tbuckley/cabot-search huggingface dataset:
Examining the Health Effects of Fructose
Authors: David S. Ludwig
Journal: JAMA (2013)

IN THE 1990S, EXCESSIVE FAT CONSUMPTION WAS COMmonly believed to be the main cause of obesity. High sugar consumption was often considered to be innocuous and possibly protective against obesity by displacing dietary fat. A decade later, the American Heart Association linked intake of added sugars to weight gain and recommended substantial decreases in consumption to a daily maximum of 100 kcal for women and 150 kcal for men. Some experts now argue that sugar comprises the single most important cause of the worldwide epidemics of obesity and diabetes, primarily through the effects of fructose at prevailing levels of consumption. This Viewpoint examines the physiological effects of common sugars and argues against a narrow public health focus on fructose.
Pre-Existing High Glucocorticoid Receptor Number Predicting Development of Posttraumatic Stress Symptoms After Military Deployment
Authors: Mirjam van Zuiden, Elbert Geuze, Hanneke L.D.M. Willemen, Eric Vermetten, Mirjam Maas, Cobi J. Heijnen, Annemieke Kavelaars
Journal: American Journal of Psychiatry (2010)

Objective: The development of posttraumatic stress disorder (PTSD) is influenced by preexisting vulnerability factors. The authors aimed at identifying a preexisting biomarker representing a vulnerability factor for the development of PTSD. To that end, they determined whether the dexamethasone binding capacity of leukocytes, as a measure of glucocorticoid receptor (GR) number, before exposure to trauma was a predictor of development of PTSD symptoms. In addition, the authors analyzed mRNA expression for GR subtypes and GR target genes. Method: Participants were selected from a large prospective study on deployment-related disorders, in which peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 and 6 months after military deployment. Participants included armed forces personnel with high levels of PTSD symptoms 6 months after deployment (N=34) and comparison subjects without high levels of PTSD or depressive symptoms (N=34) matched for age, rank, previous deployments, educational level, and function during deployment. Results: Before military deployment, the GR number in PBMCs was significantly higher in participants who developed high levels of PTSD symptoms after deployment relative to matched comparison subjects. Logistic regression analysis showed that the risk for inclusion in the PTSD group after deployment increased 7.5-fold with each GR increase of 1,000. No group differences were observed in mRNA expression of GR-α, GR-P, GR-β, glucocorticoid-induced leucine zipper (GILZ), serum and glucocorticoid-inducible kinase-1 (SGK-1), and FKBP5. The higher GR number in the PTSD group was maintained at 1 and 6 months after deployment. Conclusions: These results demonstrate that a preexisting high GR number in PBMCs is a vulnerability factor for subsequent development of PTSD symptoms.
Coffee Consumption and Risk of Stroke in Women
Authors: Esther Lopez-Garcia, Fernando Rodriguez-Artalejo, Kathryn M. Rexrode, Giancarlo Logroscino, Frank B. Hu, Rob M. van Dam
Journal: Circulation (2009)

Background— Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women. Methods and Results— We analyzed data from a prospective cohort of 83 076 women in the Nurses’ Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (&lt;1 cup per month, 1 per month to 4 per week, 5 to 7 per week, 2 to 3 per day, and ≥4 per day) were 1, 0.98 (95% CI, 0.84 to 1.15), 0.88 (95% CI, 0.77 to 1.02), 0.81 (95% CI, 0.70 to 0.95), and 0.80 (95% CI, 0.64 to 0.98) ( P for trend=0.003). After further adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the inverse association remained significant. The association was stronger among never and past smokers (RR for ≥4 cups a day versus &lt;1 cup a month, 0.57; 95% CI, 0.39 to 0.84) than among current smokers (RR for ≥4 cups a day versus &lt;1 cup a month, 0.97; 95% CI, 0.63 to 1.48). Other drinks containing caffeine such as tea and caffeinated soft drinks were not associated with stroke. Decaffeinated coffee was associated with a trend toward lower risk of stroke after adjustment for caffeinated coffee consumption (RR for ≥2 cups a day versus &lt;1 cup a month, 0.89; 95% CI, 0.73 to 1.08; P for trend=0.05). Conclusions— Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke.
THE BRITISH MEDICAL BENEVOLENT FUND
Authors: S. West
Journal: BMJ (1905)

CORRESPONDENCEt.rAPRIrz 20, 9Ig2.witlhin an endemic area, lhave occurred to my knowledge.Therefore, when it is said that lepers in this country do not communlicate the disease to others, it simply mneans tlley are not kniown to have done so.Possibly the two cases quoted may lhave been infected by intimate association with soma undiagnosed case infected by aln imported leper.At any rate, they cannot have arisen de novo.The idea that lepers taken out of an endemic area are nt dangerous is, I believe, largely due to the report that tlj-Norwegian lepers whlo emigrated to America did not spvead the disease.The recent increase of lepeosy in A,u3rica should make us cautious about accepting this Opinioin.. We do not know exactly hlow the disease is spread from pa sou to person.That it is spread from the sick to the sD md I have not the least'doubt.I lhave the accounts of
Maternal Glycemia and Risk of Large-for-Gestational-Age Babies in a Population-Based Screening
Authors: Zsuzsa Kerényi, Gyula Tamás, Mika Kivimäki, Andrea Péterfalvi, Eszter Madarász, Zsolt Bosnyák, Adam G. Tabák
Journal: Diabetes Care (2009)

OBJECTIVE Gestational diabetes is a risk factor for large-for-gestational-age (LGA) newborns, but many LGA babies are born to mothers with normal glucose tolerance. We aimed to clarify the association of maternal glycemia across the whole distribution with birth weight and risk of LGA births in mothers with normal glucose tolerance. RESEARCH DESIGN AND METHODS We undertook a population-based gestational diabetes screening in an urban area of Hungary in 2002–2005. All singleton pregnancies of mothers ≥18 years of age, without known diabetes or gestational diabetes (World Health Organization criteria) and data on a 75-g oral glucose tolerance test at 22–30 weeks of gestation, were included (n = 3,787, 78.9% of the target population). LGA was determined as birth weight greater than the 90th percentile using national sex- and gestational age–specific charts. RESULTS Mean ± SD maternal age was 30 ± 4 years, BMI was 22.6 ± 4.0 kg/m2, fasting blood glucose was 4.5 ± 0.5 mmol/l, and postload glucose was 5.5 ± 1.0 mmol/l. The mean birth weight was 3,450 ± 476 g at 39.2 ± 1.2 weeks of gestation. There was a U-shaped association of maternal fasting glucose with birth weight (Pcurve = 0.004) and risk of having an LGA baby (lowest values between 4 and 4.5 mmol/l, Pcurve = 0.0004) with little change after adjustments for clinical characteristics. The association of postload glucose with birth weight (P = 0.03) and the risk of an LGA baby (P = 0.09) was weaker and linear. CONCLUSIONS Both low and high fasting glucose values at 22–30 weeks of gestation are associated with increased risk of an LGA newborn. We suggest that the excess risk related to low glucose reflects the increased use of nutrients by LGA fetuses that also affects the mothers' fasting glucose.
Partial inhibition of the early and late asthmatic response by a single dose of salmeterol.
Authors: E J Weersink, R Aalbers, G H Koëter, H F Kauffman, J G De Monchy, D S Postma
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The long-acting beta 2-agonist salmeterol has been suggested to have other pharmacologic activities, that is, antiinflammatory capacities, in addition to its bronchodilator properties. We investigated the protective effect of 50 micrograms salmeterol in a placebo-controlled study on house dust mite-induced early- and late-phase reactions in 19 atopic asthmatic subjects. FEV1 and methacholine airway reactivity (AR) were measured. Eosinophils and their activation markers in peripheral blood were counted as indirect parameters of inflammation. Corrections were made for confounding of bronchodilator effects by salmeterol and the spontaneous diurnal variation, using saline inhalation as a control. Salmeterol completely inhibited the fall in FEV1 up to 10 h after the house dust mite challenge. Nevertheless, after correction, a biphasic response was present in the salmeterol group. Salmeterol protected against the allergen-associated increase in AR 3 h after the challenge, but no protection was observed after 24 h. Salmeterol did not inhibit the allergen-induced changes in total number of eosinophils and their activation markers in peripheral blood. These data suggest that a single dose of salmeterol modifies allergen-induced airway responses, above all by sustained bronchodilation.
Standardised PCR-based molecular epidemiology of tuberculosis
Authors: C. Allix-Béguec, P. Supply, M. Wanlin, P. Bifani, M. Fauville-Dufaux
Journal: European Respiratory Journal (2007)

A population-based molecular epidemiology investigation has been undertaken to evaluate tuberculosis transmission and control in the Brussels-Capital Region (Belgium). All tuberculosis cases reported from January 2003 to December 2004 were investigated. In total, 536 Mycobacterium tuberculosis isolates (89% of culture-positive samples) were genotyped by the newly standardised 24 loci-based mycobacterial interspersed repetitive unit-variable number tandem-repeat typing, spoligotyping and IS6110 fingerprinting. Of all the patients, 30% were grouped based on strain clusters, suggesting a transmission index of 20%. An unsuspected outbreak entailing > or = 23 patients was evidenced by molecular typing analysis and confirmed by contact tracing. Foreign-born status accounted for 79% of the studied patients, including 37.9% illegal immigrants and asylum seekers. Among foreign-born patients, asylum seekers and illegal immigrants were significantly less abundant in strain clusters than settled residents. Tuberculosis in the Brussels-Capital Region is a bi-faceted problem, comprising both persisting recent transmission and "imported diseases". Molecular epidemiology based on real-time genotyping techniques has proven invaluable in better understanding tuberculosis transmission. However, it will most efficiently contribute to tuberculosis control when implemented in an integrated public health system.
Pressure-overload-induced heart failure induces a selective reduction in glucose oxidation at physiological afterload
Authors: Pavel Zhabyeyev, Manoj Gandhi, Jun Mori, Ratnadeep Basu, Zamaneh Kassiri, Alexander Clanachan, Gary D. Lopaschuk, Gavin Y. Oudit
Journal: Cardiovascular Research (2012)

Development of heart failure is known to be associated with changes in energy substrate metabolism. Information on the changes in energy substrate metabolism that occur in heart failure is limited and results vary depending on the methods employed. Our aim is to characterize the changes in energy substrate metabolism associated with pressure overload and ischaemia–reperfusion (I/R) injury. We used transverse aortic constriction (TAC) in mice to induce pressure overload-induced heart failure. Metabolic rates were measured in isolated working hearts perfused at physiological afterload (80 mmHg) using 3H- or 14C-labelled substrates. As a result of pressure-overload injury, murine hearts exhibited: (i) hypertrophy, systolic, and diastolic dysfunctions; (ii) reduction in LV work, (iii) reduced rates of glucose and lactate oxidations, with no change in glycolysis or fatty acid oxidation and a small decrease in triacylglycerol oxidation, and (iv) increased phosphorylation of AMPK and a reduction in malonyl-CoA levels. Sham hearts produced more acetyl CoA from carbohydrates than from fats, whereas TAC hearts showed a reverse trend. I/R in sham group produced a metabolic switch analogous to the TAC-induced shift to fatty acid oxidation, whereas I/R in TAC hearts greatly exacerbated the existing imbalance, and was associated with a poorer recovery during reperfusion. Pressure overload-induced heart failure and I/R shift the preference of substrate oxidation from glucose and lactate to fatty acid due to a selective reduction in carbohydrate oxidation. Normalizing the balance between metabolic substrate utilization may alleviate pressure-overload-induced heart failure and ischaemia.
Genetics of Ischaemic Stroke among Persons of Non-European Descent: A Meta-Analysis of Eight Genes Involving ∼ 32,500 Individuals
Authors: Roshan Ariyaratnam, Juan P Casas, John Whittaker, Liam Smeeth, Aroon D Hingorani, Pankaj Sharma
Journal: PLoS Medicine (2007)

Ischaemic stroke in persons of European descent has a genetic basis, but whether the stroke-susceptibility alleles, the strength of any association, and the extent of their attributable risks are the same in persons of non-European descent remains unanswered. Whether ethnicity itself has a relevant or substantial contribution on those effect estimates is controversial. Comparative analyses between the ethnic groups may allow general conclusions to be drawn about polygenic disorders.We performed a literature-based systematic review of genetic association studies in stroke in persons of non-European descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for each gene-disease association using fixed and random effect models. We further performed a comparative genetic analysis across the different ethnic groups (including persons of European descent derived from our previous meta-analysis) to determine if genetic risks varied by ethnicity. Following a review of 500 manuscripts, eight candidate gene variants were analysed among 32,431 individuals (12,883 cases and 19,548 controls), comprising mainly Chinese, Japanese, and Korean individuals. Of the eight candidate genes studied, three were associated with ischaemic stroke: the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism with a mean OR of 1.90 (95% CI 1.23-2.93) in the Chinese and 1.74 (95% CI 0.88-3.42) in the Japanese; the summary OR for the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) was 1.18 (95% CI 0.90-1.56) in Chinese and 1.34 (95% CI 0.87-2.06) in Koreans; and the pooled OR for the apolipoprotein E (APOE) gene was 2.18 (95% CI 1.52-3.13) in Chinese and 1.51 (95% CI 0.93-2.45) in Japanese. Comparing the commonly investigated stroke genes among the Asian groups against studies in persons of European descent, we found an absence of any substantial qualitative or quantitative interaction for ORs by ethnicity. However, the number of individuals recruited per study in the studies of persons of non-European descent was significantly smaller compared to studies of persons of European descent, despite a similar number of studies conducted per gene.These data suggest that genetic associations studied to date for ischaemic stroke among persons of non-European descent are similar to those for persons of European descent. Claims of differences in genetic effects among different ethnic populations for complex disorders such as stroke may be overstated. However, due to the limited number of gene variants evaluated, the relatively smaller number of individuals included in the meta-analyses of persons of non-European descent in stroke, and the possibility of publication bias, the existence of allele variants with differential effects by ethnicity cannot be excluded.
Family-based genetic risk prediction of multifactorial disease
Authors: Douglas M Ruderfer, Joshua Korn, Shaun M Purcell
Journal: Genome Medicine (2010)

Genome-wide association studies have detected dozens of variants underlying complex diseases, although it is uncertain how often these discoveries will translate into clinically useful predictors. Here, to improve genetic risk prediction, we consider including phenotypic and genotypic information from related individuals. We develop and evaluate a family-based liability-threshold prediction model and apply it to a simulation of known Crohn's disease risk variants. We show that genotypes of a relative of known phenotype can be informative for an individual's disease risk, over and above the same locus genotyped in the individual. This approach can lead to better-calibrated estimates of disease risk, although the overall benefit for prediction is typically only very modest.
Specificity of HLA class I antigen recognition by human NK clones: evidence for clonal heterogeneity, protection by self and non-self alleles, and influence of the target cell type.
Authors: V Litwin, J Gumperz, P Parham, J H Phillips, L L Lanier
Journal: The Journal of Experimental Medicine (1993)

Prior studies using polyclonal populations of natural killer (NK) cells have revealed that expression of certain major histocompatibility complex (MHC) class I molecules on the membrane of normal and transformed hematopoietic target cells can prevent NK cell-mediated cytotoxicity. However, the extent of clonal heterogeneity within the NK cell population and the effect of self versus non-self MHC alleles has not been clearly established. In the present study, we have generated more than 200 independently derived human NK cell clones from four individuals of known human histocompatibility leukocyte antigens (HLA) type. NK clones were analyzed for cytolytic activity against MHC class I-deficient Epstein Barr virus (EBV) transformed B lymphoblastoid cell lines (B-LCL) stably transfected with several HLA-A, -B, or -C genes representing either self or non-self alleles. All NK clones killed the prototypic HLA-negative erythroleukemia K562 and most lysed the MHC class I-deficient C1R and 721.221 B-LCL. Analysis of the panel of HLA-A, -B, and -C transfectants supported the following general conclusions. (a) Whereas recent studies have suggested that HLA-C antigens may be preferentially recognized by NK cells, our findings indicate that 70% or more of all NK clones are able to recognize certain HLA-B alleles and many also recognize HLA-A alleles. Moreover, a single NK clone has the potential to recognize multiple alleles of HLA-A, HLA-B, and HLA-C antigens. Thus, HLA-C is not unique in conferring protection against NK lysis. (b) No simple patterns of HLA specificity emerged. Examination of a large number of NK clones from a single donor revealed overlapping, yet distinct, patterns of reactivity when a sufficiently broad panel of HLA transfectants was examined. (c) Both autologous and allogeneic HLA antigens were recognized by NK clones. There was neither evidence for deletion of NK clones reactive with self alleles nor any indication for an increased frequency of NK clones recognizing self alleles. (d) With only a few exceptions, protection conferred by transfection of HLA alleles into B-LCL was usually not absolute. Rather a continuum from essentially no protection for certain alleles (HLA-A*0201) to very striking protection for other alleles (HLA-B*5801), with a wide range of intermediate effects, was observed. (e) Whereas most NK clones retained a relatively stable HLA specificity, some NK clones demonstrated variable and heterogeneous activity over time. (f) NK cell recognition and specificity cannot be explained entirely by the presence or absence of HLA class I antigens on the target cell.(ABSTRACT TRUNCATED AT 400 WORDS)
Correlations Among Amino Acid Sites in bHLH Protein Domains: An Information Theoretic Analysis
Authors: William R. Atchley, Kurt R. Wollenberg, Walter M. Fitch, Werner Terhalle, Andreas W. Dress
Journal: Molecular Biology and Evolution (2000)

An information theoretic approach is used to examine the magnitude and origin of associations among amino acid sites in the basic helix-loop-helix (bHLH) family of transcription factors. Entropy and mutual information values are used to summarize the variability and covariability of amino acids comprising the bHLH domain for 242 sequences. When these quantitative measures are integrated with crystal structure data and summarized using helical wheels, they provide important insights into the evolution of three-dimensional structure in these proteins. We show that amino acid sites in the bHLH domain known to pack against each other have very low entropy values, indicating little residue diversity at these contact sites. Noncontact sites, on the other hand, exhibit significantly larger entropy values, as well as statistically significant levels of mutual information or association among sites. High levels of mutual information indicate significant amounts of intercorrelation among amino acid residues at these various sites. Using computer simulations based on a parametric bootstrap procedure, we are able to partition the observed covariation among various amino acid sites into that arising from phylogenetic (common ancestry) and stochastic causes and those resulting from structural and functional constraints. These results show that a significant amount of the observed covariation among amino acid sites is due to structural/functional constraints, over and above the covariation arising from phylogenetic constraints. These quantitative analyses provide a highly integrated evolutionary picture of the multidimensional dynamics of sequence diversity and protein structure.
Sexual Dysfunction in Jordanian Diabetic Women
Authors: Ruba M. Abu Ali, Rabaa M. Al Hajeri, Yousef S. Khader, Nadima S. Shegem, Kamel M. Ajlouni
Journal: Diabetes Care (2008)

OBJECTIVE—To estimate the prevalence of female sexual dysfunction (FSD) in diabetic and nondiabetic Jordanian women. RESEARCH DESIGN AND METHODS—Data were collected from 1,137 married women using the Arabic translation of the Female Sexual Function Index questionnaire. RESULTS—Prevalence of sexual dysfunction in diabetic women 50 years of age or older was 59.6 vs. 45.6% in nondiabetic women (P = 0.003). Diabetic women had more dysfunction of desire, arousal, lubrication, and orgasm than nondiabetic women. Glycemic control, smoking, dyslipidemia, hypertension, autonomic neuropathy, and peripheral neuropathy did not have a significant effect on FSD. Age, BMI, duration of diabetes, and the presence of coronary artery disease, nephropathy, and retinopathy had negative effects on FSD. CONCLUSIONS—Prevalence of FSD among Jordanian women was found to be significantly higher in diabetic compared with nondiabetic women.
Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia
Authors: Yitang Li, Yonghui Jia, Muriel Pichavant, Fabien Loison, Bara Sarraj, Anongnard Kasorn, Jian You, Bryanne E. Robson, Dale T. Umetsu, Joseph P. Mizgerd, Keqiang Ye, Hongbo R. Luo
Journal: Blood (2009)