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1.
Castillo-Trivino T Mowry EM Gajofatto A Chabas D Crabtree-Hartman E Cree BA Goodin DS Green AJ Okuda DT Pelletier D Zamvil SS Vittinghoff E Waubant E 《PloS one》2011,6(2):e16664
Background
Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown.Methods
This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch.Results
In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004).Conclusions
Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies. 相似文献2.
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Background
Multiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.Methods/Principal Findings
We performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35–1.63, p<10−15; non-conservative: RR 1.52, 95% CI 1.39–1.66, p<10−19). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98–3.61, p = 0.06).Discussion
Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors. 相似文献4.
Context
On May12th 2008, a devastating earthquake measuring 8.0 on the Richter scale, struck Wenchuan county and surrounding areas in China. The prevalence of mental illness among children and adolescents in a rural town far from the earthquake epicenter is unknown.Objective
To assess the prevalence of posttraumatic stress disorder (PTSD) and depression among junior middle school students in a rural town Ningqiang county, 327 km from the earthquake epicenter.Design, Setting, and Participants
A population-based mental health survey was conducted in March, 2009.Main Outcome Measure
Survey Self-designed General Condition Survey Scale, Children''s Revised Impact of Event Scale (CRIES-13), and the Depression Self-rating Scale for Children (DSRSC) were used to sample 1,841 junior middle school students in Ningqiang county, ten months after the Wenchuan earthquake.Results
The prevalence rate of a high-risk for PTSD was 28.4%, with 32.7% among females, 23.8% among males (female vs. male, p<0.001), 38.6% in the severe exposure group and 24.3% in the mild exposure group (severe vs. mild exposure, p<0.001). For depressive symptoms, the overall prevalence was 19.5%, with 24.0% among females, 14.7% among males, 24.5% in the severe exposure group and 17.5% in the mild exposure group (female vs. male, p<0.001; severe vs. mild exposure, p<0.001, respectively). In multivariate analysis, factors such as “having felt despair”, or “danger” and “having own house destroyed or damaged” were significantly associated with PTSD symptoms. Female gender and delayed evacuation in females, and earthquake related experiences in males were significantly associated with depression.Conclusion
Traumatic events experienced during the earthquake were significantly associated with symptoms of PTSD and depression in children and adolescents, ten months after the Wenchuan earthquake. These data highlight a need for mental health services for children and adolescents in rural areas, far from earthquake epicenters. 相似文献5.
Madec Y Germanaud D Moya-Alvarez V Alkassoum W Issa A Amadou M Tchiombiano S Pizzocolo C Huber F Diallo S Abdoulaye-Mamadou R 《PloS one》2011,6(7):e22787
Background
In developing countries, malnutrition is a contributing factor in over 50% of child deaths. Mortality rates are higher in underweight children, and HIV-infection is known to increase underweight. Our goals were to evaluate the prevalence of HIV among children hospitalised for severe malnutrition (SM) at the Niamey national hospital (Niger), and to compare renutrition and mortality by HIV-status.Methods
Retrospective study based on all children <5 years hospitalised for SM between January 1st 2008 and July 1st 2009. HIV-prevalence was the ratio of HIV+ children on the number of children tested. Duration of renutrition and mortality were described using survival curves.Results
During the study period, 477 children were hospitalised for SM. HIV testing was accepted in 470 (98.5%), of which 40 were HIV+ (HIV prevalence (95% confidence interval) of 8.6% (6.2–11.5)). Duration of renutrition was longer in HIV+ than HIV− children (mean: 22 vs. 15 days; p = 0.003). During renutrition, 8 (20%) and 61 (14%) HIV+ and HIV− children died, respectively (p = 0.81).Conclusion
Around 9% of children hospitalised for severe malnutrition were HIV infected, while in Niger HIV prevalence in adults is estimated at 0.8%. This pleads for wider access to HIV testing in this population. 相似文献6.
Xie P Kamei M Suzuki M Matsumura N Nishida K Sakimoto S Sakaguchi H Nishida K 《PloS one》2011,6(12):e28933
Purpose
To investigate the effect of an intravitreally administered CCR2 antagonist, INCB3344, on a mouse model of choroidal neovascularization (CNV).Methods
CNV was induced by laser photocoagulation on Day 0 in wild type mice. INCB3344 or vehicle was administered intravitreally immediately after laser application. On Day 14, CNV areas were measured on retinal pigment epithelium (RPE)-choroid flat mounts and histopathologic examination was performed on 7 µm-thick sections. Macrophage infiltration was evaluated by immunohistochemistry on RPE-choroid flat mounts and quantified by flow cytometry on Day 3. Expression of vascular endothelial growth factor (VEGF) protein in RPE-choroid tissue was examined by immunohistochemistry and ELISA, VEGF mRNA in sorted macrophages in RPE-choroid tissue was examine by real-time PCR and expression of phosphorylated extracellular signal-regulated kinase (p-ERK 1/2) in RPE-choroid tissue was measured by Western blot analysis on Day 3. We also evaluated the efficacy of intravitreal INCB3344 to spontaneous CNV detected in Cu, Zn-superoxide dismutase (SOD1) deficient mice. Changes in CNV size were assessed between pre- and 1week post-INCB3344 or vehicle administration in fundus photography and fluorescence angiography (FA).Results
The mean CNV area in INCB3344-treated mice decreased by 42.4% compared with the vehicle-treated control mice (p<0.001). INCB3344 treatment significantly inhibited macrophage infiltration into the laser-irradiated area (p<0.001), and suppressed the expression of VEGF protein (p = 0.012), VEGF mRNA in infiltrating macrophages (p<0.001) and the phosphorylation of ERK1/2 (p<0.001). The area of spontaneous CNV in Sod1 −/− mice regressed by 70.35% in INCB3344-treated animals while no change was detected in vehicle-treated control mice (p<0.001).Conclusions
INCB3344 both inhibits newly forming CNV and regresses established CNV. Controlling inflammation by suppressing macrophage infiltration and angiogenic ability via the CCR-2/MCP-1 signal may be a useful therapeutic strategy for treating CNV associated with age-related macular degeneration. 相似文献7.
Gkrania-Klotsas E Ye Z Cooper AJ Sharp SJ Luben R Biggs ML Chen LK Gokulakrishnan K Hanefeld M Ingelsson E Lai WA Lin SY Lind L Lohsoonthorn V Mohan V Muscari A Nilsson G Ohrvik J Chao Qiang J Jenny NS Tamakoshi K Temelkova-Kurktschiev T Wang YY Yajnik CS Zoli M Khaw KT Forouhi NG Wareham NJ Langenberg C 《PloS one》2010,5(10):e13405
Objective
Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and Methods
Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.Results
The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10−18). Substantial heterogeneity was present (I2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10−4), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10−13), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10−5). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.Conclusions
A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate. 相似文献8.
Sharp ER Willberg CB Kuebler PJ Abadi J Fennelly GJ Dobroszycki J Wiznia AA Rosenberg MG Nixon DF 《PloS one》2012,7(1):e29154
Background
In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied.Methodology/Principal Findings
We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA−) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells compared to slow progressing subjects (p<0.0001).Conclusions/Significance
Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells. 相似文献9.
De Stefano N Stromillo ML Rossi F Battaglini M Giorgio A Portaccio E Hakiki B Malentacchi G Gasperini C Santangelo M Bartolozzi ML Sormani MP Federico A Amato MP 《PloS one》2011,6(4):e19452
Objective
To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities highly suggestive of multiple sclerosis (MS), a condition named as “radiologically isolated syndrome” (RIS).Methods
Quantitative MRI metrics such as brain volumes and magnetization transfer (MT) were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS) patients and 20 healthy controls (HC). Specific measures were: white matter (WM) lesion volumes (LV), total and regional brain volumes, and MT ratio (MTr) in lesions, normal-appearing WM (NAWM) and cortex.Results
LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001). Lesional-MTr was lower in RRMS than in RIS (p = 0.048); NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01) in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values.Conclusions
Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS. 相似文献10.
Glas J Seiderer J Tillack C Pfennig S Beigel F Jürgens M Olszak T Laubender RP Weidinger M Müller-Myhsok B Göke B Ochsenkühn T Lohse P Diegelmann J Czamara D Brand S 《PloS one》2010,5(12):e14466
Background
The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences.Methodology/Principal Findings
Genomic DNA from 2700 Caucasians including 812 patients with Crohn''s disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10−5, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10−6; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values <10−10. The SNPs rs2066843 and rs2076756 were in linkage disequilibrium with each other and with the three main CD-associated NOD2 mutations (D''>0.9). However, in CD, SNPs rs2066843 and rs2076756 were more frequently observed than the other three common NOD2 mutations (minor allele frequencies for rs2066843 and rs2076756: 0.390 and 0.380, respectively). In CD patients homozygous for these novel NOD2 variants, genotype-phenotype analysis revealed higher rates of a penetrating phenotype (rs2076756: p = 0.015) and fistulas (rs2076756: p = 0.015) and significant associations with CD-related surgery (rs2076756: p = 0.003; rs2066843: p = 0.015). However, in multivariate analysis only disease localization (p<2×10−16) and behaviour (p = 0.02) were significantly associated with the need for surgery.Conclusion/Significance
The NOD2 variants rs2066843 and rs2076756 are novel and common CD susceptibility gene variants. 相似文献11.
Background
Chagas'' disease is an important neglected public health problem in many Latin American countries, but population-based epidemiological data are scarce. Here we present a nationwide analysis on Chagas-associated mortality, and risk factors for death from this disease.Methodology/Principal Findings
We analyzed all death certificates of individuals who died between 1999 and 2007 in Brazil, based on the nationwide Mortality Information System (a total of 243 data sets with about 9 million entries). Chagas'' disease was mentioned in 53,930 (0.6%) of death certificates, with 44,537 (82.6%) as an underlying cause and 9,387 (17.4%) as an associated cause of death. Acute Chagas'' disease was responsible for 2.8% of deaths. The mean standardized mortality rate was 3.36/100.000 inhabitants/year. Nationwide standardized mortality rates reduced gradually, from 3.78 (1999) to 2.78 (2007) deaths/year per 100,000 inhabitants (−26.4%). Standardized mortality rates were highest in the Central-West region, ranging from 15.23 in 1999 to 9.46 in 2007 (−37.9%), with a significant negative linear trend (p = 0.001; R2 = 82%). Proportional mortality considering multiple causes of death was 0.60%. The Central-West showed highest proportional mortality among regions (2.17%), with a significant linear negative trend, from 2.28% to 1.90% (−19.5%; p = 0.001; R2 = 84%). There was a significant increase in the Northeast of 38.5% (p = 0.006; R2 = 82%). Bivariable analysis on risk factors for death from Chagas'' disease showed highest relative risks (RR) in older age groups (RR: 10.03; 95% CI: 9.40–10.70; p<0.001) and those residing in the Central-West region (RR: 15.01; 95% CI: 3.90–16.22; p<0.001). In logistic regression analysis, age ≥30 years (adjusted OR: 10.81; 95% CI: 10.03–10.65; p<0.001) and residence in one of the three high risk states Minas Gerais, Goiás or the Federal District (adjusted OR: 5.12; 95% CI: 5.03–5.22, p<0.001) maintained important independent risk factors for death by Chagas'' disease.Conclusions/Significance
This is the first nationwide population-based study on Chagas mortality in Brazil, considering multiple causes of death. Despite the decline of mortality associated with Chagas'' disease in Brazil, the disease remains a serious public health problem with marked regional differences. 相似文献12.
Jankowska EA Filippatos GS von Haehling S Papassotiriou J Morgenthaler NG Cicoira M Schefold JC Rozentryt P Ponikowska B Doehner W Banasiak W Hartmann O Struck J Bergmann A Anker SD Ponikowski P 《PloS one》2011,6(1):e14506
Objectives
We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).Methods
We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology). Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.Results
Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04–1.95, p = 0.03) after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).Conclusions
Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes. 相似文献13.
N Kalema SD Boon A Cattamanchi JL Davis A Andama W Katagira C Everett N Walter P Byanyima S Kaswabuli W Worodria L Huang 《PloS one》2012,7(7):e38888
Rationale
Contamination by bacterial or fungal organisms reduces the effectiveness of mycobacterial culture for diagnosis of pulmonary tuberculosis (TB). We evaluated the effect of an anti-microbial and an anti-fungal oral rinse prior to expectoration on culture-contamination rates.Methods
We enrolled a consecutive random sample of adults with cough for ≥2 weeks and suspected TB admitted to Mulago Hospital (Kampala, Uganda) between October 2008 and June 2009. We randomly assigned patients to oral rinse (60 seconds with chlorhexidine followed by 60 seconds with nystatin) vs. no oral rinse prior to initial sputum collection. Uganda National Tuberculosis Reference Laboratory technicians blinded to the method of sputum collection (with or without oral rinse) processed all sputum specimens for smear microscopy (direct Ziehl-Neelsen) and mycobacterial culture (Lowenstein-Jensen media).Results
Of 220 patients enrolled, 177 (80%) were HIV-seropositive (median CD4-count 37 cells/uL, IQR 13–171 cells/uL). Baseline characteristics were similar between patients in the oral-rinse (N = 110) and no oral-rinse (N = 110) groups. The proportion of contaminated cultures was significantly lower in the oral-rinse group compared to the no oral-rinse group (4% vs. 15%, risk difference −11%, 95% CI −18 to −3%, p = 0.005). Oral rinse significantly reduced the proportion of contaminated cultures among HIV-infected patients (3% vs. 18%, risk difference −14%, 95% CI −23 to −6%, p = 0.002) but not HIV-uninfected (6% vs. 4%, risk difference 2%, 95% CI −12 to +15%, p = 0.81) patients. However, the proportion of smear-positive specimens (25% vs. 35%, p = 0.10) and culture-positive specimens (48% vs. 56%, p = 0.24) were lower in the oral-rinse compared to the no oral-rinse group, although the differences were not statistically significant.Conclusions
Oral rinse prior to sputum expectoration is a promising strategy to reduce mycobacterial culture contamination in areas with high HIV prevalence, if strategies can be devised to reduce the adverse impact of oral rinse on smear- and culture-positivity. 相似文献14.
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Background
Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Methodology and Principal Findings
Body composition and metabolic risk were assessed in 2,249 men, aged 17–19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Δ = −0.25, 95%CI −0.35, −0.15,p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Δ = 0.39, 95%CI 0.28–0.50, p<0.0001) and had greater mean height (Δ = 1.2 cm, 95%CI: 0.7–1.6, p<0.0001) and weight (Δ = 0.34 kg, 95%CI: 0.13–0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.Conclusions/Significance
First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors. 相似文献17.
Ivan M��ller Jean T. Coulibaly Thomas F��rst Stefanie Knopp Jan Hattendorf Stefanie J. Krauth Katarina Stete Aur��lie A. Righetti Dominik Glinz Adrien K. Yao Uwe P��hse Eli��zer K. N'Goran J��rg Utzinger 《PLoS neglected tropical diseases》2011,5(7)
Background
Schistosomiasis and soil-transmitted helminthiasis are important public health problems in sub-Saharan Africa causing malnutrition, anemia, and retardation of physical and cognitive development. However, the effect of these diseases on physical fitness remains to be determined.Methodology
We investigated the relationship between schistosomiasis, soil-transmitted helminthiasis and physical performance of children, controlling for potential confounding of Plasmodium spp. infections and environmental parameters (i.e., ambient air temperature and humidity). A cross-sectional survey was carried out among 156 school children aged 7–15 years from Côte d''Ivoire. Each child had two stool and two urine samples examined for helminth eggs by microscopy. Additionally, children underwent a clinical examination, were tested for Plasmodium spp. infection with a rapid diagnostic test, and performed a maximal multistage 20 m shuttle run test to assess their maximal oxygen uptake (VO2 max) as a proxy for physical fitness.Principal Findings
The prevalence of Schistosoma haematobium, Plasmodium spp., Schistosoma mansoni, hookworm and Ascaris lumbricoides infections was 85.3%, 71.2%, 53.8%, 13.5% and 1.3%, respectively. Children with single, dual, triple, quadruple and quintuple species infections showed VO2 max of 52.7, 53.1, 52.2, 52.6 and 55.6 ml kg−1 min−1, respectively. The VO2 max of children with no parasite infections was 53.5 ml kg−1 min−1. No statistically significant difference was detected between any groups. Multivariable analysis revealed that VO2 max was influenced by sex (reference: female, coef. = 4.02, p<0.001) and age (years, coef. = −1.23, p<0.001), but not by helminth infection and intensity, Plasmodium spp. infection, and environmental parameters.Conclusion/Significance
School-aged children in Côte d''Ivoire showed good physical fitness, irrespective of their helminth infection status. Future studies on children''s physical fitness in settings where helminthiasis and malaria co-exist should include pre- and post-intervention evaluations and the measurement of hemoglobin and hematocrit levels and nutritional parameters as potential co-factors to determine whether interventions further improve upon fitness. 相似文献18.
Background
Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.Methods
We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women''s Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10−8 as significant.Results
Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10−6. Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15–12.90; p = 2.7×10−7) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66–9.62; p = 7.7×10−7) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR = 3.05; 95% CI 1.98–4.69; p = 4.3×10−7), and the intergenic rs1406961 with CVD death (OR = 12.33; 95% CI 4.62–32.87; p = 5.2×10−7). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR = 4.67; 95% CI 2.53–8.62; p = 8.0×10−7).Conclusion
Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research. 相似文献19.
Background
Alternate day calorie restriction (CR) has been shown to be almost as beneficial as daily CR. The question arises whether this concept is also applicable to alternating dietary composition.Objective
To seek evidence that alternating high cholesterol (HC) - cholesterol-free (CON) Western diet can effectively diminish hepatic and renal inflammation and cardiovascular risk factors as compared with daily HC-supplemented Western diet.Design
Four groups of ApoE*3Leiden mice, a humanized model for atherosclerosis, were subjected to different feeding treatments for 16 weeks. Mice were fed CON diet; CON diet with 1% w/w cholesterol (HC); alternate (ALT) diet regimen of CON (4 days) and HC (3 days); or CON diet supplemented with 0.43% (w/w) cholesterol (MC), with overall dietary cholesterol intake equal to ALT. Plasma was analyzed for cardiovascular risk factors, aorta for atherosclerotic lesion formation, and liver and kidney for inflammation.Results
ALT diet but not MC was almost as effective as daily CON feeding in preventing disease development. Compared to HC, the ALT group showed 62% lower hepatic nuclear factor kappa B (NF-κB) activity (P<0.001), a reduction of the circulating inflammatory markers E-selectin (−20%; P<0.05), vascular cell adhesion molecule 1 (VCAM-1; −15%; P<0.05) and Serum Amyloid A (SAA; −31%; P<0.05), smaller atherosclerotic lesion sizes (−51%; 46497±10791 µm2 vs. 94664±16470 µm2; P<0.05) and diminished renal expression of specific inflammation and activation markers (VCAM-1, −27%; P<0.05; monocyte chemotactic protein-1 (MCP-1); −37%; P<0.01).Conclusion
Alternate HC-CON feeding reproduced most of the beneficial effects of daily cholesterol-free diet, including strongly diminished hepatic, vascular and renal activation and inflammation; also atherosclerosis was reduced by half as compared to HC, albeit still higher compared to the CON group. 相似文献20.