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Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44–8.15) (P-interaction = 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction = 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

Editors’ Summary Background Cardiometabolic diseases—cardiovascular diseases that affect the heart and/or the blood vessels and metabolic diseases that affect the cellular chemical reactions needed to sustain life—are a growing global health concern. In sub-Saharan Africa, for example, the prevalence (the proportion of a population that has a given disease) of adults with diabetes (a life-shortening metabolic disease that affects how the body handles sugars) is currently 3.8%. By 2030, it is estimated that the prevalence of diabetes among adults in this region will have risen to 4.6%. Similarly, in 2004, around 1.2 million deaths in sub-Saharan Africa were attributed to coronary heart disease, heart failure, stroke, and other cardiovascular diseases. By 2030, the number of deaths in this region attributable to cardiovascular disease is expected to double. Globally, cardiovascular disease and diabetes are now responsible for around 17.3 million and 1.3 million annual deaths, respectively, together accounting for about one-third of all deaths. Why Was This Study Done? Experts believe that increased consumption of saturated fats, sugar, and salt and reduced physical activity are partly responsible for the increasing global prevalence of cardiometabolic diseases. These lifestyle changes, they suggest, are related to urbanization—urban expansion into the countryside and migration from rural to urban areas. If this is true, the prevalence of unhealthy lifestyles should increase as rural areas adopt urban characteristics. Sub-Saharan Africa is the least urbanized region in the world, with about 60% of the population living in rural areas. However, rural settlements across the subcontinent are increasingly adopting urban characteristics. It is important to know whether urbanization is affecting the health of rural residents in sub-Saharan Africa to improve estimates of the future burden of cardiometabolic diseases in the region and to provide insights into ways to limit this burden. In this cross-sectional study (an investigation that studies participants at a single time point), the researchers examine the distribution of urban characteristics across rural communities in Uganda and the association of these characteristics with lifestyle risk factors for cardiometabolic diseases. What Did the Researchers Do and Find? For their study, the researchers used data collected in 2011 by the General Population Cohort study, a study initiated in 1989 to describe HIV infection trends among people living in 25 villages in rural southwestern Uganda that collects health-related and other information annually from its participants. The researchers quantified the “urbanicity” of the 25 villages using a multi-component scale that included information such as village size and economic activity. They then used statistical models to examine associations between urbanicity and lifestyle risk factors such as body mass index (BMI, a measure of obesity) and self-reported fruit and vegetable consumption for more than 7,000 study participants living in those villages. None of the villages had paved roads or running water. However, urbanicity varied markedly across the villages, largely because of differences in economic activity, civil infrastructure, and the availability of educational and healthcare services. Notably, increasing urbanicity was associated with an increase in lifestyle risk factors for cardiovascular diseases. So, for example, people living in villages with the highest urbanicity scores were nearly 20% more likely to be physically inactive and to eat less fruits and vegetables and nearly 50% more likely to have a high BMI than people living in villages with the lowest urbanicity scores. What Do These Findings Mean? These findings indicate that, across rural communities in Uganda, even a small increase in urbanicity is associated with a higher prevalence of potentially modifiable lifestyle risk factors for cardiometabolic diseases. These findings suggest, therefore, that simply classifying settlements as either rural or urban may not be adequate to capture the information needed to target strategies for cardiometabolic disease management and control in rural areas as they become more urbanized. Because this study was cross-sectional, it is not possible to say how long a rural population needs to experience a more urban environment before its risk of cardiometabolic diseases increases. Longitudinal studies are needed to obtain this information. Moreover, studies of other countries in sub-Saharan Africa are needed to show that these findings are generalizable across the region. However, based on these findings, and given that more than 553 million people live in rural areas across sub-Saharan Africa, it seems likely that increasing urbanization will have a substantial impact on the future health of populations throughout sub-Saharan Africa. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001683. This study is further discussed in a PLOS Medicine Perspective by Fahad Razak and Lisa Berkman The American Heart Association provides information on all aspects of cardiovascular disease and diabetes; its website includes personal stories about heart attacks, stroke, and diabetes The US Centers for Disease Control and Prevention has information on heart disease, stroke, and diabetes (in English and Spanish) The UK National Health Service Choices website provides information about cardiovascular disease and diabetes (including some personal stories) The World Health Organization’s Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle-income countries reduce illness and death caused by cardiometabolic and other non-communicable diseases The World Heart Federation has recently produced a report entitled “Urbanization and Cardiovascular Disease” Wikipedia has a page on urbanization (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) Background Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases. Methods and Findings Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77). Conclusions This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA. Please see later in the article for the Editors' Summary Johanna Riha and colleagues evaluate the association of lifestyle risk factors with elements of urbanicity, such as having a public telephone, a primary school, or a hospital, among individuals living in rural settings in Uganda. Please see later in the article for the Editors' Summary

Background:\ud Campylobacter jejuni is the most common bacterial cause of human infectious intestinal disease.\ud \ud Methods:\ud We genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993–1996; n = 293] and IID2 [isolates from 2008–2009; n = 93]), the INTEGRATE project [isolates from 2016–2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163].\ud \ud Results:\ud There was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation.\ud \ud Discussion:\ud Four population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation.

To investigate implementation of outpatient pulse oximetry among children with pneumonia, in Malawi.In 2011, 72 health-care providers at 18 rural health centres and 38 community health workers received training in the use of pulse oximetry to measure haemoglobin oxygen saturations. Data collected, between 1 January 2012 and 30 June 2014 by the trained individuals, on children aged 2-59 months with clinically diagnosed pneumonia were analysed.Of the 14 092 children included in the analysis, 13 266 (94.1%) were successfully checked by oximetry. Among the children with chest indrawing and/or danger signs, those with a measured oxygen saturation below 90% were more than twice as likely to have been referred as those with higher saturations (84.3% [385/457] vs 41.5% [871/2099];Implementation of pulse oximetry by our trainees substantially increased the referrals of Malawian children with severe hypoxaemic pneumonia. When data from oximetry were excluded, retrospective application of the guidelines published by WHO in 2014 failed to identify a considerable proportion of severely hypoxaemic children eligible only via oximetry.Étudier l'utilisation de l'oxymétrie de pouls chez les enfants atteints de pneumonie en traitement ambulatoire au Malawi.En 2011, 72 prestataires de soins de santé de 18 centres de santé ruraux et 38 agents de santé communautaires ont été formés à l'utilisation de l'oxymétrie de pouls pour mesurer la saturation en oxygène de l'hémoglobine. Des données collectées entre le 1er janvier 2012 et le 30 juin 2014 par les individus formés sur des enfants âgés de 2 à 59 mois atteints d'une pneumonie cliniquement diagnostiquée ont été analysées.Sur les 14 092 enfants inclus dans l'analyse, 13 266 (94,1%) ont été examinés avec succès grâce à l'oxymétrie. Parmi les enfants présentant un tirage sous-costal et/ou des signes de danger, ceux dont la saturation en oxygène mesurée était inférieure à 90% avaient plus de deux fois plus de chances d'être orientés vers un spécialiste que ceux présentant une saturation plus importante (84,3% [385/457] contre 41,5% [871/2099]; P 0,001). L'utilisation de l'oxymétrie semble avoir augmenté de 0% à 27,2% (P 0.001) le taux d'orientation vers un spécialiste dans le cas des enfants souffrant d'hypoxémie sévère sans tirage sous-costal ni signes de danger. En l'absence d'oxymétrie, si les directives en la matière publiées par l'Organisation mondiale de la Santé (OMS) en 2014 avaient été appliquées, 390/568 (68,7%) enfants souffrant d'hypoxémie sévère examinés dans les centres de santé considérés et 52/84 (61,9%) enfants souffrant d'hypoxémie sévère examinés par des agents de santé communautaires n'auraient pas pu bénéficier d'une orientation vers un spécialiste.L'utilisation de l'oxymétrie de pouls par les individus formés a considérablement accru l'orientation vers un spécialiste des enfants malawites atteints de pneumonie sévère et ayant développé une hypoxémie. Lorsque les données provenant de l'oxymétrie étaient exclues, l'application rétrospective des directives publiées par l'OMS en 2014 ne permettait pas d'identifier une proportion considérable d'enfants souffrant d'hypoxémie sévère qui remplissaient les conditions requises uniquement au vu de l'oxymétrie.Investigar la implementación de la oximetría de pulso ambulatoria en niños con neumonía en Malawi.En 2011, 72 profesionales de la salud de 18 centros de salud en zonas rurales y 38 trabajadores de la salud comunitarios recibieron formación con respecto al uso de la oximetría de pulso para medir las saturaciones de oxígeno de la hemoglobina. Se analizaron los datos, que las personas formadas recopilaron entre el 1 de enero de 2012 y el 30 de junio de 2014, de niños de 2 a 59 meses de edad con un diagnóstico clínico de neumonía.De los 14 092 niños incluidos en el análisis, se realizaron las pruebas con oximetría de manera satisfactoria a 13 266 (94,1%). Entre los niños con retracción costal y/o signos de peligro, aquellos con una medida de saturación de oxígeno por debajo del 90% tenían más del doble de probabilidades de haber sido derivados que aquellos con saturaciones más elevadas (84,3% [385/457] frente al 41,5% [871/2 099];La implementación de la oximetría de pulso por las personas formadas incrementó de forma sustancial las derivaciones de los niños de Malawi con neumonía hipoxémica grave. Cuando se excluyeron los datos procedentes de la oximetría, la aplicación retrospectiva de las directrices publicadas por la OMS en 2014 no pudo identificar un porcentaje considerable de niños hipoxémicos graves que cumplían los requisitos únicamente a través de la oximetría.الاستقصاء بشأن تنفيذ عمليات قياس التأكسج في العيادات الخارجية للأطفال المصابين بالالتهاب الرئوي في ملاوي.حصل 72 من مقدمي خدمات الرعاية الصحية في 18 مركزًا طبيًا ريفيًا و38 عاملاً في مجال الخدمات الصحية المجتمعية في عام 2011 على تدريبات متعلقة باستخدام تقنية قياس التأكسج بهدف قياس نسب تشبع الأكسجين والهيموجلوبين. وتم تحليل البيانات المجمعة في الفترة بين 1 كانون الثاني/يناير 2012 و 30 حزيران/يونيو 2014 بواسطة الأفراد المدرّبين، وهذه البيانات خاصة بالأطفال البالغ أعمارهم ما بين 2 إلى 59 شهرًا والمصابين بمرض الالتهاب الرئوي الذي تم تشخيصه داخل العيادات.من بين 14092 طفلاً شملهم التحليل، كان 13266 طفلاً منهم (بنسبة ‏94.1‏%) قد تم فحصه بنجاح بواسطة تقنية قياس التأكسج. ومن بين الأطفال الذين يعانون من بروز القفص الصدري أثناء التنفس و/أو علامات الخطر، كان أولئك الذين لديهم نسبة تشبع الأكسجين أقل من 90‏% لديهم أرجحية مضاعفة لإحالتهم للعلاج باعتبارهم من الأطفال الذين لديهم نسبة تشبع أعلى (84.3‏% [385/457] مقابل ‏41.5‏% [871/2099[؛إن تنفيذ عملية قياس التأكسج بواسطة المتدربين لدينا أدى بشكل كبير إلى زيادة حالات الإحالة للعلاج بالنسبة للأطفال المصابين بالالتهاب الرئوي الحاد في ملاوي. وعندما تم استبعاد بيانات قياس التأكسج، فشل التطبيق بأثر رجعي للمبادئ التوجيهية الصادرة من منظمة الصحة العالمية في عام 2014 في تحديد نسبة كبيرة من الأطفال المصابين بخلل الجهاز التنفسي الحاد والذين كانوا مؤهلين للعلاج نتيجة استخدام تقنية قياس التأكسج فقط.旨在调查马拉维肺炎患儿门诊脉搏血氧饱和度检测的实施情况。.2011 年，18 个农村医疗中心的 72 位医疗护理人员和 38 位社区医疗工作者接受了培训，学习使用脉搏血氧饱和度检测法测量血氧饱和度。 我们分析了受训人员于 2012 年 1 月 1 日到 2014 年 6 月 30 日期间采集的年龄在 2-59 个月、临床诊断为肺炎的儿童的数据。.在我们分析的 14 092 位儿童中，13 266 (94.1%) 位已经成功接受血氧饱和度检测。 在出现胸部凹陷和/或危险症状的儿童中，测量的血氧饱和度低于 90% 的儿童转诊的可能性是饱和度更高儿童的两倍以上（分别为 84.3% [385/457] 和 41.5% [871/2099];受训人员对脉搏血氧饱和度检测的实施大幅度提高了马拉维重度低氧性肺炎患儿的转诊率。 但是如果不采用血氧饱和度检测中的数据，而是追溯式采纳 WHO 2014 年发布的指南，则相当大比例的仅通过血氧饱和度检测才能确诊的重度低氧血症儿童无法得到确诊。.Изучить амбулаторное применение пульсоксиметрии у больных пневмонией детей в Малави.В течение 2011 года 72 врача из 18 сельских больниц и 38 местных медицинских работников были обучены использованию пульсоксиметрии для измерения насыщенности гемоглобина кислородом. Были проанализированы данные, собранные обученными лицами на протяжении периода с 1 января 2012 года по 30 июня 2014 года у детей в возрасте от 2 до 59 месяцев, которым был поставлен диагноз «пневмония».Из 14 092 детей, включенных в анализ, у 13 266 (94,1%) удалось успешно провести пульсоксиметрию. Дети со впалой грудью и (или) опасными симптомами, у которых измеренная насыщенность кислородом была менее 90%, более чем в два раза чаще направлялись в больницу, чем дети с высокой оксигенацией (84,3% (385 из 457 детей) против 41,5% (871 ребенок из 2099), р 0,001). Доступность оксиметрии привела к повышению уровня направления в больницу для детей с серьезной гипоксемией без впалой груди или опасных симптомов с 0 до 27,2% (p 0,001). В отсутствие оксиметрии и при использовании соответствующих рекомендаций Всемирной организации здравоохранения (ВОЗ), опубликованных в 2014 году, 390 из 568 детей (68,7%) с серьезной гипоксемией в центрах проведения исследования и 52 из 84 детей (61,9%) с серьезной гипоксемией, которых осматривали местные медицинские работники, не были бы направлены в больницу ввиду отсутствия показаний.Внедрение пульсоксиметрии нашими стажерами значительно повысило частоту направления в больницу малавийских детей с серьезной гипоксемией пневмонийного происхождения. При исключении из анамнеза данных пульсоксиметрии ретроспективное применение рекомендаций ВОЗ от 2014 года не позволяло выявить значительное количество детей с серьезной гипоксемией, необходимость госпитализации которых оказалось возможным определить только с помощью оксиметрии.

Background: Industrial swine operations emit odorant chemicals including ammonia, hydrogen sulfide (H2S), and volatile organic compounds. Malodor and pollutant concentrations have been associated with self-reported stress and altered mood in prior studies. Objectives: We conducted a repeated-measures study of air pollution, stress, and blood pressure in neighbors of swine operations. Methods: For approximately 2 weeks, 101 nonsmoking adult volunteers living near industrial swine operations in 16 neighborhoods in eastern North Carolina sat outdoors for 10 min twice daily at preselected times. Afterward, they reported levels of hog odor on a 9-point scale and measured their blood pressure twice using an automated oscillometric device. During the same 2- to 3-week period, we measured ambient levels of H2S and PM10 at a central location in each neighborhood. Associations between systolic and diastolic blood pressure (SBP and DBP, respectively) and pollutant measures were estimated using fixed-effects (conditional) linear regression with adjustment for time of day. Results: PM10 showed little association with blood pressure. DBP [β (SE)] increased 0.23 (0.08) mmHg per unit of reported hog odor during the 10 min outdoors and 0.12 (0.08) mmHg per 1-ppb increase of H2S concentration in the same hour. SBP increased 0.10 (0.12) mmHg per odor unit and 0.29 (0.12) mmHg per 1-ppb increase of H2S in the same hour. Reported stress was strongly associated with BP; adjustment for stress reduced the odor–DBP association, but the H2S–SBP association changed little. Conclusions: Like noise and other repetitive environmental stressors, malodors may be associated with acute blood pressure increases that could contribute to development of chronic hypertension.

Background Long-term conditions pose major challenges for healthcare systems. Optimizing self-management of people with long-term conditions is an important strategy to improve quality of life, health outcomes, patient experiences in healthcare, and the sustainability of healthcare systems. Much research on self-management focuses on individual competencies, while the social systems of support that facilitate self-management are underexplored. The presented study aims to explore the role of social systems of support for self-management and quality of life, focusing on the social networks of people with diabetes and community organisations that serve them. Methods The protocol concerns a cross-sectional study in 18 geographic areas in six European countries, involving a total of 1800 individuals with diabetes and 900 representatives of community organisations. In each country, we include a deprived rural area, a deprived urban area, and an affluent urban area. Individuals are recruited through healthcare practices in the targeted areas. A patient questionnaire comprises measures for quality of life, self-management behaviours, social network and social support, as well as individual characteristics. A community organisations’ survey maps out interconnections between community and voluntary organisations that support patients with chronic illness and documents the scope of work of the different types of organisations. We first explore the structure of social networks of individuals and of community organisations. Then linkages between these social networks, self-management and quality of life will be examined, taking deprivation and other factors into account. Discussion This study will provide insight into determinants of self-management and quality of life in individuals with diabetes, focusing on the role of social networks and community organisations.

Background In 2011 there were 5.5 million HIV infected people in South Africa and 71% of those requiring antiretroviral therapy (ART) received it. The effective integration of traditional medical practitioners and biomedical providers in HIV prevention and care has been demonstrated. However concerns remain that the use of traditional treatments for HIV-related disease may lead to pharmacokinetic interactions between herbal remedies and ART drugs and delay ART initiation. Here we analyse the changing prevalence and determinants of traditional healthcare use amongst those dying of HIV-related disease, pulmonary tuberculosis and other causes in a rural South African community between 2003 and 2011. ART was made available in this area in the latter part of this period. Methods Data was collected during household visits and verbal autopsy interviews. InterVA-4 was used to assign causes of death. Spatial analyses of the distribution of traditional healthcare use were performed. Logistic regression models were developed to test associations of determinants with traditional healthcare use. Results There were 5929 deaths in the study population of which 47.7% were caused by HIV-related disease or pulmonary tuberculosis (HIV/AIDS and TB). Traditional healthcare use declined for all deaths, with higher levels throughout for those dying of HIV/AIDS and TB than for those dying of other causes. In 2003-2005, sole use of biomedical treatment was reported for 18.2% of HIV/AIDS and TB deaths and 27.2% of other deaths, by 2008–2011 the figures were 49.9% and 45.3% respectively. In bivariate analyses, higher traditional healthcare use was associated with Mozambican origin, lower education levels, death in 2003–2005 compared to the later time periods, longer illness duration and moderate increases in prior household mortality. In the multivariate model only country of origin, time period and illness duration remained associated. Conclusions There were large decreases in reported traditional healthcare use and increases in the sole use of biomedical treatment amongst those dying of HIV/AIDS and TB. No associations between socio-economic position, age or gender and the likelihood of traditional healthcare use were seen. Further qualitative and quantitative studies are needed to assess whether these figures reflect trends in healthcare use amongst the entire population and the reasons for the temporal changes identified. Electronic supplementary material The online version of this article (doi:10.1186/1472-6882-14-504) contains supplementary material, which is available to authorized users.