IL-4 alpha chain receptor (IL-4Rα) polymorphisms in allergic bronchopulmonary sspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis occurs in 7–10% of cystic fibrosis (CF) and 1–2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations. OBJECTIVE: We examined for the presence of IL-4 receptor alpha chain (IL-4Rα) single nucleotide polymorphisms (SNPs) in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation. METHODS: One extracellular (ile75val) and four cytoplasmic IL-4Rα SNPs were analyzed in 40 CF and 22 asthmatic patients and in 56 non-ABPA CF and asthmatic patients. Sensitivity to IL-4 stimulation was measured by induction of CD23 expression on B cells. RESULTS: IL-4Rα SNPs were observed in 95% of ABPA patients. The predominant IL-4Rα SNP was the extracellular IL-4Rα SNP, ile75val, observed in 80% of ABPA patients. CONCLUSION: The presence of IL-4Rα SNPs, principally ile75val, appears to be a genetic risk for the development of ABPA

Family history as a risk factor for pelvic organ prolapse

Abstract The aim of this study was to determine whether a family history of prolapse and/or hernia is a risk factor for prolapse. A cohort of 458 women seeking gynecological care was classified as exposed (family history) or unexposed (without family history). We used χ 2 to assess confounding and logistic regression to determine risk. Nearly half (47.3%) of the 458 participants reported a positive family history. Of these, 52.5% had prolapse. This was significantly higher than the 28.9% rate of prolapse in women without a family history (p<0.001). The crude risk ratio for family history of prolapse and/or hernia and prolapse was 1.8 (95% CI 1.4-2.3). After adjusting for vaginal deliveries, incontinence, and hysterectomy, the risk of prolapse was 1.4 (95% CI 1.2-1.8) times higher in women with a family history of prolapse and/or hernia. Heredity is a risk factor for prolapse. History taking should include both male and female family members

Identification of production challenges and benefits using value chain mapping of egg food systems in Nairobi, Kenya

Commercial layer and indigenous chicken farming in Nairobi and associated activities in the egg value chains are a source of livelihood for urban families. A value chain mapping framework was used to describe types of inputs and outputs from chicken farms, challenges faced by producers and their disease control strategies. Commercial layer farms were defined as farms keeping exotic breeds of chicken, whereas indigenous chicken farms kept different cross breeds of indigenous chicken. Four focus group discussions were held with producers of these chickens in peri-urban area: Dagoretti, and one informal settlement: Kibera. Qualitative data were collected on interactions between farmers, sources of farm inputs and buyers of poultry products, simple ranking of production challenges, farmers' perception on diseases affecting chicken and strategies for management of sick chicken and waste products. Value chain profiles were drawn showing sources of inputs and channels for distribution of chicken products. Production challenges and chicken disease management strategies were presented as qualitative summaries. Commercial layer farms in Dagoretti kept an average of 250 chickens (range 50–500); while flock sizes in Kibera were 12 chickens (range 5–20). Farms keeping indigenous chicken had an average of 23 chickens (range 8–40) in Dagoretti, and 10 chickens (range 5–16) in Kibera. Commercial layer farms in Dagoretti obtained chicks from distributors of commercial hatcheries, but farms in Kibera obtained chicks from hawkers who in turn sourced them from distributors of commercial hatcheries. Indigenous chicken farms from Dagoretti relied on natural hatching of fertilised eggs, but indigenous chicken farms in Kibera obtained chicks from their social connection with communities living in rural areas. Outlets for eggs from commercial layer farms included local shops, brokers, restaurants and hawkers, while eggs from indigenous chicken farms were sold to neighbours and restaurants. Sieved chicken manure from Dagoretti area was fed to dairy cattle; whereas non-sieved manure was used as fertilizer on crops. Production challenges included poor feed quality, lack of space for expansion, insecurity, occurrence of diseases and lack of sources of information on chicken management. In Kibera, sick and dead chickens were slaughtered and consumed by households; this practice was not reported in Dagoretti. The chicken layer systems contribute to food security of urban households, yet they have vulnerabilities and deficiencies with regard to disease management and food safety that need to be addressed with support on research and extension

The broiler meat system in Nairobi, Kenya: using a value chain framework to understand animal and product flows, governance and sanitary risks

Livestock food systems play key subsistence and income generation roles in low to middle income countries and are important networks for zoonotic disease transmission. The aim of this study was to use a value chain framework to characterize the broiler chicken meat system of Nairobi, its governance and sanitary risks. A total of 4 focus groups and 8 key informant interviews were used to collect cross-sectional data from: small-scale broiler farmers in selected Nairobi peri-urban and informal settlement areas; medium to large integrated broiler production companies; traders and meat inspectors in live chicken and chicken meat markets in Nairobi. Qualitative data were collected on types of people operating in the system, their interactions, sanitary measures in place, sourcing and selling of broiler chickens and products. Framework analysis was used to identify governance themes and risky sanitary practices present in the system. One large company was identified to supply 60% of Nairobi’s day-old chicks to farmers, mainly through agrovet shops. Broiler meat products from integrated companies were sold in high-end retailers whereas their low value products were channelled through independent traders to consumers in informal settlements. Peri-urban small-scale farmers reported to slaughter the broilers on the farm and to sell carcasses to retailers (hotels and butcheries mainly) through brokers (80%), while farmers in the informal settlement reported to sell their broilers live to retailers (butcheries, hotels and hawkers mainly) directly. Broiler heads and legs were sold in informal settlements via roadside vendors. Sanitary risks identified were related to lack of biosecurity, cold chain and access to water, poor hygiene practices, lack of inspection at farm slaughter and limited health inspection in markets. Large companies dominated the governance of the broiler system through the control of day-old chick production. Overall government control was described as relatively weak leading to minimal official regulatory enforcement. Large companies and brokers were identified as dominant groups in market information dissemination and price setting. Lack of farmer association was found to be system-wide and to limit market access. Other system barriers included lack of space and expertise, leading to poor infrastructure and limited ability to implement effective hygienic measures. This study highlights significant structural differences between different broiler chains and inequalities in product quality and market access across the system. It provides a foundation for food safety assessments, disease control programmes and informs policy-making for the inclusive growth of this fast-evolving sector

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010.

BACKGROUND: National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. METHODS: Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. FINDINGS: In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm-SGA. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. INTERPRETATION: The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. FUNDING: Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG)

Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

<p>Abstract</p> <p>Background</p> <p>Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked <it>Alternaria </it>sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying <it>Alternaria </it>sensitivity and asthma, in these studies we examined T cell responses to <it>Alternaria </it>antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma.</p> <p>Methods</p> <p>Sixty children with <it>Alternaria</it>-sensitive moderate-severe asthma were compared to 49 children with <it>Alternaria</it>-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in <it>Alternaria</it>-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 <it>Alternaria</it>-specific T-cells, cultures were stimulated in media alone, <it>Alternaria alternata </it>extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells.</p> <p>Results</p> <p>Children with <it>Alternaria</it>-sensitive moderate-severe asthma trended to have increased sensitivities to <it>Cladosporium </it>(46% versus 35%), to <it>Aspergillus </it>(43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to <it>Alternaria</it>-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of <it>Alternaria</it>-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics to <it>Alternaria </it>extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398.</p> <p>Summary</p> <p>In children with <it>Alternaria</it>-sensitive moderate severe asthma, there was an increased Th2 response to <it>Alternaria </it>stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in <it>Alternaria</it>-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.</p

Estimates of Burden and Consequences of Infants Born Small for Gestational Age in Low and Middle Income Countries with INTERGROWTH-21(st) Standard: Analysis of CHERG Datasets.

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (\u3c2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countrie

Mapping of beef, sheep and goat food systems in Nairobi — A framework for policy making and the identification of structural vulnerabilities and deficiencies

Nairobi is a large rapidly-growing city whose demand for beef, mutton and goat products is expected to double by 2030. The study aimed to map the Nairobi beef, sheep and goat systems structure and flows to identify deficiencies and vulnerabilities to shocks. Cross-sectional data were collected through focus group discussions and interviews with people operating in Nairobi ruminant livestock and meat markets and in the large processing companies. Qualitative and quantitative data were obtained about the type of people, animals, products and value adding activities in the chains, and their structural, spatial and temporal interactions. Mapping analysis was done in three different dimensions: people and product profiling (interactions of people and products), geographical (routes of animals and products) and temporal mapping (seasonal fluctuations). The results obtained were used to identify structural deficiencies and vulnerability factors in the system. Results for the beef food system showed that 44–55% of the city's beef supply flows through the ‘local terminal markets’, but that 54–64% of total supply is controlled by one ‘meat market’. Numerous informal chains were identified, with independent livestock and meat traders playing a pivotal role in the functionality of these systems, and where most activities are conducted with inefficient quality control and under scarce and inadequate infrastructure and organisation, generating wastage and potential food safety risks in low quality meat products. Geographical and temporal analysis showed the critical areas influencing the different markets, with larger markets increasing their market share in the low season. Large processing companies, partly integrated, operate with high quality infrastructures, but with up to 60% of their beef supply depending on similar routes as the informal markets. Only these companies were involved in value addition activities, reaching high-end markets, but also dominating the distribution of popular products, such as beef sausages, to middle and low-end market. For the small ruminant food system, 73% of the low season supply flows through a single large informal market, Kiamaiko, located in an urban informal settlement. No grading is done for these animals or the meat produced. Large companies were reported to export up to 90% of their products. Lack of traceability and control of animal production was a common feature in all chains. The mapping presented provides a framework for policy makers and institutions to understand and design improvement plans for the Nairobi ruminant food system. The structural deficiencies and vulnerabilities identified here indicate the areas of intervention needed

Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study

For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS–identified variants in diverse population-based studies. We genotyped 49 GWAS–identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (∼20,000), African American (∼9,000), American Indian (∼6,000), Mexican American/Hispanic (∼2,500), Japanese/East Asian (∼690), and Pacific Islander/Native Hawaiian (∼175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits