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Waste glycerol is produced in excess by several industries, such as during biodiesel production. In this work, the metabolic versatility of anaerobic sludge was explored towards waste glycerol valorization. By applying different environmental (methanogenic and sulfate-reducing) conditions, three distinct microbial cultures were obtained from the same inoculum (anaerobic granular sludge), with high microbial specialization, within three different phyla (Thermodesulfobacteriota, Euryarchaeota and Pseudomonadota). The cultures are capable of glycerol conversion through different pathways: (i) glycerol conversion to methane by a bacterium closely related to Solidesulfovibrio alcoholivorans (99.8% 16S rRNA gene identity), in syntrophic relationship with Methanofollis liminatans (98.8% identity), (ii) fermentation to propionate by Propionivibrio pelophilus strain asp66 (98.6% identity), with a propionate yield of 0.88 mmol mmol-1 (0.71 mg mg-1) and a propionate purity of 80-97% and (iii) acetate production coupled to sulfate reduction by Desulfolutivibrio sulfoxidireducens (98.3% identity). In conclusion, starting from the same inoculum, we could drive the metabolic and functional potential of the microbiota towards the formation of several valuable products that can be used in industrial applications or as energy carriers. KEY POINTS: Versatility of anaerobic cultures was explored for waste glycerol valorization Different environmental conditions lead to metabolic specialization Biocommodities such as propionate, acetate and methane were produced.
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Fermentación , Glicerol , Metano , ARN Ribosómico 16S , Aguas del Alcantarillado , Glicerol/metabolismo , Aguas del Alcantarillado/microbiología , Anaerobiosis , ARN Ribosómico 16S/genética , Metano/metabolismo , Filogenia , Sulfatos/metabolismo , Propionatos/metabolismo , Biocombustibles , Acetatos/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genéticaRESUMEN
DNA manipulation is an essential tool in molecular microbiology research that is dependent on the ability of bacteria to take up and preserve foreign DNA by horizontal gene transfer. This process can be significantly impaired by the activity of bacterial restriction modification systems; bacterial operons comprising paired enzymatic activities that protectively methylate host DNA, while cleaving incoming unmodified foreign DNA. Ocr is a phage-encoded protein that inhibits Type I restriction modification systems, the addition of which significantly improves bacterial transformation efficiency. We recently established an improved and highly efficient transformation protocol for the important human pathogen group A Streptococcus using commercially available recombinant Ocr protein, manufacture of which has since been discontinued. In order to ensure the continued availability of Ocr protein within the research community, we have generated tools and methods for in-house Ocr production and validated the activity of the purified recombinant protein.
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Proteínas Recombinantes , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/aislamiento & purificación , Proteínas Virales/genética , Proteínas Virales/metabolismo , Bacteriófagos/genética , Bacteriófagos/enzimología , Streptococcus pyogenes/genética , Streptococcus pyogenes/enzimología , Streptococcus pyogenes/metabolismo , Transformación Bacteriana , Desoxirribonucleasas de Localización Especificada Tipo I/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo I/genética , Expresión Génica , Escherichia coli/genética , Escherichia coli/metabolismoRESUMEN
BACKGROUND: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context. METHODS: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence). DISCUSSION: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system. TRIAL REGISTRATION NUMBER: NCT05841732.
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Terapia por Ejercicio , Dolor de la Región Lumbar , Prevención Secundaria , Adulto , Femenino , Humanos , Masculino , Análisis Costo-Beneficio , Terapia por Ejercicio/métodos , Conductas Relacionadas con la Salud , Dolor de la Región Lumbar/prevención & control , Dolor de la Región Lumbar/terapia , Dimensión del Dolor , Calidad de Vida , Recurrencia , Prevención Secundaria/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Obesity has been extensively studied over the years, primarily focusing on the physiological aspects of the disease. However, the general burden of obesity mainly the financial implications and its influence on hospitalization and length of stay have only recently garnered attention in the literature, particularly in the case of Portugal. Aim: This study aimed to investigate the association between obesity and hospitalizations in the Portuguese adult population and compare the average costs of hospitalization among participants with and without obesity. Methods: At baseline, the analytic sample consisted of 10,102 participants aged ≥18 years from the Portuguese population-based Epidemiology of Chronic Diseases Cohort (EpiDoC). Participants were then followed for up to 10 years from 2011 to 2021 in three more waves of data collection. Body mass index was derived from self-reported weight and height, and instances of hospitalization were self-reported by the participants. The associated costs for each hospitalization episode were categorized according to national legislation and valued according to the pricing for Diagnosis Related Groups. Results: Obesity was associated with more hospitalizations (for example, Obesity class I vs. normal weight: OR = 1.33 [1.14-1.55]). However, when the presence of multimorbidity was considered, this association diminished. While longer hospital length of stay was observed in individuals with higher obesity categories, this difference did not reach statistical significance. On average, the total hospitalization costs per patient with obesity amounted to 200.4 per year. Conclusion: Obesity is as a risk factor for hospitalizations and potentially with higher length of stay hospitalizations, with this effect being partially mediated by the concurrent presence of multimorbidity. Consequently, obesity constitutes an additional burden on healthcare systems. This underscores the imperative of implementing cost-effective prevention programs aimed at addressing and managing this significant public health concern.
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Hospitalización , Obesidad , Humanos , Portugal/epidemiología , Obesidad/epidemiología , Obesidad/economía , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Índice de Masa Corporal , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/economía , Estudios de Cohortes , Adolescente , Adulto Joven , Costos de Hospital/estadística & datos numéricosRESUMEN
Epilactose is a disaccharide composed of galactose and mannose, and it is currently considered an "under development" prebiotic. In this study, we described the prebiotic potential of epilactose by in vitro fermentation using human fecal inocula from individuals following a Mediterranean diet (DM) or a Vegan diet (DV). The prebiotic effect of epilactose was also compared with lactulose and raffinose, and interesting correlations were established between metabolites and microbiota modulation. The production of several metabolites (lactate, short-chain fatty acids, and gases) confirmed the prebiotic properties of epilactose. For both donors, the microbiota analysis showed that epilactose significantly stimulated the butyrate-producing bacteria, suggesting that its prebiotic effect could be independent of the donor diet. Butyrate is one of the current golden metabolites due to its benefits for the gut and systemic health. In the presence of epilactose, the production of butyrate was 70- and 63-fold higher for the DM donor, when compared to lactulose and raffinose, respectively. For the DV donor, an increase of 29- and 89-fold in the butyrate production was obtained when compared to lactulose and raffinose, respectively. In conclusion, this study suggests that epilactose holds potential functional properties for human health, especially towards the modulation of butyrate-producing strains.
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Staphylococcus aureus is a major pathogen associated with important diseases in humans and animals. Macrophages are a key component of the innate immune response to S. aureus infection and play a major role in disease outcomes. To investigate the adaptive evolution of S. aureus in response to macrophages, we developed an experimental infection assay. S. aureus strains representing major human epidemic clones were passaged many times in a macrophage cell line, accumulating mutations in an array of genomic loci. Phenotypic analysis revealed the emergence of a lineage exhibiting increased survival in macrophages and human blood, and resistance to vancomycin. The evolved lineage exhibited a previously undescribed small colony variant (SCV) phenotype characterized by hyper-pigmentation, which resulted from a missense mutation in rsbW. Notably, the novel SCV was a conditional adaptive trait that was unstable in nutrient-replete conditions in vitro, rapidly converting from hyper-pigmented SCV to a non-pigmented large colony variant via spontaneous sigB deletion events. Importantly, we identified similar deletions in the genome sequences of a limited number of clinical S. aureus isolates from public databases, indicating that related events may occur during clinical infection. Experimental infection of zebrafish did not reveal a difference in virulence between parent and novel SCV but demonstrated an in vivo fitness cost for the compensatory sigB deletion events. Taken together, we report an experimental evolutionary approach for investigating bacterial innate immune cell interactions, revealing a conditional adaptation that promotes S. aureus survival in macrophages and resistance to vancomycin. IMPORTANCE: Staphylococcus aureus is an important human bacterial pathogen. The host response to S. aureus involves the production of innate immune cells such as macrophages which are important for fighting infection. Here we report a new model of experimental evolution for studying how S. aureus can evade killing by macrophages. We identified a novel adaptive phenotype that promotes survival in macrophages and blood and resistance to antibiotics. The phenotype is lost rapidly upon growth in nutrient-rich conditions via disruption of the alternative sigma factor sigB, revealing a conditional niche-specific fitness advantage. Genomic analysis of clinical isolates suggests similar adaptations may occur during human infections. Our model may be used broadly to identify adaptations of S. aureus to the innate immune response.
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Macrófagos , Infecciones Estafilocócicas , Staphylococcus aureus , Pez Cebra , Staphylococcus aureus/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Macrófagos/microbiología , Macrófagos/inmunología , Humanos , Animales , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/inmunología , Pez Cebra/microbiología , Fenotipo , Viabilidad Microbiana , Antibacterianos/farmacología , Adaptación Fisiológica/genética , Línea Celular , Ratones , Genoma Bacteriano , Evolución MolecularRESUMEN
Older adults hospitalized in internal medicine wards or long-term care facilities (LTCF) are progressively increasing. Older adults with multimorbidity are more susceptible to infections, as well as to more vulnerable to adverse effects (and interactions) of antibiotics, resulting in a need for effective and safer strategies for antimicrobial stewardship (ASM), both in hospitalization wards and long-term care facilities. Studies on antimicrobial stewardship in older patients are scarce and guidelines are required. Given the peculiarities of the optimization of antimicrobial prescription in individual older adults for common infections, tactics to overcome barriers need an update. The use of rapid diagnosis tests, biomarkers, de-escalation and switching from intravenous to oral/subcutaneous therapy strategies are examples of successful AMS interventions. AMS interventions are associated with reduced side effects, lower mortality, shorter hospital stays, and reduced costs. The proposed AMS framework in LTCF should focus on five domains: strategic vision, team, interventions, patient-centred care and awareness. Internists can partner with geriatrists, pharmacists and infectious disease specialists to address barriers and to improve patient care.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Humanos , Anciano , Antibacterianos/uso terapéutico , Cuidados a Largo Plazo , Hospitalización , Medicina Interna , Atención Dirigida al PacienteRESUMEN
Honey bee colonies have great societal and economic importance. The main challenge that beekeepers face is keeping bee colonies healthy under ever-changing environmental conditions. In the past two decades, beekeepers that manage colonies of Western honey bees (Apis mellifera) have become increasingly concerned by the presence of parasites and pathogens affecting the bees, the reduction in pollen and nectar availability, and the colonies' exposure to pesticides, among others. Hence, beekeepers need to know the health condition of their colonies and how to keep them alive and thriving, which creates a need for a new holistic data collection method to harmonize the flow of information from various sources that can be linked at the colony level for different health determinants, such as bee colony, environmental, socioeconomic, and genetic statuses. For this purpose, we have developed and implemented the B-GOOD (Giving Beekeeping Guidance by computational-assisted Decision Making) project as a case study to categorize the colony's health condition and find a Health Status Index (HSI). Using a 3-tier setup guided by work plans and standardized protocols, we have collected data from inside the colonies (amount of brood, disease load, honey harvest, etc.) and from their environment (floral resource availability). Most of the project's data was automatically collected by the BEEP Base Sensor System. This continuous stream of data served as the basis to determine and validate an algorithm to calculate the HSI using machine learning. In this article, we share our insights on this holistic methodology and also highlight the importance of using a standardized data language to increase the compatibility between different current and future studies. We argue that the combined management of big data will be an essential building block in the development of targeted guidance for beekeepers and for the future of sustainable beekeeping.
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Border fences have severely impeded the transboundary migration of a number of large mammals worldwide, with central Asia being one of the most impacted. The Marco Polo sheep (Ovis ammon polii), an iconic species of Pamir, is threatened in its transboundary movement by increasing border fencing among their five distributed countries, including Tajikistan, Kyrgyzstan, China, Afghanistan, and Pakistan. In this study, by building ensemble species distribution models, we found that eastern Tajikistan had the largest suitable Macro Polo sheep habitat (about 42 % of the total suitable habitat), followed by China (about 32 %). We used least-cost paths to identify 51 ecological corridors including 5 transboundary ecological corridors, which may be important to maintain connectivity in both domestic and transboundary regions. To assess the potential barrier effect of border fences, we assessed four scenarios (30, 40, 50 and 60°) corresponding to the upper limit of the slope for the construction of fences. In areas too steep for fencing, these could be used by wild sheep to cross barriers or borders and may represent migration or movement routes, defined as natural passages. In the most pessimistic Scenario 60, only 25 migratory passages along the border fences were identified, compared to 997 in the most optimistic scenario (Scenario 30), indicating a strong negative effect of intensive border fencing on the transboundary movement of Marco Polo sheep. The establishment of transnational conservation parks, and ensuring permeability is maintained in key areas, could have a positive impact on the connectivity and persistence of Marco Polo sheep populations, and provide important lessons for other large migratory mammals in transboundary regions.
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Ecosistema , Mamíferos , Animales , Ovinos , China , Afganistán , Kirguistán , Conservación de los Recursos NaturalesRESUMEN
The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C. The magnetic moments obtained for the Gd(III) salts were, as expected, smaller than those obtained for the Tb(III)-based compounds. The values for Gd(III) and Tb(III) magnetic salts are in the range of 6.55-7.30 MB and 8.22-9.34 MB, respectively. It is important to note a correlation between the magnetic moments obtained for lanthanides, and the structural features of the cation. The cytotoxicity of lanthanide-based salts was also evaluated using 3T3, 293T, Caco2, and HepG2 cells, and it was revealed that most of the prepared compounds are not toxic.
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Elementos de la Serie de los Lantanoides , Humanos , Elementos de la Serie de los Lantanoides/farmacología , Elementos de la Serie de los Lantanoides/química , Sales (Química) , Células CACO-2 , Aniones , CationesRESUMEN
Infection with the varicella-zoster virus (VZV) is very common worldwide and is one of the main causes of infectious encephalitis. Immunosuppressed patients are at increased risk of severe disease and central nervous system (CNS) involvement. We report the case of a 43-year-old man with HIV infection and poor adherence to antiretroviral therapy who presented to the emergency department (ER) with complaints of diplopia and a frontal headache, referring to having a child with chickenpox. Brain magnetic resonance imaging revealed three hyperintense T2-weighted lesions surrounded by edema in the right sublenticular, left occipital and left parietal regions, and VZV DNA was detected in the cerebrospinal fluid (CSF). After admitting the diagnosis of VZV encephalitis, the patient was treated with intravenous acyclovir, with clinical improvement and a favorable outcome.
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INTRODUCTION: Neurodevelopmental disorders are characterized by delay or variation in the acquisition of abilities or skills in several domains of development: motor, social, language, and cognitive. These disorders can manifest from childhood to adulthood, and therefore continuity of care is essential throughout these various developmental periods. However, several studies show that there is limited access to adult health care in this clinical domain. METHODS: A cross-sectional observational study was carried out by distributing an anonymous survey among psychiatry physicians, at a national level, in the period between October 6 and December 6, 2020. RESULTS: Data was collected from 83 psychiatry physicians (43 residents and 40 specialists). At the national level, only 16.9% of psychiatric departments had a subspecialized neurodevelopment clinic. Physicians reported that they observed few patients with neurodevelopment disorders: 72.3% observed one or none per week. When there was a neurodevelopmental disorders clinic in the psychiatry department, 64.3% of physicians reported that this clinic did not include a multidisciplinary team. The transition of these patients from the pediatric/child and adolescent psychiatry department to the psychiatric department occurred through regular intrahospital transfer in 51.8% of cases, but it occurred through a specific protocol or with a transitional medical appointment in only 15.7% of cases. Finally, 88% of psychiatry physicians considered the existence of a neurodevelopmental disorders clinic in adults to be pertinent and reported not having specialized training in the field of neurodevelopment. CONCLUSION: This study made it possible to identify some difficulties and barriers regarding adequate access for patients with neurodevelopmental disorders throughout the various developmental stages, from childhood to adulthood: lack of training in this clinical field, need of better communication between departments, lack of specific protocols, shortage of multidisciplinary teams, and asymmetry in the distribution of differentiated care.
Introdução: As perturbações do neurodesenvolvimento são caracterizadas pelo atraso ou alteração na aquisição de capacidades em vários domínios do desenvolvimento: motor, social, de linguagem e cognitivo. Deste modo, estas perturbações podem manifestar-se desde a infância até à vida adulta, exigindo a continuidade dos cuidados de saúde. Contudo, vários estudos mostram que existem limitações de acesso dos adultos aos cuidados de saúde nesta área clínica. Métodos: Foi realizado um estudo observacional descritivo transversal através da aplicação de um questionário anónimo a médicos de Psiquiatria, a nível nacional, no período compreendido entre 6 de outubro e 6 de dezembro de 2020. Resultados: Foram recolhidos dados de 83 médicos de Psiquiatria (43 internos de especialidade e 40 especialistas). A nível nacional, apenas 16,9% dos serviços de Psiquiatria tinham uma consulta diferenciada de neurodesenvolvimento. Os médicos respondentes reportaram ter observado poucos doentes com perturbações do neurodesenvolvimento: 72,3% observaram um ou nenhum por semana. Dos médicos que referiram ter consulta de neurodesenvolvimento no seu serviço, a maioria (64,3%) não dispunha de equipa multidisciplinar. A transição destes doentes da consulta de Pediatria do Neurodesenvolvimento/Pedopsiquiatria para a de Psiquiatria ocorria em 51,8% por transferência regular intra-hospitalar, contudo em apenas 15,7% ocorria através de protocolo específico ou com a realização de consulta de transição. Por fim, 88% dos médicos de Psiquiatria consideraram ser pertinente a existência de uma consulta de perturbações do neurodesenvolvimento no adulto e relataram não possuir formação especializada na área do neurodesenvolvimento. Conclusão: Este estudo possibilitou enumerar alguns obstáculos para que os doentes com perturbações do neurodesenvolvimento usufruam de uma transição de cuidados de saúde para a vida adulta favorável: carência de conhecimento na área, necessidade de melhor comunicação entre serviços, falta de protocolos específicos, escassez de equipas multidisciplinares e assimetria na distribuição de cuidados de saúde diferenciados.
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Trastornos del Neurodesarrollo , Médicos , Psiquiatría , Adulto , Adolescente , Humanos , Niño , Adulto Joven , Estudios Transversales , Trastornos del Neurodesarrollo/diagnóstico , Derivación y ConsultaRESUMEN
BACKGROUND: While it is known that educational inequalities in smoking start during early and middle adolescence, it is unknown how they further develop until adulthood. The aim of this article is to map, in the Portuguese context, how educational inequalities in smoking emerge from pre-adolescence until young adulthood. METHODS: This study used longitudinal data from the EPITeen Cohort, which recruited adolescents enrolled in schools in Porto, Portugal. We included the 1,038 participants followed at ages 13 (2003/2004), 17, 21, and 24 years. We computed the odds ratio (OR) for the prevalence of smoking states (never smoking, experimenter, less-than-daily, daily and former smoker) and the incidence of transitions between these states, as function of age and education, stratified by sex. We also added interaction terms between age and education. RESULTS: Educational inequalities in daily smoking prevalence, with higher prevalence among those with lower educational level, emerged at 17 years old and persisted until higher ages. They were formed in a cumulative way by the increased risk of experimenting between 13 and 17 years, and increased risk of becoming daily smoker between 17 and 21 years. The incidence of smoking cessation was higher among the higher educated. Inequalities were formed similarly for women and men, but with lower level and showed no significance among women. CONCLUSIONS: These results highlight that actions to prevent smoking should also take in account the potential impact in smoking inequalities, and should focus not only on middle adolescence but also on late adolescence and early adulthood.
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Cese del Hábito de Fumar , Fumar , Masculino , Humanos , Adolescente , Femenino , Adulto Joven , Adulto , Fumar/epidemiología , Escolaridad , Fumar Tabaco , Portugal/epidemiología , Prevalencia , Factores SocioeconómicosRESUMEN
Genetic intractability presents a fundamental barrier to the manipulation of bacteria, hindering advancements in microbiological research. Group A Streptococcus (GAS), a lethal human pathogen currently associated with an unprecedented surge of infections worldwide, exhibits poor genetic tractability attributed to the activity of a conserved type 1 restriction modification system (RMS). RMS detect and cleave specific target sequences in foreign DNA that are protected in host DNA by sequence-specific methylation. Overcoming this "restriction barrier" thus presents a major technical challenge. Here, we demonstrate for the first time that different RMS variants expressed by GAS give rise to genotype-specific and methylome-dependent variation in transformation efficiency. Furthermore, we show that the magnitude of impact of methylation on transformation efficiency elicited by RMS variant TRDAG, encoded by all sequenced strains of the dominant and upsurge-associated emm1 genotype, is 100-fold greater than for all other TRD tested and is responsible for the poor transformation efficiency associated with this lineage. In dissecting the underlying mechanism, we developed an improved GAS transformation protocol, whereby the restriction barrier is overcome by the addition of the phage anti-restriction protein Ocr. This protocol is highly effective for TRDAG strains including clinical isolates representing all emm1 lineages and will expedite critical research interrogating the genetics of emm1 GAS, negating the need to work in an RMS-negative background. These findings provide a striking example of the impact of RMS target sequence variation on bacterial transformation and the importance of defining lineage-specific mechanisms of genetic recalcitrance. IMPORTANCE Understanding the mechanisms by which bacterial pathogens are able to cause disease is essential to enable the targeted development of novel therapeutics. A key experimental approach to facilitate this research is the generation of bacterial mutants, through either specific gene deletions or sequence manipulation. This process relies on the ability to transform bacteria with exogenous DNA designed to generate the desired sequence changes. Bacteria have naturally developed protective mechanisms to detect and destroy invading DNA, and these systems severely impede the genetic manipulation of many important pathogens, including the lethal human pathogen group A Streptococcus (GAS). Many GAS lineages exist, of which emm1 is dominant among clinical isolates. Based on new experimental evidence, we identify the mechanism by which transformation is impaired in the emm1 lineage and establish an improved and highly efficient transformation protocol to expedite the generation of mutants.
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Epigenoma , Streptococcus pyogenes , Humanos , Streptococcus pyogenes/genética , Genotipo , Técnicas Genéticas , Proteínas Portadoras/genética , Enzimas de Restricción-Modificación del ADN/genéticaRESUMEN
Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.
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Rifamicinas , Infecciones Estafilocócicas , Animales , Humanos , Staphylococcus aureus , Proteínas Fluorescentes Verdes/genética , Rifamicinas/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/microbiología , MacrófagosRESUMEN
Intravenous (i.v.) prostacyclin is the cornerstone treatment in high-risk pulmonary arterial hypertension (PAH) patients. Selexipag is an orally available prostacyclin receptor agonist. Limited data are available regarding the feasibility of transitioning from i.v. epoprostenol to selexipag. A 50-year-old woman with idiopathic PAH was diagnosed in a World Health Organization (WHO) Functional Class (FC) IV. She improved with upfront triple combination therapy, including i.v. epoprostenol. Over 2 years of follow-up, the patient remained at low risk and expressed strong preference towards oral therapies. After careful risk-benefit clinical consideration, she was transitioned from i.v. epoprostenol to selexipag. Selexipag was started at dosage of 200 µg twice daily (b.i.d.) and titrated up to 1600 µg b.i.d. over 8 weeks (up-titration of 200 µg b.i.d. every week). Simultaneously, i.v. epoprostenol was down-titrated 3.0 ng/kg/min every week from a dosage of 27.5 ng/kg/min. The transition occurred under strict medical surveillance and was well tolerated. One year after discontinuation of epoprostenol, the patient remains in WHO FC I and has no signs of clinical deterioration. Although not generalizable to most PAH patients, this case highlights that a carefully planned transition from epoprostenol to selexipag is feasible in selected low-risk patients within a shared medical decision-making framework.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Femenino , Humanos , Persona de Mediana Edad , Epoprostenol/uso terapéutico , Antihipertensivos/uso terapéutico , Hipertensión Pulmonar Primaria Familiar/inducido químicamente , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/tratamiento farmacológicoRESUMEN
The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority.
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Despite the COVID-19 pandemic having affected the lives of all citizens, some groups, as people with disabilities (PwD), have felt its effects more intensely, specifically due to social distancing measures adopted. However, PwD are a heterogeneous group and the impacts of COVID-19 are, therefore, experienced differently. Blind people (BP) face considerable challenges during the COVID-19 pandemic, since they "access the world" through touch, something strongly discouraged in order to control the spread of the virus. Nevertheless, no studies are known which analyze the constraints experienced by BP during COVID-19 on participating in recreation and tourism activities. To extend knowledge in this field, the intention of this study is to examine the constraints faced by BP during COVID-19 on participation in outdoor recreation and tourism activities and the strategies used to overcome these constraints. A qualitative methodology (in-depth interviews with BP) was used. The results reveal that during the COVID-19 pandemic, BP faced several constraints that made their participation in outdoor recreation and tourism activities difficult. The paper ends with a discussion of the strategies used by BP to overcome these constraints. Management implications: Understanding the impact of COVID-19 on the recreation and tourism practices of blind people, and the constraints that they face as a consequence of this pandemic, this study provides relevant implications managers for public and private tourism supply agents. Therefore, managers and planners can use the findings of this study to design strategies to overcome the strong constraints faced by blind people due to the COVID-19 pandemic, to minimize risk exposure and to increase their quality of life. Thus, the type of activities offered and the marketing strategy should be rethought to increase the engagement of blind people in recreation and tourism experiences in an "untouchable world."
RESUMEN
The COVID-19 pandemic has drastically affected people's social habits, especially those related to outdoor activities. We intended to understand the effects of the two national lockdowns in Portugal on the presence and activity of a wild population of red deer (Cervus elaphus) by analysing data from camera traps installed at Lousã mountain, in the central part of Portugal. The cameras were set between 2019 and 2021, and a total of 2434 individual contacts of red deer and 182 contacts of people were recorded. Results showed a higher human presence in the mountain area during the COVID-19 outbreak, especially during the first lockdown in 2020 (0.05 ± 0.17 individuals/day), compared to the same period of the year before the pandemic (0.02 ± 0.05 individuals/day), which resulted in an increase of people by 150%. The increase in human presence did not have a significant direct effect on the presence of red deer. Despite the low overlap of activity patterns between people and red deer, deer showed avoidance behaviour in the 24 h after the detection of human presence on camera traps, as well as an increase in daily activity during the 2020 lockdown, showing red deer's awareness of human visitation. These results showed that people's increased search for cultural services in wild environments during COVID-19 lockdowns, such as hiking and biking, seemed to influence the population of red deer, albeit momentarily.