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BACKGROUND: In response to the COVID-19 pandemic, WHO launched a strategic preparedness and response plan, outlining public health measures to support countries worldwide. Healthcare workers have an increased risk of becoming infected and their behaviour regarding infection prevention and control (IPC) influences infection dynamics. IPC strategies are important across the globe, but even more in low-resource settings where capacities for testing and treatment are limited. Our study aimed to assess and implement COVID-19 pandemic preparedness and response measures in Faranah, Guinea, primarily focusing on healthcare workers' IPC knowledge, attitude and practice (KAP). METHODS: The study was conducted between April 2020 and April 2021 assessing IPC pandemic preparedness and response measures such as healthcare workers' KAP, alcohol-based handrub (ABHR) consumption and COVID-19 triaging in the Faranah Regional Hospital and two associated healthcare centres. The assessment was accompanied by IPC training and visual workplace reminders and done in pre- and post- phases to evaluate possible impact of these IPC activities. RESULTS: The overall knowledge score in the Faranah Regional Hospital was 32.0 out of 44 at baseline, and did not change in the first, but increased significantly by 3.0 points in the second follow-up. The healthcare workers felt closer proximity to SARS-CoV-2 overtime in addition to higher stress levels in all study sites. There was significant improvement across the observed triaging practices. Hand hygiene compliance showed a significant increase across study sites leading to 80% in Faranah Regional Hospital and 63% in healthcare centers. The average consumption of ABHR per consultation was 3.29 mL with a peak in February 2020 of 23 mL. CONCLUSION: Despite increased stress levels among HCWs, the ongoing IPC partnership well prepared the FRH in terms of triaging processes with a stronger impact on IPC practice than on theoretical knowledge. Throughout the pandemic, global shortages and surges in consumption did not affect the continuous ABHR provision of the FRH. This highlights local ABHR production as a key pandemic preparedness strategy.
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COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Control de Infecciones , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Guinea/epidemiología , Control de Infecciones/métodos , Masculino , Femenino , Adulto , Pandemias/prevención & control , Encuestas y Cuestionarios , Actitud del Personal de SaludRESUMEN
The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them. Using a unique dataset containing 1904 metadata, we identified patterns of metadata distribution and intensity of research conducted in Brazil, as well as where we should concentrate research efforts in the next decades. We found that the majority of metadata were about vertebrates, followed by plants, invertebrates, and fungi. Caatinga was the biome with least metadata, and that there's still a lack of information regarding all biomes in Brazil, with none of them being sufficiently sampled. We hope that these results will have implications for broader conservation and management guiding, as well as to funding allocation programs.
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We describe the composition of endoparasites associated with leaf litter anurans from an Atlantic Forest area, in southeastern Brazil. We tested if body size, sex, and reproductive modes of anuran hosts influence endoparasite abundance and richness. We sampled 583 individuals from 11 anuran species and recorded 1,600 helminths from 14 taxa. The helminths that infected the greatest number of anuran host species were the nematodes Cosmocerca parva (8 spp.), Physaloptera sp. (8 spp.), and Cosmocerca brasiliense (7 spp.), and the most abundant helminth species were Physaloptera sp. (14.6%), Cosmocerca brasiliense (13.7%) and Cosmocerca parva (12.6%). Both helminth abundance and richness were positively affected by anuran body size and dependence on water for reproduction. Larger hosts can contain a higher abundance of parasites because they may provide more physical space than smaller ones, or it can simply be a function of age. Besides, parasite species richness can be highly correlated with the amount of time a host spends in association with aquatic habitats, a conservative aspect of both parasite and host natural history. Within host species, there was a positive and significant influence of body size on helminth abundance. Haddadus binotatus females had greater helminth abundance than males, probably due to sex-related differences in behavior and/or in physiology. Our data suggest that reproductive modes could also influence helminth infection parameters in other anuran communities and should be considered in detail in future analyses.
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Anuros , Tamaño Corporal , Helmintos , Reproducción , Animales , Anuros/parasitología , Brasil , Femenino , Masculino , Helmintos/clasificación , Helmintos/fisiología , Helmintos/aislamiento & purificación , Biodiversidad , Interacciones Huésped-ParásitosRESUMEN
BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.
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Lacticaseibacillus rhamnosus , Macrófagos , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica , Receptores Acoplados a Proteínas G , Animales , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Humo/efectos adversos , Dexametasona/farmacología , Butiratos/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismoRESUMEN
The history of pharmacology is deeply intertwined with plant-derived compounds, which continue to be crucial in drug development. However, their complex structures and limited availability in plants challenge drug discovery, optimization, development, and industrial production via chemical synthesis or natural extraction. This review delves into the integration of metabolic and enzyme engineering to leverage micro-organisms as platforms for the sustainable and reliable production of therapeutic phytochemicals. We argue that engineered microbes can serve a triple role in this paradigm: facilitating pathway discovery, acting as cell factories for scalable manufacturing, and functioning as platforms for chemical derivatization. Analyzing recent progress and outlining future directions, the review highlights microbial biotechnology's transformative potential in expanding plant-derived human therapeutics' discovery and supply chains.
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Ingeniería Metabólica , Fitoquímicos , Ingeniería Metabólica/métodos , Fitoquímicos/metabolismo , Fitoquímicos/química , Humanos , Biotecnología , Bacterias/metabolismo , Bacterias/enzimología , Plantas/metabolismoRESUMEN
Across the globe, hand hygiene (HH) is promoted to fight the spread of healthcare associated infections. Despite multiple ongoing HH campaigns and projects, the healthcare associated infection rates remain high especially in low- and middle-income countries. In the narrative overview presented here, we aim to share objectives, framework, successes and challenges of our long-term partnership in Guinea to offer guidance for other projects aiming to sustainably improve HH.
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Infección Hospitalaria , Higiene de las Manos , Humanos , Guinea , Creación de Capacidad , Infección Hospitalaria/prevención & controlRESUMEN
Biotin synthase (BioB) is a member of the Radical SAM superfamily of enzymes that catalyzes the terminal step of biotin (vitamin B7) biosynthesis, in which it inserts a sulfur atom in desthiobiotin to form a thiolane ring. How BioB accomplishes this difficult reaction has been the subject of much controversy, mainly around the source of the sulfur atom. However, it is now widely accepted that the sulfur atom inserted to form biotin stems from the sacrifice of the auxiliary 2Fe-2S cluster of BioB. Here, we bioinformatically explore the diversity of BioBs available in sequence databases and find an unexpected variation in the coordination of the auxiliary iron-sulfur cluster. After in vitro characterization, including the determination of biotin formation and representative crystal structures, we report a new type of BioB utilized by virtually all obligate anaerobic organisms. Instead of a 2Fe-2S cluster, this novel type of BioB utilizes an auxiliary 4Fe-5S cluster. Interestingly, this auxiliary 4Fe-5S cluster contains a ligated sulfide that we propose is used for biotin formation. We have termed this novel type of BioB, Type II BioB, with the E. coli 2Fe-2S cluster sacrificial BioB representing Type I. This surprisingly ubiquitous Type II BioB has implications for our understanding of the function and evolution of Fe-S clusters in enzyme catalysis, highlighting the difference in strategies between the anaerobic and aerobic world.
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Proteínas de Escherichia coli , Proteínas Hierro-Azufre , Escherichia coli/metabolismo , Biotina/química , Proteínas de Escherichia coli/química , Azufre/química , Sulfurtransferasas/metabolismo , Proteínas Hierro-Azufre/químicaRESUMEN
The chemical evolution of a synthetic cell endowed with a synthetic amino acid as building block, analog to tryptophan, required the emergence of key mutations in genes involved in, inter alia, the general stress response, amino acid metabolism, stringent response, and chemotaxis. Understanding adaptation mechanisms to non-canonical biomass components will inform strategies for engineering synthetic metabolic pathways and cells.
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Células Artificiales , Aminoácidos , Mutación , Triptófano , Redes y Vías Metabólicas , Biología Sintética , Ingeniería MetabólicaRESUMEN
Directed evolution and rational design have been used widely in engineering enzymes for their application in synthetic organic chemistry and biotechnology. With stereoselectivity playing a crucial role in catalysis for the synthesis of valuable chemical and pharmaceutical compounds, rational design has not achieved such wide success in this specific area compared to directed evolution. Nevertheless, one bottleneck of directed evolution is the laborious screening efforts and the observed trade-offs in catalytic profiles. This has motivated researchers to develop more efficient protein engineering methods. As a prime approach, mutability landscaping avoids such trade-offs by providing more information of sequence-function relationships. Here, we describe an application of this efficient protein engineering method to improve the regio-/stereoselectivity and activity of P450BM3 for steroid hydroxylation, while keeping the mutagenesis libraries small so that they will require only minimal screening.
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Sistema Enzimático del Citocromo P-450 , Ingeniería de Proteínas , Sistema Enzimático del Citocromo P-450/metabolismo , Hidroxilación , Ingeniería de Proteínas/métodos , Esteroides , CatálisisRESUMEN
Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of.
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Infecciones por Citomegalovirus , Trasplante de Riñón , Humanos , Antivirales/farmacología , Citomegalovirus/genética , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/genética , Ganciclovir/farmacología , Mutación/genética , Estudios RetrospectivosRESUMEN
We systematically explore a simple class of global attractors, called Sturm due to nodal properties, for the semilinear scalar parabolic partial differential equation (PDE) ut=uxx+f(x,u,ux) on the unit interval 0
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The Ría de Vigo catchment is situated in the largest radon-prone area of the Iberian Peninsula. High local indoor radon (222Rn) levels are the preeminent source of radiation exposure, with negative effects on health. Nevertheless, information on radon levels of natural waters and the potential human exposure risks associated with their domestic use is very sparse. To elucidate the environmental factors increasing human exposure risk to radon during domestic water use, we undertook a survey of local water sources, including springs, rivers, wells, and boreholes, over different temporal scales. Continental waters were highly enriched in 222Rn: activities ranged from 1.2 to 20.2 Bq L-1 in rivers and levels one to two orders of magnitude higher were found in groundwaters (from 8.0 to 2737 Bq L-1; median 121.1 Bq L-1). The geology and hydrogeology of local crystalline aquifers support one order of magnitude higher 222Rn activities in groundwater stored in deeper fractured rock compared to that contained within the highly weathered regolith at the surface. During the mean dry season, 222Rn activities nearly doubled in most sampled waters in comparison to the wet period (from 94.9 during the dry season to 187.3 Bq L-1 during wet period; n = 37). Seasonal water use and recharge cycles and thermal convection are postulated to explain this variation in radon activities. The high 222Rn activities cause the total effective dose of radiation received from domestic use of untreated groundwaters to exceed the recommended 0.1 mSv y-1. Since more than 70% of this dose comes from indoor water degassing and subsequent 222Rn inhalation, preventative health policy in the form of 222Rn remediation and mitigation measures should be implemented prior to pumping untreated groundwater into dwellings, particularly during the dry period.
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Agua Subterránea , Monitoreo de Radiación , Radón , Contaminantes Radiactivos del Agua , Humanos , Radón/análisis , Agua , Prevalencia , Contaminantes Radiactivos del Agua/análisis , Agua Subterránea/químicaRESUMEN
Elpidium is the most common ostracod genus occurring in phytotelmata in the Neotropical region, with distributions ranging from Florida, USA in the north to Rio Grande do Sul, Brazil in the south. However, the genus remains poorly known both in terms of diversity and of the distributional pattern of its species. Here, we describe six new species of Elpidium, E. oxumae n. sp., E. cordiforme n. sp., E. picinguabaense n. sp., E. eriocaularum n. sp., E. higutiae n. sp., E. purium n. sp., all from phytotelm environments in the Brazilian Atlantic rain forest. In addition, we discuss the distributional pattern and endemicity levels of Elpidium species in the light of these new taxonomic results and argue about possible misunderstandings on the distribution of the type species E. bromeliarum.
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Crustáceos , Animales , BrasilRESUMEN
Healthcare-associated infections are a serious burden globally. Few qualitative studies have explored healthcare workers' knowledge, attitudes and practices of hand hygiene. Prior to the implementation of the World Health Organization's Hand Hygiene Improvement Strategy at Faranah Regional Hospital in the Upper Region of Guinea in December 2018, we conducted a qualitative baseline assessment of knowledge, attitudes and practices of hand hygiene among healthcare workers to guide future hand hygiene interventions. The qualitative study consisted of direct observations, In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). We found that the 2013-16 Ebola outbreak had had a pivotal impact on healthcare workers' knowledge, attitudes and practices. The severity of the disease and the training provided for infection control were responsible for their knowledge acquisition and adoption of good attitudes and practices. However, negligence, resulting in poor hand hygiene practices, rose after the outbreak, once the "cue of fear" that had motivated workers for their own self-protection had waned. Our results suggest that local capacity building through training and availability of hand hygiene materials would be a sustainable approach to enhance hand hygiene culture at the hospital. Our study suggests that there is a need for a high and long-term commitment of authorities and healthcare workers at all levels for a sustainable hand hygiene culture.
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The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis.
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Background: Emergency risk communication (ERC) is key to achieving compliance with public health measures during pandemics. Yet, the factors that facilitated ERC during COVID-19 have not been analyzed. We compare ERC in the early stages of the pandemic across four socio-economic settings to identify how risk communication can be improved in public health emergencies (PHE). Methods: To map and assess the content, process, actors, and context of ERC in Germany, Guinea, Nigeria, and Singapore, we performed a qualitative document review, and thematically analyzed semi-structured key informant interviews with 155 stakeholders involved in ERC at national and sub-national levels. We applied Walt and Gilson's health policy triangle as a framework to structure the results. Results: We identified distinct ERC strategies in each of the four countries. Various actors, including governmental leads, experts, and organizations with close contact to the public, collaborated closely to implement ERC strategies. Early integration of ERC into preparedness and response plans, lessons from previous experiences, existing structures and networks, and clear leadership were identified as crucial for ensuring message clarity, consistency, relevance, and an efficient use of resources. Areas of improvement primarily included two-way communication, community engagement, and monitoring and evaluation. Countries with recurrent experiences of pandemics appeared to be more prepared and equipped to implement ERC strategies. Conclusion: We found that considerable potential exists for countries to improve communication during public health emergencies, particularly in the areas of bilateral communication and community engagement as well as monitoring and evaluation. Building adaptive structures and maintaining long-term relationships with at-risk communities reportedly facilitated suitable communication. The findings suggest considerable potential and transferable learning opportunities exist between countries in the global north and countries in the global south with experience of managing outbreaks.
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COVID-19 , Humanos , COVID-19/epidemiología , Urgencias Médicas , Salud Pública/métodos , Comunicación , Brotes de EnfermedadesRESUMEN
L-Lipoic acid (LA) is an important antioxidant with various industrial applications as a nutraceutical and therapeutic. Currently, LA is produced by chemical synthesis. Cell factory development is complex as LA and its direct precursors only occur naturally in protein-bound forms. Here we report a rationally engineered LA cell factory and demonstrate de novo free LA production from glucose for the first time in E. coli. The pathway represents a significant challenge as the three key enzymes, native Octanoyltransferase (LipB) and Lipoyl Synthase (LipA), and heterologous Lipoamidase (LpA), are all toxic to overexpress in E. coli. To overcome the toxicity of LipB, functional metagenomic selection was used to identify a highly active and non-toxic LipB and LipA from S. liquefaciens. Using high throughput screening, we balanced translation initiation rates and dual, orthogonal induction systems for the toxic genes, LipA and LpA. The optimized strain yielded 2.5 mg free LA per gram of glucose in minimal media, expressing carefully balanced LipB and LipA, Enterococcus faecalis LpA, and a truncated, native, Dihydrolipoyllysine-residue acetyltransferase (AceF) lipoylation domain. When the optimized cell factory strain was cultivated in a fed-batch fermentation, a titer of 87 mg/L free LA in the supernatant was reached after 48 h. This titer is â¼3000-fold higher than previously reported free LA titer and â¼8-fold higher than the previous best total, protein-bound LA titer. The strategies presented here could be helpful in designing, constructing and balancing biosynthetic pathways that harbor toxic enzymes with protein-bound intermediates or products.