently entails increased competition for resources and reproduction, and may also be associated with mating among relatives, which carries costs of inbreeding. Nonetheless, group living and sociality is found in many animals, and understanding the direct and indirect benefits of cooperation that override the inherent costs remains a challenge in evolutionary ecology. Individuals in groups may benefit from more efficient management of energy or water reserves, for example in the form of reduced water or heat loss from groups of animals huddling, or through reduced energy demands afforded by shared participation in tasks. We investigated the putative benefits of group living in the permanently social spider Stegodyphus dumicola by comparing the effect of group size on standard metabolic rate, lipid/protein content as a body condition measure, feeding efficiency, per capita web investment, and weight/water loss and survival during desiccation. Because energetic expenditure is temperature sensitive, some assays were performed under varying temperature conditions. We found that feeding efficiency increased with group size, and the rate of weight loss was higher in solitary individuals than in animals in groups of various sizes during desiccation. Interestingly, this was not translated into differences in survival or in standard metabolic rate. We did not detect any group size effects for other parameters, and group size effects did not co-vary with experimental temperature in a predictive manner. Both feeding efficiency and mass loss during desiccation are relevant ecological factors as the former results in lowered predator exposure time, and the latter benefits social spiders which occupy arid, hot environments. PMID:26869936

  17. Factors parents use in selecting play spaces for young children.

    PubMed

    Sallis, J F; McKenzie, T L; Elder, J P; Broyles, S L; Nader, P R

    1997-04-01

    The amount of time children spend in play spaces (ie, physical locations that are appropriate for children's physical activity) near their homes is correlated with their level of physical activity. To examine factors used in parents' decisions about the selection of play spaces for their children. Parents (primarily mothers) of 178 Mexican American and 122 white children who were a mean age of 4.9 years old at the first measurement. In individual interviews, parents rated 24 factors on their importance in selecting for their children a play space that is away from their home or yard. Decision factors were rated from 1 (ie, not important at all) to 5 (ie, very important). The most important factors, with ratings ranging from 4.8 to 4.2, were safety and availability of toilets, drinking water, lighting, and shade. Mexican American parents rated 8 of 24 items significantly higher than did white parents, including lighted at night, organized activities, play supplies, and drinking water. White parents rated 5 of 24 items significantly higher than did Mexican American parents, including distance from home, cost of admission, and child's friends go there. The rated importance of 7 of 24 items increased during 1 year, including play supplies, drinking water, distance from home, and parents' friends or relatives go there. These results indicate that parents can identify factors they use in selecting places for their young children to play, and selection factors differ somewhat by ethnicity or socioeconomic status. Further studies are needed to determine whether improvements on the most important selection factors might be effective in increasing the use of play spaces by children and their parents. Clinicians may be able to use the most highly rated decision factors to help parents assess the acceptability of play spaces in their areas.

  18. Egg mass drift increases vulnerability during early development of Cascades frogs (Rana casadae).

    Treesearch

    Justin M. Garwood; Clara A. Wheeler; Ryan M. Bourque; Monty D. Larson; Hartwell H. Welsh

    2007-01-01

    Many anuran species exhibit oviposition site selection. Female selection of oviposition sites may influence the success of offspring and increase overall fitness (Resetarits 1996). Egg mass placement (location and attachment substrate) may be determined by a number of factors including detectability by predators, water velocity, risk of desiccation or flooding, and...

  19. Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.

    PubMed

    Erem, Cihangir

    2006-03-01

    Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation

  20. Increased pro-angiogenic factors, infiltrating neutrophils and CD163(+) macrophages in bronchoalveolar lavage fluid from lung cancer patients.

    PubMed

    Chen, Lu; Li, Qian; Zhou, Xiang-dong; Shi, Yu; Yang, Lang; Xu, Sen-lin; Chen, Cong; Cui, You-hong; Zhang, Xia; Bian, Xiu-wu

    2014-05-01

    Infiltration of inflammatory cells and production of pro-angiogenic factors are important in lung cancer immunity. The distributions of those cells and their contributions to the production of pro-angiogenic factors and the activation phenotype of macrophages in bronchoalveolar lavage fluid (BALF) from lung cancer patients remain unclear. We analyzed the presence of distinct inflammatory cells and the macrophage activation phenotype together with the levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) within BALF from 54 smoking lung cancer patients including 36 squamous cell carcinoma (SCC), 9 adenocarcinoma (AC), and 9 small cell lung cancer (SCLC) in comparison with those from 13 non-smoking and 7 smoking patients with nonspecific chronic inflammation and 8 non-smoking normal controls. We found a significantly lower percentage of total macrophages and a much higher percentage of neutrophils among all inflammatory cells in BALF from lung cancer and non-specific chronic inflammation patients. BALF from AC patients had a significantly higher percentage of lymphocytes. CD163(+)) macrophages predominantly existed in BALF from SCLC patients. BALF of lung cancer patients had markedly higher levels of IL-8 and VEGF. Interestingly, IL-8 level was positively correlated to the numbers of neutrophils and lymphocytes. VEGF level was inversely correlated to the number of lymphocytes but positively to cancer cells in SCC cases, whereas no correlation existed between CD163(+)) macrophages and the levels of IL-8 and VEGF. Our results suggest that the detection of infiltrating inflammatory cells and pro-angiogenic factors in BALF will be helpful for diagnosis of cancerous inflammation in lungs. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas.

    PubMed

    Singal, Sahil S; Nygard, Karen; Gratton, Robert; Jansson, Thomas; Gupta, Madhulika B

    2018-05-01

    Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.

  2. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy

    PubMed Central

    Li, Chao; Vu, Kent; Hazelgrove, Krystina

    2015-01-01

    The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. PMID:26428636

  3. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

    PubMed

    Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

    2015-12-01

    The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

  4. Toward a Molecular Understanding of Protein Solubility: Increased Negative Surface Charge Correlates with Increased Solubility

    PubMed Central

    Kramer, Ryan M.; Shende, Varad R.; Motl, Nicole; Pace, C. Nick; Scholtz, J. Martin

    2012-01-01

    Protein solubility is a problem for many protein chemists, including structural biologists and developers of protein pharmaceuticals. Knowledge about how intrinsic factors influence solubility is limited due to the difficulty of obtaining quantitative solubility measurements. Solubility measurements in buffer alone are difficult to reproduce, because gels or supersaturated solutions often form, making it impossible to determine solubility values for many proteins. Protein precipitants can be used to obtain comparative solubility measurements and, in some cases, estimations of solubility in buffer alone. Protein precipitants fall into three broad classes: salts, long-chain polymers, and organic solvents. Here, we compare the use of representatives from two classes of precipitants, ammonium sulfate and polyethylene glycol 8000, by measuring the solubility of seven proteins. We find that increased negative surface charge correlates strongly with increased protein solubility and may be due to strong binding of water by the acidic amino acids. We also find that the solubility results obtained for the two different precipitants agree closely with each other, suggesting that the two precipitants probe similar properties that are relevant to solubility in buffer alone. PMID:22768947

  5. Feedback in web-based questionnaires as incentive to increase compliance in studies on lifestyle factors.

    PubMed

    Bälter, Olle; Fondell, Elinor; Bälter, Katarina

    2012-06-01

    We explored the use of feedback in interactive web-based questionnaires for collecting data on lifestyle factors in epidemiological studies. Here we report from a cohort study on lifestyle factors and upper respiratory tract infections among 1805 men and women. We introduced interactivity in the form of personalized feedback and feedback on a group level regarding dietary intake, physical activity and incidence of infections in web-based questionnaires as incentives for the respondents to continue answering questions and stay in the study. The study was performed in Sweden. All participants were randomly selected from the population registry. Personalized feedback was offered in the baseline questionnaire and feedback on a group level in the five follow-up questionnaires. In total, 88 % of the participants actively chose to get personalized feedback at least once in the baseline questionnaire. The follow-up questionnaires were sent by email and the overall compliance at each follow-up was 83-84 %, despite only one reminder. In total, 74 % completed all five follow-ups. However, the compliance was higher among those who chose feedback in the baseline questionnaire compared with those who did not choose feedback. The results show that it is possible to use feedback in web questionnaires and that it has the potential to increase compliance. The majority of the participants actively chose to take part in the personalized feedback in the baseline questionnaire and future research should focus on improving the design of the feedback, which may ultimately result in even higher compliance in research studies.

  6. Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor.

    PubMed

    Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Cui, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

    2013-05-01

    Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. We isolated human PSCs from fresh pancreatic ductal adenocarcinomas and analyzed functional differences in PSCs between normoxia (21% O2) and hypoxia (1% O2), including expression of various factors related to tumor-stromal interactions. We particularly analyzed effects on PC invasiveness of an overexpressed molecule-connective tissue growth factor (CTGF)-in PSCs under hypoxic conditions, using RNA interference techniques. Conditioned media from hypoxic PSCs enhanced PC cell invasiveness more intensely than that from normoxic PSCs (P < 0.01). When co-cultured with PSCs, PC cell invasion was more enhanced under hypoxia than under normoxia (P < 0.05). Among various soluble factors, which were related to invasiveness, CTGF was one of the overexpressed molecules in hypoxic PSCs. A higher level of CTGF expression was also found in supernatant of hypoxic PSCs than in supernatant of normoxic PSCs. PC cell invasiveness was reduced by CTGF knockdown in hypoxic PSCs co-cultured with PC cells (P < 0.05). Hypoxia induces PSCs' secretion of CTGF, leading to enhancement of PC invasiveness. CTGF derived from hypoxia-stimulated PSCs may be a new therapeutic target for pancreatic cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Organizational Factors Affecting the Likelihood of Cancer Screening Among VA Patients.

    PubMed

    Chou, Ann F; Rose, Danielle E; Farmer, Melissa; Canelo, Ismelda; Yano, Elizabeth M

    2015-12-01

    Preventive service delivery, including cancer screenings, continues to pose a challenge to quality improvement efforts. Although many studies have focused on person-level characteristics associated with screening, less is known about organizational influences on cancer screening. This study aims to understand the association between organizational factors and adherence to cancer screenings. This study employed a cross-sectional design using organizational-level, patient-level, and area-level data. Dependent variables included breast, cervical, and colorectal cancer screening. Organizational factors describing resource sufficiency were constructed using factor analyses from a survey of 250 Veterans Affairs primary care directors. We conducted random-effects logistic regression analyses, modeling cancer screening as a function of organizational factors, controlling for patient-level and area-level factors. Overall, 87% of the patients received mammograms, 92% received cervical and 78% had colorectal screening. Quality improvement orientation increased the odds of cervical [odds ratio (OR): 1.27; 95% confidence interval (CI), 1.03-1.57] and colorectal cancer screening (OR: 1.10; 95% CI, 1.00-1.20). Authority in determining primary care components increased the odds of mammography screening (OR: 1.23; 95% CI, 1.03-1.51). Sufficiency in clinical staffing increased the odds of mammography and cervical cancer screenings. Several patient-level factors, serving as control variables, were associated with achievement of screenings. Resource sufficiency led to increased odds of screening possibly because they promote excellence in patient care by conveying organizational goals and facilitate goal achievement with resources. Complementary to patient-level factors, our findings identified organizational processes associated with better performance, which offer concrete strategies in which facilities can evaluate their capabilities to implement best practices to foster and

  8. 42 CFR 410.10 - Medical and other health services: Included services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... (p) Hepatitis B vaccine. (q) Blood clotting factors for hemophilia patients competent to use these... furnished without charge or included in the physicians' bills. (c) Services and supplies, including partial... dialysis patients, and, on or after January 1, 1994, for dialysis patients, competent to use the drug; self...

  9. Recipient Risk Factors for Graft Failure in the Cornea Donor Study

    PubMed Central

    Sugar, Alan; Tanner, Jean Paul; Dontchev, Mariya; Tennant, Brad; Schultze, Robert L.; Dunn, Steven P.; Lindquist, Thomas D.; Gal, Robin L.; Beck, Roy W.; Kollman, Craig; Mannis, Mark J.; Holland, Edward J.

    2009-01-01

    Purpose Identify recipient factors which may be related to risk of corneal graft failure Design Multi-center prospective, double-masked, controlled clinical trial Participants 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) Methods Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea including donor age. Surgery and post-operative care were performed according to the surgeons’ usual routines and subjects were followed for five years. Baseline factors were evaluated for their association with graft failure. Main Outcome Measures Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of three consecutive months. Results Preoperative diagnosis of pseudophakic/aphakic corneal edema increased graft failure risk approximately 4-fold compared with Fuchs’ dystrophy (27% vs. 7%). Prior glaucoma surgery with preoperative glaucoma medication use substantially increased the graft failure rate. Factors not strongly associated with graft failure included age, gender, diabetes, smoking, and graft size. Conclusion The risk of graft failure is significantly increased in eyes with pseudophakic or aphakic corneal edema compared with Fuchs’ dystrophy, independent of lens status, and in eyes with a history of glaucoma. PMID:19395036

  10. Increasing physical activity through mobile device interventions: A systematic review.

    PubMed

    Muntaner, Adrià; Vidal-Conti, Josep; Palou, Pere

    2016-09-01

    Physical inactivity is a health problem that affects people worldwide and has been identified as the fourth largest risk factor for overall mortality (contributing to 6% of deaths globally). Many researchers have tried to increase physical activity levels through traditional methods without much success. Thus, many researchers are turning to mobile technology as an emerging method for changing health behaviours. This systematic review sought to summarise and update the existing scientific literature on increasing physical activity through mobile device interventions, taking into account the methodological quality of the studies. The articles were identified by searching the PubMed, SCOPUS and SPORTDiscus databases for studies published between January 2003 and December 2013. Studies investigating efforts to increase physical activity through mobile phone or even personal digital assistant interventions were included. The search results allowed the inclusion of 11 studies that gave rise to 12 publications. Six of the articles included in this review reported significant increases in physical activity levels. The number of studies using mobile devices for interventions has increased exponentially in the last few years, but future investigations with better methodological quality are needed to draw stronger conclusions regarding how to increase physical activity through mobile device interventions. © The Author(s) 2015.

  11. Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

    PubMed

    Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

    1999-04-01

    Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

  12. Social factors matter in cancer risk and survivorship.

    PubMed

    Dean, Lorraine T; Gehlert, Sarah; Neuhouser, Marian L; Oh, April; Zanetti, Krista; Goodman, Melody; Thompson, Beti; Visvanathan, Kala; Schmitz, Kathryn H

    2018-07-01

    Greater attention to social factors, such as race/ethnicity, socioeconomic position, and others, are needed across the cancer continuum, including breast cancer, given differences in tumor biology and genetic variants have not completely explained the persistent Black/White breast cancer mortality disparity. In this commentary, we use examples in breast cancer risk assessment and survivorship to demonstrate how the failure to appropriately incorporate social factors into the design, recruitment, and analysis of research studies has resulted in missed opportunities to reduce persistent cancer disparities. The conclusion offers recommendations for how to better document and use information on social factors in cancer research and care by (1) increasing education and awareness about the importance of inclusion of social factors in clinical research; (2) improving testing and documentation of social factors by incorporating them into journal guidelines and reporting stratified results; and (3) including social factors to refine extant tools that assess cancer risk and assign cancer care. Implementing the recommended changes would enable more effective design and implementation of interventions and work toward eliminating cancer disparities by accounting for the social and environmental contexts in which cancer patients live and are treated.

  13. Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor.

    PubMed

    Li, Guo-Bo; Yang, Ling-Ling; Feng, Shan; Zhou, Jian-Ping; Huang, Qi; Xie, Huan-Zhang; Li, Lin-Li; Yang, Sheng-Yong

    2011-03-15

    Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Technologies to Increase PV Hosting Capacity in Distribution Feeders: Preprint

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

    Ding, Fei; Mather, Barry; Gotseff, Peter

    This paper studies the distributed photovoltaic (PV) hosting capacity in distribution feeders by using the stochastic analysis approach. Multiple scenario simulations are conducted to analyze several factors that affect PV hosting capacity, including the existence of voltage regulator, PV location, the power factor of PV inverter and Volt/VAR control. Based on the conclusions obtained from simulation results, three approaches are then proposed to increase distributed PV hosting capacity, which can be formulated as the optimization problem to obtain the optimal solution. All technologies investigated in this paper utilize only existing assets in the feeder and therefore are implementable for amore » low cost. Additionally, the tool developed for these studies is described.« less

  15. [Psychological violence against women: What factors increase the risk of this kind of intimate partner abuse?

    PubMed

    Safranoff, Ana

    2017-01-01

    Using data from Argentina's National Study on Violence Against Women [Estudio nacional sobre violencias contra las mujeres] carried out in 2015, the article identifies the risk factors that increase women's vulnerability to psychological abuse. Findings show that women who are more prone to be victims of this kind of partner violence are those who are less educated, older, do not earn a wage for their work, live with children at home, are involved in less "formal" long-term relationships, as well as those whose male partners have a lower educational level than their own and/or have alcohol problems and/or were victims or witnesses of violence during their childhood. The article suggests possible intervention strategies to eradicate abuse, which should be primarily targeted at empowering women and strengthening their independence from their partners.

  16. Increased red blood cell transfusions are associated with worsening outcomes in pediatric heart transplant patients.

    PubMed

    Howard-Quijano, Kimberly; Schwarzenberger, Johanna C; Scovotti, Jennifer C; Alejos, Alexandra; Ngo, Jason; Gornbein, Jeffrey; Mahajan, Aman

    2013-06-01

    Red blood cell (RBC) transfusions are associated with increased morbidity. Children receiving heart transplants constitute a unique group of patients due to their risk factors. Although previous studies in nontransplant patients have focused primarily on the effects of postoperative blood transfusions, a significant exposure to blood occurs during the intraoperative period, and a larger percentage of heart transplant patients require intraoperative blood transfusions when compared with general cardiac surgery patients. We investigated the relationship between clinical outcomes and the amount of blood transfused both during and after heart transplantation. We hypothesized that larger amounts of RBC transfusions are associated with worsening clinical outcomes in pediatric heart transplant patients. A database comprising 108 pediatric patients undergoing heart transplantation from 2004 to 2010 was queried. Preoperative and postoperative clinical risk factors, including the amount of blood transfused intraoperatively and 48 hours postoperatively, were analyzed. The outcome measures were length of hospital stay, duration of tracheal intubation, inotrope score, and major adverse events. Bivariate and multivariate analyses were performed to control for simultaneous risk factors and determine outcomes in which the amount of blood transfused was an independent risk factor. Ninety-four patients with complete datasets were included in the final analysis. Eighty-eight percent received RBC transfusions, with a median transfusion amount of 38.7 mL/kg. A multivariate analysis correcting for 8 covariate risk factors, including the Index for Mortality Prediction After Cardiac Transplantation, age, weight, United Network for Organ Sharing status, warm and cold ischemia time, repeat sternotomy, and pretransplant hematocrit, showed RBC transfusions were independently associated with increased length of intensive care unit stay (means ratio = 1.34; 95% confidence interval, 1.03-1.76; P

  17. Increased c-kit and stem cell factor expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.

    PubMed

    Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

    2016-05-01

    Persistent pulmonary hypertension(PPH) in congenital diaphragmatic hernia (CDH) is caused by increased vascular cell proliferation and endothelial cell (EC) dysfunction, thus leading to obstructive changes in the pulmonary vasculature. C-Kit and its ligand, stem cell factor(SCF), are expressed by ECs in the developing lung mesenchyme, suggesting an important role during lung vascular formation. Conversely, absence of c-Kit expression has been demonstrated in ECs of dysplastic alveolar capillaries. We hypothesized that c-Kit and SCF expression is increased in the pulmonary vasculature of nitrofen-induced CDH. Timed-pregnant rats received nitrofen or vehicle on gestational day 9(D9). Fetuses were sacrificed on D15, D18, and D21, and divided into control and CDH group. Pulmonary gene expression levels of c-Kit and SCF were analyzed by qRT-PCR. Immunofluorescence double staining for c-Kit and SCF was combined with CD34 to evaluate protein expression in ECs of the pulmonary vasculature. Relative mRNA levels of c-Kit and SCF were significantly increased in lungs of CDH fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly increased vascular c-Kit and SCF expression in mesenchymal ECs of CDH lungs on D15, D18, and D21 compared to controls. Increased expression of c-Kit and SCF in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that increased c-Kit signaling during lung vascular formation may contribute to vascular remodeling and thus to PPH. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Stillbirth risk factors according to timing of exposure.

    PubMed

    Dodds, Linda; King, Will D; Fell, Deshayne B; Armson, B Anthony; Allen, Alexander; Nimrod, Carl

    2006-08-01

    The purpose of the present study is to identify risk factors for stillbirth and explore hypotheses about the cause of stillbirth based on the time in gestation when exposures occur. Relationships between lifestyle factors, pregnancy conditions, medication use, and occupation on risk for stillbirth were examined within a population-based case-control study. Women who had a stillbirth and a random sample of women who had a live birth between 1999 and 2001 were identified through perinatal databases in Nova Scotia and Eastern Ontario, Canada. Exposure data were collected for each month of pregnancy and analyzed within trimesters. Case-control data were converted to case-cohort data, and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined from Cox proportional hazards models. This study included 105 stillbirth cases and 389 live-birth controls. Fertility treatment in the present pregnancy was associated with increased risk for stillbirth (adjusted HR, 4.0; 95% CI, 1.4-11.6). Smoking during the first trimester also was associated with increased risk for stillbirth (adjusted HR, 2.4; 95% CI, 1.2-4.9). Other risk factors included antiemetic use during the first trimester, second-trimester antibiotic use, low family income, and age older than 35 years. Risk factors identified in this study concur with findings of previous studies and support the importance of early pregnancy exposures on stillbirth risk.

  19. In vivo increase in thrombin generation by four-factor prothrombin complex concentrate in apixaban-treated healthy volunteers.

    PubMed

    Cheung, Y W; Barco, S; Hutten, B A; Meijers, J C M; Middeldorp, S; Coppens, M

    2015-10-01

    Four-factor prothrombin complex concentrate (PCC) (Cofact; Sanquin Blood Supply) 50 IU kg(-1) increased thrombin generation beyond baseline values in healthy, rivaroxaban-treated subjects. To assess whether infusion with doses of 37.5 IU kg(-1) and 25 IU kg(-1) PCC reverses the anticoagulant effect of high-dose apixaban, another oral direct factor Xa inhibitor. In a randomized, double-blind, placebo-controlled, crossover study, six healthy subjects received twice-daily apixaban 10 mg for 3.5 days followed by a single bolus of 37.5 IU kg(-1) PCC, 25 IU kg(-1) PCC, or placebo. The primary outcome was the effect of PCC 15 min after infusion on thrombin generation (endogenous thrombin potential [ETP]); secondary outcomes were the immediate effect of PCC on prothrombin time (PT) and the effect of PCC as compared with placebo over a period of 24 h on ETP and PT. Fifteen minutes after infusion of 37.5 IU kg(-1) and 25 IU kg(-1) PCC, ETP increased from 41% ± 11% to 56% ± 23% (P = 0.06) and from 44% ± 12% to 51% ± 15% (P = 0.03), respectively. ETP significantly differed over time between 37.5 IU kg(-1) PCC and placebo during 24 h after infusion (P < 0.01). Both PCC doses restored apixaban-induced PT prolongation after 15 min (P < 0.01), and this was sustained over a period of 24 h. Both 37.5 IU kg(-1) PCC and 25 IU/kg PCC improved coagulation parameters in healthy subjects, suggesting partial reversal of the anticoagulant effect of apixaban. This implies that PCC might be considered in patients with apixaban-associated bleeding. However, ETP was not immediately restored to pre-apixaban levels, suggesting that these doses are too low to instantly and fully restore hemostasis at peak apixaban levels. © 2015 International Society on Thrombosis and Haemostasis.

  20. Increased global transcription activity as a mechanism of replication stress in cancer

    PubMed Central

    Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M.; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

    2016-01-01

    Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer. PMID:27725641

  1. Increased global transcription activity as a mechanism of replication stress in cancer.

    PubMed

    Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

    2016-10-11

    Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12 , elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.

  2. Food choices and health during military service: increases in sugar- and fibre-containing foods and changes in anthropometric and clinical risk factors.

    PubMed

    Bingham, Clarissa M L; Lahti-Koski, Marjaana; Absetz, Pilvikki; Puukka, Pauli; Kinnunen, Marja; Pihlajamäki, Harri; Sahi, Timo; Uutela, Antti; Jallinoja, Piia

    2012-07-01

    To analyse changes in food choices, diet-related risk factors and their association during 6 months of military service. Longitudinal cohort study in Finland, where all men are liable to military service and a clear majority of each age group completes service. Dietary intake data were collected by self-administered questionnaire before and at 6 months of service. Three dietary indices based on food frequencies were developed to characterize the diet: Sugar Index, Fibre Index and Fat Index. Thirteen diet-related risk factors were measured at the beginning and at 6 months of service. Military environment, two geographically distinct garrisons. Male conscripts aged 18-21 years (n 256) performing military service. During 6 months of service, positive changes concerned more frequent use of fibre-rich foods (P = 0·011), improved body composition (BMI, waist circumference, muscle mass, fat mass and percentage body fat, P ≤ 0·003 for all), decreased systolic blood pressure and increased HDL cholesterol (P < 0·001 for both). Negative changes concerned more frequent use of sugar-rich foods and increased total cholesterol, TAG and blood glucose (P < 0·001 for all). The consumption of fibre-rich foods was inversely associated with anthropometric risk factors at baseline and with sugar-rich foods at both time points. Despite more frequent consumption of sweet foods, military service with a unified, nutritionally planned diet, a controlled environment and high physical load has a positive effect on conscripts' health risk factors. The negative changes in blood lipids and glucose may reflect more varied free-time eating.

  3. Public health leadership development: factors contributing to growth.

    PubMed

    Olson, Linda G

    2013-01-01

    This study compares pre- and posttest Leadership Practices Inventory (LPI-Self) scores for public health leaders who completed the Regional Institute for Health and Environmental Leadership (RIHEL) training program at least 2 years earlier; it seeks to identify factors contributing to changes in practices and overall leadership development for public health and environment leaders. Sixty-seven alumni who completed the yearlong RIHEL program between 1999 and 2002 participated through mailed surveys and phone interviews. The Leadership Practices Inventory, an alumni leadership development survey, and interviews provided evidence for positive change in leadership practices. Alumni experienced significant increases in pre- to post-LPI scores, collaborative leadership practices, and communication skills consistent with those taught in the RIHEL program. Women presented higher Encourage the Heart scores than men. Years of public health service negatively correlated with Total Change scores of LPI. The RIHEL program as a training intervention was credited significantly with changes in leadership practices for alumni studied. Nine influencing factors were identified for leadership development and are embedded in a Leadership Development Influence Model. These include self-awareness, a leadership development framework, and skills important in multiple leadership situations. Confidence was both an encouraging factor and a resulting factor to the increased exemplary leadership practices. Leadership development in public health must include multiple factors to create consistent increases in exemplary leadership practices. While the study focused on the leadership development process itself, RIHEL training was reported as having a positive, significant impact overall in participant leadership development. This study adds research data as a foundation for training content areas of focus. Studies to further test the Leadership Development Influence Model will allow public health

  4. Strategies to Increase Adenoma Detection Rates.

    PubMed

    Brand, Eelco C; Wallace, Michael B

    2017-03-01

    The adenoma detection rate (ADR), i.e., the proportion of average risk patients with at least one adenoma detected during screening colonoscopy, is inversely associated with the development of interval colorectal cancer. Increasing the ADR is therefore an important proxy for increase in quality and efficacy of (screening) colonoscopy. Several potentially modifiable factors, such as, procedural and technological factors, and quality improvement programs, and their effect on the ADR will be reviewed. Procedural factors, such as, bowel preparation, withdrawal time, and position changes of the patient are associated with the ADR. While the relation of others, such as inspection during insertion, use of antispasmodic agents, and second inspection in the proximal colon, with the ADR is not completely clear. Many new colonoscopy technologies have been evaluated over recent years and are still under evaluation, but no unequivocal positive effect on the ADR has been observed in randomized trials that have mostly been performed by experienced endoscopists with high baseline ADRs. Several quality improvement programs have been evaluated and seem to have a positive effect on endoscopists' ADR. Increase in ADR is important for the protective benefit of colonoscopy. There are now extensive methods to measure, benchmark, and improve ADR but increased awareness of these is critical. We have provided an overview of potential factors that can be used to increase personal ADRs in every day practice.

  5. Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006

    PubMed Central

    2012-01-01

    Background Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. Methods The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Results Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Conclusion Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD. PMID:22958443

  6. Factor Analysis and Counseling Research

    ERIC Educational Resources Information Center

    Weiss, David J.

    1970-01-01

    Topics discussed include factor analysis versus cluster analysis, analysis of Q correlation matrices, ipsativity and factor analysis, and tests for the significance of a correlation matrix prior to application of factor analytic techniques. Techniques for factor extraction discussed include principal components, canonical factor analysis, alpha…

  7. Understanding the increased risk of neural tube defect-affected pregnancies among Mexico-born women in California: immigration and anthropometric factors.

    PubMed

    Velie, Ellen M; Shaw, Gary M; Malcoe, Lorraine H; Schaffer, Donna M; Samuels, Steven J; Todoroff, Karen; Block, Gladys

    2006-05-01

    Mexico-born women in the United States have an unexplained twofold increased risk of neural tube defect (NTD)-affected pregnancies. We examined whether immigration characteristics were associated with the NTD risk and whether anthropometric factors contributed to the increased risk among Mexico-born women. Data were derived from a large population-based case-control study in California. In-person interviews were conducted with mothers of 538 (88% of eligible) NTD-affected fetuses/infants and mothers of 539 (88%) randomly selected non-malformed control infants. The crude odds ratio (OR) for NTDs among all Mexico-born women, women residing <2 years in the US, and women >16 years old at immigration compared with non-Hispanic white women was 2.4 [95% confidence interval (CI) = 1.8, 3.3], 7.2 [95% CI = 3.7, 14.0] and 3.0 [95% CI = 2.0, 4.4], respectively. Risk for second- or third-generation Mexican-Americans was similar to that of white women. The crude OR for all Mexico-born women was reduced from 2.4 to 2.0 [95% CI = 1.3, 3.0] and for those residing <2 years in the US from 8.4 to 7.1 [95% CI = 3.2, 15.3] after adjustment for maternal body mass index (BMI), height, compromised diet, diabetes, and other known risk factors. In term pregnancies, additional adjustment for pregnancy weight gain reduced the OR in all Mexico-born women and recent immigrants by 16% and 25%, respectively. Low pregnancy weight gain (<10 vs. 10-14 kg) was particularly associated with increased NTD risk among Mexico-born women (OR(ADJ) = 5.8; 95% CI = 2.1, 15.8). Findings indicate that recent Mexican immigrants have a sevenfold increased risk for NTDs. Maternal BMI and height contributed very little, and inadequate weight gain contributed modestly to the NTD risk disparity for Mexican immigrants.

  8. Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

    PubMed Central

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-01-01

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2

  9. Stormwater Volume Control to Prevent Increases in Lake Flooding and Dam Failure Risk

    NASA Astrophysics Data System (ADS)

    Potter, K. W.

    2017-12-01

    Urban expansion is not often considered a major factor contributing to dam failure. But if urbanization occurs without mitigation of the hydrologic impacts, the risk of dam failure will increase. Of particular concern are increases in the volume of storm runoff resulting from increases in the extent of impervious surfaces. Storm runoff volumes are not regulated for much the U.S, and where they are, the required control is commonly less than 100%. Unmitigated increases in runoff volume due to urbanization can pose a risk to dams. A recent technical advisory committee of Dane County has recommended that the county require 100% control of stormwater volumes for new developments. The primary motivation was to prevent increases in the water levels in the Yahara Lakes, slowly draining lakes that are highly sensitive to runoff volume. The recommendations included the use of "volume trading" to achieve efficient compliance. Such recommendations should be considered for other slowly draining lakes, including those created by artificial structures.

  10. Factors associated with self-assessed increase in tobacco consumption among over-indebted individuals in Germany: a cross-sectional study.

    PubMed

    Rueger, Heiko; Weishaar, Heide; Ochsmann, Elke B; Letzel, Stephan; Muenster, Eva

    2013-03-13

    Over-indebtedness is an increasing phenomenon in industrialised nations causing individual hardship and societal problems. Nonetheless, few studies have explored smoking among over-indebted individuals. A cross-sectional survey (n=949) on retrospectively assessed changes in tobacco consumption was carried out in 2006 and 2007 among clients of 84 officially approved debt and insolvency counselling centres in Germany (response rate 39.7%). Logistic regressions were performed to explore factors associated with reports of increased smoking after onset of over-indebtedness. 63% of all respondents stated daily or occasional tobacco consumption. Almost one fifth reported an increase in smoking after becoming over-indebted. Females were less likely to report increased smoking than men (aOR 0.66, 95% CI 0.44-0.99) whereas respondents who had been over-indebted for more than 10 years were more likely to report increased smoking than those who had been over-indebted for less than five years (aOR 1.66; 95%-CI 1.00-2.76). The odds of increased smoking were also elevated among those who reported that their families and friends had withdrawn from them as a consequence of their over-indebtedness (aOR 1.82; 95%-CI 1.06-3.14). The study identifies over-indebted individuals and particularly over-indebted men as a high-risk group of smokers. Low levels of social embeddedness/support were associated with a further increase in smoking after becoming over-indebted. Given recent increases of over-indebtedness, the findings highlight the need to develop appropriate public health policies.

  11. Factors associated with self-assessed increase in tobacco consumption among over-indebted individuals in Germany: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Over-indebtedness is an increasing phenomenon in industrialised nations causing individual hardship and societal problems. Nonetheless, few studies have explored smoking among over-indebted individuals. Methods A cross-sectional survey (n=949) on retrospectively assessed changes in tobacco consumption was carried out in 2006 and 2007 among clients of 84 officially approved debt and insolvency counselling centres in Germany (response rate 39.7%). Logistic regressions were performed to explore factors associated with reports of increased smoking after onset of over-indebtedness. Results 63% of all respondents stated daily or occasional tobacco consumption. Almost one fifth reported an increase in smoking after becoming over-indebted. Females were less likely to report increased smoking than men (aOR 0.66, 95% CI 0.44-0.99) whereas respondents who had been over-indebted for more than 10 years were more likely to report increased smoking than those who had been over-indebted for less than five years (aOR 1.66; 95%-CI 1.00-2.76). The odds of increased smoking were also elevated among those who reported that their families and friends had withdrawn from them as a consequence of their over-indebtedness (aOR 1.82; 95%-CI 1.06-3.14). Conclusions The study identifies over-indebted individuals and particularly over-indebted men as a high-risk group of smokers. Low levels of social embeddedness/support were associated with a further increase in smoking after becoming over-indebted. Given recent increases of over-indebtedness, the findings highlight the need to develop appropriate public health policies. PMID:23497337

  12. Immigrant status and increased risk of heart failure: the role of hypertension and life-style risk factors.

    PubMed

    Borné, Yan; Engström, Gunnar; Essén, Birgitta; Hedblad, Bo

    2012-03-26

    Studies from Sweden have reported association between immigrant status and incidence of cardiovascular diseases. The nature of this relationship is unclear. We investigated the relationship between immigrant status and risk of heart failure (HF) hospitalization in a population-based cohort, and to what extent this is mediated by hypertension and life-style risk factors. We also explored whether immigrant status was related to case-fatality after HF. 26,559 subjects without history of myocardial infarction (MI), stroke or HF from the community-based Malmö Diet and Cancer (MDC) cohort underwent a baseline examination during 1991-1996. Incidence of HF hospitalizations was monitored during a mean follow-up of 15 years. 3,129 (11.8%) subjects were born outside Sweden. During follow-up, 764 subjects were hospitalized with HF as primary diagnosis, of whom 166 had an MI before or concurrent with the HF. After adjustment for potential confounding factors, the hazard ratios (HR) for foreign-born were 1.37 (95% CI: 1.08-1.73, p = 0.009) compared to native Swedes, for HF without previous MI. The results were similar in a secondary analysis without censoring at incident MI. There was a significant interaction (p < 0.001) between immigrant status and waist circumference (WC), and the increased HF risk was limited to immigrants with high WC. Although not significant foreign-born tended to have lower one-month and one-year mortality after HF. Immigrant status was associated with long-term risk of HF hospitalization, independently of hypertension and several life-style risk factors. A significant interaction between WC and immigrant status on incident HF was observed.

  13. Immigrant status and increased risk of heart failure: the role of hypertension and life-style risk factors

    PubMed Central

    2012-01-01

    Background Studies from Sweden have reported association between immigrant status and incidence of cardiovascular diseases. The nature of this relationship is unclear. We investigated the relationship between immigrant status and risk of heart failure (HF) hospitalization in a population-based cohort, and to what extent this is mediated by hypertension and life-style risk factors. We also explored whether immigrant status was related to case-fatality after HF. Methods 26,559 subjects without history of myocardial infarction (MI), stroke or HF from the community-based Malmö Diet and Cancer (MDC) cohort underwent a baseline examination during 1991-1996. Incidence of HF hospitalizations was monitored during a mean follow-up of 15 years. Results 3,129 (11.8%) subjects were born outside Sweden. During follow-up, 764 subjects were hospitalized with HF as primary diagnosis, of whom 166 had an MI before or concurrent with the HF. After adjustment for potential confounding factors, the hazard ratios (HR) for foreign-born were 1.37 (95% CI: 1.08-1.73, p = 0.009) compared to native Swedes, for HF without previous MI. The results were similar in a secondary analysis without censoring at incident MI. There was a significant interaction (p < 0.001) between immigrant status and waist circumference (WC), and the increased HF risk was limited to immigrants with high WC. Although not significant foreign-born tended to have lower one-month and one-year mortality after HF. Conclusions Immigrant status was associated with long-term risk of HF hospitalization, independently of hypertension and several life-style risk factors. A significant interaction between WC and immigrant status on incident HF was observed. PMID:22443268

  14. Factors contributing to managerial competence of first-line nurse managers: A systematic review.

    PubMed

    Gunawan, Joko; Aungsuroch, Yupin; Fisher, Mary L

    2018-02-01

    To determine the factors contributing to managerial competence of first-line nurse managers. Understanding factors affecting managerial competence of nurse managers remains important to increase the performance of organizations; however, there is sparse research examining factors that influence managerial competence of first-line nurse managers. Systematic review. The search strategy was conducted from April to July 2017 that included 6 electronic databases: Science Direct, PROQUEST Dissertations and Theses, MEDLINE, CINAHL, EMBASE, and Google Scholar for the years 2000 to 2017 with full text in English. Quantitative and qualitative research papers that examined relationships among managerial competence and antecedent factors were included. Quality assessment, data extractions, and analysis were completed on all included studies. Content analysis was used to categorize factors into themes. Eighteen influencing factors were examined and categorized into 3 themes-organizational factors, characteristics and personality traits of individual managers, and role factors. Findings suggest that managerial competence of first-line nurse managers is multifactorial. Further research is needed to develop strategies to develop managerial competence of first-line nurse managers. © 2017 John Wiley & Sons Australia, Ltd.

  15. Physiological factors that regulate skin pigmentation

    PubMed Central

    Yamaguchi, Yuji; Hearing, Vincent J.

    2009-01-01

    More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1 and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2 and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including α-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. PMID:19449448

  16. The protein level of hypoxia-inducible factor-1alpha is increased in the plateau pika (Ochotona curzoniae) inhabiting high altitudes.

    PubMed

    Li, Hong-Ge; Ren, Yong-Ming; Guo, Song-Chang; Cheng, Long; Wang, De-Peng; Yang, Jie; Chang, Zhi-Jie; Zhao, Xin-Quan

    2009-02-01

    The plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant species living only at 3,000-5,000 m above sea-level on the Qinghai-Tibetan plateau. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates a variety of cellular and systemic adaptations to hypoxia. To investigate how the plateau pika adapts to a high-altitude hypoxic environment at the molecular level, we examined the expression pattern of the HIF-1alpha protein in the pika by Western blot and immunohistochemical analysis. We found that HIF-1alpha protein is expressed at a significantly high level in the pika, which is higher in most tissues (particularly in the lung, liver, spleen and kidney) of the plateau pika than that of mice living at sea-level. Importantly, we found that the protein levels of HIF-1alpha in the lung, liver, spleen and kidney of the pika were increased with increased habitat altitudes. We observed that the plateau pika HIF-1alpha localized to the nucleus of cells by an immunostaining analysis, and enhanced HRE-driven gene expression by luciferase reporter assays. Our study suggests that the HIF-1alpha protein levels are related to the adaptation of the plateau pika to the high-altitude hypoxic environment.

  17. Temporal expression of growth factors triggered by epiregulin regulates inflammation development.

    PubMed

    Harada, Masaya; Kamimura, Daisuke; Arima, Yasunobu; Kohsaka, Hitoshi; Nakatsuji, Yuji; Nishida, Makoto; Atsumi, Toru; Meng, Jie; Bando, Hidenori; Singh, Rajeev; Sabharwal, Lavannya; Jiang, Jing-Jing; Kumai, Noriko; Miyasaka, Nobuyuki; Sakoda, Saburo; Yamauchi-Takihara, Keiko; Ogura, Hideki; Hirano, Toshio; Murakami, Masaaki

    2015-02-01

    In this study, we investigated the relationship between several growth factors and inflammation development. Serum concentrations of epiregulin, amphiregulin, betacellulin, TGF-α, fibroblast growth factor 2, placental growth factor (PLGF), and tenascin C were increased in rheumatoid arthritis patients. Furthermore, local blockades of these growth factors suppressed the development of cytokine-induced arthritis in mice by inhibiting chemokine and IL-6 expressions. We found that epiregulin expression was early and followed by the induction of other growth factors at different sites of the joints. The same growth factors then regulated the expression of epiregulin at later time points of the arthritis. These growth factors were increased in patients suffering from multiple sclerosis (MS) and also played a role in the development of an MS model, experimental autoimmune encephalomyelitis. The results suggest that the temporal expression of growth factors is involved in the inflammation development seen in several diseases, including rheumatoid arthritis and MS. Therefore, various growth factor pathways might be good therapeutic targets for various inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

  18. Including the spatial variability of metal speciation in the effect factor in life cycle impact assessment: Limits of the equilibrium partitioning method.

    PubMed

    Tromson, Clara; Bulle, Cécile; Deschênes, Louise

    2017-03-01

    In life cycle assessment (LCA), the potential terrestrial ecotoxicity effect of metals, calculated as the effect factor (EF), is usually extrapolated from aquatic ecotoxicological data using the equilibrium partitioning method (EqP) as it is more readily available than terrestrial data. However, when following the AMI recommendations (i.e. with at least enough species that represents three different phyla), there are not enough terrestrial data for which soil properties or metal speciation during ecotoxicological testing are specified to account for the influence of soil property variations on metal speciation when using this approach. Alternatively, the TBLM (Terrestrial Biotic Ligand Model) has been used to determine an EF that accounts for speciation, but is not available for metals; hence it cannot be consistently applied to metals in an LCA context. This paper proposes an approach to include metal speciation by regionalizing the EqP method for Cu, Ni and Zn with a geochemical speciation model (the Windermere Humic Aqueous Model 7.0), for 5213 soils selected from the Harmonized World Soil Database. Results obtained by this approach (EF EqP regionalized ) are compared to the EFs calculated with the conventional EqP method, to the EFs based on available terrestrial data and to the EFs calculated with the TBLM (EF TBLM regionalized ) when available. The spatial variability contribution of the EF to the overall spatial variability of the characterization factor (CF) has been analyzed. It was found that the EFs EqP regionalized show a significant spatial variability. The EFs calculated with the two non-regionalized methods (EqP and terrestrial data) fall within the range of the EFs EqP regionalized . The EFs TBLM regionalized cover a larger range of values than the EFs EqP regionalized but the two methods are not correlated. This paper highlights the importance of including speciation into the terrestrial EF and shows that using the regionalized EqP approach is not

  19. Are Global Economic Losses from Natural Hazards Increasing?

    NASA Astrophysics Data System (ADS)

    McMullan, Caroline; Simic, Milan; Tosco, Antonello; Latchman, Shane

    2016-04-01

    Global society has long been influenced by natural hazards, but it has been widely noted that the economic cost of natural hazards has been rising rapidly over recent decades. This upward trend highlights the increasing exposure of the global economy to natural hazards and the need for society to understand the driving factors to help improve the resilience of communities. However disaster risk is driven by a plethora of factors, including population, wealth, land-use, and demographics. Consider also the natural variability in the frequency and severity of events, climate change, and implementation of resilience policies, and it becomes clear that disaster-risk management is a challenging field. To investigate the apparent upward trend in reported annual economic losses from natural disasters, socioeconomic factors known to influence the magnitude of losses must first be accounted for. Adjustment for these factors, known as loss normalisation, aims to estimate the losses sustained if historical events were to impact present day society. We have undertaken a detailed assessment of global economic losses from natural disasters for the period 1995 through 2013. Although the studied time-period is relatively short, expanding the investigated period would not necessarily produce more reliable insights owing to the inherent difficulty in obtaining accurate economic loss estimates for earlier periods and the challenge of finding consistent and reliable sources of socioeconomic data for the normalisation process. The results of the study, presented at a global and regional level, appear to suggest that the main driver of perceived increase in economic losses over the last ~20 years was the development of nations' economies (i.e. increase in population and wealth/GDP) and not in the natural hazards themselves. As populations all over the world migrate into areas of higher natural hazards regions (e.g. coastal areas or floodplain zones) and global wealth continues to

  20. Nationwide Increase in Cryptorchidism After the Fukushima Nuclear Accident.

    PubMed

    Murase, Kaori; Murase, Joe; Machidori, Koji; Mizuno, Kentaro; Hayashi, Yutaro; Kohri, Kenjiro

    2018-05-08

    To estimate the change of discharge rate after cryptorchidism surgery between pre- and postdisaster in Japan. Cryptorchidism cannot be diagnosed before birth and is not a factor that would influence a woman's decision to seek an abortion. Therefore, this disease is considered suitable for assessing how the Great East Japan Earthquake and the subsequent Fukushima Daiichi nuclear accident (2011) influenced congenital diseases. We obtained cryptorchidism discharge data collected over 6 years from hospitals that were included in an impact assessment survey of the Diagnosis Procedure Combination survey database in Japan and used these data to estimate the discharge rate after cryptorchidism surgery before and after the disaster. The 94 hospitals in Japan that participated in Diagnosis Procedure Combination system and had 10 or more discharges after cryptorchidism surgery within successive 6 years covering pre- and postdisaster period (FY2010-FY2015) were involved. The change in discharge rate between pre- and postdisaster was analyzed using a Bayesian generalized linear mixed model. Nationwide, a 13.4% (95% credible interval 4.7%-23.0%) increase in discharge rates was estimated. The results of all sensitivity analyses were similar to the reported main results. The discharge rate of cryptorchidism was increased nationwide. The rates of low-weight babies or preterm births, risk factors of cryptorchidism, were almost constant during the study period, and age distribution of the surgery was also not changed, which suggested that the other factors that associated with the disaster increased the incidence of cryptorchidism. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. An Analysis of Selected Factors Influencing Enrollment Patterns.

    ERIC Educational Resources Information Center

    Heck, James

    This report presents an analysis of factors influencing enrollment patterns at Lake City Community College (LCCC; Florida) and recommends ways to increase enrollments at the college. Section I reviews the methods of collecting data for the report, which included interviews with key college personnel, an examination of social indicators such as…

  2. Does first line antiretroviral therapy increase the prevalence of cardiovascular risk factors in Indian patients?: A cross sectional study.

    PubMed

    Carey, R A B; Rupali, P; Abraham, O C; Kattula, D

    2013-01-01

    Antiretroviral therapy (ART) is associated with a myriad of metabolic complications which are potential cardiovascular risk factors. Early detection of these risk factors could help in alleviating morbidity and mortality in human immunodeficiency virus (HIV) infected patients on ART. To study the prevalence of cardiovascular risk factors in patients on a combination of nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) - the standard combination first line ART regimen used in tertiary referral center. The prevalence of cardiovascular risk factors in HIV infected subjects with stage 1t disease on standard first line ART for at least 1 year, HIV infected subjects with stage 1 disease and not on ART and HIV negative subjects was assessed. The study was a cross-sectional study design. Basic demographic data was collected and patients were examined for anthropometric data and blood was collected for analysis of blood glucose, serum lipids, and fasting insulin levels. Chi-square test was used to calculate significance. Statistical Package for Social Sciences (SPSS) software version 16.0 was used for data analysis. The prevalence of hypercholesterolemia and hypertriglyceridemia was higher in the patients on ART when compared to patients not on ART (P<0.001). There was no difference in the prevalence of abnormal glycemic status, obesity, abdominal obesity, insulin resistance, and hyperinsulinemia between patients on ART and those not on ART. First line ART is associated with increased prevalence of dyslipidemia. Early detection and treatment of dyslipidemia should help in reducing the cardiovascular morbidity in patients on ART.

  3. Stromal-Derived Factor-1α (CXCL12) Levels Increase in Periodontal Disease

    PubMed Central

    Havens, Aaron M.; Chiu, Evonne; Taba, Mario; Wang, Jincheng; Shiozawa, Yusuke; Jung, Younghun; Taichman, L. Susan; D'Silva, Nisha J.; Gopalakrishnan, R.; Wang, CunYu; Giannobile, William V.; Taichman, Russell S.

    2008-01-01

    Background The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell–derived factor-1 (SDF-1α or CXC chemokine ligand 12) are involved in the trafficking of leukocytes into and out of extravascular tissues. The purpose of this study was to determine whether SDF-1α secreted by host cells plays a role in recruiting inflammatory cells into the periodontia during local inflammation. Methods SDF-1α levels were determined by enzyme-linked immunosorbent assay in gingival crevicular fluid (GCF) of 24 individuals with periodontitis versus healthy individuals in tissue biopsies and in a preclinical rat model of Porphyromonas gingivalis lipopolysaccharide–induced experimental bone loss. Neutrophil chemotaxis assays were also used to evaluate whether SDF-1α plays a role in the recruitment of host cells at periodontal lesions. Results Subjects with periodontal disease had higher levels of SDF-1α in their GCF compared to healthy subjects. Subjects with periodontal disease who underwent mechanical therapy demonstrated decreased levels of SDF-1α. Immunohistologic staining showed that SDF-1α and CXCR4 levels were elevated in samples obtained from periodontally compromised individuals. Similar results were observed in the rodent model. Neutrophil migration was enhanced in the presence of SDF-1α, mimicking immune cell migration in periodontal lesions. Conclusions SDF-1α may be involved in the immune defense pathway activated during periodontal disease. Upon the development of diseased tissues, SDF-1α levels increase and may recruit host defensive cells into sites of inflammation. These studies suggest that SDF-1α may be a useful biomarker for the identification of periodontal disease progression. PMID:18454663

  4. Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms.

    PubMed

    Godoy, Jaime; Mellado, Patricio; Tapia, Jorge; Santín, Julia

    2009-03-01

    Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.

  5. Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

    PubMed

    Fisher, Brian T; Robinson, Paula D; Lehrnbecher, Thomas; Steinbach, William J; Zaoutis, Theoklis E; Phillips, Bob; Sung, Lillian

    2017-05-26

    Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

    PubMed

    Lin, W-Y; Chang, P-J; Lin, Y-P; Wu, S-B; Chen, C-S; Levin, R M; Wei, Y-H

    2012-02-01

    There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-β1 (TGF-β1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-β1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-β1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-β1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  7. Six Increasingly Higher Levels of Wellness Based on Holistic Principles and Risk Factor Science.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1987-01-01

    Describes program for achievement of higher wellness levels based on holistic principles and risk factor science. Levels focus on (1) heart disease risk factors and how to reverse them; (2) unconscious needs at conflict with one's conscious goals; (3) identity status, meaning to love and to be loved; (4) autogenics; and (5) full ego development…

  8. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

    PubMed

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T; Gavrilyuk, Oxana; Quirós, J Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Allen, Naomi E; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-03-15

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination. © 2016 UICC.

  9. Identification and Quantification of Cumulative Factors that Increase Environmental Exposures and Impacts

    EPA Science Inventory

    Evaluating the combined adverse effects of multiple stressors upon human health is an imperative component of cumulative risk assessment (CRA)1. In addition to chemical stressors, other non-chemical factors are also considered. For examples, smoking will elevate the risks of havi...

  10. Risk factors for epistaxis in jump racing in Great Britain (2001-2009).

    PubMed

    Reardon, Richard J M; Boden, Lisa A; Mellor, Dominic J; Love, Sandy; Newton, Richard J; Stirk, Anthony J; Parkin, Timothy D

    2015-07-01

    The aim of this study was to evaluate risk factors associated with developing epistaxis in jump racing in Great Britain (GB). A retrospective analysis of records from horses running in all hurdle and steeplechase races in GB between 2001 and 2009 identified diagnoses of epistaxis whilst still at the racecourse. Data were used from 603 starts resulting in epistaxis (event) and 169,065 starts resulting in no epistaxis (non-event) in hurdle racing, and from 550 event starts and 102,344 non-event starts in steeplechase racing. Two multivariable logistic regression models to evaluate risk factors associated with epistaxis were produced. The potential effect of clustering of data (within horse, horse dam, horse sire, trainer, jockey, course, race and race meet) on the associations between risk factors and epistaxis was examined using mixed-effects models. Multiple factors associated with increased risk of epistaxis were identified. Those identified in both types of jump racing included running on firmer ground; horses with >75% of career starts in flat racing and a previous episode of epistaxis recorded during racing. Risk factors identified only in hurdle racing included racing in the spring and increased age at first race; and those identified only in steeplechase racing included running in a claiming race and more starts in the previous 3-6 months. The risk factors identified provide important information about the risk of developing epistaxis. Multiple avenues for further investigation are highlighted, including unmeasured variables at the level of the racecourse. The results of this study can be used to guide the development of interventions to minimise the risk of epistaxis in jump racing. Copyright © 2015. Published by Elsevier Ltd.

  11. Investigation of Model Sunscreen Formulations Comparing the Sun Protection Factor, the Universal Sun Protection Factor and the Radical Formation Ratio.

    PubMed

    Syring, Felicia; Weigmann, Hans-Jürgen; Schanzer, Sabine; Meinke, Martina C; Knorr, Fanny; Lademann, Jürgen

    2016-01-01

    In view of globally rising skin cancer rates and harmful effects exerted by sunlight throughout the ultraviolet, visible and infrared ranges, an objective, safe and comprehensive method for determining sunscreen efficacy is required in order to warrant safe sun exposure. In this study, the influence of characteristic active ingredients (chemical filters, physical filters and antioxidants) on different sunscreen indicators, including the universal sun protection factor and the radical formation ratio, was determined and compared to their influence on sun protection factor values. Spectroscopic universal sun protection factor measurements were conducted ex vivo by analyzing tape strips taken from human skin, and radical formation ratio determination was performed via electron paramagnetic resonance spectroscopy using porcine ear skin ex vivo. The sun protection factor determination was conducted according to ISO standards (ISO 24444:2010). It was shown that chemical filters provide a protective effect which was measurable by all methods examined (spectroscopy, electron paramagnetic resonance spectroscopy and erythema formation). Physical filters, when used as single active ingredients, increased protective values in universal sun protection factor and sun protection factor measurements but exhibited no significant effect on universal sun protection factor measurements when used in combination with chemical filters or antioxidants. Antioxidants were shown to increase sun protection factor values. Radical formation ratio values were shown to be influenced merely by chemical filters, leading to the conclusion that the universal sun protection factor is the most suitable efficacy indicator for the ultraviolet range. © 2015 S. Karger AG, Basel.

  12. Factors Impacting Online Ratings for Otolaryngologists.

    PubMed

    Calixto, Nathaniel E; Chiao, Whitney; Durr, Megan L; Jiang, Nancy

    2018-06-01

    To identify factors associated with online patient ratings and comments for a nationwide sample of otolaryngologists. Ratings, demographic information, and written comments were obtained for a random sample of otolaryngologists from HealthGrades.com and Vitals.com . Online Presence Score (OPS) was based on 10 criteria, including professional website and social media profiles. Regression analyses identified factors associated with increased rating. We evaluated for correlations between OPS and other attributes with star rating and used chi-square tests to evaluate content differences between positive and negative comments. On linear regression, increased OPS was associated with higher ratings on HealthGrades and Vitals; higher ratings were also associated with younger age on Vitals and less experience on HealthGrades. However, detailed correlation studies showed weak correlation between OPS and rating; age and graduation year also showed low correlation with ratings. Negative comments more likely focused on surgeon-independent factors or poor bedside manner. Though younger otolaryngologists with greater online presence tend to have higher ratings, weak correlations suggest that age and online presence have only a small impact on the content found on ratings websites. While most written comments are positive, deficiencies in bedside manner or other physician-independent factors tend to elicit negative comments.

  13. Process performance assessment of advanced anaerobic digestion of sewage sludge including sequential ultrasound-thermal (55 °C) pre-treatment.

    PubMed

    Neumann, Patricio; Barriga, Felipe; Álvarez, Claudia; González, Zenón; Vidal, Gladys

    2018-03-15

    The aim of this study was to evaluate the performance and digestate quality of advanced anaerobic digestion of sewage sludge including sequential ultrasound-thermal (55 °C) pre-treatment. Both stages of pre-treatment contributed to chemical oxygen demand (COD) solubilization, with an overall factor of 11.4 ± 2.2%. Pre-treatment led to 19.1, 24.0 and 29.9% increased methane yields at 30, 15 and 7.5 days solid retention times (SRT), respectively, without affecting process stability or accumulation of intermediates. Pre-treatment decreased up to 4.2% water recovery from the digestate, but SRT was a more relevant factor controlling dewatering. Advanced digestion showed 2.4-3.1 and 1.5 logarithmic removals of coliforms and coliphages, respectively, and up to a 58% increase in the concentration of inorganics in the digestate solids compared to conventional digestion. The COD balance of the process showed that the observed increase in methane production was proportional to the pre-treatment solubilization efficiency. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. [Association between risk factors of cardiovascular diseases and osteoporosis in postmenopausal Chinese women].

    PubMed

    Xue, Wen-qiong; Deng, Juan; Li, Jing-jing; Liu, Jing; He, Li-ping; Chen, Zong-qiu; Chen, Yu-ming

    2011-06-01

    To assess the relationship between cardiovascular risk factors and osteoporosis. 2202 women aged 50 - 73 years were included in this cross-sectional study from the communities in Guangzhou, from July 2008 to January 2010. Cardiovascular risk factors including age, years since menopause, physical activity, anthropometrics, body composition, blood pressure, fasting serum lipids, glucose and uric acid, intima-media thickness (IMT) of carotid artery were assessed. Ultrasonic bone density (speed of sound) at the radius and tibia were determined. Osteoporosis was defined as T-score ≤ -2.5. Common factors for the cardiovascular risk factors were extracted using the factor analysis method. Eight common factors representing obesity, lean mass, blood triglycerides and uric acid, cholesterol, age, blood pressure, IMT and physical activity were extracted. Data from the Multivariate logistic regression showed a dose-dependent association of greater scores of age and IMT factors and lower score of lean mass factor with the increased risk of osteoporosis at the radius and tibia. As compared with the bottom quartile, the OR (95%CI) of radius and tibia osteoporosis were 0.62 (0.44 - 0.88) and 0.62 (0.48 - 0.80) for lean mass factor, 4.02 (2.72 - 5.94) and 3.68 (2.81 - 4.82) for age factor, 1.41 (1.00 - 2.00) and 1.54 (1.19 - 2.00) for IMT factors, respectively. Moreover, greater blood pressure score was associated with higher risk of radius osteoporosis while the higher obese score, was correlated with the increased risk of tibia osteoporosis. The cardiovascular-related risk factors of greater IMT, obesity, blood pressure and lower lean mass scores were associated with increased osteoporosis risks while called for more concern among the Chinese women.

  15. Factor V Leiden as a common genetic risk factor for venous thromboembolism.

    PubMed

    Horne, McDonald K; McCloskey, Donna Jo

    2006-01-01

    To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism. An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated. FVL is the most commonly recognized genetic trait associated with venous thrombosis. It is found predominantly in Caucasian populations. Biochemically it causes "activated protein C resistance (APCR)." The decision to test for FVL depends on whether the information gained will potentially improve the health care of the person or family. For people who have had deep venous thrombosis, testing for FVL will likely not alter treatment approaches. Currently the advantage for testing is primarily limited to asymptomatic family members who carry FVL and who have had deep vein thrombosis. Close relatives who also carry the mutated gene might benefit from prophylactic anticoagulation when their risk of thrombosis is increased by temporary factors such as surgery. Nurses are in a unique position to provide accurate information and counseling when patients and their family members are presented with the results of thrombophilia testing.

  16. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research.

    PubMed

    Husain, Sohail Z; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y; Schwarzenberg, Sarah J; Usatin, Danielle; Uc, Aliye

    2016-04-01

    Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies, and their rationale. We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: hyperlipidemia, hypercalcemia, chronic renal failure, smoking exposure, alcohol, and medications. Areas of additional research were identified. Hypertriglyceridemia of 1000 mg/dL or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end-stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and bystander status may be implicated. Other pancreatitis risk factors must be sought in all cases. The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children.

  17. Increased expression of connective tissue growth factor (CTGF) in multiple organs after exposure of non-human primates (NHP) to lethal doses of radiation

    PubMed Central

    Zhang, Pei; Cui, Wanchang; Hankey, Kim G.; Gibbs, Allison M.; Smith, Cassandra P.; Taylor-Howell, Cheryl; Kearney, Sean R.; MacVittie, Thomas J.

    2015-01-01

    Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP, and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition respectively, suggesting possible crosstalk between spleen and other organs. Our data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs. PMID:26425899

  18. Use of recombinant factor VII for tooth extractions in a patient with severe congenital factor VII deficiency: a case report.

    PubMed

    Weinstock, Robert J; Onyejiuwa, Andrew; Shnayder, Garry; Clarkson, Earl I

    2015-04-01

    Patients with factor VII deficiency have an increased risk of prolonged perioperative hemorrhage. In this article, the authors present a case of severe factor VII deficiency in a patient who required tooth extraction. A 44-year-old woman with severe congenital factor VII deficiency sought care for a symptomatic, carious, and nonrestorable maxillary right second molar that required extraction. The authors obtained hematologic consultation, and the patient underwent the extraction under general anesthesia in the inpatient setting. Perioperative management included performing relevant laboratory studies, preoperative recombinant factor VII infusion, and postoperative intravenous aminocaproic acid administration. No hemorrhagic complications occurred throughout the perioperative course. The degree of factor VII deficiency correlates poorly with bleeding risk. Perioperative management is variable, requiring preoperative consultation with a hematologist. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

  19. Including the Group Quarters Population in the US Synthesized Population Database

    PubMed Central

    Chasteen, Bernadette M.; Wheaton, William D.; Cooley, Philip C.; Ganapathi, Laxminarayana; Wagener, Diane K.

    2011-01-01

    In 2005, RTI International researchers developed methods to generate synthesized population data on US households for the US Synthesized Population Database. These data are used in agent-based modeling, which simulates large-scale social networks to test how changes in the behaviors of individuals affect the overall network. Group quarters are residences where individuals live in close proximity and interact frequently. Although the Synthesized Population Database represents the population living in households, data for the nation’s group quarters residents are not easily quantified because of US Census Bureau reporting methods designed to protect individuals’ privacy. Including group quarters population data can be an important factor in agent-based modeling because the number of residents and the frequency of their interactions are variables that directly affect modeling results. Particularly with infectious disease modeling, the increased frequency of agent interaction may increase the probability of infectious disease transmission between individuals and the probability of disease outbreaks. This report reviews our methods to synthesize data on group quarters residents to match US Census Bureau data. Our goal in developing the Group Quarters Population Database was to enable its use with RTI’s US Synthesized Population Database in the Modeling of Infectious Diseases Agent Study. PMID:21841972

  20. Risk factors increasing health hazards after air dives.

    PubMed

    Kaczerska, Dorota; Pleskacz, Katarzyna; Siermontowski, Piotr; Olszański, Romuald; Krefft, Karolina

    2015-01-01

    The aim of the present study was to determine the effect of postprandial hypertriglyceridemia on the risk of decompression stress following hyperbaric air exposures. The study involved 55 male individuals aged 20-48 years (31.47 ± 5.49 years), body mass index 20.3-33.2 kg/m2 (25.5 ± 2.58 kg/m2). Blood was sampled two hours after a meal each participant had in accordance with individual dietary preferences to determine the following parameters: blood cell counts, activity of aspartate aminotransferase (AST) and alanine ammotransterase (ALT), concentrations of total cholesterol and triglycerides. After each hyperbaric exposure, the presence and intensity of decompression stress were assessed using the Doppler method. Decompression stress was found in 30 individuals. Postprandial hypertriglyceridemia and hypercholesterolemia increased the risk of decompression stress after hyperbaric air exposures.

  1. Hiring and Retention: Key Factors in Increasing Gender Diversity in the Geosciences

    NASA Astrophysics Data System (ADS)

    Holmes, M.; O'Connell, S.; Frey, C.

    2004-12-01

    Graduation and hiring data of geoscientists over the last ten years indicate that the largest leak in the academic pipeline for women geoscientists is at hiring into tenure-track positions. Anecdotal explanations for this leak generally cite a lack of females in the applicant pool, but women in tenure-track positions anecdotally cite a lack of family-friendly practices by academic departments. Both ideas are currently being tested via surveys of geoscience departments. Is there a way to attract more women to the field to increase the applicant pool? Results of focus groups of geoscientists indicate that both men and women are attracted into the field of geosciences by the same types of events: over one-third became a geoscientist by randomly walking into an undergraduate class and finding themselves captivated by the topic and/or a dynamic instructor. The subject matter itself attracts another one-fourth, and family members encourage another one-fifth of geoscientists to initially enter the field. Slightly more women cite the first attractor of undergraduate class, but the principal draw for our future workforce, male and female, is good instruction of freshman courses. Retention of women in academia is another key issue. The proportion that considers leaving after working towards one or more degrees is highly skewed by gender: one-half of female and only one-third of male geoscientists considered leaving the field at some time in their career. The reasons for considering leaving also differ by gender. Males cite financial issues, including an uncertain job market. Females cite two principal reasons for considering leaving: family issues and difficulties with a graduate advisor. Strategies currently exist for "family issues", including stop-the-clock (of tenure for family needs), assignment shift, on-campus daycare facilities, and unflinching administrative support for such practices. Graduate advising is a learnable skill, and more attention needs to be paid to

  2. Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury‡

    PubMed Central

    Liang, Hongliang; Hou, Huiyuan; Yi, Wei; Yang, Guodong; Gu, Chunhu; Lau, Wayne Bond; Gao, Erhe; Ma, Xinliang; Lu, Zifan; Wei, Xufeng; Pei, Jianming; Yi, Dinghua

    2013-01-01

    Aims Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. Methods and results Reverse transcriptase–polymerized chain reaction  and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. Conclusions This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy. PMID:21606086

  3. Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection

    PubMed Central

    Venkataraman, Thiagarajan; Coleman, Christopher M.

    2017-01-01

    ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. PMID:28404843

  4. Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

    PubMed

    Venkataraman, Thiagarajan; Coleman, Christopher M; Frieman, Matthew B

    2017-06-15

    Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. Copyright © 2017 American Society for Microbiology.

  5. Factors that increase diagnostic yield of surgical lung biopsy in pediatric oncology patients.

    PubMed

    Acker, Shannon N; Gonzales, Danielle; Ross, James T; Dishop, Megan K; Deterding, Robin R; Partrick, David A

    2015-09-01

    Recent data demonstrate that surgical lung biopsy in immunocompromised children, including oncology patients, alters therapy in only 50% of cases. We hypothesized that there are factors identifiable preoperatively which can predict the patients who will or will not benefit from surgical biopsy. We reviewed the medical records of all children with malignancy who underwent surgical lung biopsy between 2004 and 2013 at a single institution, excluding those children who had previously undergone a solid organ or bone marrow transplant. Eighty lung wedge biopsies were performed (median age 13 years, IQR 5.25-16; 63% male, n=50) 53 (66%) of which led to a change in patient management. The majority of biopsies were performed to diagnose a new mass or differentiate infection from metastases (mass group) (n=68, 85%), and 12 biopsies (15%) were performed to diagnose a known infection for antibiotic guidance (infection group). Children in the infection group were more likely to be febrile preoperatively, were more likely to be an inpatient preoperatively, and had a lower absolute neutrophil count at the time of biopsy. Patients in the infection group had higher postoperative mortality rates and higher rates of major complications. In pediatric oncology patients, surgical lung biopsy has a lower diagnostic yield and higher complication rate when performed for antibiotic guidance. Prior to proceeding with biopsy in this high-risk patient population, surgeons and oncologists should carefully weigh the potential risks and benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Increased recombinant activated factor VII use and need for surgical reexploration following a switch from aprotinin to epsilon-aminocaproic acid in infant cardiac surgery.

    PubMed

    Scott, John P; Costigan, Daniel J; Hoffman, George M; Simpson, Pippa M; Dasgupta, Mahua; Punzalan, Rowena; Berens, Richard J; Tweddell, James S; Stuth, Eckehard A E

    2014-05-01

    To evaluate whether conversion from aprotinin to epsilon-aminocaproic acid (EACA) during infant cardiac surgery was associated with increased perioperative bleeding. Structured retrospective chart review. University-affiliated large congenital cardiac surgery program. Records from 145 infants (age < 1 yr) receiving aprotinin as antifibrinolytic therapy for cardiac surgery between 6/1/2006 and 12/31/2006 were compared with a cohort of infants receiving EACA for cardiac surgery between 6/1/2008 and 12/31/2008. Sixty-eight infants received aprotinin and 77 infants received EACA. Measured indicators of perioperative bleeding included transfusion volumes, recombinant activated clotting factor VIIa (rFVIIa) administration, need for reexploration, and perioperative chest tube output. EACA treated patients received significantly more rFVIIa for uncontrolled bleeding (19/77 [25%] vs 3/68 [4%]; P < 0.001) and required surgical reexploration more frequently (21/77 [27%] vs 7/68 [10%]; P = 0.01]. Median (25th-75th percentiles) intraoperative platelet transfusion requirements were also increased after the switch to EACA (28 mL [0-58 mL] vs 0 mL [0 mL - 34.5 mL]), but this difference did not reach statistical significance (P = 0.06). Bleeding in infant cardiac surgery increased following the change in antifibrinolytic therapy from aprotinin to EACA. Given the potential for major harm, especially thrombotic complications, from rFVIIa use, prospective studies examining the safety of postcardiopulmonary bypass rFVIIa administration in infants are necessary before the routine off-label use may be recommended. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells.

    PubMed

    Burdick, Andrew D; Davis, John W; Liu, Ke Jian; Hudson, Laurie G; Shi, Honglian; Monske, Michael L; Burchiel, Scott W

    2003-11-15

    Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are known mammary carcinogens in rodents and may be involved in human breast cancer. We have reported previously that BaP can mimic growth factor signaling and increase cell proliferation in primary human mammary epithelial cells and the human mammary epithelial cell line MCF-10A. BaP-quinones (BPQs) are important metabolites of BaP that have been associated with the production of reactive oxygen species. Using a model of epidermal growth factor (EGF) withdrawal in MCF-10A, we hypothesized that production of reactive oxygen species by BPQs could lead to the activation of the EGF receptor (EGFR). Here, we demonstrate through electron paramagnetic resonance spectroscopy and flow cytometry that 1,6-BPQ and 3,6-BPQ produce superoxide anion and hydrogen peroxide in MCF-10A cells. Furthermore, we show that BPQs increase EGFR, Akt, and extracellular signal-regulated kinase activity, leading to increased cell number in the absence of EGF. The BPQ-induced EGFR activity and associated cell proliferation were attenuated by the EGFR inhibitor AG1478, as well as by the antioxidant N-acetyl cysteine. Overexpression of catalase, but not Cu/Zn superoxide dismutase, reduced the extent of BPQ-dependent increased cell number and EGFR pathway activation. Moreover, the direct treatment of MCF-10A cells with hydrogen peroxide enhanced EGFR, Akt, and extracellular-regulated kinase phosphorylation that could be similarly inhibited by AG1478, N-acetyl cysteine, and catalase. Taken together, these data indicate that BPQs, through the generation of hydrogen peroxide, activate the EGFR in MCF-10A cells, leading to increased cell number under EGF-deficient conditions.

  8. Sources, factors, mechanisms and possible solutions to pollutants in marine ecosystems.

    PubMed

    Mostofa, Khan M G; Liu, Cong-Qiang; Vione, Davide; Gao, Kunshan; Ogawa, Hiroshi

    2013-11-01

    Algal toxins or red-tide toxins produced during algal blooms are naturally-derived toxic emerging contaminants (ECs) that may kill organisms, including humans, through contaminated fish or seafood. Other ECs produced either naturally or anthropogenically ultimately flow into marine waters. Pharmaceuticals are also an important pollution source, mostly due to overproduction and incorrect disposal. Ship breaking and recycle industries (SBRIs) can also release various pollutants and substantially deteriorate habitats and marine biodiversity. Overfishing is significantly increasing due to the global food crisis, caused by an increasing world population. Organic matter (OM) pollution and global warming (GW) are key factors that exacerbate these challenges (e.g. algal blooms), to which acidification in marine waters should be added as well. Sources, factors, mechanisms and possible remedial measures of these challenges to marine ecosystems are discussed, including their eventual impact on all forms of life including humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Moving beyond GPA: Alternative Measures of Success and Predictive Factors in Honors Programs

    ERIC Educational Resources Information Center

    Mould, Tom; DeLoach, Stephen B.

    2017-01-01

    While studies of predictive factors for success in honors have been increasingly creative and expansive on what these factors might include, they have rarely challenged the dominant, virtually monolithic definitions of success. The majority of studies measure success either by collegiate grade point averages (GPAs) or retention rates in honors,…

  10. Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

    PubMed Central

    Snow, Wanda M.; Pahlavan, Payam S.; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E.; Alashmali, Shoug; Bernstein, Michael J.; Suh, Miyoung; Albensi, Benedict C.

    2015-01-01

    Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory. PMID:26635523

  11. Increased optical contrast in imaging of epidermal growth factor receptor using magnetically actuated hybrid gold/iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Aaron, Jesse S.; Oh, Junghwan; Larson, Timothy A.; Kumar, Sonia; Milner, Thomas E.; Sokolov, Konstantin V.

    2006-12-01

    We describe a new approach for optical imaging that combines the advantages of molecularly targeted plasmonic nanoparticles and magnetic actuation. This combination is achieved through hybrid nanoparticles with an iron oxide core surrounded by a gold layer. The nanoparticles are targeted in-vitro to epidermal growth factor receptor, a common cancer biomarker. The gold portion resonantly scatters visible light giving a strong optical signal and the superparamagnetic core provides a means to externally modulate the optical signal. The combination of bright plasmon resonance scattering and magnetic actuation produces a dramatic increase in contrast in optical imaging of cells labeled with hybrid gold/iron oxide nanoparticles.

  12. Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study

    PubMed Central

    Millett, Elizabeth R C; De Stavola, Bianca L; Smeeth, Liam; Thomas, Sara L

    2015-01-01

    Objectives To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time. Design Cohort study. Setting Primary and secondary care in England. Population 39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011. Main outcome measures The association between hospitalisation within 28 days of CAP diagnosis (a ‘post-CAP’ hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period. Results 14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period. Conclusions The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and

  13. Fractures and the increased risk of suicide.

    PubMed

    Chang, C-F; Lai, E C-C; Yeh, M-K

    2018-06-01

    Aims A high rate of suicide has been reported in patients who sustain fractures, but the association remains uncertain in the context of other factors. The aim of this study was to examine the association between fractures and the risk of suicide in this contextual setting. Patients and Methods We performed a case-control study of patients aged 40 years or older who died by suicide between 2000 and 2011. We included patients' demographics, physical and mental health problems, and socioeconomic factors. We performed conditional logistic regression to evaluate the associations between fractures and the risk of suicide. Results We included a total of 34 794 patients who died by suicide and 139 176 control patients. We found that fractures as a homogenous group (adjusted odds ratios (aOR), 1.48; 95% confidence interval (CI) 1.43 to 1.53), and specifically pelvic (aOR 2.04; 95% CI 1.68 to 2.47) and spinal fractures (aOR 1.53; 95% CI 1.43 to 1.64), were associated with a higher risk of suicide. In addition, we found that patients who had a lower income, had never married, had lower levels of educational attainment, or had coexistent physical and mental conditions such as anxiety, mood disorders, and psychosis-related disorders had a higher risk of suicide. Conclusion Fractures, specifically those of the hip and spine, were associated with an increased risk of suicide. The findings suggest that greater clinical attention should be given to this risk in patients with fractures, especially for those with additional risk factors. Cite this article: Bone Joint J 2018;100-B:780-6.

  14. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    NASA Technical Reports Server (NTRS)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

  15. Are diseases increasing in the ocean?

    USGS Publications Warehouse

    Lafferty, Kevin D.; Porter, James W.; Ford, Susan E.

    2004-01-01

    Many factors (climate warming, pollution, harvesting, introduced species) can contribute to disease outbreaks in marine life. Concomitant increases in each of these makes it difficult to attribute recent changes in disease occurrence or severity to any one factor. For example, the increase in disease of Caribbean coral is postulated to be a result of climate change and introduction of terrestrial pathogens. Indirect evidence exists that (a) warming increased disease in turtles; (b) protection, pollution, and terrestrial pathogens increased mammal disease; (c) aquaculture increased disease in mollusks; and (d) release from overfished predators increased sea urchin disease. In contrast, fishing and pollution may have reduced disease in fishes. In other taxa (e.g., sea grasses, crustaceans, sharks), there is little evidence that disease has changed over time. The diversity of patterns suggests there are many ways that environmental change can interact with disease in the ocean.

  16. Is greater acculturation associated with an increased prevalence of cardiovascular risk factors among Latinos in South Florida?

    PubMed

    Chang, Aileen; Kenya, Sonjia; Ilangovan, Kumar; Li, Hua; Koru-Sengul, Tulay; Alonzo, Yisel; Carrasquillo, Olveen

    2015-05-01

    To examine the association of acculturation with various cardiovascular risk factors (CRFs) among Latinos with diabetes in South Florida. In a cross-sectional analysis of data collected from 300 Latinos with poorly controlled diabetes we measured acculturation using the Marin Short Acculturation Scale. We examined correlations between acculturation and the following 7 CRFs: hemoglobin A1C, low-density lipoprotein, systolic blood pressure, body mass index, smoking status, physical activity, and fruit and vegetable intake. Cubans made up 38% of our population; no other Latino subgroup represented over 17% of the sample. Of the 8 outcomes examined, only smoking was associated with increased acculturation; 12% of Latinos in the 2 lowest acculturation groups were current smokers versus 25% in the highest acculturation group (P=0.02). Furthermore, Cuban Americans from our sample had over double the prevalence of smoking compared with non-Cubans in both the lowest and highest acculturation groups. With the exception of smoking, our data does not support a link between increased acculturation and higher prevalence of CRFs in Latinos with diabetes. Smoking prevention and cessation programs targeting Latinos and particularly among Cubans are needed.

  17. Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity.

    PubMed

    Palmer, Kirsten R; Kaitu'u-Lino, Tu'uhevaha J; Hastie, Roxanne; Hannan, Natalie J; Ye, Louie; Binder, Natalie; Cannon, Ping; Tuohey, Laura; Johns, Terrance G; Shub, Alexis; Tong, Stephen

    2015-12-01

    In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal circulation, causing endothelial dysfunction and organ injury. A recently described splice variant, sFLT-1 e15a, is primate specific and the most abundant placentally derived sFLT-1. Therefore, it may be the major sFLT-1 isoform contributing to the pathophysiology of preeclampsia. sFLT-1 e15a protein remains poorly characterized: its bioactivity has not been comprehensively examined, and serum levels in normal and preeclamptic pregnancy have not been reported. We generated and validated an sFLT-1 e15a-specific ELISA to further characterize serum levels during pregnancy, and in the presence of preeclampsia. Furthermore, we performed assays to examine the bioactivity and antiangiogenic properties of sFLT-1 e15a protein. sFLT-1 e15a was expressed in the syncytiotrophoblast, and serum levels rose across pregnancy. Strikingly, serum levels were increased 10-fold in preterm preeclampsia compared with normotensive controls. We confirmed sFLT-1 e15a is bioactive and is able to inhibit vascular endothelial growth factor signaling of vascular endothelial growth factor receptor 2 and block downstream Akt phosphorylation. Furthermore, sFLT-1 e15a has antiangiogenic properties. sFLT-1 e15a decreased endothelial cell migration, invasion, and inhibited endothelial cell tube formation. Administering sFLT-1 e15a blocked vascular endothelial growth factor induced sprouts from mouse aortic rings ex vivo. We have demonstrated that sFLT-1 e15a is increased in preeclampsia, antagonizes vascular endothelial growth factor signaling, and has antiangiogenic activity. Future development of diagnostics and therapeutics for preeclampsia should consider targeting placentally derived sFLT-1 e15a. © 2015 American Heart Association, Inc.

  18. Validity of a questionnaire measuring motives for choosing foods including sustainable concerns.

    PubMed

    Sautron, Valérie; Péneau, Sandrine; Camilleri, Géraldine M; Muller, Laurent; Ruffieux, Bernard; Hercberg, Serge; Méjean, Caroline

    2015-04-01

    Since the 1990s, sustainability of diet has become an increasingly important concern for consumers. However, there is no validated multidimensional measurement of motivation in the choice of foods including a concern for sustainability currently available. In the present study, we developed a questionnaire that measures food choice motives during purchasing, and we tested its psychometric properties. The questionnaire included 104 items divided into four predefined dimensions (environmental, health and well-being, economic and miscellaneous). It was administered to 1000 randomly selected subjects participating in the Nutrinet-Santé cohort study. Among 637 responders, one-third found the questionnaire complex or too long, while one-quarter found it difficult to fill in. Its underlying structure was determined by exploratory factor analysis and then internally validated by confirmatory factor analysis. Reliability was also assessed by internal consistency of selected dimensions and test-retest repeatability. After selecting the most relevant items, first-order analysis highlighted nine main dimensions: labeled ethics and environment, local and traditional production, taste, price, environmental limitations, health, convenience, innovation and absence of contaminants. The model demonstrated excellent internal validity (adjusted goodness of fit index = 0.97; standardized root mean square residuals = 0.07) and satisfactory reliability (internal consistency = 0.96, test-retest repeatability coefficient ranged between 0.31 and 0.68 over a mean 4-week period). This study enabled precise identification of the various dimensions in food choice motives and proposed an original, internally valid tool applicable to large populations for assessing consumer food motivation during purchasing, particularly in terms of sustainability. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Aging in the Male Face: Intrinsic and Extrinsic Factors.

    PubMed

    Keaney, Terrence C

    2016-07-01

    Gender is one of the most significant factors that influence facial anatomy and behavior, both key factors in the aging process. To review male facial anatomy, physiology, and behavior and how it contributes to sexual dimorphism in facial aging. A MEDLINE search was performed for publications on gender differences in facial anatomy, aging, cutaneous physiology, and behavior. There are differences in both intrinsic and extrinsic aging factors in men. Men have a thicker epidermis and dermis with more active cutaneous appendages including hair growth. Male skin has a reduced antioxidant capacity and increased ultraviolet-induced immunosuppression. The male face is larger and has a unique square shape with less subcutaneous soft tissue, especially at the medial cheek. Men are also more prone to smoking and exhibiting poor sun-protective behavior. The differences in intrinsic and extrinsic aging factors contribute to poor facial aging in men. Men develop more severe rhytides in a unique pattern, show increased periocular aging changes, and are more prone to hair loss. This review provides insight into the factors contributing to accelerated male facial aging. Understanding gender differences in aging will help physicians tailor cosmetic treatments for men and minimize extrinsic aging factors.

  20. Health-related quality of life and hand eczema--a comparison of two instruments, including factor analysis.

    PubMed

    Wallenhammar, Lena-Marie; Nyfjäll, Mats; Lindberg, Magnus; Meding, Birgitta

    2004-06-01

    Hand eczema is a disease of long duration, affecting the individual and society. The purpose of this study of 100 patients (51 females and 49 males) at an occupational dermatology clinic was to investigate whether the generic questionnaire Short Form-36 (SF-36), and the dermatology-specific Dermatology Life Quality Index (DLQI) are appropriate for assessing health-related quality of life (HRQL) in patients with hand eczema, and whether gender differences in HRQL could be detected. HRQL was affected by hand eczema, measured with both SF-36 and DLQI. The SF-36 showed more impaired HRQL for females than for males, in the mental health dimension, whereas no gender-related differences were detected with the DLQI. To compare the instruments we used factor analysis, with a polychoric correlation matrix as input, thus taking the ordinal aspect of the data into account. There was a high correlation between the instruments for physical health, but lower for mental health. In this context our interpretation of the factor analysis is that the SF-36 measures mental health better than the DLQI. The SF-36 therefore appears suitable for use in future studies for measuring HRQL, and gender differences in HRQL, in persons with reported hand eczema.