A controlled, before-and-after trial of an urban sanitation intervention to reduce enteric infections in children: research protocol for the Maputo Sanitation (MapSan) study, Mozambique.

INTRODUCTION: Access to safe sanitation in low-income, informal settlements of Sub-Saharan Africa has not significantly improved since 1990. The combination of a high faecal-related disease burden and inadequate infrastructure suggests that investment in expanding sanitation access in densely populated urban slums can yield important public health gains. No rigorous, controlled intervention studies have evaluated the health effects of decentralised (non-sewerage) sanitation in an informal urban setting, despite the role that such technologies will likely play in scaling up access. METHODS AND ANALYSIS: We have designed a controlled, before-and-after (CBA) trial to estimate the health impacts of an urban sanitation intervention in informal neighbourhoods of Maputo, Mozambique, including an assessment of whether exposures and health outcomes vary by localised population density. The intervention consists of private pour-flush latrines (to septic tank) shared by multiple households in compounds or household clusters. We will measure objective health outcomes in approximately 760 children (380 children with household access to interventions, 380 matched controls using existing shared private latrines in poor sanitary conditions), at 2 time points: immediately before the intervention and at follow-up after 12 months. The primary outcome is combined prevalence of selected enteric infections among children under 5 years of age. Secondary outcome measures include soil-transmitted helminth (STH) reinfection in children following baseline deworming and prevalence of reported diarrhoeal disease. We will use exposure assessment, faecal source tracking, and microbial transmission modelling to examine whether and how routes of exposure for diarrhoeagenic pathogens and STHs change following introduction of effective sanitation. ETHICS: Study protocols have been reviewed and approved by human subjects review boards at the London School of Hygiene and Tropical Medicine, the Georgia Institute of Technology, the University of North Carolina at Chapel Hill, and the Ministry of Health, Republic of Mozambique. TRIAL REGISTRATION NUMBER: NCT02362932

The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols

Effects of an urban sanitation intervention on childhood enteric infection and diarrhea in Maputo, Mozambique: A controlled before-and-after trial.

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting

Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence

International audienceAgeing is the biggest risk factor for cardiovascular health and is associated with increased incidence of cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening, has been implicated in age-related tissue dysfunction. Here, we address the question of how senescence is induced in rarely dividing/post-mitotic cardiomyocytes and investigate if clearance of senescent cells attenuates age related cardiac dysfunction. During ageing, human and murine cardiomyocytes acquire a senescent-like phenotype characterised by persistent DNA damage at telomere regions that can be driven by mitochondrial dysfunction, and crucially can occur independently of cell-division and telomere length. Length-independent telomere damage in cardiomyocytes activates the classical senescence-inducing pathways, p21 CIP and p16 INK4a and results in a non-canonical senescence-associated secretory phenotype. Pharmacological or genetic clearance of senescent cells in mice alleviates myocardial hypertrophy and fibrosis, detrimental features 2 of cardiac ageing, and promotes cardiomyocyte regeneration. Our data describes a mechanism by which senescence can occur and contribute to ageing in post-mitotic tissues