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AbstractObjectiveTo evaluate trends in organisms causing early-onset neonatal sepsis (EONS). Congruent with recent reports, we hypothesized there would be an increase in EONS caused by Escherichia coli.Study DesignNational data on infants admitted to neonatal intensive care units from 2009 to 2014 were compared to previously reported data from 2003 to 2008. We report 430 cases of EONS from 2009 to 2014. Bivariate analyses were used to analyze the distribution of causative organisms over time and differences by gestational age. Linear regression was used to estimate trends in causative organisms.ResultsSince 2003, there has been a trend of increasing numbers of cases caused by E coli (P<0.01). The predominant organism was E coli in preterm infants and Group B Streptococcus in term infants.ConclusionsWith the majority of EONS cases now caused by E coli, our findings emphasize the importance of continued surveillance of causative organism patterns and developing approaches to reduce cases caused by E coli.

Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

India is blessed with an abundance of diverse rice landraces in its traditional cultivated areas. Two marker systems (simple sequence repeats (SSR) and single nucleotide polymorphism (SNP)) were used to study a set of 298 rice landrace accessions collected from six different regions of India (Andaman and Nicobar Islands, Chhattisgarh, Jharkhand, Uttar Pradesh, Uttarakhand, and West Bengal). Thirty hyper-variable simple sequence repeats (HvSSRs) and 32,782 single nucleotide polymorphisms (SNPs) were used in inferring genetic structure and geographical isolation. Rice landraces from Uttar Pradesh were the most diverse, with a gene diversity value of 0.42 and 0.49 with SSR and SNP markers, respectively. Neighbor-joining trees classified the rice landraces into two major groups with SSR and SNP markers, and complete geographical isolation was observed with SSR markers. Fast STRUCTURE analysis revealed four populations for SSR markers and three populations for SNP markers. The population structure with SSR markers showed that few individuals from Uttarakhand and Andaman and Nicobar Islands were grouped in small clusters. Population structure analysis with SNP markers showed not very distinct region-wise clustering among the rice landraces. Discriminant analysis of principal components (DAPC) and minimum spanning network (MSN) using SSR markers showed region-wise grouping of landraces with some intermixing, but DAPC and MSN with SNP markers showed very clear region-wise clustering. Genetic differentiation of rice landraces between the regions was significant with both SSR (Fst 0.094–0.487) and SNP markers (Fst 0.047–0.285). A Mantel test revealed a positive correlation between the genetic and geographic distance of rice landraces. The present study concludes that rice landraces investigated in this study were very diverse, and unlinked SSR markers show better geographical isolation than a large set of SNP markers.

Background: Collaboration between the human and animal health sectors, including the sharing of disease surveillance data, has the potential to improve public health outcomes through the rapid detection of zoonotic disease events prior to widespread transmission in humans. Kenya has been at the forefront of embracing a collaborative approach in Africa with the inception of the Zoonotic Disease Unit in 2011. Joint outbreak responses have been coordinated at the national level, yet little is currently documented on cross-sectoral collaboration at the sub-national level.Methods: Key informant interviews were conducted with 28 disease surveillance officers from the human and animal health sectors in three counties in western Kenya. An inductive process of thematic analysis was used to identify themes relating to barriers and drivers for cross-sectoral collaboration.Results: The study identified four interlinking themes related to drivers and barriers for cross-sectoral collaboration. To drive collaboration at the sub-national level there needs to be a clear identification of “common objectives,” as currently exemplified by the response to suspected rabies and anthrax cases and routine meat hygiene activities. The action of collaboration, be it integrated responses to outbreaks or communication and data sharing, require “operational structures” to facilitate them, including the formalisation of reporting lines, supporting legislation and the physical infrastructure, from lab equipment to mobile phones, to facilitate the activities. These structures in turn require “appropriate resources” to support them, which will be allocated based on the “political will” of those who control the resources.Conclusions: Ongoing collaborations between human and animal disease surveillance officers at the sub-national level were identified, driven by common objectives such as routine meat hygiene and response to suspected rabies and anthrax cases. In these areas a suitable operational structure is present, including a supportive legislative framework and clearly designated roles for officers within both sectors. There was support from disease surveillance officers to increase their collaboration, communication and data sharing across sectors, yet this is currently hindered by the lack of these formal operational structures and poor allocation of resources to disease surveillance. It was acknowledged that improving this resource allocation will require political will at the sub-national, national and international levels.

Objective To examine the prevalence and trends in overweight and obesity among non-pregnant urban women in Africa over the past two and a half decades. Design Cross-sectional surveys conducted between 1991 and 2014. Settings Demographic and Health Surveys (DHS), repeated cross-sectional data collected in 24 African countries. Participants Adult non-pregnant women aged 15–49 years. The earlier DHS collected anthropometric data on only those women who had children aged 0–5 years. The main analyses were limited to this subgroup. The participants were classified as overweight (25.0–29.9 kg/m2) and obese (≥30.0 kg/m2). Results The prevalence of overweight and obesity among women increased in all the 24 countries. Trends were statistically significant in 17 of the 24 countries in the case of obesity and 13 of the 24 for overweight. In Ghana, overweight almost doubled (p=0.001) while obesity tripled (p=0.001) between 1993 and 2014. Egypt has the highest levels of overweight and obesity at 44% (95% CI 42%, 46.5%) and 39% (95% CI 36.6%, 41.8%), respectively, in 2014 and the trend showed significant increase (p=0.005) from 1995 levels. Also, obesity doubled in Kenya, Benin, Niger, Rwanda, Ivory Coast and Uganda, while tripled in Zambia, Burkina Faso, Mali, Malawi and Tanzania. Ethiopia and Madagascar had the lowest prevalence of both obesity and overweight, with overweight ranging from 7% to 12% and obesity from 1% to 4%. Conclusions Overweight and obesity are increasing among women of reproductive age in urban Africa, with obesity among this age group having more than doubled or tripled in 12 of the 24 countries. There is an urgent need for deliberate policies and interventions to encourage active lifestyles and healthy eating behaviour to curb this trend in urban Africa.

BACKGROUND: In parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial.OBJECTIVE: The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals.METHODS: Total PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans.RESULTS: In a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05-2.08, P = 0.02).CONCLUSION: Our data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

ObjectiveTo evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. MethodsThis retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan-Meier methods and survival analyses were undertaken using Cox proportional-hazards models. ResultsTwenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m(2)/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m(2)/4 weeks). Mean follow-up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan-Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log-rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7-2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9-91.8, P = 0.059). InterpretationThis study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG.

AbstractThere is now widespread acceptance of the universal coverage approach, presented in the 2010 World Health Report. There are more and more voices for the benefit of creating a single national risk pool. Now, a body of literature is emerging on institutional design and organizational practice for universal coverage, related to management of the three health-financing functions: collection, pooling and purchasing. While all countries can move towards universal coverage, lower-income countries face particular challenges, including scarce resources and limited capacity. Recently, the Lao PDR has been preparing options for moving to a single national health insurance scheme. The aim is to combine four different social health protection schemes into a national health insurance authority (NHIA) with a single national fund- and risk-pool. This paper investigates the main institutional and organizational challenges related to the creation of the NHIA. The paper uses a qualitative approach, drawing on the World Health Organization's institutional and Organizational Assessment for Improving and Strengthening health financing (OASIS) conceptual framework for data analysis. Data were collected from a review of key health financing policy documents and from 17 semi-structured key informant interviews. Policy makers and advisors are confronting issues related to institutional arrangements, funding sources for the authority and government support for subsidies to the demand-side health financing schemes. Compulsory membership is proposed, but the means for covering the informal sector have not been resolved. While unification of existing schemes may be the basis for creating a single risk pool, challenges related to administrative capacity and cross-subsidies remain. The example of Lao PDR illustrates the need to include consideration of national context, the sequencing of reforms and the time-scale appropriate for achieving universal coverage.

This paper highlights important environmental dimensions of HIV vulnerability by describing how the sex trade operates in Nairobi, Kenya. Although sex workers there encounter various forms of violence and harassment, as do sex workers globally, we highlight how they do not merely fall victim to a set of environmental risks but also act upon their social environment, thereby remaking it, as they strive to protect their health and financial interests. In so doing, we illustrate the mutual constitution of 'agency' and 'structure' in social network formations that take shape in everyday lived spaces. Our findings point to the need to expand the focus of interventions to consider local ecologies of security in order to place the local knowledges, tactics, and capacities that communities might already possess on centre stage in interventions. Planning, implementing, and monitoring interventions with a consideration of these ecologies would tie interventions not only to the risk reduction goals of global public health policy, but also to the very real and grounded financial priorities of what it means to try to safely earn a living through sex work.