Genomics of Trypanosomatidae: Where We Stand and What Needs to Be Done?
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ABSTRACT:
SUBMITTER: Yurchenko V
PROVIDER: S-EPMC8472099 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Deaths from air pollution in the UK are higher by a factor of 10 than from car crashes, 7 for drug-related deaths and 52 for murders, and yet awareness seems to be lacking in local government. We conducted an 18-year retrospective cohort study using routinely collected health care records from Ninewells Hospital, Dundee, and Perth Royal Infirmary, in Tayside, Scotland, UK, from 2000 to 2017. Hospitalisation events and deaths were linked to daily nitric oxides (NOX, NO, NO2), and particulate matter 10 (PM10) levels extracted from publicly available data over this same time period. Distributed lag models were used to estimate risk ratios for hospitalisation and mortality, adjusting for temperature, humidity, day of the week, month and public holiday. Nitric oxides and PM10 were associated with an increased risk of all hospital admissions and cardiovascular (CV) admissions on day of exposure to pollutant. This study shows a significant increase in all cause and CV hospital admissions, on high pollution days in Tayside, Scotland.
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Project description:Globally, 5-15% of hospitalized patients acquire infections (often caused by antimicrobial-resistant microbes) due to inadequate infection prevention and control (IPC) measures. We used the World Health Organization's (WHO) 'Infection Prevention and Control Assessment Framework' (IPCAF) tool to assess the IPC compliance at Lira University hospital (LUH), a teaching hospital in Uganda. We also characterized challenges in completing the tool. This was a hospital-based, cross-sectional study conducted in November 2020. The IPC focal person at LUH completed the WHO IPCAF tool. Responses were validated, scored, and interpreted per WHO guidelines. The overall IPC compliance score at LUH was 225/800 (28.5%), implying a basic IPC compliance level. There was no IPC committee, no IPC team, and no budgets. Training was rarely or never conducted. There was no surveillance system and no monitoring/audit of IPC activities. Bed capacity, water, electricity, and disposal of hospital waste were adequate. Disposables and personal protective equipment were not available in appropriate quantities. Major challenges in completing the IPCAF tool were related to the detailed questions requiring repeated consultation with other hospital stakeholders and the long time it took to complete the tool. IPC compliance at LUH was not optimal. The gaps identified need to be addressed urgently.
| S-EPMC8167580 | biostudies-literature
Project description:The global propagation of SARS-CoV-2 and the detection of a large number of variants, some of which have replaced the original clade to become dominant, underscores the fact that the virus is actively exploring its evolutionary space. The longer high levels of viral multiplication occur - permitted by high levels of transmission -, the more the virus can adapt to the human host and find ways to success. The third wave of the COVID-19 pandemic is starting in different parts of the world, emphasizing that transmission containment measures that are being imposed are not adequate. Part of the consideration in determining containment measures is the rationale that vaccination will soon stop transmission and allow a return to normality. However, vaccines themselves represent a selection pressure for evolution of vaccine-resistant variants, so the coupling of a policy of permitting high levels of transmission/virus multiplication during vaccine roll-out with the expectation that vaccines will deal with the pandemic, is unrealistic. In the absence of effective antivirals, it is not improbable that SARS-CoV-2 infection prophylaxis will involve an annual vaccination campaign against 'dominant' viral variants, similar to influenza prophylaxis. Living with COVID-19 will be an issue of SARS-CoV-2 variants and evolution. It is therefore crucial to understand how SARS-CoV-2 evolves and what constrains its evolution, in order to anticipate the variants that will emerge. Thus far, the focus has been on the receptor-binding spike protein, but the virus is complex, encoding 26 proteins which interact with a large number of host factors, so the possibilities for evolution are manifold and not predictable a priori. However, if we are to mount the best defence against COVID-19, we must mount it against the variants, and to do this, we must have knowledge about the evolutionary possibilities of the virus. In addition to the generic cellular interactions of the virus, there are extensive polymorphisms in humans (e.g. Lewis, HLA, etc.), some distributed within most or all populations, some restricted to specific ethnic populations and these variations pose additional opportunities for/constraints on viral evolution. We now have the wherewithal - viral genome sequencing, protein structure determination/modelling, protein interaction analysis - to functionally characterize viral variants, but access to comprehensive genome data is extremely uneven. Yet, to develop an understanding of the impacts of such evolution on transmission and disease, we must link it to transmission (viral epidemiology) and disease data (patient clinical data), and the population granularities of these. In this editorial, we explore key facets of viral biology and the influence of relevant aspects of human polymorphisms, human behaviour, geography and climate and, based on this, derive a series of recommendations to monitor viral evolution and predict the types of variants that are likely to arise.
| S-EPMC8251359 | biostudies-literature
Project description:IntroductionCross-border cholera outbreaks are a major public health problem in Sub-Saharan Africa contributing to the high annual reported cholera cases and deaths. These outbreaks affect all categories of people and are challenging to prevent and control. This article describes lessons learnt during the cross-border cholera outbreak control in Eastern and Southern Africa sub-regions using the case of Uganda-DRC and Malawi-Mozambique borders and makes recommendations for future outbreak prevention and control.Materials and methodsWe reviewed weekly surveillance data, outbreak response reports and documented experiences on the management of the most recent cross-border cholera outbreaks in Eastern and Southern Africa sub-regions, namely in Uganda and Malawi respectively. Uganda-Democratic Republic of Congo and Malawi-Mozambique borders were selected because the countries sharing these borders reported high cholera disease burden to WHO.ResultsA total of 603 cross-border cholera cases with 5 deaths were recorded in Malawi and Uganda in 2015. Uganda recorded 118 cases with 2 deaths and CFR of 1.7%. The under-fives and school going children were the most affected age groups contributing 24.2% and 36.4% of all patients seen along Malawi-Mozambique and Uganda-DRC borders, respectively. These outbreaks lasted for over 3 months and spread to new areas leading to 60 cases with 3 deaths, CRF of 5%, and 102 cases 0 deaths in Malawi and Uganda, respectively. Factors contributing to these outbreaks were: poor sanitation and hygiene, use of contaminated water, floods and rampant cross-border movements. The outbreak control efforts mainly involved unilateral measures implemented by only one of the affected countries.ConclusionsCross-border cholera outbreaks contribute to the high annual reported cholera burden in Sub-Saharan Africa yet they remain silent, marginalized and poorly identified by cholera actors (governments and international agencies). The under-fives and the school going children were the most affected age groups. To successfully prevent and control these outbreaks, guidelines and strategies should be reviewed to assign clear roles and responsibilities to cholera actors on collaboration, prevention, detection, monitoring and control of these epidemics.
| S-EPMC4892562 | biostudies-literature
Project description:Despite a multitude of recent technical breakthroughs speeding high-resolution structural analysis of biological macromolecules, production of sufficient quantities of well-behaved, active protein continues to represent the rate-limiting step in many structure determination efforts. These challenges are only amplified when considered in the context of ongoing structural genomics efforts, which are now contending with multi-domain eukaryotic proteins, secreted proteins, and ever-larger macromolecular assemblies. Exciting new developments in eukaryotic expression platforms, including insect and mammalian-based systems, promise enhanced opportunities for structural approaches to some of the most important biological problems. Development and implementation of automated eukaryotic expression techniques promises to significantly improve production of materials for structural, functional, and biomedical research applications.
| S-EPMC4163025 | biostudies-literature
Project description:BackgroundAboriginal Health Workers (AHWs) are core providers of primary health care (PHC) for First Nations peoples in Australia. However, the national AHW workforce is aging and in short supply. There is a poor understanding of the factors contributing to this attrition from the perspectives of AHWs themselves. This study aimed to systematically explore the current functioning and sustainability of AHWs in NSW PHC by amplifying AHW voices.Materials and methodsThis study was co-designed with three Aboriginal health services in NSW. It included a literature review exploring the role of AHWs in NSW, and yarns with AHWs and their supervisors at participating services. Yarning is an Indigenous approach to knowledge generation centered upon storytelling. The yarns were guided by the USAID-developed Community Health Worker Assessment and Improvement Matrix. Yarn transcripts were analyzed using cyclical thematic analysis to identify key facilitators and challenges for AHW practice.ResultsThe yarns highlighted five categories of change that are required to ensure AHW sustainability: community connection, recognition, value, support, and an inclusive health system. The yarns revealed that there are both service- and system-level factors influencing each of these categories of change.ConclusionsThe lived experiences of AHWs in NSW emphasize five key categories of change that are required to ensure workforce sustainability. It is evident that a system-wide paradigm shift to better include holistic approaches to health is necessary to truly ensure sustainability. Co-designing similar studies with ACCHOs across NSW can help inform this change.
| S-EPMC9893014 | biostudies-literature
Project description:The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or "Pathogen Box" (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.
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Project description:Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children's Hospital located in Freetown, Sierra Leone. We used the World Health Organization's Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children's Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a 'Basic' IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified.
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Project description:Genome sequencing of the genus Fusarium has revealed a great capacity for discovery of new natural products of potential economical and therapeutic importance. Several of these are unknown. In this study, we investigated the product of the PKS8 gene in Fusarium graminearum, which was recently linked to gibepyrones in F. fujikuroi. Genomic analyses showed that PKS8 constitutes a stand-alone gene in F. graminearum and related species. Overexpression of PKS8 resulted in production of gibepyrones A, B, D, G and prolipyrone B, which could not be detected in the wild type strain. Our results suggest that PKS8 produces the entry compound gibepyrone A, which is subsequently oxidized by one or several non-clustering cytochrome P450 monooxygenases ending with prolipyrone B.
| S-EPMC6225250 | biostudies-other