Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China:A nested case-control study

Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Referral patterns of children with glaucoma and their caretakers in Northern Tanzania

AIM:To describe the referral patterns of children with primary childhood glaucoma(PCG)or secondary childhood glaucoma(SCG)and their presenting symptoms in Northern Tanzania.METHODS:A retrospective observational study of children<17 y with PCG or SCG who were referred to Kilimanjaro Christian Medical Centre(KCMC)Eye Department between 2000 and 2013 was conducted.Presenting symptoms,age at presentation,place of origin,distance to hospital,type of glaucoma,visual acuity,optic disc appearance(vertical cupto-disc ratio)and type of referral were described.RESULTS:Seventy patients with PCG and 27 patients with SCG were included in the study.Median age at first presentation was 1 y in the PCG group(range 0-16 y)and 9 y in the SCG group(range 1-15 y).In both groups around 87%of the children presented already with low vision(logM AR>0.48,better eye).Most of the children(60%)and their caretakers presented on their own initiative,while 24%were sent by different general health cadres and 16%by eye care professionals.Buphthalmos was the main symptom mentioned as a trigger for presentation.CONCLUSION:The study shows that most of the children presented late resulting in advanced stages of glaucoma at the time of initiation of treatment.The majority attended the referral eye department on their own initiative with buphthalmos being the most commonly 452described symptom.Awareness creation among caretakers of children,general health and eye care providers,ideally embedded in general child health promotion activities,is needed to increase and accelerate referrals.

Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

The association between area of residence and sufficient antenatal tetanus vaccination in women ages 15-49 in Afghanistan:an analysis of the 2015 DHS dataset

Background:Neonatal tetanus(NT)is a deadly nervous system disorder that is endemic to Afghanistan.Administering sufficient doses of tetanus toxoid containing vaccine(TTCV)during pregnancy can pass antibodies to the fetus and therefore prevent NT.Using survey data,we investigated the association between area of residence(urban or rural)and sufficient antenatal TTCV coverage among women aged 15-49 years in Afghanistan during their most recent pregnancy in the past 5 years that resulted in a live birth.Mother’s education level was also assessed as a potential effect modifier.Methods:Secondary analysis was performed on data from the 2015 Afghanistan Demographic and Health Survey(AfDHS).The 2015 AfDHS was a nationally representative survey with participants selected in a stratified two-stage sample design from urban and rural areas across Afghanistan’s 34 provinces.Data were analyzed on 19,737 women ages 15-49 that had a live birth in the 5 years preceding the survey.The relationship between area of residence and sufficient antenatal TTCV was assessed in a multivariable logistic regression model,adjusting for several confounding variables.Results:55.1%(95%CI=51.6-58.5%)of urban women and 53.9%(95%CI=49.7-57.9%)of rural women had sufficient tetanus vaccination coverage in their most recent pregnancy.In multivariate analysis,there was strong evidence for greater odds of sufficient antenatal tetanus vaccination in rural areas(OR=1.62;95%CI=1.18-2.24,p=0.003).There was no effect modification on this association by mother’s education level.Conclusions:Women in rural areas of Afghanistan have greater odds of receiving sufficient antenatal tetanus vaccination than women in urban areas.Further study into factors contributing to this urban-rural disparity is needed.Targeted antenatal tetanus vaccination strategies for urban and rural women will be necessary as Afghanistan continues to work towards NT eradication.

Does the gap between health workers’expectations and the realities of implementing a performance-based financing project in Mali create frustration?

Background:Performance-Based Financing(PBF),an innovative health financing initiative,was recently implemented in Mali.PBF aims to improve quality of care by motivating health workers.The purpose of this research was to identify and understand how health workers’expectations related to their experiences of the first cycle of payment of PBF subsidies,and how this experience affected their motivation and sentiments towards the intervention.We pose the research question,“how does the process of PBF subsidies impact the motivation of health workers in Mali?”Methods:We adopted a qualitative approach using multiple case studies.We chose three district hospitals(DH 1,2 and 3)in three health districts(district 1,2 and 3)among the ten in the Koulikoro region.Our cases correspond to the three DHs.We followed the principle of data source triangulation;we used 53 semi-directive interviews conducted with health workers(to follow the principle of saturuation),field notes,and documents relating to the distribution grids of subsidies for each DH.We analyzed data in a mixed deductive and inductive manner.Results:The results show that the PBF subsidies led to health workers feeling more motivated to perform their tasks overall.Beyond financial motivation,this was primarily due to PBF allowing them to work more efficiently.However,respondents perceived a discrepancy between the efforts made and the subsidies received.The fact that their expectations were not met led to a sense of frustration and disappointment.Similarly,the way in which the subsidies were distributed and the lack of transparency in the distribution process led to feelings of unfairness among the vast majority of respondents.The results show that frustrations can build up in the early days of the intervention.Conclusion:The PBF implementation in Mali left health workers frustrated.The short overall implementation period did not allow actors to adjust their initial expectations and motivational responses,neither positive nor negative.This underlines how short-term interventions might not just lack impact,but instil negative sentiments likely to carry on into the future.

克氏锥虫的新过氧化物酶基因克隆表达研究(英文)

目的为了探索克氏锥虫的谷胱甘肽依赖的过氧化物酶活性。方法使用基因克隆与表达鉴定的方法学对克氏锥虫谷胱甘肽依赖的过氧化物酶基因克隆和表达。结果一个全新的、18kDa的克氏锥虫单拷贝过氧化物酶基因被完全克隆到E.coli的表达载体pHrcHis上,并测序。蛋白序列分析表明与基因库谷胱甘肽依赖的过氧化物酶有高度的同源性。其表达蛋白被纯化分离,测定其酶活性显示了良好的活性,并能被亚油酸-氢过氧化物饱和。结论结果证实克氏锥虫仍然存在过氧化物酶介导的生物代谢。

三级眼科机构中眼科护士的多种角色

为了满足病人和同事的期望和需求,眼科护士每天不得不应付不同的任务,尤其是在繁忙的教学医院工作时。所以,我们怎么去定义眼科护士?眼科护士在全球诸多眼健康服务中皆扮演了重要角色,这其中包括促进眼健康,预防疾病,诊断与治疗以及视力低下的康复服务。在缺乏眼科医生的国家,眼科护士通常还肩负起诊断和治疗病人的职责,并且在必要和条件允许时将他们转诊。

眼科检查

所有眼科医务工作者应能够对眼前节进行良好的检查。在本文中,我们将说明如何在有限的资源下进行眼部检查。大多数具有眼部疾病或视力问题的患者首诊是由非眼科专业的卫生工作者进行的。在资源丰富的国家,这可能是普通医师或验光师,而在资源匮乏的国家,更多见的是社区或初级卫生保健工作者。这些全科医务工作者,通常在眼疾方面的知识和经验有限,同时检查眼部的设备也有限。

建立初级眼保健远程会诊服务

信息和通信技术的进步可以使得建立并改善初级眼保健的远程会诊服务成为可能。信息和通信技术(ICT)的进步使我们能够在全球范围内推广数字健康解决方案。从早期对电视和电话的探索到现在使用智能手机和智能设备,远程医疗会诊已经走过了漫长的道路。今天,初级眼保健服务可以通过ICT得到极大改善,使社区或初级眼科中心的眼保健人员能够与三级中心和教学医院的临床医生直接接触。患者甚至可以通过在线视频会议解决方案直接与临床医生交谈。以下是建立全面的初级眼保健远程会诊服务时的主要考虑因素。

眼部的病毒性疾病

眼睛的病毒感染可影响眼睛的任何部位和周围组织。它们是急性红眼和视力丧失的重要原因。在本文中,我们概述了最常见、最重要的眼部病毒感染的诊断,治疗和预防。病毒是无法在宿主细胞外复制或存活很长时间的微小粒子。但是它们仍然可以对我们的身体和眼部健康构成持续风险。

近视：需要我们注意的严重疾病

近视是一种日益流行的流行病,到2050年将 影响全球一半的人口,其并发症可导致不可逆的视力丧失。患有近视的人无法看到远处的物体,但可以 清楚地看到近处的物体。 这影响到他们生活的方方面面,包括教育,就业和安全。

Predictors of Global Disparities in COVID-19 Vaccination Coverage — 219 Countries and Territories, December 2020–July 2022

What is already known about this topic?The significant disparities in global coronavirus disease 2019(COVID-19)vaccine coverage hamper the pace of epidemic control.There is a need to better understand the factors contributing to disparities in COVID-19 vaccination rates across countries.What is added by this report?This report revealed significant associations between vaccination coverage and various country-level indicators.Better pandemic preparedness,higher levels of trust,and a lower proportion of young population aged 0–14 were strongly correlated with higher COVID-19 vaccination coverage.What are the implications for public health practices?Our findings emphasize the need for enhanced pandemic preparedness and governance,coupled with building trust in government and healthcare systems.It also needs to address the hesitancy of vaccinating children and adolescents aged 0–14 as the vaccination campaign progresses.

Public and health professional epidemic risk perceptions in countries that are highly vulnerable to epidemics: a systematic review

Background Risk communication interventions during epidemics aim to modify risk perceptions to achieve rapid shifts in population health behaviours.Exposure to frequent and often concurrent epidemics may influence how the public and health professionals perceive and respond to epidemic risks.This review aimed to systematically examine the evidence on risk perceptions of epidemic-prone diseases in countries highly vulnerable to epidemics.Methods We conducted a systematic review using PRISMA standards.We included peer-reviewed studies describing or measuring risk perceptions of epidemic-prone diseases among the general adult population or health professionals in 62 countries considered highly vulnerable to epidemics.We searched seven bibliographic databases and applied a four-stage screening and selection process,followed by quality appraisal.We conducted a narrative meta-synthesis and descriptive summary of the evidence,guided by the Social Amplification of Risk Framework.Results Fifty-six studies were eligible for the final review.They were conducted in eighteen countries and addressed thirteen epidemic-prone diseases.Forty-five studies were quantitative,six qualitative and five used mixed methods.Forty-one studies described epidemic risk perceptions in the general public and nineteen among health professionals.Perceived severity of epidemic-prone diseases appeared high across public and health professional populations.However,perceived likelihood of acquiring disease varied from low to moderate to high among the general public,and appeared consistently high amongst health professionals.Other occupational groups with high exposure to specific diseases,such as bushmeat handlers,reported even lower perceived likelihood than the general population.Among health professionals,the safety and effectiveness of the work environment and of the broader health system response influenced perceptions.Among the general population,disease severity,familiarity and controllability of diseases were influential factors.However,the evidence on how epidemic risk perceptions are formed or modified in these populations is limited.Conclusions The evidence affords some insights into patterns of epidemic risk perception and influencing factors,but inadequately explores what underlies perceptions and their variability,particularly among diseases,populations and over time.Approaches to defining and measuring epidemic risk perceptions are relatively underdeveloped.

Report of the first international workshop on onchocerciasis-associated epilepsy

Background:Recently,several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy(OAE)may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic.Main text:On October 12-14th 2017,the first international workshop on onchocerciasis-associated epilepsy(OAE)was held in Antwerp,Belgium.The workshop was attended by 79 participants from 20 different countries.Recent research findings strongly suggest that O.volvulus is an important contributor to epilepsy,particularly in meso-and hyperendemic areas for onchocerciasis.Infection with O.volvulus is associated with a spectrum of epileptic seizures,mainly generalised tonic-clonic seizures but also atonic neck seizures(nodding),and stunted growth.OAE is characterised by an onset of seizures between the ages of 3-18 years.Multidisciplinary working groups discussed topics such as how to 1)strengthen the evidence for an association between onchocerciasis and epilepsy,2)determine the burden of disease caused by OAE,3)prevent OAE,4)improve the treatment/care for persons with OAE and affected families,5)identify the pathophysiological mechanism of OAE,and 6)deal with misconceptions,stigma,discrimination and gender violence associated with OAE.An OAE Alliance was created to increase awareness about OAE and its public health importance,stimulate research and disseminate research findings,and create partnerships between OAE researchers,communities,advocacy groups,ministries of health,non-governmental organisations,the pharmaceutical industry and funding organizations.Conclusions:Although the exact pathophysiological mechanism underlying OAE remains unknown,there is increasing evidence that by controlling and eliminating onchocerciasis,OAE will also disappear.Therefore,OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts.Given the high numbers of people with epilepsy in O.volvulus-endemic regions,more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families.

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda’s human African trypanosomiasis elimination programme

Background:The recent development of rapid diagnostic tests(RDTs)for human African trypanosomiasis(HAT)enables elimination programmes to decentralise serological screening services to frontline health facilities.However,patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases.Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions.This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile,Uganda.Methods:Between August 2013 and June 2015,85%(295/346)people who screened RDT-positive were examined by microscopy at least once;10 cases were detected.We interviewed 20 RDT-positive suspects who had not completed referral(16 who had not presented for their first microscopy examination,and 4 who had not returned for a second to dismiss them as cases after receiving discordant[RDT-positive,but microscopy-negative results]).Interviews were analysed thematically to examine experiences of each step of the referral process.Results:Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample.Most patients were unaware they were tested for HAT until receiving results,and some did not know they had screened positive.While HAT testing and treatment is free,anticipated costs for transportation and ancillary health services fees deterred many.Most expected a positive RDT result would lead to HAT treatment.RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers.For the four individuals who missed their second examination,complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given.Conclusions:An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations.In Uganda,a key structural weakness was poor provider communication about the possibility of discordant HAT test results,which is the most common outcome for serological RDT suspects in a HAT elimination programme.Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes.

Operational adaptations of the trachoma pre-validation surveillance strategy employed in Ghana:a qualitative assessment of successes and challenges

Background:In 2009 Ghana began to design a trachoma pre-validation surveillance plan,based on then-current WHO recommendations.The plan aimed to identify active trachoma resurgence and identify and manage trichiasis cases,through both active and passive surveillance approaches.This paper outlines and reviews the adaptations made by Ghana between 2011 and 2016.The assessment will provide a learning opportunity for a number of countries as they progress towards elimination status.Methods:A mixed methods approach was taken,comprising in-depth interviews and documents review.Between January and April 2016,20 in-depth interviews were conducted with persons involved in the operationalisation of the trachoma surveillance system from across all levels of the health system.A three-tier thematic coding framework was developed using a primarily inductive approach but also allowed for a more iterative approach,which drew on aspects of grounded theory.Results:During the operationalisation of the Ghana surveillance plan there were a number of adaptations(as compared to the WHO recommendations),these included:(i)Inclusion of surveillance of active trachoma in the passive surveillance approach,as compared to trichiasis alone.Issues with case identification,challenges in implementation coverage and a non-specific reporting structure hampered effectiveness;(ii)Random selection and increase in number of sites selected for the active surveillance component.This likely lacked the spatiotemporal power to be able to identify recrudescence in a timely manner;(iii)Targeted trichiasis door-to-door case searches,led by ophthalmic nurses.An effective methodology to identify trichiasis cases but resource intensive;(iv)A buddy system between ophthalmic nurses to support technical skills in an elimination setting where it is difficult to attain diagnostic and surgical skills,due to a lack of cases.The strategy did not take into account the loss of proficiency within experienced personnel.Conclusions:Ghana developed a comprehensive surveillance system that exceeded the WHO recommendations but issues with sensitivity and specificity likely led to an inefficient use of resources.Improved targeted surveillance strategies for identification of recrudescence and trichiasis case searches,need to be evaluated.Strategies must address the contextual changes that arise because of transmission decline,such as loss of surgical skills.

Effects of improved sanitation on diarrheal reduction for children under five in Idiofa,DR Congo:a cluster randomized trial

Background:The lack of safe water and sanitation contributes to the rampancy of diarrhea in many developing countries.Methods:This study describes the design of a cluster-randomized trial in Idiofa,the Democratic Republic of the Congo,seeking evidence of the impact of improved sanitation on diarrhea for children under four.Of the 276 quartiers,18 quartiers were randomly allocated to the intervention or control arm.Seven hundred and-twenty households were sampled and the youngest under-four child in each household was registered for this study.The primary endpoint of the study is diarrheal incidence,prevalence and duration in children under five.Discussion:Material subsidies will be provided only to the households who complete pit digging plus superstructure and roof construction,regardless of their income level.This study employs a Sanitation Calendar so that the mother of each household can record the diarrheal episodes of her under-four child on a daily basis.The diary enables examination of the effect of the sanitation intervention on diarrhea duration and also resolves the limitation of the small number of clusters in the trial.In addition,the project will be monitored through the‘Sanitation Map’,on which all households in the study area,including both the control and intervention arms,are registered.To avoid information bias or courtesy bias,photos will be taken of the latrine during the household visit,and a supervisor will determine well-equipped latrine uptake based on the photos.This reduces the possibility of recall bias and under-or over-estimation of diarrhea,which was the main limitation of previous studies.Trial registration:The study was approved by the Institutional Review Board of the School of Public Health,Kinshasa University(ESP/CE/040/15;April 13,2015)and registered as an International Standard Randomized Controlled Trial(ISRCTN:10,419,317)on March 13,2015.

Evaluating the probability of silent circulation of polio in small populations using the silent circulation statistic

As polio-endemic countries move towards elimination,infrequent first infections and incomplete surveillance make it difficult to determine when the virus has been eliminated from the population.Eichner and Dietz[American Journal of Epidemiology,143,8(1996)]proposed a model to estimate the probability of silent polio circulation depending upon when the last paralytic case was detected.Using the same kind of stochastic model they did,we additionally model waning polio immunity in the context of isolated,small,and unvaccinated populations.We compare using the Eichner and Dietz assumption of an initial case at the start of the simulation to a more accurate determination that observes the first case.The former estimates a higher probability of silent circulation in small populations,but this effect diminishes with increasing model population.We also show that stopping the simulation after a specific time estimates a lower probability of silent circulation than when all replicates are run to extinction,though this has limited impact on small populations.Our extensions to the Eichner and Dietz work improve the basis for decisions concerning the probability of silent circulation.Further model realism will be needed for accurate silent circulation risk assessment.

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature.We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke trial.Development of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were assessed.Analyses are adjusted for baseline prognostic factors and give OR and mean difference(MD)with 95%CI.Results In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;p<0.001).Nitrate-related headache was associated with:younger age,female sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(p<0.05).Nitrate headache was not associated with improved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,MD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,MD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or cognition.Discussion and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.