Body adiposity in later life and the incidence of dementia: the health in men study

Objective

To determine if adiposity in later life increases dementia hazard.

Methods

Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease.

Results

Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR.

Conclusions

Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.     

HURP expression-assisted risk scores identify prognosis distinguishable subgroups in early stage liver cancer

Background

Hepatoma up-regulated protein (HURP) is a component of the chromatin-dependent pathway for spindle assembly. We examined the prognostic predictive value of HURP in human hepatocellular carcinoma (HCC).

Methods

HURP expression was evaluated by immunocytochemistry of fine needle aspirated hepatoma cells in 97 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage A. Subsequently, these patients underwent partial hepatectomy (n = 18) or radiofrequency ablation (n = 79) and were followed for 2 to 35 months. The clinicopathological parameters were submitted for survival analysis.

Results

HURP expression in aspirated HCC cells was detected in 19.6% patients. Kaplan-Meier survival analysis showed that positive HURP expression (P = 0.023), cytological grading ≥3 (P = 0.008), AFP ≥35 ng/mL (P = 0.039), bilirubin ≥1.3 mg/dL (P = 0.010), AST ≥50 U/L (P = 0.003) and ALT ≥35 U/L (P = 0.005) were all associated with a shorter disease-free survival. A stepwise multivariate Cox proportional hazard model revealed that positive HURP expression (HR, 2.334; 95% CI, 1.165–4.679, P = 0.017), AST ≥50 U/L (HR, 3.697; 95% CI, 1.868–7.319, p<0.001), cytological grade ≥3 (HR, 4.249; 95% CI, 2.061–8.759, P<0.001) and tumor number >1 (HR, 2.633; 95% CI, 1.212–5.722, P = 0.014) were independent predictors for disease-free survival. By combining the 4 independent predictors, patients with different risk scores (RS) showed distinguishable disease-free survival (RS≤1 vs. RS = 2, P = 0.001; RS = 2 vs. RS = 3, P<0.001). In contrast, the patients cannot be separated into prognosis distinguishable subgroups by using AJCC/UICC TNM staging system.

Conclusion

HCC patients with BCLC stage A can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression in aspirated HCC cells, ALT, cytological grade and tumor number.     

Opposite associations of trunk and leg fat depots with plasma ferritin levels in middle-aged and older Chinese men and women

Background

Few data have been published on the associations of ferritin with trunk and leg fat depots. We aimed to investigate these associations in a Chinese population.

Methodology

Trunk fat mass and leg fat mass were determined in a cross-sectional sample of 1,150 Chinese (479 men and 671 women) aged 50–70 years by dual-energy X-ray absorptiometry scan. Fasting plasma ferritin was measured.

Principal Findings

Plasma ferritin was positively correlated with waist circumference, waist-to-hip ratio, total body fat and trunk fat mass, but inversely correlated with leg fat mass in men (r = 0.16, 0.26, 0.19, 0.22 and −0.12, respectively, all P<0.05) and women (r = 0.16, 0.16, 0.08, 0.17 and −0.12, respectively, all P<0.05). Multivariate regression analysis showed that ferritin levels increased with larger trunk fat mass (β = 0.33 ± 0.08 for men and β = 0.21 ± 0.05 for women, both P<0.001) while decreased with larger leg fat mass (β = −0.12 ± 0.09, P = 0.15 for men; and β = −0.14 ± 0.05, P = 0.005 for women). Moreover, plasma ferritin levels decreased with increasing tertile of leg fat mass among each tertile of trunk fat mass.

Conclusion

This is the first study to report the opposite associations of trunk and leg fat depots with plasma ferritin levels.     

Alcohol consumption and ankle-to-brachial index: results from the Cardiovascular Risk Survey

Background and Methodology

A low ankle-to-brachial index (ABI) is a strong correlate of cardiovascular disease and subsequent mortality. The relationship between ABI and alcohol consumption remains unclear. Data are from the Cardiovascular Risk Survey (CRS), a multiple-ethnic, community-based, cross-sectional study of 14 618 Chinese people (5 757 Hans, 4 767 Uygurs, and 4 094 Kazakhs) aged 35 years and over at baseline from Oct. 2007 to March 2010. The relationship between alcohol intake and ABI was determined by use of analysis of covariance and multivariable regressions.

Principal Findings

In men, alcohol consumption was significantly associated with ABI (P<0.001). After adjusted for the confounding factors, such as age, sex, ethnicity, body mass index, smoking, work stress, diabetes, and fasting blood glucose, the difference remained significant (P<0.001); either the unadjusted or multivariate-adjusted odds ratio (OR) for peripheral artery disease (PAD) was significantly higher in men who consumed >60.0 g/d [OR  = 3.857, (95% CI: 2.555–5.824); OR = 2.797, (95% CI: 1.106–3.129); OR = 2.878, (95% CI: 1.215–4.018); respectively] and was significantly lower in men who consumed 20.1–40.0 g/d [OR  = 0.330, (95% CI: 0.181–0.599); OR = 0.484, (95% CI: 0.065–0.894); OR = 0.478, (95% CI: 0.243–1.534); respectively] and 40.1–60.0 g/d [OR  = 0.306, (95% CI: 0.096–0.969); OR = 0.267, (95% CI: 0.087–0.886); OR = 0.203, (95% CI: 0.113–0.754); respectively] compared with never drinking, respectively (all P<0.01). Neither in unadjusted nor in multivariate-adjusted model was the association between ABI and alcohol consumption significant (all P>0.05) in women. Similarly, PAD was not correlated with alcohol intake in women (all P>0.05).

Conclusions/Significance

Our results indicated that in Chinese men, alcohol consumption was associated with peripheral artery disease, and consumption of less than 60 g/d had an inverse association with peripheral atherosclerosis whereas consumption of 60 g/d or more had a positive association.     

Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion

Objective

Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.

Design

Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.

Methods

Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.

Results

A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).

Conclusions

The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.     

The effect of hOGG1 Ser326Cys polymorphism on cancer risk: evidence from a meta-analysis

Background

Human oxoguanine glycosylase 1 (hOGG1) in base excision repair (BER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between hOGG1 Ser326Cys polymorphism and the risk of cancer. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the association, we conducted a meta-analysis.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies of hOGG1 Ser326Cys polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We found that the hOGG1 Ser326Cys polymorphism was significantly associated with overall cancer risk (Cys/Cys vs. Ser/Ser: OR = 1.19, 95%CI = 1.09–1.30, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.16, 95%CI = 1.08–1.26, P<0.001). Moreover, in subgroup analyses by cancer types, the stronger significant association between hOGG1 Ser326Cys polymorphism and lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.29, 95%CI = 1.16–1.44, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.22, 95%CI = 1.12–1.33, P<0.001). The significant effects of hOGG1 Ser326Cys polymorphism on colorectal, breast, bladder, prostate, esophageal, and gastric cancer were not detected. In addition, in subgroup analyses by ethnicities, we found that the hOGG1 Ser326Cys polymorphism was associated with overall cancer risk in Asians (Cys/Cys vs. Ser/Ser: OR = 1.21, 95%CI = 1.10–1.33, P<0.001).

Conclusions

This meta-analysis showed that hOGG1 326Cys allele might be a low-penetrant risk factor for lung cancer.     

Intake of Dairy Products,Calcium, Magnesium,and Phosphorus in Childhood and Age at Menarche in the Tehran Lipid and Glucose Study

Purpose

Studies indicate that milk intake is associated with insulin-like growth factor 1 (IGF-1) concentrations and height in childhood, whether milk and other dairy products promote puberty remains unclear. This study aimed to investigate influences of pre-pubertal intakes of milk, yogurt and cheese on menarcheal age in Tehranian girls. The associations of total dietary calcium (Ca), magnesium (Mg), and phosphorus (P) with menarcheal age were also examined.

Methods

This prospective study was conducted on 134 pre-pubertal girls, aged 4-12 years at baseline, who participated in the Tehran Lipid and Glucose Study (TLGS), and were followed for a median of 6.5 years. Dietary intakes were determined at initiation of the study using two non-consecutive 24-h dietary recalls and the age of menarche was documented during the follow-up. Logistic regression was used to calculate the risk of reaching menarche ≤ 12 years according to pre-pubertal levels of dairy or mineral intakes.

Results

The risk of earlier menarche was higher in girls with higher intakes of milk [OR: 2.28 (95% CI: 1.03–5.05)], Ca [OR: 3.20 (95%CI: 1.39–7.42)], Mg [OR: 2.43 (95% CI: 1.12–5.27)] and P [OR: 3.37 (95 % CI: 1.44–7.87) after controlling for energy and protein intake, interval between the age at study initiation and the age of menarche, and maternal age at menarche (Model 1). Girls in the middle tertile of cheese intakes had a lower risk of reaching menarche ≤ 12 years than those in the lowest tertile after controlling for covariates in model 1. These associations remained significant after further adjustment of BMI Z-score at baseline. The relationship of Ca, Mg, and P with menarche remained after further adjustment for height Z-score at baseline, whereas the association between milk and cheese intakes became non-significant.

Conclusions

Pre-pubertal intake of milk, but not cheese and yogurt, may hasten age at menarche.     

A geographically-restricted but prevalent Mycobacterium tuberculosis strain identified in the West Midlands Region of the UK between 1995 and 2008

Background

We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.

Methodology/Principal Findings

Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the “Mercian” strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95%CI = 4.56–17.87, p<0.01), Black Caribbean (OR = 5.68, 95%CI = 2.96–10.91, p<0.01) resident in Wolverhampton (OR = 9.29, 95%CI = 5.69–15.19, p<0.01) and negatively associated with age >65 years old (OR = 0.25, 95%CI = 0.09–0.67, p<0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95%CI = 2.00–46.78, p<0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95%CI = 1.45–27.02, p = .01) were observed as social risk factors for infection.

Conclusions/Significance

The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain.     

Combined effect of hemostatic gene polymorphisms and the risk of myocardial infarction in patients with advanced coronary atherosclerosis

Background

Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI.

Methodology/Principal Findings

We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen β -455G>A, FV Leiden and “R2”, FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (χ² for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (≤2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13–0.93), while those with more (≥8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03–6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential.

Conclusions

The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.     

Blood vessel invasion as a strong independent prognostic indicator in non-small cell lung cancer: a systematic review and meta-analysis

Background and Objective

Blood vessel invasion plays a very important role in the progression and metastasis of cancer. However, blood vessel invasion as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial. The aim of this study is to explore the relationship between blood vessel invasion and outcome in patients with NSCLC using meta-analysis.

Methods

A meta-analysis of published studies was conducted to investigate the effects of blood vessel invasion on both relapse-free survival (RFS) and overall survival (OS) for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of this association.

Results

A total of 16,535 patients from 52 eligible studies were included in the systematic review and meta-analysis. In total, blood vessel invasion was detected in 29.8% (median; range from 6.2% to 77.0%) of patients with NSCLC. The univariate and multivariate estimates for RFS were 3.28 (95% CI: 2.14–5.05; P<0.0001) and 3.98 (95% CI: 2.24–7.06; P<0.0001), respectively. For the analyses of blood vessel invasion and OS, the pooled HR estimate was 2.22 (95% CI: 1.93–2.56; P<0.0001) by univariate analysis and 1.90 (95% CI: 1.65–2.19; P<0.0001) by multivariate analysis. Furthermore, in stage I NSCLC patients, the meta-risk for recurrence (HR = 6.93, 95% CI: 4.23–11.37, P<0.0001) and death (HR = 2.15, 95% CI: 1.68–2.75; P<0.0001) remained highly significant by multivariate analysis.

Conclusions

This study shows that blood vessel invasion appears to be an independent negative prognosticator in surgically managed NSCLC. However, adequately designed large prospective studies and investigations are warranted to confirm the present findings.     

Relation of Pulse Pressure to Long-Distance Gait Speed in Community-Dwelling Older Adults: Findings from the LIFE-P Study

Background

Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.

Methods

Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.

Results

Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.

Conclusions

Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.     

Variations of CHI3L1, Levels of the Encoded Glycoprotein YKL-40 and Prediction of Fatal and Non-fatal Ischemic Stroke

Background

Polymorphisms of CHI3L1 are associated with inter-individual YKL-40 levels and YKL-40 is associated with an increased mortality and is elevated in patients with cardiovascular disease. We investigated the association between single nucleotide polymorphisms (SNPs) of CHI3L1, serum YKL-40 levels and all-cause and cardiovascular mortality and first-time incidence of myocardial infarction, ischemic heart disease (IHD) and stroke.

Methodology/Principal Findings

12 SNPs of CHI3L1 were genotyped and serum YKL-40 was measured in 2656 Danes representative of the general population. Median follow-up period was 15 (0–16) years. Admission data and deaths were ascertained from registers from the Danish National Board of Health. Fourth quartile YKL-40 levels were associated with an increased mortality risk of ischemic stroke (HR 2.44 (1.01–5.88), p = 0.041) and so were homozygotes of the minor allele of rs872129 (HR 9.35 (1.25–69.87, p = 0.022)). Both continuous YKL-40 levels and 4^th quartile YKL-40 values (>85 ng/ml) were associated with all-cause mortality (HRs 1.22 (95% CI, 1.10–1.35), p<0.0001, and 1.40 (1.15–1.71), p<0.0001), an increased risk of first-time stroke (HR 1.16 (1.01–1.33), p = 0.04, and 1.63 (1.23–2.16), p = 0.001) and a decreased risk of incidence of IHD (HR 0.77 (0.65–0.91), p = 0.002, and 0.61 (0.44–0.85), p = 0.003).

Conclusions/Signficance

High YKL-40 levels (>85 ng/ml) and rs872129 were associated with an increased mortality risk of ischemic stroke, but high YKL-40 levels were also inverse related with the risk of incidence of IHD. This could be a chance finding but could also elucidate that YKL-40 plays different roles in development of thromboembolisms versus the formation of local thrombosis.     

Age at menarche, schooling, and sexual debut in northern Malawi

Background

Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.

Methods and Findings

A cross-sectional sexual behaviour survey was conducted on all individuals age 15–59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25^th centile was used to define “early” sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (<16 years) was less likely in those with menarche at age 14–15 (odds ratio (OR) 0.31, 95%CI 0.26–0.36), and ≥16 (OR 0.04, 95%CI 0.02–0.05) compared to those with menarche at <14. The proportion of women who completed primary school was 46% in those with menarche at <14, 60% in those with menarche at 14–15 and 70% in those with menarche at ≥16. The association between age at menarche and schooling was partly explained by age at sexual debut. The association between age at menarche and early sex was not altered by adjusting for schooling.

Conclusions

Women with early menarche start sex and marry early, leading to school drop-out. It is important to find ways to support those who reach menarche early to access the same opportunities as other young women.     

Dietary calcium but not elemental calcium from supplements is associated with body composition and obesity in Chinese women

Objective

We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population.

Methods

A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%). Height, weight, fat mass (FM), waist circumference (WC) and hip circumference were measured. Obesity definition: body mass index (BMI) ≥28 kg/m² (overall obesity); WC ≥85 cm for men or ≥80 cm for women (abdominal obesity І) and waist hip ratio (WHR) ≥0.90 for men or ≥0.85 for women (abdominal obesity П). The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity.

Principal Findings

The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, −0.086, P<0.001 for BMI; β, −0.072, P<0.001 for WC; β, −0.044, P<0.05 for WHR; and β, −0.058, P<0.01 for FM, respectively) and both measures of abdominal obesity (Odds Ratio [OR] = 0.86, 95% Confidence Interval [CI], 0.80–0.93; P<0.001, for abdominal obesity I; OR = 0.92, 95% CI, 0.86–0.99; P = 0.026, for abdominal obesity II). These associations were not observed among men (P>0.05). Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05).

Conclusions

Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women.     

Cognitive performance in late adolescence and the subsequent risk of subdural hematoma: an observational study of a prospective nationwide cohort

Background

There are few identified risk factors for traumatic brain injuries such as subdural hematoma (SDH). The aim of the present study was to investigate whether low cognitive performance in young adulthood is associated with SDH later in life. A second aim was to investigate whether this risk factor was associated with education and physical fitness.

Methods and Findings

Word recollection, logical, visuospatial, and technical performances were tested at a mean age of 18.5 years in a prospective nation-wide cohort of 440,742 men. An estimate of global intelligence was calculated from these four tests. Associations between cognitive performance, education, physical fitness, and SDH during follow-up were explored using Cox regression analyses. During a median follow-up of 35 years, 863 SDHs were diagnosed in the cohort. Low global intelligence was associated with an increased risk of SDH during follow-up (hazard ratio [HR]: 1.33, per standard deviation decrease, 95% CI = 1.25–1.43). Similar results were obtained for the other measures of cognitive performance (HR: 1.24–1.33, p<0.001 for all). In contrast, a high education (HR: 0.27, comparing more than 2 years of high school and 8 years of elementary school, 95% CI = 0.19–0.39), and a high level of physical fitness (HR: 0.76, per standard deviation increase, 95% CI = 0.70–0.83), was associated with a decreased risk of suffering from a SDH.

Conclusions

The present findings suggest that reduced cognitive function in young adulthood is strongly associated with an increased risk of SDH later in life. In contrast, a higher level of education and a higher physical fitness were associated with a decreased risk of SDH. Please see later in the article for the Editors'' Summary     

Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement

Background

In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria.

Methods and Findings

Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350–1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991–1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log₁₀ plasma PfHRP2 and risk of death. Mortality increased 20% per log₁₀ increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05–1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44–0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69–1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings.

Conclusions

Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of “true” severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children. Please see later in the article for the Editors'' Summary.     

Attenuating effect of vigorous physical activity on the risk for inherited obesity: a study of 47,691 runners

Objective

Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history.

Design

We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother''s and father''s adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of <3, 3–6, 6–9, ≥9 km/day.

Results

BMI and waist circumferences of runners who ran <3 km/day were significantly related to their parents adiposity (P<10⁻¹⁵ and P<10⁻¹¹, respectively). These relationships (i.e., kg/m² or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance×exercise interaction, males: P<10⁻¹⁰; females: P<10⁻⁵) and waist circumference (inheritance×exercise interaction, males: P<10⁻⁹; females: P = 0.004). Compared to <3 km/day, the parental contribution to runners who averaged ≥9 km/day was diminished by 48% for male BMI, 58% for female BMI, 55% for male waist circumference, and 58% for female waist circumference. These results could not be attributed to self-selection.

Conclusions

Exceeding the minimum exercise dose currently recommended for general health benefits (energy equivalent to running 2–3 km/day) may substantially diminish the risk for inherited obesity. The results are consistent with other research suggesting the physical activity dose required to prevent unhealthy weight gain is greater than that recommended for other health benefits.     

Association of the European Lactase Persistence Variant (LCT-13910 C>T Polymorphism) with Obesity in the Canary Islands

Background

European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization.

Methods

A representative, randomly sampled population of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain, aged 18–75 years (n = 551), was genotyped for the LCT – 13910 C>T polymorphism. Milk consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured. WHO classification of BMI was used.

Results

LP individuals were significantly more obese than LNP subjects (χ² = 10.59; p<0.005). LP showed in a multivariate linear regression analysis showed a positive association of LP with BMI compared to LNP, (β = 0.96; 95% CI: 0.08–1.85, p = 0.033). In a multinomial logistic regression analysis normal range weight LP subjects showed an odds ratio for obesity of 2.41; 95%CI 1.39–418, (p = 0.002) compared to LNP.

Conclusions

The T-13910 of the allele LCT-13910 C>T polymorphism is positively associated with BMI. LP increases significantly the risk to develop obesity in the studied population. The LCT-13910 C>T polymorphism stands proxy for the lifetime exposure pattern, milk intake, that may increase susceptibility to obesity and to obesity related pathologies.     

Discordance between Liver Biopsy and FibroScan? in Assessing Liver Fibrosis in Chronic Hepatitis B: Risk Factors and Influence of Necroinflammation

Background

Few studies have investigated predictors of discordance between liver biopsy (LB) and liver stiffness measurement (LSM) using FibroScan®. We assessed predictors of discordance between LB and LSM in chronic hepatitis B (CHB) and investigated the effects of necroinflammatory activity.

Methods

In total, 150 patients (107 men, 43 women) were prospectively enrolled. Only LSM with ≥10 valid measurements was considered reliable. Liver fibrosis was evaluated using the Laennec system. LB specimens <15 mm in length were considered ineligible. Reference cutoff LSM values to determine discordance were calculated from our cohort (6.0 kPa for ≥F2, 7.5 kPa for ≥F3, and 9.4 kPa for F4).

Results

A discordance, defined as a discordance of at least two stages between LB and LSM, was identified in 21 (14.0%) patients. In multivariate analyses, fibrosis stages F3–4 and F4 showed independent negative associations with discordance (P = 0.002; hazard ratio [HR], 0.073; 95% confidence interval [CI], 0.014–0.390 for F3–4 and P = 0.014; HR, 0.067; 95% CI, 0.008–0.574 for F4). LSM values were not significantly different between maximal activity grades 1–2 and 3–4 in F1 and F2 fibrosis stages, whereas LSM values were significantly higher in maximal activity grade 3–4 than 1–2 in F3 and F4 fibrosis stage (median 8.6 vs. 11.3 kPa in F3, P = 0.049; median 11.9 vs. 19.2 kPa in F4, P = 0.009).

Conclusion

Advanced fibrosis stage (F3–4) or cirrhosis (F4) showed a negative correlation with discordance between LB and LSM in patients with CHB, and maximal activity grade 3–4 significantly influenced LSM values in F3 and F4.     

Early Hemoperfusion May Improve Survival of Severely Paraquat-Poisoned Patients

Background

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2−4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown.

Methods

We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed.

Results

The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16–0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39–0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05–0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24–0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables.

Conclusion

The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.