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Porcine Mx1 is a type of interferon-induced GTPase that inhibits the replication of certain RNA viruses. However, the antiviral effects and the underlying mechanism of porcine Mx1 for porcine reproductive and respiratory syndrome virus (PRRSV) remain unknown. In this study, we demonstrated that porcine Mx1 could significantly inhibit PRRSV replication in MARC-145 cells. By Mx1 segment analysis, it was indicated that the GTPase domain (68-341aa) was the functional area to inhibit PRRSV replication and that Mx1 interacted with the PRRSV-N protein through the GTPase domain (68-341aa) in the cytoplasm. Amino acid residues K295 and K299 in the G domain of Mx1 were the key sites for Mx1-N interaction while mutant proteins Mx1(K295A) and Mx1(K299A) still partially inhibited PRRSV replication. Furthermore, we found that the GTPase activity of Mx1 was dominant for Mx1 to inhibit PRRSV replication but was not essential for Mx1-N interaction. Finally, mechanistic studies demonstrated that the GTPase activity of Mx1 played a dominant role in inhibiting the N-Nsp9 interaction and that the interaction between Mx1 and N partially inhibited the N-Nsp9 interaction. We propose that the complete anti-PRRSV mechanism of porcine Mx1 contains a two-step process: Mx1 binds to the PRRSV-N protein and subsequently disrupts the N-Nsp9 interaction by a process requiring the GTPase activity of Mx1. Taken together, the results of our experiments describe for the first time a novel mechanism by which porcine Mx1 evolves to inhibit PRRSV replication. IMPORTANCE: Mx1 protein is a key mediator of the interferon-induced antiviral response against a wide range of viruses. How porcine Mx1 affects the replication of porcine reproductive and respiratory syndrome virus (PRRSV) and its biological function has not been studied. Here, we show that Mx1 protein inhibits PRRSV replication by interfering with N-Nsp9 interaction. Furthermore, the GTPase activity of porcine Mx1 plays a dominant role and the Mx1-N interaction plays an assistant role in this interference process. This study uncovers a novel mechanism evolved by porcine Mx1 to exert anti-PRRSV activities.
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Proteínas de Resistência a Myxovirus , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteínas não Estruturais Virais , Replicação Viral , Animais , Linhagem Celular , Interferons/imunologia , Interferons/metabolismo , Mutação , Proteínas de Resistência a Myxovirus/química , Proteínas de Resistência a Myxovirus/genética , Proteínas de Resistência a Myxovirus/metabolismo , Síndrome Respiratória e Reprodutiva Suína/enzimologia , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/crescimento & desenvolvimento , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Ligação Proteica , Suínos/virologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismoRESUMO
OBJECTIVES: To examine if intergenerational transmission of parent weight talk occurs, the contextual factors prompting weight talk, and whether parent weight talk is associated with child weight, dietary intake, psychosocial outcomes, and food parenting practices. STUDY DESIGN: Children aged 5-9 years and their families (n = 1307) from 6 racial and ethnic groups (African-American, Hispanic, Hmong, Native American, Somali/Ethiopian, White) were recruited for a longitudinal cohort study through primary care clinics in Minneapolis/St. Paul, Minnesota from 2016 through 2019. Parents filled out surveys at 2 time points, 18 months apart. Adjusted regression models examined associations of interest. RESULTS: Intergenerational transmission of parent weight talk was observed. In addition, significant associations were found between parent engagement in weight talk and higher weight status and poorer psychosocial outcomes in children 18 months later. Parent engagement in weight talk was also associated with more restrictive food parenting practices 18 months later. CONCLUSIONS: Parents' exposure to weight talk as children increased the likelihood of engaging in weight talk with their own children and had harmful associations over time with parent restrictive feeding practices, child weight, and psychosocial wellbeing in children. Health care providers may want to consider both modeling positive health-focused conversations and educating parents about the potential harmful and long-lasting consequences of engaging in weight talk with their children.
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Relações Pais-Filho , Poder Familiar , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Estudos Longitudinais , Poder Familiar/psicologia , Saúde da Criança , Pais/psicologia , Peso Corporal , Relação entre Gerações , Adulto , Obesidade Infantil/psicologia , Comportamento Alimentar/psicologiaRESUMO
In brief: In light of the increasing age of first-time fathers, this article summarizes the current scientific knowledge base on reproductive aging in the male, including sperm quality and health impacts for the offspring. The emerging role of NAD decline in reproductive aging is highlighted. Abstract: Over the past decades, the age of first-time fathers has been steadily increasing due to socio-economic pressures. While general mechanisms of aging are subject to intensive research, male reproductive aging has remained an understudied area, and the effects of increased age on the male reproductive system are still only poorly understood, despite new insights into the potential dire consequences of advanced paternal age for the health of their progeny. There is also growing evidence that reproductive aging is linked to overall health in men, but this review mainly focuses on pathophysiological consequences of old age in men, such as low sperm count and diminished sperm genetic integrity, with an emphasis on mechanisms underlying reproductive aging. The steady decline of NAD levels observed in aging men represents one of the emerging concepts in that regard. Because it offers some mechanistic rationale explaining the effects of old age on the male reproductive system, some of the NAD-dependent functions in male reproduction are briefly outlined in this review. The overview also provides many questions that remain open about the basic science of male reproductive aging.
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Envelhecimento , Pai , NAD , Reprodução , Saúde Reprodutiva , Espermatozoides , Humanos , Masculino , Envelhecimento/fisiologia , Reprodução/fisiologia , Espermatozoides/fisiologia , Espermatozoides/metabolismo , NAD/metabolismo , Idade PaternaRESUMO
Intracellular levels of glutathione, the major mammalian antioxidant, are reported to decline with age in several species. To understand whether ageing affects circulating glutathione levels in cats, blood was sampled from two age groups, < 3 years and > 9 years. Further, to determine whether dietary supplementation with glutathione precursor glycine (GLY) affects glutathione concentrations in senior cats (> 8 years), a series of free GLY inclusion level dry diets were fed. Subsequently, a 16-week GLY feeding study was conducted in senior cats (> 7 years), measuring glutathione, and markers of oxidative stress. Whole blood and erythrocyte total, oxidised and reduced glutathione levels were significantly decreased in senior cats, compared with their younger counterparts (P ≤ 0·02). The inclusion level study identified 1·5 % free GLY for the subsequent dry diet feeding study. Significant increases in erythrocyte total and reduced glutathione were observed between senior cats fed supplemented and control diets at 4 weeks (P ≤ 0·03; maximum difference of 1·23 µM). Oxidative stress markers were also significantly different between groups at 8 (P = 0·004; difference of 0·68 nG/ml in 8-hydroxy-2'-deoxyguanosine) and 12 weeks (P ≤ 0·049; maximum difference of 0·62 nG/mG Cr in F2-isoprostane PGF2α). Senior cats have lower circulating glutathione levels compared with younger cats. Feeding senior cats a complete and balanced dry diet supplemented with 1·5 % free GLY for 12 weeks elevated initial erythrocyte glutathione and altered markers of oxidative stress. Dietary supplementation with free GLY provides a potential opportunity to restore age-associated reduction in glutathione in cats.
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Envelhecimento , Suplementos Nutricionais , Eritrócitos , Glutationa , Glicina , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Gatos , Glutationa/sangue , Glicina/sangue , Masculino , Eritrócitos/metabolismo , Feminino , Biomarcadores/sangue , Ração Animal/análise , Antioxidantes/análise , Dieta/veterinária , Dinoprosta/análogos & derivados , Dinoprosta/sangueRESUMO
We have made the compound 2O-BaPtO3 by high-pressure, high-temperature synthesis, determined its structure, and tested its catalytic activity. Compounds of the same stoichiometry have been reported and tentatively identified as hexagonal perovskites, and although no structural model was ever established, 2O-BaPtO3 is clearly different and, to the best of our knowledge, unique. It features continuous chains of face-sharing PtO6 octahedra, like the well-known 2H hexagonal perovskite type, but with a staggered offset between the chains that breaks hexagonal symmetry and disrupts the close-packed array of A = Ba and X = O that is a defining characteristic of ABX3 perovskites. We investigated this structure and its stability vs the conventional 2H form using X-ray and neutron diffraction, X-ray absorption spectroscopy, and ab initio calculations. Catalytic testing of 2O-BaPtO3 showed that it is active for hydrogen evolution.
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AIM: To examine child-led goal setting and evaluation tools and approaches for children with a disability or developmental delay. METHOD: Six databases were searched for studies that included population (children aged less than 18 years with disability or developmental delay); construct (child-led goal setting tool or approach); and context (developmental therapy or rehabilitation). The utility of tools and approaches across the goal setting and evaluation process was investigated using abductive content analysis. RESULTS: Fifty articles met the inclusion criteria. Three approaches and four tools for child-led goal setting and evaluation were identified. No studies reported the clinimetric properties of tools specifically for child self-respondents. Qualitative analysis revealed six distinct goal phases in which tools and approaches were used, which were synthesized into a new framework for child-led goal setting and evaluation titled DECIDE: Direct children to goal setting; Elicit goal topics and priorities; Construct a goal statement; Indicate baseline goal performance; Develop an action plan to address the goal; and Evaluate goal progress after the intervention. INTERPRETATION: Children actively participated in goal setting and evaluation across six DECIDE goal phases. Further clinimetric information is required to support use of goal setting and evaluation tools with child self-respondents. Future research should emphasize the development of multi-phase goal setting tools and approaches for diverse populations of children.
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Perinatal mental health conditions have been associated with adverse pregnancy outcomes, including maternal death. This quality improvement project analyzed pregnancy-associated death among veterans with mental health conditions in order to identify opportunities to improve healthcare and reduce maternal deaths. Pregnancy-associated deaths among veterans using Veterans Health Administration (VHA) maternity care benefits between fiscal year 2011 and 2020 were identified from national VHA databases. Deaths among individuals with active mental health conditions underwent individual chart review using a standardized abstraction template adapted from the Centers for Disease Control and Prevention (CDC). Thirty-two pregnancy-associated deaths were identified among 39,720 paid deliveries with 81% (n = 26) occurring among individuals with an active perinatal mental health condition. In the perinatal mental health cohort, most deaths (n = 16, 62%) occurred in the late postpartum period and 42% (n = 11) were due to suicide, homicide, or overdose. Opportunities to improve care included addressing (1) racial disparities, (2) mental health effects of perinatal loss, (3) late postpartum vulnerability, (4) lack of psychotropic medication continuity, (5) mental health conditions in intimate partners, (6) child custody loss, (7) lack of patient education or stigmatizing patient education, and (8) missed opportunities for addressing reproductive health concerns in mental health contexts. Pregnancy-associated deaths related to active perinatal mental health conditions can be reduced. Mental healthcare clinicians, clinical teams, and healthcare systems have opportunities to improve care for individuals with perinatal mental health conditions.
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Transtornos Mentais , Complicações na Gravidez , United States Department of Veterans Affairs , Humanos , Feminino , Gravidez , Estados Unidos/epidemiologia , Adulto , Transtornos Mentais/epidemiologia , Transtornos Mentais/mortalidade , Complicações na Gravidez/psicologia , Complicações na Gravidez/mortalidade , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Mortalidade Materna/tendências , Saúde Mental , Melhoria de Qualidade , Resultado da Gravidez/epidemiologia , Período Pós-PartoRESUMO
BACKGROUND: Nutritional prehabilitation may improve haematopoietic cell transplantation (HCT) outcomes, although little evidence exists. The present study aimed to understand healthcare professional (HCP) perceptions of prehabilitation and nutritional care pre-HCT in UK centres. METHODS: An anonymous online survey (developed and refined via content experts and piloting) was administered via email to multidisciplinary HCPs in 39 UK adult centres, between July 2021 and June 2022. Data are presented as proportions of responses. Routine provision denotes that care was provided >70% of time. RESULTS: Seventy-seven percent (n = 66) of HCPs, representing 61.5% (n = 24) of UK adult HCT centres, responded. All HCPs supported prehabilitation, proposing feasible implementation between induction chemotherapy (60.4%; n = 40) and first HCT clinic (83.3%; n = 55). Only 12.5% (n = 3) of centres had a dedicated prehabilitation service. Nutrition (87.9%; n = 58), emotional wellbeing (92.4%; n = 61) and exercise (81.8%; n = 54) were considered very important constituents. HCPs within half of the HCT centres (n = 12 centres) reported routine use of nutrition screening pre-HCT with a validated tool; 66.7% of HCPs (n = 36) reported using the malnutrition universal screening tool (MUST). Sixty-two percent (n = 41) of HCPs reported those at risk, received nutritional assessments, predominantly by dietitians (91.6%; n = 22) using the dietetic care process (58.3%; n = 14). Body mass index (BMI) was the most frequently reported body composition measure used by HCPs (70.2%, n = 33). Of 59 respondents, non-dietitians most routinely provided dietary advice pre-HCT (82.4%; n = 28 vs. 68%; n = 17, p = 0.2); including high-energy/protein/fat and neutropenic diet advice. Prophylactic enteral feeding pre-HCT was rare, indicated by low BMI and significant unintentional weight loss. Just under half (n = 25 of 59, 42.4%) HCPs reported exercise advice was given routinely pre-HCT. CONCLUSIONS: Nutrition and prehabilitation pre-HCT are considered important and deliverable by HCPs, but current provision in UK centres is limited and inconsistent.
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Atitude do Pessoal de Saúde , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/psicologia , Reino Unido , Inquéritos e Questionários , Masculino , Feminino , Adulto , Cuidados Pré-Operatórios/métodos , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Estado Nutricional , Terapia Nutricional/métodos , Exercício Pré-OperatórioRESUMO
For organisms to have robust locomotion, their neuromuscular organization must adapt to constantly changing environments. In jellyfish, swimming robustness emerges when marginal pacemakers fire action potentials throughout the bell's motor nerve net, which signals the musculature to contract. The speed of the muscle activation wave is dictated by the passage times of the action potentials. However, passive elastic material properties also influence the emergent kinematics, with time scales independent of neuromuscular organization. In this multimodal study, we examine the interplay between these two time scales during turning. A three-dimensional computational fluid-structure interaction model of a jellyfish was developed to determine the resulting emergent kinematics, using bidirectional muscular activation waves to actuate the bell rim. Activation wave speeds near the material wave speed yielded successful turns, with a 76-fold difference in turning rate between the best and worst performers. Hyperextension of the margin occurred only at activation wave speeds near the material wave speed, suggesting resonance. This hyperextension resulted in a 34-fold asymmetry in the circulation of the vortex ring between the inside and outside of the turn. Experimental recording of the activation speed confirmed that jellyfish actuate within this range, and flow visualization using particle image velocimetry validated the corresponding fluid dynamics of the numerical model. This suggests that neuromechanical wave resonance plays an important role in the robustness of an organism's locomotory system and presents an undiscovered constraint on the evolution of flexible organisms. Understanding these dynamics is essential for developing actuators in soft body robotics and bioengineered pumps.
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Cifozoários/fisiologia , Natação/fisiologia , Animais , Fenômenos Biomecânicos , Módulo de Elasticidade , Hidrodinâmica , Modelos Biológicos , Músculos/fisiologiaRESUMO
Farmer suicide rates continue to increase, with levels being 1.5 times higher than the national rate. This has led agricultural and public health groups to craft and distribute farm stress and suicide messages to help farmers. However, suicide rates remain at critical levels indicating that there may be a disconnect between existing efforts and farmer sensemaking of the crisis. Utilizing the Theory of Memorable Messages (ToMM), this study explored how farmers are reacting to messages and conversations about the farmer suicide crisis. Interviews with 25 participants found most had heard about farmer suicide concerns. When asked about their memorable conversations, farmers reflected a complex sensemaking process that included themes of memorable conversation types ranging from externalization to acceptance and message themes oriented around concern for self and others within these conversation types. Overall, most farmers externalized the risk of suicide to other farmers. However, even though participants did not see themselves at risk, their responses often showed deep concern for helping other farmers. These results are discussed in light of sensemaking and memorable conversations, with practical implications for future messaging efforts around farmer suicide.
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This study examined the formation of trust judgments of information sources about COVID-19 and the role played by emotions in this information seeking process. Twenty-seven in-depth interviews with Americans revealed that both trust and affective responses were present in information seeking of health messages, thus discovering the applicability of Risk Information Seeking and Processing (RISP) model's propositions during pandemics. Using qualitative methods to assess RISP variables in a new context (COVID-19), the study proposes modifications to the existing model. It also extends the socio-psychological traditions on which the RISP model was based, by finding that when evaluating information sources during pandemics, under conditions of high issue relevance, individuals' peripheral evaluation of messages might precede systematic evaluation and might be used as a selection criteria for further elaboration. Finally, the assessments of source credibility as a peripheral cue in this study expand current theoretical understandings by including compassion as a possible new dimension.
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COVID-19 , Humanos , COVID-19/epidemiologia , Confiança , Comportamento de Busca de Informação , Julgamento , EmpatiaRESUMO
Protein SUMOylation represents an important cellular process that regulates the activities of numerous host proteins as well as of many invasive viral proteins. Foot-and-mouth disease virus (FMDV) is the first animal virus discovered. However, whether SUMOylation takes place during FMDV infection and what role it plays in FMDV pathogenesis have not been investigated. In the present study, we demonstrated that SUMOylation suppressed FMDV replication by small interfering RNA (siRNA) transfection coupled with pharmaceutical inhibition of SUMOylation, which was further confirmed by increased virus replication for SUMOylation-deficient FMDV with mutations in 3C protease, a target of SUMOylation. Moreover, we provided evidence that four lysine residues, Lys-51, -54, -110, and -159, worked together to confer the SUMOylation to the FMDV 3C protease, which may make SUMOylation of FMDV 3C more stable and improve the host's chance of suppressing the replication of FMDV. This is the first report that four lysine residues can be alternatively modified by SUMOylation. Finally, we showed that SUMOylation attenuated the cleavage ability, the inhibitory effect of the interferon signaling pathway, and the protein stability of FMDV 3C, which appeared to correlate with a decrease in FMDV replication. Taken together, the results of our experiments describe a novel cellular regulatory event that significantly restricts FMDV replication through the SUMOylation of 3C protease. IMPORTANCE FMD is a highly contagious and economically important disease in cloven-hoofed animals. SUMOylation, the covalent linkage of a small ubiquitin-like protein to a variety of substrate proteins, has emerged as an important posttranslational modification that plays multiple roles in diverse biological processes. In this study, four lysine residues of FMDV 3C were found to be alternatively modified by SUMOylation. In addition, we demonstrated that SUMOylation attenuated FMDV 3C function through multiple mechanisms, including cleavage ability, the inhibitory effect of the interferon signaling pathway, and protein stability, which, in turn, resulted in a decrease of FMDV replication. Our findings indicate that SUMOylation of FMDV 3C serves as a host cell defense against FMDV replication. Further understanding of the cellular and molecular mechanisms driving this process should offer novel insights to design an effective strategy to control the dissemination of FMDV in animals.
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Cisteína Endopeptidases/metabolismo , Vírus da Febre Aftosa , Proteases Virais 3C , Animais , Antivirais , Febre Aftosa , Vírus da Febre Aftosa/genética , Interações Hospedeiro-Patógeno , Lisina/metabolismo , Peptídeo Hidrolases/metabolismo , Sumoilação , Replicação ViralRESUMO
Gorgonians, including sea fans, are soft corals well known for their elaborate branching structure and how they sway in the ocean. This branching structure can modify environmental flows to be beneficial for feeding in a particular range of velocities and, presumably, for a particular size of prey. As water moves through the elaborate branches, it is slowed, and recirculation zones can form downstream of the colony. At the smaller scale, individual polyps that emerge from the branches expand their tentacles, further slowing the flow. At the smallest scale, the tentacles are covered in tiny pinnules where exchange occurs. In this paper, we quantified the gap to diameter ratios for various gorgonians at the scale of the branches, the polyp tentacles and the pinnules. We then used computational fluid dynamics to determine the flow patterns at all three levels of branching. We quantified the leakiness between the branches, tentacles and pinnules over the biologically relevant range of Reynolds numbers and gap-to-diameter ratios, and found that the branches and tentacles can act as either leaky rakes or solid plates depending upon these dimensionless parameters. The pinnules, in contrast, mostly impede the flow. Using an agent-based modeling framework, we quantified plankton capture as a function of the gap-to-diameter ratio of the branches and the Reynolds number. We found that the capture rate depends critically on both morphology and Reynolds number. The results of the study have implications for how gorgonians modify ambient flows for efficient feeding and exchange.
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Antozoários , Animais , HidrodinâmicaRESUMO
BACKGROUND: The veterinary care of cats and dogs is increasingly embracing innovations first applied to human health, including an increased emphasis on preventative care and precision medicine. Large scale human population biobanks have advanced research in these areas; however, few have been established in veterinary medicine. The MARS PETCARE BIOBANK™ (MPB) is a prospective study that aims to build a longitudinal bank of biological samples, with paired medical and lifestyle data, from 20,000 initially healthy cats and dogs (10,000 / species), recruited through veterinary hospitals over a ten-year period. Here, we describe the MPB protocol and discuss its potential as a platform to increase understanding of why and how diseases develop and how to advance personalised veterinary healthcare. METHODS: At regular intervals, extensive diet, health and lifestyle information, electronic medical records, clinicopathology and activity data are collected, genotypes, whole genome sequences and faecal metagenomes analysed, and blood, plasma, serum, and faecal samples stored for future research. DISCUSSION: Proposed areas for research include the early detection and progression of age-related disease, risk factors for common conditions, the influence of the microbiome on health and disease and, through genome wide association studies, the identification of candidate loci for disease associated genetic variants. Genomic data will be open access and research proposals for access to data and samples will be considered. Over the coming years, the MPB will provide the longitudinal data and systematically collected biological samples required to generate important insights into companion animal health, identifying biomarkers of disease, supporting earlier identification of risk, and enabling individually tailored interventions to manage disease.
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Doenças do Gato , Doenças do Cão , Humanos , Gatos , Cães , Animais , Estudos Longitudinais , Bancos de Espécimes Biológicos , Doenças do Gato/genética , Estudo de Associação Genômica Ampla/veterinária , Estudos Prospectivos , Doenças do Cão/genéticaRESUMO
Healthcare providers in hospital emergency departments (EDs) work under high uncertainty and pressure to manage a variety of patients efficiently. Whereas much existing research has examined communicative implications of uncertainty from patients' perspectives, we explored ED physicians' experiences of uncertainty in their everyday work environment. Through an ethnographic fieldwork in an ED, we identified three main sources of uncertainty routinely faced by physicians: (a) patients' incorrect expectation about the role of ED; (b); patient variability and ED physicians' breadth of expertise; and (c) emerging and unexpected changes in patient cases after handoffs. We also found how ED physicians managed these uncertainties, including: (1) direct admission of scientific uncertainty to patients; (2) lowering epistemic uncertainty through swift Internet searches; and (3) maintenance of situational uncertainty. We discuss implications of these findings for researchers, providers, and hospital organizations.
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Médicos , Humanos , Incerteza , Comunicação , Antropologia Cultural , Hospitalização , Serviço Hospitalar de EmergênciaRESUMO
In Canada, primary care providers are the front door to other services in the health system, such as specialist care. Compared to other countries, Canadians experience long wait times for specialist referrals and appointments leading to poorer health outcomes for patients. Although there is attention paid to the impacts of these waits on patients, little is known about how long specialist care wait times impact primary care providers. As part of a larger study surveying primary care clinics in Nova Scotia, primary care providers were invited to participate in a follow-up survey on comprehensive care and specialist wait times. We thematically analyzed responses to an open text field about specialist wait times. Respondents shared experiences with challenging specialist wait times, strategies to manage patients waiting for specialist care, and recommendations for improving access to specialist care in Nova Scotia, Canada.
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Acessibilidade aos Serviços de Saúde , Listas de Espera , Humanos , Estudos Transversais , Nova Escócia , Atenção Primária à SaúdeRESUMO
Legionella pneumophila is the cause of Legionnaires' disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in stagnant, warm-to-hot water (77°F-113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires' disease has not previously been associated with the park or other hot springs in the United States. During 2018-2019, Legionnaires' disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These findings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow.
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Fontes Termais , Legionella pneumophila , Doença dos Legionários , Arkansas , Humanos , Doença dos Legionários/epidemiologia , Doença dos Legionários/prevenção & controle , Parques Recreativos , Estados Unidos/epidemiologia , Água , Microbiologia da Água , Abastecimento de ÁguaRESUMO
Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (Lpro) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2',5'-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wild-type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that Lpro interfered with the OAS/RNase L pathway by interacting with the N-terminal domain of swine RNase L (sRNase L). Remarkably, Lpro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey, or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV Lpro inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that Lpro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway. IMPORTANCE FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here, we show that Lpro of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with the N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, Lpro inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.
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2',5'-Oligoadenilato Sintetase/metabolismo , Endopeptidases/metabolismo , Endorribonucleases/metabolismo , Vírus da Febre Aftosa/imunologia , Evasão da Resposta Imune/imunologia , Imunidade Inata/imunologia , Animais , Apoptose/imunologia , Linhagem Celular , Cricetinae , Cães , Endopeptidases/genética , Endopeptidases/imunologia , Endorribonucleases/genética , Febre Aftosa/imunologia , Febre Aftosa/virologia , Células HEK293 , Haplorrinos , Humanos , Evasão da Resposta Imune/genética , Células Madin Darby de Rim Canino , Domínios Proteicos , SuínosRESUMO
OBJECTIVES/BACKGROUND: Correlational studies show that short sleep is associated with negative daytime outcomes in school-aged children, but there are few experimental sleep manipulation studies to assess whether this is a causal relation. The aim of this study was to determine the impact of mild, cumulative sleep restriction on daytime functioning of typically developing (TD) children and children with attention-deficit/hyperactivity disorder (ADHD). PARTICIPANTS: A total of 36 school-aged children (n = 18 TD; n = 18 ADHD), aged 6-11 years participated. METHODS: Children participated in two sleep conditions (order counter-balanced). The Restricted condition required a 1 h reduction of time in bed for one week, and the Controlled Typical condition was based on participant's average baseline sleep. At the end of each condition, participants attended the sleep lab for overnight polysomnography and daytime functioning assessments. RESULTS: Children successfully reduced time in bed by ~1 h. Due to compensatory changes, total sleep time (TST) was reduced by only ~20 min, as children fell asleep faster and spent less time awake after sleep onset during the Restricted compared to Controlled Typical condition. Many daytime functions were not affected by this very mild sleep restriction, however, both groups showed significant changes in performance on an objective attention task and on a parent-rated emotional lability measure after six nights of minimal reductions in TST. There were no significant differences between groups. CONCLUSIONS: Results suggest that a very mild sleep restriction can affect children's attention and emotional regulation, even with evidence of compensatory sleep mechanisms.