Three-nucleotide periodicity of nucleotide diversity in a population enables the identification of open reading frames.

Accurate prediction of open reading frames (ORFs) is important for studying and using genome sequences. Ribosomes move along mRNA strands with a step of three nucleotides and datasets carrying this information can be used to predict ORFs. The ribosome-protected footprints (RPFs) feature a significant 3-nt periodicity on mRNAs and are powerful in predicting translating ORFs, including small ORFs (sORFs), but the application of RPFs is limited because they are too short to be accurately mapped in complex genomes. In this study, we found a significant 3-nt periodicity in the datasets of populational genomic variants in coding sequences, in which the nucleotide diversity increases every three nucleotides. We suggest that this feature can be used to predict ORFs and develop the Python package 'OrfPP', which recovers ~83% of the annotated ORFs in the tested genomes on average, independent of the population sizes and the complexity of the genomes. The novel ORFs, including sORFs, identified from single-nucleotide polymorphisms are supported by protein mass spectrometry evidence comparable to that of the annotated ORFs. The application of OrfPP to tetraploid cotton and hexaploid wheat genomes successfully identified 76.17% and 87.43% of the annotated ORFs in the genomes, respectively, as well as 4704 sORFs, including 1182 upstream and 2110 downstream ORFs in cotton and 5025 sORFs, including 232 upstream and 234 downstream ORFs in wheat. Overall, we propose an alternative and supplementary approach for ORF prediction that can extend the studies of sORFs to more complex genomes.

A qualitative exploration of factors that influence the uptake of tuberculosis services by low-skilled migrant workers in Singapore.

INTRODUCTION: Singapore relies heavily on migrant workers to build its country and harbours a relatively large population of these workers. Importantly, tuberculosis (TB) remains a pernicious threat to the health of these workers and in line with the United Nations High-Level Meeting in 2023, this paper aims to uncover the qualitative discourse facing migrant workers' uptake of TB services and provide policy recommendations to enable more equitable access to TB services for this population. METHODS: In-depth interviews were carried out with the migrant worker population recruited from a non-governmental organisation in Singapore that serves migrant workers through the provision of primary healthcare services, counselling, and social assistance. Interviews stopped once thematic saturation was achieved and no new themes and subthemes were found. RESULTS: A total of 29 participants were interviewed, including 16 Bangladeshis and 13 Chinese, aged between 22 and 54 years old, all worked in the construction sector. Four key themes emerged. They are (1) General TB knowledge: Misconceptions are prevalent, where we found that participants were aware of the disease but did not possess a clear understanding of its pathophysiology and associated health effects, (2) Contextual knowledge and perception of associated policies related to TB in Singapore: low awareness among migrant workers as participants' accounts depicted a lack of information sources in Singapore especially on issues related to healthcare including TB, (3) Attitude to towards TB: Motivation to seek treatment is underpinned by ability to continue working and (4) Stigma: mixed perception of how society views TB patients. The gaps identified in migrant workers' TB knowledge, their attitude towards the disease and their perception of the availability of TB-related services is despite Singapore's efforts to curb community spread of TB and its proactive initiatives to reduce the prevalence. CONCLUSION: Our study illuminates the various aspects that policymakers need to home in on to ensure this vulnerable group is sufficiently supported and equitably cared for if they develop active TB during their stay in Singapore as they contribute to the nation's economy. Leveraging the COVID-19 pandemic as a window of opportunity to improve overall healthcare access for vulnerable groups in Singapore can be a starting point.

Study on the effects of different postprandial positions on blood pressure and heart rate in older adults with primary hypertension and postprandial hypotension.

This randomized controlled trial explored the effects of a supine position or a semi-fowler position on postprandial blood pressure (BP) of older adults with primary hypertension and postprandial hypotension (PPH). Ninety-six participants were divided into the supine group, the semi-fowler group, and the control group with block-randomization. After a meal, the patients were placed in a supine position, a 45° semi-fowler position, or allowed daily activities, respectively. BP, heart rate and PPH symptoms were measured 5 times in 120 minutes after the meal. Repeated measurement analysis showed no statistical difference in BP, heart rate and PPH symptom scores among the three groups. BP in all groups decreased rapidly at the 30-minute point, and then moved steadily downward. Taking a supine position or semi-fowler position after meals had no effect on postprandial BP and heart rate after meals in older adults with hypertension and PPH.

A new strain of Volutella citrinella with nematode predation and nematicidal activity, isolated from the cysts of potato cyst nematodes in China.

BACKGROUND: Plant parasitic nematodes (PPNs) are responsible for causing many plant diseases and are extremely difficult to control at present. Currently, due to the negative effects of chemical agents on the environment and human health, the development of new biological pesticides has become an important part of plant nematode control. Nematophagous fungi refers to a class of fungi that kill plant nematodes. Notably, a large number of nematophagous fungi resources remain to be studied. The objective of our study was to use in vitro screening to identify nematophagous fungi and select strains that were highly active against nematodes, providing a primary research for the development and utilization of new nematophagous fungi. RESULTS: A new nematophagous fungal strain (GUCC2219) was isolated from cysts of possibly Globodera spp. and Heterodera spp., identified as Volutella citrinella. The hyphae of V. citrinella produced ring structures of variable size and exhibited predatory and nematicidal activity. The hyphal predation rates (in vitro) against three species of nematodes, Aphelenchoides besseyi, Bursaphelenchus xylophilus, and Ditylenchus destructor, averaged 59.45, 33.35, and 50.95%, respectively, while the fermentation broth produced by the fungus exhibited mortality rates of 100, 100, and 55.63%, respectively, after 72 h. CONCLUSION: V. citrinella is a new strain with nematophagous properties, which are a novel discovery. At the same time, this is the first report of nematicidal and nematode predation activity in the genus Volutella.

Variations in regulations to control standards for training and licensing of physicians: a multi-country comparison.

BACKGROUND: To strengthen health systems, the shortage of physicians globally needs to be addressed. However, efforts to increase the numbers of physicians must be balanced with controls on medical education imparted and the professionalism of doctors licensed to practise medicine. METHODS: We conducted a multi-country comparison of mandatory regulations and voluntary guidelines to control standards for medical education, clinical training, licensing and re-licensing of doctors. We purposively selected seven case-study countries with differing health systems and income levels: Canada, China, India, Iran, Pakistan, UK and USA. Using an analytical framework to assess regulations at four sequential stages of the medical education to relicensing pathway, we extracted information from: systematically collected scientific and grey literature and online news articles, websites of regulatory bodies in study countries, and standardised input from researchers and medical professionals familiar with rules in the study countries. RESULTS: The strictest controls we identified to reduce variations in medical training, licensing and re-licensing of doctors between different medical colleges, and across different regions within a country, include: medical education delivery restricted to public sector institutions; uniform, national examinations for medical college admission and licensing; and standardised national requirements for relicensing linked to demonstration of competence. However, countries analysed used different combinations of controls, balancing the strictness of controls across the four stages. CONCLUSIONS: While there is no gold standard model for medical education and practise regulation, examining the combinations of controls used in different countries enables identification of innovations and regulatory approaches to address specific contextual challenges, such as decentralisation of regulations to sub-national bodies or privatisation of medical education. Looking at the full continuum from medical education to licensing is valuable to understand how countries balance the strictness of controls at different stages. Further research is needed to understand how regulating authorities, policy-makers and medical associations can find the right balance of standardisation and context-based flexibility to produce well-rounded physicians.

Framing global discourses on non-communicable diseases: a scoping review.

BACKGROUND: The choices that policymakers make are shaped by how their problems are framed. At last, non-communicable diseases (NCDs) have risen high on the global policy agenda, but there are many disputed issues. First, what are they? Their name refers not to what they are but what they are not. Second, where do their boundaries lie? What diseases are included? Third, should we view their causes as mainly biomedical, behavioural, or social, or a combination? Our failure to resolve these issues has been invoked as a reason for our limited progress in developing and implementing effective remedies. In this scoping review, we ask "What is known from the existing literature about how NCDs are framed in the global policy discourses?" We answer it by reviewing the frames employed in policy and academic discourses. METHODS: We searched nine electronic databases for articles published since inception to 31 May 2019. We also reviewed websites of eight international organisations to identify global NCDs policies. We extracted data and synthesised findings to identify key thematic frames. RESULTS: We included 36 articles and nine policy documents on global NCDs policies. We identified five discursive domains that have been used and where there are differing perspectives. These are: "Expanding the NCDs frame to include mental health and air pollution"; "NCDs and their determinants"; "A rights-based approach to NCDs"; "Approaches to achieving policy coherence in NCDs globally"; and "NCDs as part of Sustainable Socio-economic Development". We further identified 12 frames within the five discursive domains. CONCLUSIONS: This scoping review identifies issues that remain unresolved and points to a need for alignment of perspectives among global health policy actors, as well as synergies with those working on mental health, maternal health, and child health. The current COVID-19 pandemic warrants greater consideration of its impact on global NCDs policies. Future global strategies for NCDs need to consider explicitly how NCDs are framed in a changing global health discourse and ensure adequate alignment with implementation and global health issues. There is a need for global strategies to recognise the pertinent role of actors in shaping policy discourses.

Effects of Spo0A on Clostridium acetobutylicum with an emphasis on biofilm formation.

Clostridium acetobutylicum is a well-known strain for biofuel production. In previous work, it was found that this strain formed biofilm readily during fermentation processes. Biofilm formation could protect cells and enhance productivities under environmental stresses in our previous work. To explore the molecular mechanism of biofilm formation, Spo0A of C. acetobutylicum was selected to investigate its influences on biofilm formation and other physiological performances. When spo0A gene was disrupted, the spo0A mutant could hardly form biofilm. The aggregation and adhesion abilities of the spo0A mutant as well as its swarming motility were dramatically reduced compared to those of wild type strain. Sporulation was also negatively influenced by spo0A disruption, and solvent production was almost undetectable in the spo0A mutant fermentation. Furthermore, proteomic differences between wild type strain and the spo0A mutant were consistent with physiological performances. This is the first study confirming a genetic clue to C. acetobutylicum biofilm and will be valuable for biofilm optimization through genetic engineering in the future.

Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

BACKGROUND: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control. METHODS: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation. RESULTS: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF. CONCLUSIONS: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

Designing evaluation studies to optimally inform policy: what factors do policy-makers in China consider when making resource allocation decisions on healthcare worker training programmes?

BACKGROUND: In light of the gap in evidence to inform future resource allocation decisions about healthcare provider (HCP) training in low- and middle-income countries (LMICs), and the considerable donor investments being made towards training interventions, evaluation studies that are optimally designed to inform local policy-makers are needed. The aim of our study is to understand what features of HCP training evaluation studies are important for decision-making by policy-makers in LMICs. We investigate the extent to which evaluations based on the widely used Kirkpatrick model - focusing on direct outcomes of training, namely reaction of trainees, learning, behaviour change and improvements in programmatic health indicators - align with policy-makers' evidence needs for resource allocation decisions. We use China as a case study where resource allocation decisions about potential scale-up (using domestic funding) are being made about an externally funded pilot HCP training programme. METHODS: Qualitative data were collected from high-level officials involved in resource allocation at the national and provincial level in China through ten face-to-face, in-depth interviews and two focus group discussions consisting of ten participants each. Data were analysed manually using an interpretive thematic analysis approach. RESULTS: Our study indicates that Chinese officials not only consider information about the direct outcomes of a training programme, as captured in the Kirkpatrick model, but also need information on the resources required to implement the training, the wider or indirect impacts of training, and the sustainability and scalability to other settings within the country. In addition to considering findings presented in evaluation studies, we found that Chinese policy-makers pay close attention to whether the evaluations were robust and to the composition of the evaluation team. CONCLUSIONS: Our qualitative study indicates that training programme evaluations that focus narrowly on direct training outcomes may not provide sufficient information for policy-makers to make decisions on future training programmes. Based on our findings, we have developed an evidence-based framework, which incorporates but expands beyond the Kirkpatrick model, to provide conceptual and practical guidance that aids in the design of training programme evaluations better suited to meet the information needs of policy-makers and to inform policy decisions.

Association study of genetic variants at newly identified lipid gene TRIB1 with coronary heart disease in Chinese Han population.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified the variants near TRIB1 gene affecting blood lipid levels. However, the association between the reported variants and risk of coronary heart disease (CHD) was not confirmed. METHODS: We conducted two independent case-control studies. The first study consisted of 300 CHD patients and 300 controls and the second study had 1,332 CHD patients and 2,811 controls. The genotypes of two variants rs3201475 and rs17321515 in TRIB1 were determined by TaqMan assay. The dual-luciferase reporter assay was performed for evaluating the function of the SNP rs3201475. RESULTS: The statistical analysis indicated that single nucleotide polymorphism (SNP) rs17321515 was replicated to be associated with triglyceride (TG) level, which was also significantly associated with CHD risk when using the stratified analysis after adjusting for conventional risk factors. Compared with GG genotype, AA carriers of SNP rs17321515 had higher risk in males (odds ratio (OR)=1.28, 95%CI=1.01-1.61; P=0.03) and smokers (OR=1.41, 95%CI=1.09-1.88; P=0.01). We did not find significantly association between genotypes of rs3201475 and CHD risk. In addition, no significant difference was found in the luciferase activity assay of SNP rs3201475. CONCLUSIONS: Our findings indicated that SNP rs17321515 is significantly associated with plasma TG level and the increasing risk of CHD among males and smokers in Chinese, whereas there is no positive association between SNP rs3201475 and CHD risk. Smoking could modify the effects of TRIB1 on CHD risk.

Evaluating population-level interventions to reduce inappropriate antibiotic use in healthcare and community settings: A systematic review protocol.

BACKGROUND: Inappropriate antibiotic use contributes significantly to the global challenge of antimicrobial resistance. While government-initiated population-level interventions are fundamental in addressing this issue, their full potential remains to be explored. This systematic review aims to assess the effectiveness of such interventions in reducing inappropriate antibiotic use among antibiotic providers and users in healthcare and community settings. METHODS: We will conduct a systematic literature search across multiple databases and grey literature sources. We will include studies which evaluate the effectiveness of population-level interventions to reduce inappropriate antibiotic use in healthcare and community settings in both high-income and low- and middle-income countries. This includes government-initiated measures targeting antibiotic use through education, restriction, incentivization, coercion, training, persuasion, context modification, behavior modeling, or barrier reduction. Two reviewers will independently perform screening to select eligible studies, followed by data extraction. The outcomes of interest are various measures of antibiotic prescription and consumption, such as Defined Daily Dose (DDD) or number of prescriptions per year. We anticipate including a broad range of study designs and outcome measures. Therefore, we will narratively synthesize results using the categories of the population-level policy interventions of the Behavior Change Wheel Framework. We will organize outcome data by economic contexts, target populations, and implementation settings. DISCUSSION: This review will strengthen the evidence base for the use of population-level interventions to address inappropriate antibiotic use. Drawing lessons from global experiences, the findings will provide valuable guidance to health policymakers, public health authorities, and researchers on tailoring interventions to specific economic contexts, populations, and settings, thereby enhancing their capacity to drive substantial improvement in appropriate antibiotic use.

Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

BACKGROUND: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. METHODS AND FINDINGS: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. CONCLUSION: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Burden of tuberculosis among vulnerable populations worldwide: an overview of systematic reviews.

BACKGROUND: Tuberculosis is a communicable disease of public health concern that inequitably impacts the most vulnerable populations worldwide. Vulnerable populations are those with a high risk for tuberculosis disease and whose disadvantaged or marginalised socioeconomic position limits their access to the health system. We conducted an overview of reviews that aimed to assess the burden (ie, prevalence and incidence) of tuberculosis disease among 12 vulnerable populations globally. METHODS: We did an overview of reviews using a systematic search in MEDLINE, Embase, and the Cochrane Database for Systematic Reviews for articles published in English, French, and Chinese, from Jan 1, 2010 to March 8, 2023. We did an initial search on Oct 28, 2021, and updated our search on March 8, 2023. We included systematic and scoping reviews reporting on the prevalence or incidence of active tuberculosis among 12 vulnerable populations. Evidence gaps were supplemented with primary or secondary database studies. Study characteristics and outcome data related to tuberculosis burden were tabulated, including prevalence ratios and incidence rate ratios, and evidence was synthesised narratively. This trial is registered with PROSPERO (CRD42022324421). FINDINGS: We screened 13 169 citations and included 44 publications (23 reviews and 21 primary or database studies) in the final synthesis. The comprehensiveness and methodological quality of the evidence differed across population groups. Prevalence of more than 1000 cases per 100 000 were reported in all vulnerable populations. On the basis of pooled estimates, prevalence ratios were often more than 25 among people experiencing homelessness, incarcerated populations, refugees, asylum seekers, and people living with HIV compared with the general population. Incidence was infrequently reported, with the best-available incidence rate ratios documented for people who were incarcerated. There was scarce evidence specific to miners, nomadic populations, sex workers, men who have sex with men, and transgender individuals. INTERPRETATION: The burden of tuberculosis is substantially higher among vulnerable populations than general populations, suggesting a need for improved integration of these groups, including dedicated efforts for their identification, targeted screening and prevention measures, as well as treatment support. FUNDING: WHO.

Defining tuberculosis vulnerability based on an adapted social determinants of health framework: a narrative review.

The World Health Organization's new End TB Strategy emphasises socioeconomic interventions to reduce access barriers to TB care and address the social determinants of TB. To facilitate developing interventions that align with this strategy, we examined how TB vulnerability and vulnerable populations were defined in literature, with the aim to propose a definition and operational criteria for TB vulnerable populations through social determinants of health and equity perspectives. We searched for documents providing explicit definition of TB vulnerability or list of TB vulnerable populations. Guided by the Commission on the Social Determinants of Health framework, we synthesised the definitions, compiled vulnerable populations, developed a conceptual framework of TB vulnerability, and derived definition and criteria for TB vulnerable populations. We defined TB vulnerable populations as those whose context leads to disadvantaged socioeconomic positions that expose them to systematically higher risks of TB, but having limited access to TB care, thus leading to TB infection or progression to TB disease. We propose that TB vulnerable populations can be determined in three dimensions: disadvantaged socioeconomic position, higher risks of TB infection or progression to disease, and poor access to TB care. Examining TB vulnerability facilitates identification and support of vulnerable populations.

Insight into protein synthesis in axon regeneration.

Successful axon regeneration is crucial for the treatment of numerous nerve injuries and neurodegenerative diseases, which requires adequate and accurate protein synthesis, including mRNA translation, both in the neuron somas and locally in the axons. Recent studies have shed light on novel functions and mechanisms of protein synthesis that are relevant for axon regeneration, with a particular focus on local translation. Here, we review the new developed technologies and approaches for investigating local translation, discuss the roles of local translation in axon regeneration, and summarize the key signaling molecules and pathways that regulate local translation during axon regeneration. Additionally, we give an overview of local translation in the peripheral and central nervous systems neurons and the latest progress in protein synthesis in neuron somas respectively. Finally, we consider the potential directions for future research in this field to provide insights into protein synthesis in axon regeneration.

Barriers to and Facilitators of the Implementation of a Micronutrient Powder Program for Children: A Systematic Review Based on the Consolidated Framework for Implementation Research.

BACKGROUND: As one of the most cost-effective investments for improving child nutrition, micronutrient powder (MNP) has been widely used in many countries to underpin the Sustainable Development Goals, yet challenges remain regarding its implementation on a large scale. However, few studies have explored the factors that facilitate or impede the implementation process using implementation science theories and frameworks. To address this gap, we adopted the Consolidated Framework of Implementation Research (CFIR) and conducted a systematic review of studies on the implementation barriers to and facilitators of MNP interventions. METHOD: Five publication databases, including EMBASE, Medline, PubMed, Web of Science, and Scopus, were searched for studies on the influencing factors of MNP interventions. Based on the CFIR framework, the facilitators and barriers for the MNP program implementation reported in the included studies were extracted and synthesized by five domains: intervention characteristics, outer setting, inner setting, individual characteristics, and process. RESULTS: A total of 50 articles were eligible for synthesis. The majority of the studies were conducted in lower-middle-income countries (52%) through the free delivery model (78%). The inner setting construct was the most prominently reported factor influencing implementation, specifically including available resources (e.g., irregular or insufficient MNP supply), structural characteristics (e.g., public-driven community-based approach), and access to information and knowledge (e.g., lack of training for primary-level workers). The facilitators of the engagement of private sectors, external guidelines, and regular program monitoring were also highlighted. On the contrary, monotonous tastes and occasional side effects impede intervention implementation. Additionally, we found that the inner setting had an interrelation with other contributing factors in the MNP program implementation. CONCLUSION: Our results suggest that MNP program implementation was prominently influenced by the available resources, organizational structure, and knowledge of both providers and users. Mobilizing local MNP suppliers, engaging public-driven free models in conjunction with market-based channels, and strengthening the training for primary-level health workers could facilitate MNP interventions.

Effect of the incremental protection of previous infection against Omicron infection among individuals with a hybrid of infection- and vaccine-induced immunity: a population-based cohort study in Canada.

OBJECTIVES: We examined the incremental protection and durability of infection-acquired immunity against Omicron infection in individuals with hybrid immunity in Ontario, Canada. METHODS: We followed up 6 million individuals with at least one multiplex reverse transcriptase-polymerase chain reaction test before November 21, 2021, until an Omicron infection. Protection via infection-acquired immunity was assessed by comparing Omicron infection risk between previously infected individuals and those without documented infection under different vaccination scenarios and stratified by time since the last infection or vaccination. RESULTS: A previous infection was associated with 68% (95% CI 61-73) and 43% (95% CI 27-56) increased protection against Omicron infection in individuals with two and three doses, respectively. Among individuals with two-dose vaccination, the incremental protection of infection-induced immunity decreased from 79% (95% CI 75-81) within 3 months after vaccination or infection to 27% (95% CI 14-37) at 9-11 months. In individuals with three-dose vaccination, it decreased from 57% (95% CI 50-63) within 3 months to 37% (95% CI 19-51) at 3-5 months after vaccination or infection. CONCLUSION: Previous SARS-CovV-2 infections provide added cross-variant immunity to vaccination. Given the limited durability of infection-acquired protection in individuals with hybrid immunity, its influence on shield-effects at the population level and reinfection risks at the individual level may be limited.

Identification of quorum sensing-regulated Vibrio fortis as potential pathogenic bacteria for coral bleaching and the effects on the microbial shift.

Coastal pollution, global warming, ocean acidification, and other reasons lead to the imbalance of the coral reef ecosystem, resulting in the increasingly serious problem of coral degradation. Coral bleaching is often accompanied by structural abnormalities of coral symbiotic microbiota, among which Vibrio is highly concerned. In this study, Vibrio fortis S10-1 (MCCC 1H00104), isolated from sea cucumber, was used for the bacterial infection on coral Seriatopora guttatus and Pocillopora damicornis. The infection of S10-1 led to coral bleaching and a significant reduction of photosynthetic function in coral holobiont, and the pathogenicity of V. fortis was regulated by quorum sensing. Meanwhile, Vibrio infection also caused a shift of coral symbiotic microbial community, with significantly increased abundant Proteobacteria and Actinobacteria and significantly reduced abundant Firmicutes; on genus level, the abundance of Bacillus decreased significantly and the abundance of Rhodococcus, Ralstonia, and Burkholderia-Caballeronia-Paraburkholderia increased significantly; S10-1 infection also significantly impacted the water quality in the micro-ecosystem. In contrast, S10-1 infection showed less effect on the microbial community of the live stone, which reflected that the microbes in the epiphytic environment of the live stone might have a stronger ability of self-regulation; the algal symbionts mainly consisted of Cladocopium sp. and showed no significant effect by the Vibrio infection. This study verified that V. fortis is the primary pathogenic bacterium causing coral bleaching, revealed changes in the microbial community caused by its infection, provided strong evidence for the "bacterial bleaching" hypothesis, and provided an experimental experience for the exploration of the interaction mechanism among microbial communities, especially coral-associated Vibrio in the coral ecosystem, and potential probiotic strategy or QS regulation on further coral disease control.

Health financing policies during the COVID-19 pandemic and implications for universal health care: a case study of 15 countries.

BACKGROUND: The COVID-19 pandemic was a health emergency requiring rapid fiscal resource mobilisation to support national responses. The use of effective health financing mechanisms and policies, or lack thereof, affected the impact of the pandemic on the population, particularly vulnerable groups and individuals. We provide an overview and illustrative examples of health financing policies adopted in 15 countries during the pandemic, develop a framework for resilient health financing, and use this pandemic to argue a case to move towards universal health coverage (UHC). METHODS: In this case study, we examined the national health financing policy responses of 15 countries, which were purposefully selected countries to represent all WHO regions and have a range of income levels, UHC index scores, and health system typologies. We did a systematic literature review of peer-reviewed articles, policy documents, technical reports, and publicly available data on policy measures undertaken in response to the pandemic and complemented the data obtained with 61 in-depth interviews with health systems and health financing experts. We did a thematic analysis of our data and organised key themes into a conceptual framework for resilient health financing. FINDINGS: Resilient health financing for health emergencies is characterised by two main phases: (1) absorb and recover, where health systems are required to absorb the initial and subsequent shocks brought about by the pandemic and restabilise from them; and (2) sustain, where health systems need to expand and maintain fiscal space for health to move towards UHC while building on resilient health financing structures that can better prepare health systems for future health emergencies. We observed that five key financing policies were implemented across the countries-namely, use of extra-budgetary funds for a swift initial response, repurposing of existing funds, efficient fund disbursement mechanisms to ensure rapid channelisation to the intended personnel and general population, mobilisation of the private sector to mitigate the gaps in public settings, and expansion of service coverage to enhance the protection of vulnerable groups. Accountability and monitoring are needed at every stage to ensure efficient and accountable movement and use of funds, which can be achieved through strong governance and coordination, information technology, and community engagement. INTERPRETATION: Our findings suggest that health systems need to leverage the COVID-19 pandemic as a window of opportunity to make health financing policies robust and need to politically commit to public financing mechanisms that work to prepare for future emergencies and as a lever for UHC. FUNDING: Bill & Melinda Gates Foundation.

Barriers and facilitators of implementing interventions to improve appropriate antibiotic use in low- and middle-income countries: a systematic review based on the Consolidated Framework for Implementation Research.

BACKGROUND: Behavior change interventions that aim to improve rational antibiotic use in prescribers and users have been widely conducted in both high- and LMICs. However, currently, no review has systematically examined challenges unique to LMICs and offered insights into the underlying contextual factors that influence these interventions. We adopted an implementation research perspective to systematically synthesize the implementation barriers and facilitators in LMICs. METHODS: We conducted literature searches in five electronic databases and identified studies that involved the implementation of behavior change interventions to improve appropriate antibiotic use in prescribers and users in LMICs and reported implementation barriers and facilitators. Behavior change interventions were defined using the behavior change wheel, and the coding and synthesis of barriers and facilitators were guided by the Consolidated Framework for Implementation Research (CFIR). RESULTS: We identified 52 eligible studies, with the majority targeting prescribers practicing at tertiary facilities (N=39, 75%). The most commonly reported factors influencing implementation were found in the inner setting domain of the CFIR framework, particularly related to constraints in resources and the infrastructure of the facilities where interventions were implemented. Barriers related to the external policy environment (e.g., lack of national initiatives and policies on antibiotic use), and individual characteristics of target populations (e.g., reluctance to change prescribing behaviors) were also common, as well as facilitators related to intervention characteristics (e.g., embedding interventions in routine practice) and process (e.g., stakeholder engagement). We also provided insights into the interrelationships between these factors and the underlying causes contributing to the implementation challenges in LMICs. CONCLUSION: We presented a comprehensive overview of the barriers and facilitators of implementing behavior change interventions to promote rational antibiotic use in LMICs. Our findings suggest that facilitating the implementation of interventions to improve rational antibiotic use needs comprehensive efforts to address challenges at policy, organizational, and implementation levels. Specific strategies include (1) strengthening political commitment to prompt mobilization of domestic resources and formulation of a sustainable national strategy on AMR, (2) improving the infrastructure of health facilities that allow prescribers to make evidence-based clinical decisions, and (3) engaging local stakeholders to improve their buy-in and facilitate contextualizing interventions. TRIAL REGISTRATION: PROSPERO: CRD42021252715 .