Causal relationships between gut microbiota and dementia:A twosample,bidirectional,Mendelian randomization study

BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.

Bibliometric analysis of research on the effects of human immunodeficiency virus in orthopaedic and trauma surgery

BACKGROUND There is little research investigating how human immunodeficiency virus(HIV)affects outcomes in orthopaedic surgery.With advances in treatment,HIV has become a chronic health problem and the chance of orthopaedic surgeons encountering it in clinical practice is increasing.AIM To ascertain the quantity and quality of peer-reviewed publications in orthopaedic journals about HIV.METHODS A search of the Web of Science database was carried out,identifying any articles relating to HIV published in orthopaedic journals.These were assessed for geographic origin and level of evidence.RESULTS Of 48.7%of orthopaedic journals listed on the Web of Science database had published articles relating to HIV.There were 168 articles about HIV in orthopaedic journals with only 40.5%(n=68)published in the time frame we analysed(January 2007 to September 2017).Very few articles came from lowincome countries and any articles published from that setting were collaborations.All of the articles were low level of evidence.CONCLUSION There is a need for more high level orthopaedic and trauma research investigating the effects of HIV,particularly research from low-income countries,where higher level research will help to guide improvements in their treatment of its musculoskeletal manifestations and complications.

Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine: An in silico pharmacological model

Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.

<i>Anopheles leesoni</i>Evans 1931, a Member of the <i>Anopheles funestus</i>Group, Is a Potential Malaria Vector in Cameroon

Background: Understanding the biology of Anopheles malaria vector species is essential to planning effective and sustainable malaria control strategies in endemic countries. This study reported the implication of Anopheles leesoni in malaria transmission in Cameroon, Central Africa. Methods: Mosquitoes were collected in three localities from May 2015 to March 2018 using electric aspirators and Centers for Disease Control light traps (CDC-LT). Anopheles funestus sensu lato (s.l.) mosquitoes were identified as species using polymerase chain reaction assay (PCR). Furthermore, Plasmodium falciparum infection status was determined using the enzyme-linked immunosorbent assay (ELISA) method. Results: A total of 12,744 Anopheles mosquitoes were collected by electric aspirator (N = 4844) and CDC-LT (N = 7900). Anopheles funestus s.l. (86.95%) was the major species and the main malaria vector in rural savannah and rural forest sites followed by A. gambiae s.l. (13.05%) whereas in urban areas, A. gambiae s.l. was by far the most abundant representing 91.45% of Anopheles mosquitoes collected. Two members of the A. funestus group were identified among 1389 analysed by PCR: 1307 A. funestus sensu stricto (s.s.) (94.10%) and 82 A. leesoni (5.9%). Plasmodium falciparum infection rate was 21.04% in A. funestus s.s. For the first time, A. leesoni was found positive for P. falciparum (infection rate: 10.98%) in Cameroon. Conclusion: A very high P. falciparum infection rate was observed in this study in A. funestus s.s., highlighting its high implication in malaria transmission in Cameroon. Furthermore, the detection of P. falciparum infection in A. leesoni calls for more attention towards this neglected vector species.

Folic Acid Supplementation in Chinese Periconceptional Population:Results from the SPCC Study

Objective To determine the prevalence and determinants of folic acid(FA)supplementation in Chinese couples planning for pregnancy and in women during early pregnancy.Methods This was a cross-sectional study based on the Shanghai PreConception Cohort(SPCC)study.Data on FA supplementation and socio-demographic features were collected using questionnaires.Couples visiting clinics for pre-pregnancy examination and pregnant women at<14 gestational weeks were recruited in Shanghai,China,between March 2016 and September 2018.Results Among the pregnancy planners,42.4%(4,710/11,099)women and 17.1%(1,377/8,045)men used FA supplements,while 93.4%(14,585/15,615)of the pregnant women used FA supplements.FA supplement use was higher in female pregnancy planners who were older(RR:1.13,95%CI:1.08–1.18),had higher education(RR:1.71,95%CI:1.53–1.92),and were residing in urban districts(RR:1.06,95%CI:1.01–1.11)of FA supplementation;female pregnancy planners with alcohol consumption(RR:0.95,95%CI:0.90–0.99)had lower odds of FA supplementation.In early pregnancy,women with higher educational level(RR:1.04,95%CI:1.03–1.06),who underwent pre-pregnancy examination(RR:1.02,95%CI:1.01–1.03)had higher odds of using an FA supplement;older aged(RR:0.99,95%CI:0.98–0.99),and multigravida(RR:0.97,95%CI:0.96–0.98)had lower odds of FA supplementation.Conclusion Although the majority of pregnant women took FA supplements,more than half of the women planning for pregnancy did not.Urgent strategies are needed to improve pre-conception FA supplementation.

实行院长负责制的背景、内容及对人员表现的影响

研究院长负责制的实施北景、内容及对人员表现的影响。选择社会经济水平不同的B县(较富裕)和C县(较贫困)两个县进行调查,以召开专题小组讨论(focus group discussion)和知情者访谈(key informant interview)的定性调查方法为主,结合医院收支、诊疗等方面的定量数据进行分析。结果提示院长负责制受到院长、卫技人员的普遍拥护,调动院长与职工的工作积极性。实行院长负责制期间,两个县医院的医疗活动、经济创收、满意度与人员培训方面均有所改善。分析“放权”政策的局限性以及改善人员表现应采取的措施。讨论实行并完善院长负责制要正确处理扩大自主权和强化束约力的辩证关系和正确认识与理解新形势下的院长负责制等问题。

新型农村合作医疗对灾难性卫生支出的影响研究

研究对2006年和2008年山东和宁夏两省(自治区)样本地区新农合补偿前后住院费用造成灾难性卫生支出发生率和灾难性卫生支出平均差距进行了分析。结果发现,新农合补偿在降低灾难性卫生支出发生率和灾难性卫生支出平均差距上起到了越来越明显的作用,但是从目前的整体补偿水平看,这种作用还是比较小的。

山东、宁夏农村居民住院卫生服务利用研究

文章对山东、宁夏农村居民2006和2008两年住院卫生服务利用的情况进行了分析。经多元logistic回归发现年龄、文化、职业、不同时间(2006和2008年)和地区(山东和宁夏)是影响农村居民住院服务利用的主要因素。通过住院费用的分析得出虽然新农合报销比例在逐年增加,但由于医疗费用的不断上涨,新农合并没有减轻农村居民住院的经济负担。

新型农村合作医疗受益公平性研究

利用收入五分组法对调查的农村居民进行分组,利用集中指数、集中曲线等方法,从不同收入人群新农合覆盖率、卫生服务利用和新农合补偿三方面分析2006年和2008年新农合受益公平性的变化。结果显示:新农合使低收入人群潜在的卫生服务需要得到释放,新农合受益公平性得到改善。

10个卫生院卫生服务情况的8种方法综合评价结果

多指标综合评价方法极其常用.为了综合评价卫生管理"放权"政策对人员表现的影响,本文以10个卫生服务指标、多种(8种)综合评价法,对福建省小康的B县与较贫困的C县,共10个卫生院(B县的DX、HF、LM、SZ与JS卫生院;C县的XQ、GT、LF、WH与QX卫生院)的卫生服务状况,进行综合评价,结果如下.

新型农村合作医疗受益率和实际补偿比的实例研究

对山东和宁夏地区2006年和2008年新型农村合作医疗制度对门诊和住院费用补偿的受益率和补偿比进行了分析。结果显示,随着筹资水平的提高,参合农民门诊和住院费用的补偿受益率和实际补偿比均有提高;但当前实际补偿比仍较低,具体补偿方式对受益率和补偿比影响较大。

乡镇卫生院管理权下放的条件初探

对乡镇卫生院管理权由县卫生局下放到乡政府的有关条件进行研究,采取召开专题小组讨论、知情者访谈等定性研究的方法,调查3个不同经济状况县的乡镇卫生院管理权下放前后的变化。结果提示,不同经济状况的地区卫生主管部门、乡镇政府、乡镇卫生院对乡镇卫生院管理权下放态度明显不同。因此,提出乡镇卫生院管理权下放的必备条件是:乡镇经济发展到一定程度;乡镇政府分管领导必须学习必要的卫生管理知识;必须具备相应的配套政策。建议乡镇卫生院管理权“上收”应因时因地、区别对待,不搞“一刀切”。

乡镇卫生院服务若干指标的对应分析与同质分析

目的:研究福建省卫生政策下放(“放权”)调研现场10个卫生院卫生服务指标(业务收入比重、门急诊数和住院数等)的相互关系,为提高卫生服务水平提供参考。方法:调查指标据其百分位数分为3个水平。以SPSS软件包中较新颖的对应分析(ANACOR)与同质分析(HOMALS)进行数据处理与绘图。结果:对应分析表明,“业务收入比重”与“门急诊数”、“住院数”关系密切(线性x^2值P<0.05);同质分析表明,“业务收入比重”与“门急诊数”、“住院数”3个变量的3个水平间关系也密切。“业务收入比重”与“总收入”随“门急诊数”、“住院数”的增加而增加。结论:对应分析与同质分析法不但能像x^2检验那样分析各指标不同分类间的关系,而且还能以2维、3维坐标图更直观、形象,更易理解地表达,但涉及的统计学知识较复杂是其难点。1993年“放权”以来,乡镇卫主院的“业务收入比重”与“总收入”随“门急诊数”的增加而增加;增加“门急诊数”并收治住院,可增加“业务收入比重”,更可提高卫技人员的积极性,使卫生院的运转进入良性循环。

扩大医院自主权对卫生人力培训与发展的影响

目的:探讨扩大医院自主权对卫生人力培训发展的影响,从中吸取经验和教训。方法:采取定量与定性调查相结合,定量资料来源于县、乡两级医疗保健机构1987—2000年工作记录与报表;定性调查采取了召开专题小组讨论会、知情者访谈两种方式。结果:放权后领导观念变化,医务人员进修培训的积极性提高,培训数量增加;卫生人力结构优化,且知识和技术水平相应提高。结论:卫生服务管理权下放有利于卫生人力的培训与发展;但在贫困地区的乡镇卫生院由于资金紧缺,在扩大自主权的同时,政府还应辅以必要的前期入员培训经费。对培训造成的人才流失等负面影响,应通过制定政策,对预期亏损建立补偿机制,由受益单位与个人共同分担。

权力下放过程中人事制度改革对卫生人力素质与结构的影响研究

为了解权力下放过程中人事制度改革措施对中国农村卫生人力的影响,采用定性与定量相结合的方法在福建省某地区的两个县开展研究。结果发现:人事制度改革政策有利于扩大医院及院长的自主权,但许多改革措施难以贯彻落实;卫生人员的录用机制有所改善,但人员调动及解聘仍存在障碍,且人才流失难以遏制;权力下放政策实施后,卫生人力的数量、素质、结构有所改善。

尼日利亚非洲盘尾丝虫病项目实施效果的评价

目的:了解不同利益相关方对非洲盘尾丝虫病项目(African Programme for Onchocerciasis Control,APOC)的评价,调查该项目在社区实施中的进展及所存在的问题,为未来被忽视的热带病(neglected tropical diseases,NTD)控制项目提供政策建议。方法:采用个人深度访谈和焦点组访谈作为研究方法,使用主题框架法作为资料处理方法。结果:药物发放取得了一定的效果,社区居民普遍认可并接受了发放的预防药物。同时,研究还发现社区缺乏对NTD的健康教育,社区没有充分认识到疾病预防的责任,社区志愿者力量尚未得到可持续发展。结论:APOC项目目标部分得到实现,与其他非洲国家相比,尼日利亚在项目实施上遇到一些挑战和困难。该项目对于中国也具有借鉴意义。

Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming.In this study,we investigated the inhibiting effects of the small molecules varespladib(nonspecific phospholipase A2 inhibitor),marimastat(broad spectrum matrix metalloprotease inhibitor)and dimercaprol(metal ion chelator)against coagulopathic toxins found in Crotalinae(pit vipers)snake venoms.Venoms from Bothrops asper,Bothrops jararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in parallel.Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study.Anticoagulant venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases.Varespladib was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant toxins.Contrastingly,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins.The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments.

Impact of body fat changes in mediating the effects of antiretroviral therapy on blood pressure in HIV-infected persons in a sub-Saharan African setting

Background:Previous studies of HIV-infected patients have shown significant associations between highly active antiretroviral therapy(HAART)and increased blood pressure;however,the mechanisms involved are less clear.Therefore,we sought to investigate the potential impact of body fat changes in mediating the effects of HAART on blood pressure changes among people living with HIV.Methods:Four hundred six consenting patients(≥18 years of age)attending a tertiary HIV clinic in semi-urban Nigeria were recruited between August and November 2014 as part of a cross-sectional study.We performed bias-corrected bootstrap tests of mediation using 95%confidence intervals(CI)to determine the mediating effects of body mass index and waist circumference(mediators)on the total effects of HAART exposure(primary predictor)on blood pressure(outcome),while controlling for age,sex and other potential confounders.Results:Waist circumference remained a significant partial mediator of the total effects of HAART exposure on increasing systolic blood pressure(coefficient:1.01,95%CI:0.33 to 2.52,11%mediated)and diastolic blood pressure(coefficient:0.68,95%CI:0.26 to 1.89,9%mediated)after adjusting for age,sex,smoking status,CD4 count and duration of HIV infection.No significant mediating effect was observed with body mass index alone or in combination with waist circumference after adjusting for all potential confounders.Conclusion:Waist circumference significantly mediates the effects of HAART on blood pressure in persons living with HIV,independent of the role of traditional risk factors.The use of waist circumference as a complementary body fat measure to body mass index may improve the clinical prediction of hypertension in HIV-infected patients on antiretroviral therapy.

The new WHO guideline for control and elimination of human schistosomiasis:implications for the Schistosomiasis Elimination Programme in Nigeria

Background With some 134,073,166 people living in endemic communities at risk of infection[1],Nigeria is the most endemic country in Africa and requires preventive chemotherapy(PC)for a total of 26.3 million persons[2].The National Schistosomiasis Elimination Programme(NSCHEP),with the support of international partners,has been implementing PC in Nigeria since 2009 and most recently will need to revise its current strategy(Additional file 1).For example,the new World Health Organization(WHO)guideline has six key recommendations that will dramatically change the implementation of schistosomiasis elimination in endemic countries[3].However,its impact and programmatic implications will vary from country to country,hence the need for a country-specific analysis.

Building a global schistosomiasis alliance:an opportunity to join forces to fight inequality and rural poverty

Schistosomiasis,one of the 17 neglected tropical diseases listed by the World Health Organization,presents a substantial public health and economic burden.Of the 261 million people requiring preventive chemotherapy for schistosomiasis in 2013,92%of them lived in sub-Saharan Africa and only 12.7%received preventive chemotherapy.Moreover,in 2010,the WHO reported that schistosomiasis mortality could be as high as 280000 per year in Africa alone.In May 2012 delegates to the sixty-fifth World Health Assembly adopted resolution WHA65.21 that called for the elimination of schistosomiasis,and foresees the regular treatment of at least 75%of school age children in at-risk areas.The resolution urged member states to intensify schistosomiasis control programmes and to initiate elimination campaigns where possible.Despite this,in June 2015,schistosomiasis was indicated to have the lowest level of preventive chemotherapy implementation in the spectrum of neglected tropical diseases.It was also highlighted as the disease most lacking in progress.This is perhaps unsurprising,given that it was also the only NTD with access to drug donations but without a coalition of stakeholders that collaborates to boost commitment and implementation.As a consequence,and to ensure that the WHO NTDs Roadmap Targets of 2012 and World Health Assembly Resolution WHA65.21 are met,the Global Schistosomiasis Alliance(GSA)has been set up.Diverse and representative,the GSA aims to be a partnership of endemic countries,academic and research institutions,international development agencies and foundations,international organizations,non-governmental development organizations,private sector companies and advocacy and resource mobilisation partners.Ultimately,the GSA calls for a partnership to work for the benefit of endemic countries by addressing health inequity and rural poverty.