Anaemia is a chief determinant of globalill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P <10−8, which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

SummaryBackgroundA city-wide sanitation intervention was started in Salvador, Brazil, in 1997 to improve sewerage coverage from 26% of households to 80%. Our aim was to investigate the epidemiological effect of this city-wide sanitation programme on diarrhoea morbidity in children less than 3 years of age.MethodsThe investigation was composed of two longitudinal studies done in 1997–98 before the intervention (the sanitation programme) and in 2003–04 after the intervention had been completed. Each study consisted of a cohort of children (841 in the preintervention study and 1007 in the postintervention study; age 0–36 months at baseline) who were followed up for a maximum of 8 months. Children were sampled from 24 sentinel areas that were randomly chosen to represent the range of environmental conditions in the study site. At the start of each study an individual or household questionnaire was applied by trained fieldworkers; an environmental survey was done in each area before and after introduction of the sanitation programme to assess basic neighbourhood and household sanitation conditions. Daily diarrhoea data were obtained during home visits twice per week. The effect of the intervention was estimated by a hierarchical modelling approach fitting a sequence of multivariate regression models.FindingsDiarrhoea prevalence fell by 21% (95% CI 18–25%)—from 9·2 (9·0–9·5) days per child-year before the intervention to 7·3 (7·0–7·5) days per child-year afterwards. After adjustment for baseline sewerage coverage and potential confounding variables, we estimated an overall prevalence reduction of 22% (19–26%).InterpretationOur results show that urban sanitation is a highly effective health measure that can no longer be ignored, and they provide a timely support for the launch of 2008 as the International Year of Sanitation.

BackgroundThe prevalence of asthma and allergic diseases has increased in industrialised countries, and it is known that rates vary according whether the area is urban or rural and to socio-economic status. Surveys conducted in some urban settings in Latin America found high prevalence rates, only exceeded by the rates observed in industrialised English-speaking countries. It is likely that the marked changes in the environment, life style and living conditions in Latin America are responsible for these observations. The understanding of the epidemiological and immunological changes that underlie the increase in asthma and allergic diseases in Latin America aimed by SCAALA studies in Brazil and Ecuador will be crucial for the identification of novel preventive interventions.Methods/DesignThe Salvador-SCAALA project described here is a longitudinal study involving children aged 4–11 years living in the city of Salvador, Northeastern Brazil. Data on asthma and allergic diseases (rhinitis and eczema) and potential risk factors will be collected in successive surveys using standardised questionnaire. This will be completed with data on dust collection (to dust mite and endotoxin), skin test to most common allergens, stool examinations to helminth and parasites, blood samples (to infection, total and specific IgE, and immunological makers), formaldehyde, physical inspection to diagnoses of eczema, and anthropometric measures. Data on earlier exposures when these children were 0–3 years old are available from a different project.DiscussionIt is expected that knowledge generated may help identify public health interventions that may enable countries in LA to enjoy the benefits of a "modern" lifestyle while avoiding – or minimising – increases in morbidity caused by asthma and allergies.

ObjectiveTo systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease.DesignSystematic review and meta-analysis.Data sourcesMedline, EMBASE and COCHRANE from 1990 to June 2018.Eligibility criteriaRandomised controlled trials (≥14 days) excluding hypercholesterolaemia, alcoholic liver disease, polycystic ovary syndrome and children <3 years.ResultsOne hundred and five articles met inclusion criteria, representing 6826 subjects. In overweight but not obese subjects, probiotics induced improvements in: body weight (k=25 trials, d=−0.94 kg mean difference, 95% CI −1.17 to −0.70, I²=0.0%), body mass index (k=32, d=−0.55 kg/m², 95% CI −0.86 to −0.23, I²=91.9%), waist circumference (k=13, d=−1.31 cm, 95% CI −1.79 to −0.83, I²=14.5%), body fat mass (k=11, d=−0.96 kg, 95% CI −1.21 to −0.71, I²=0.0%) and visceral adipose tissue mass (k=5, d=−6.30 cm², 95% CI −9.05 to −3.56, I²=0.0%). In type 2 diabetics, probiotics reduced fasting glucose (k=19, d=−0.66 mmol/L, 95% CI −1.00 to −0.31, I²=27.7%), glycated haemoglobin (k=13, d=−0.28 pp, 95% CI −0.46 to −0.11, I²=54.1%), insulin (k=13, d=−1.66 mU/L, 95% CI −2.70 to −0.61, I²=37.8%) and homeostatic model of insulin resistance (k=10, d=−1.05 pp, 95% CI −1.48 to −0.61, I²=18.2%). In subjects with fatty liver diseases, probiotics reduced alanine (k=12, d=−10.2 U/L, 95% CI −14.3 to −6.0, I²=93.50%) and aspartate aminotransferases (k=10, d=−9.9 U/L, 95% CI −14.1 to -5.8, I²=96.1%). These improvements were mostly observed with bifidobacteria (Bifidobacterium breve, B. longum), Streptococcus salivarius subsp. thermophilus and lactobacilli (Lactobacillus acidophilus, L. casei, L. delbrueckii) containing mixtures and influenced by trials conducted in one country.ConclusionsThe intake of probiotics resulted in minor but consistent improvements in several metabolic risk factors in subjects with metabolic diseases.Trial registration numberCRD42016033273.

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Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes.Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults.Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), γ-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed.Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels.Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.

Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.

Animal studies suggest that perfluorocarbons (PFCs) may alter sexual maturation. Relationships of human PFC exposure with puberty are not clear. We conducted a cross-sectional study to investigate whether perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were associated with indicators of sexual maturation in a 2005-2006 survey of residents with PFOA water contamination from the Mid-Ohio Valley. Participants were 3076 boys and 2931 girls aged 8-18 years. They were classified as having reached puberty based on either hormone levels (total >50 ng/dL and free >5 pg/mL testosterone in boys and estradiol >20 pg/mL in girls) or onset of menarche. We estimated the odds of having reached puberty classified by these criteria and the fitted median age of reaching puberty in relation to serum PFOA and PFOS concentrations measured when puberty status was assigned. For boys, there was a relationship of reduced odds of reached puberty (raised testosterone) with increasing PFOS (delay of 190 days between the highest and lowest quartile). For girls, higher concentrations of PFOA or PFOS were associated with reduced odds of postmenarche (130 and 138 days of delay, respectively). In conclusion, our study showed a later age of puberty in this population correlated with PFC concentrations.