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Purpose: Epidemiological TB data indicate differences in infection prevalence, progression rates, and clinical disease incidence between sexes. In contrast, evidence on sex-specific differential (post) TB case fatality in Europe has not been synthesized systematically., Methods: We searched electronic databases and grey literature up to December 2020 for studies reporting sex-stratified TB death data for Europe. The JBI critical appraisal tools served for bias risk assessment and subgroup analyses for studying heterogeneity. Random-effects models meta-analyses enabled estimating pooled relative risks of sex-associated TB fatality. Considering associations of comorbidities and risk factors on fatality differences, we applied relative risk meta-regression., Results: Based on 17,400 records screened, 117 studies entered quantitative analyses. Seventy-five studies providing absolute participant data with moderate quality and limited sex stratification reported 33 to 235,000 TB cases and 7 to 27,108 deaths. The pooled male-to-female TB fatality risk ratio was 1.4 [1.3-1.5]. Heterogeneity was high between studies and subgroups. Study time, concurrent comorbidities (e.g., HIV, diabetes, cancers), and mean participant ages showed no effect modification. We identified higher male TB fatality in studies with higher homelessness (coefficient 3.18, 95% CI [-0.59 to 6.94], p-value 0.10) and lower migrants proportion (coefficient - 0.24, 95% CI [- 0.5 to 0.04], p-value 0.09)., Conclusion: We found 30-50% higher TB case fatality for males in Europe. Except for homelessness, migration, and a trend for some comorbidities, assessing effect modification could not reduce our meta-analysis' high heterogeneity. Public health authorities should take heed of this higher risk of dying in male patients' treatment services., (© 2024. The Author(s).)

Wheat is one of the main staple food crops, and 775 million tonnes of wheat were produced worldwide in 2022. Fungal diseases such as Fusarium head blight, Septoria tritici blotch, spot blotch, tan spot, stripe rust, leaf rust, and powdery mildew cause serious yield losses in wheat and can impact quality. We aimed to investigate the incidence of spores from major fungal pathogens of cereals in the field by comparing microscopic and metagenomic based approaches for spore identification. Spore traps were set up in four geographically distinct UK wheat fields (Carnoustie, Angus; Bishop Burton, Yorkshire; Swindon, Wiltshire; and Lenham, Kent). Six major cereal fungal pathogen genera ( Alternaria spp. , Blumeria graminis, Cladosporium spp., Fusarium spp., Puccinia spp., and Zymoseptoria spp.) were found using these techniques at all sites. Using metagenomic and BLAST analysis, 150 cereal pathogen species (33 different genera) were recorded on the spore trap tapes. The metagenomic BLAST analysis showed a higher accuracy in terms of species-specific identification than the taxonomic tool software Kraken2 or microscopic analysis. Microscopic data from the spore traps was subsequently correlated with weather data to examine the conditions which promote ascospore release of Fusarium spp. and Zymoseptoria spp. This revealed that Zymoseptoria spp. and Fusarium spp. ascospore release show a positive correlation with relative humidity (%RH). Whereas air temperature (°C) negatively affects Zymoseptoria spp. ascospore release., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pilo, Lawless, Tiley, Karki, Burke and Feechan.)

The fungus Zymoseptoria tritici causes Septoria Tritici Blotch (STB), which is one of the most devastating diseases of wheat in Europe. There are currently no fully durable methods of control against Z. tritici, so novel strategies are urgently required. One of the ways in which fungi are able to respond to their surrounding environment is through the use of photoreceptor proteins which detect light signals. Although previous evidence suggests that Z. tritici can detect light, no photoreceptor genes have been characterised in this pathogen. This study characterises ZtWco-1, a predicted photoreceptor gene in Z. tritici. The ZtWco-1 gene is a putative homolog to the blue light photoreceptor from Neurospora crassa, wc-1. Z. tritici mutants with deletions in ZtWco-1 have defects in hyphal branching, melanisation and virulence on wheat. In addition, we identify the putative circadian clock gene ZtFrq in Z. tritici. This study provides evidence for the genetic regulation of light detection in Z. tritici and it open avenues for future research into whether this pathogen has a circadian clock., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To summarise the comparative risk of infection in school staff and their contribution to SARS-CoV-2 transmission., Design: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline., Data Sources: MEDLINE, WHO COVID-19 database and preView were searched on 29 January 2021., Eligibility Criteria: We included studies that reported risk of SARS-CoV-2 infection in school staff or transmission of SARS-CoV-2 in school settings., Data Extraction and Synthesis: Data extraction was done in duplicates. Data synthesis was qualitative. We report attack rates and infection risk in school settings for staff and students stratified by control measures taken and infection dynamics at the point of data collection., Results: Eighteen studies were included. Three studies in low incidence settings showed low attack rates similar for teachers and students. Five studies in medium incidence settings and two studies in high incidence settings showed secondary attack rates up to 16% in school staff.Seroprevalence studies, two in each low and high incidence settings showed an infection risk of 0%-0.2% and 1.7%-28% for teachers.The risk of infection for teachers compared with students were similar in one study in low incidence setting, higher in three studies (RR 1.2-4.4) and lower in three studies in medium to high incidence settings. The risk of infection for teachers in a high infection environment is higher in face-to-face than in distance classes when compared with general population groups. The risk of infections as well as risk of hospitalisation both increased for teachers during school openings compared with school closure., Conclusion: While in low incidence settings there is little evidence for school staff to be at high risk of SARS-CoV-2 infection, in high incidence settings there is an increased risk of SARS-CoV-2 infection in school staff teaching face-to-face compared to staff teaching digitally and general population., Prospero Registration Number: CRD42021239225., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Septoria tritici blotch (STB), caused by the ascomycete fungus Zymoseptoria tritici, is a major threat to wheat production worldwide. The Z. tritici genome encodes many small secreted proteins (ZtSSPs) that are likely to play a key role in the successful colonization of host tissues. However, few of these ZtSSPs have been functionally characterized for their role during infection. In this study, we identified and characterized a small, conserved cysteine-rich secreted effector from Z. tritici which has homologues in other plant pathogens in the Dothideomycetes. ZtSSP2 was expressed throughout Z. tritici infection in wheat, with the highest levels observed early during infection. A yeast two-hybrid assay revealed an interaction between ZtSSP2 and wheat E3 ubiquitin ligase (TaE3UBQ) in yeast, and this was further confirmed in planta using bimolecular fluorescence complementation and co-immunoprecipitation. Down-regulation of this wheat E3 ligase using virus-induced gene silencing increased the susceptibility of wheat to STB. Together, these results suggest that TaE3UBQ is likely to play a role in plant immunity to defend against Z. tritici., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Septoria tritici blotch (STB) is an important foliar disease of wheat that is caused by the fungal pathogen Zymoseptoria tritici . The grass Brachypodium distachyon has been used previously as a model system for cereal-pathogen interactions. In this study, we examined the nonhost resistance (NHR) response of B. distachyon to two different Z. tritici isolates in comparison with wheat. These isolates vary in aggressiveness on wheat cultivar Remus, displaying significant differences in disease and pycnidia coverage. Using microscopy, we found that similar isolate-specific responses were observed for hydrogen peroxide accumulation and cell death in both wheat and B. distachyon . Despite this, induction of isolate-specific patterns of defense gene expression by Z. tritici did differ between B. distachyon and wheat. Our results suggest that expression of the phenylalanine ammonia lyase PAL gene may be important for NHR in B. distachyon , while pathogenesis-related PR genes and expression of genes regulating reactive oxygen species may be important to limit disease in wheat. Future studies of the B. distachyon - Z. tritici interaction may allow identification of conserved plant immunity targets that are responsible for the isolate-specific responses observed in both plant species.

During plant-pathogen interactions, pathogens secrete many rapidly evolving, small secreted proteins (SSPs) that can modify plant defense and permit pathogens to colonize plant tissue. The fungal pathogen Zymoseptoria tritici is the causal agent of Septoria tritici blotch (STB), one of the most important foliar diseases of wheat, globally. Z. tritici is a strictly apoplastic pathogen that can secrete numerous proteins into the apoplast of wheat leaves to promote infection. We sought to determine if, during STB infection, wheat also secretes small proteins into the apoplast to mediate the recognition of pathogen proteins and/or induce defense responses. To explore this, we developed an SSP-discovery pipeline to identify small, secreted proteins from wheat genomic data. Using this pipeline, we identified 6,998 SSPs, representing 2.3% of all proteins encoded by the wheat genome. We then mined a microarray dataset, detailing a resistant and susceptible host response to STB, and identified 141 Z. tritici - responsive SSPs, representing 4.7% of all proteins encoded by Z. tritici - responsive genes. We demonstrate that a subset of these SSPs have a functional signal peptide and can interact with Z. tritici SSPs. Transiently silencing two of these wheat SSPs using virus-induced gene silencing (VIGS) shows an increase in susceptibility to STB, confirming their role in defense against Z. tritici ., (Copyright © 2020 Zhou, Benbow, Brennan, Arunachalam, Karki, Mullins, Feechan, Burke and Doohan.)

Understanding the nuances of host/pathogen interactions are paramount if we wish to effectively control cereal diseases. In the case of the wheat/ Zymoseptoria tritici interaction that leads to Septoria tritici blotch (STB) disease, a 10,000-year-old conflict has led to considerable armaments being developed on both sides which are not reflected in conventional model systems. Taxonomically restricted genes (TRGs) have evolved in wheat to better allow it to cope with stress caused by fungal pathogens, and Z. tritici has evolved specialized effectors which allow it to manipulate its' host. A microarray focused on the latent phase response of a resistant wheat cultivar (cv. Stigg) and susceptible wheat cultivar (cv. Gallant) to Z. tritici infection was mined for TRGs within the Poaceae. From this analysis, we identified two TRGs that were significantly upregulated in response to Z. tritici infection, Septoria-responsive TRG6 and 7 (TaSRTRG6 and TaSRTRG7) . Virus induced silencing of these genes resulted in an increased susceptibility to STB disease in cvs. Gallant and Stigg, and significantly so in the latter (2.5-fold increase in STB disease). In silico and localization studies categorized TaSRTRG6 as a secreted protein and TaSRTRG7 as an intracellular protein. Yeast two-hybrid analysis and biofluorescent complementation studies demonstrated that both TaSRTRG6 and TaSRTRG7 can interact with small proteins secreted by Z. tritici (potential effector candidates). Thus we conclude that TRGs are an important part of the wheat- Z. tritici co-evolution story and potential candidates for modulating STB resistance., (Copyright © 2020 Brennan, Zhou, Benbow, Ajaz, Karki, Hehir, O’Driscoll, Feechan, Mullins and Doohan.)

Introduction: To address regional differences in the distribution of health workers between rural and urban areas, the Nepal government has adopted the policy of deploying fresh medical graduates to remote areas for 2 years under a compulsory bonding service program. However, the impact of such an approach of redistribution of human resources for health is not well understood, nor is the experience of the health workers who are deployed. This study aimed to understand the experience of the medical graduates who have served under the bonding service program and suggest ways to improve the program as well as to make health service provision easier through the young doctors., Methods: A semi-structured questionnaire-based survey was administered online to 69 young medical doctors who had worked under the bonding service program. The responses were analysed qualitatively and the findings were presented in separate pre-established domains., Results: Most young doctors felt they were not adequately prepared for the bonding service program. Adapting to the deployed place and to the local culture was a challenge to some young doctors, which hindered their potential to serve the local community. Most found the response from the rural communities to be positive even though they faced some challenges in the beginning. While the young doctors found serving the rural communities motivating, they felt that they were limited in their capacity to provide an optimal level of health service due to limitations of infrastructure and medical equipment. They also felt that the compulsory bonding program had stunted their growth potential as medical doctors without adequately compensating them for their time and service., Conclusion: Despite the program's noble intentions, the medical doctors who were involved with the bonding service program felt that the program had yet to address several basic needs of the doctors who were deployed for service provision. In order to motivate the doctors to work in rural areas in future after the compulsory binding has ended, the stakeholders need to address the existing gaps in policies and infrastructure.