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Objetivo: avaliar pontuação da National Early Warning Score (NEWS) em relação ao tipo de desfecho e perfil dos pacientes da enfermaria clínica médica de um hospital em Teresina, Piauí, Brasil. Método: estudo quantitativo realizado num hospital público, em Teresina, com 150 prontuários de pacientes internados no setor clínica médica de fevereiro de 2022 a dezembro de 2022, a partir de registros demográficos, clínicos e valores da escala na admissão e desfecho. Resultados: houve associação dos valores da escala com a faixa etária (p=0,029), tempo de internação (p=0,023) e tipo de desfecho (p < 0,001). Alto risco clínico prevaleceu entre pacientes do sexo masculino (13%), na faixa etária de 60 a 94 anos (13%), com permanência de 21 a 57 dias (19,2%) e óbito como desfecho (100%). Conclusão: implementação da referida escala evidenciou ser fundamental para prever agravos clínicos e melhorar qualidade da assistência.
Objective: to evaluate the National Early Warning Score (NEWS) in relation to the type of outcome and profile of patients in the medical clinical ward of a hospital in Teresina, Piauí, Brazil. Method: a quantitative study conducted in a public hospital in Teresina, with 150 medical records of patients admitted to the medical clinic sector from February 2022 to December 2022, based on demographic and clinical records and scale values at admission and outcome. Results: there was an association between the scale values and the age group (p=0.029), length of stay (p=0.023) and type of outcome (p < 0.001). High clinical risk prevailed among male patients (13%), aged between 60 and 94 years (13%), with a stay of 21 to 57 days (19.2%), and death as an outcome (100%). Conclusion: implementation of the aforementioned scale proved to be fundamental for predicting clinical problems and improving care quality.
Objetivo: evaluar el puntaje de la National Early Warning Score (NEWS) con respecto al tipo de desenlace y el perfil de los pacientes de la enfermería clínica médica de un hospital en Teresina, Piauí, Brasil. Método: estudio cuantitativo realizado en un hospital público en Teresina, con 150 historiales médicos de pacientes internados en el sector de clínica médica desde febrero de 2022 hasta diciembre de 2022, a partir de registros demográficos, clínicos y valores de la escala en la admisión y desenlace. Resultados: hubo asociación de los valores de la escala con la edad (p=0,029), tiempo de internación (p=0,023) y tipo de desenlace (p < 0,001). El alto riesgo clínico prevaleció entre los pacientes del sexo masculino (13%), en la franja de edad entre 60 y 94 años (13%), con una estancia de 21 a 57 días (19,2%) y fallecimiento como desenlace (100%). Conclusión: la implementación de dicha escala demostró ser fundamental para prever agravios clínicos y mejorar la calidad de la asistencia.
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Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.
Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.
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Inbreeding can lead to the accumulation of homozygous single nucleotide polymorphisms (SNPs) in the genome, which can significantly affect gene expression and phenotype. In this study, we examined the impact of homozygous SNPs resulting from inbreeding on alternative polyadenylation (APA) site selection and the underlying genetic mechanisms using inbred Luchuan pigs. Genome resequencing revealed that inbreeding results in a high accumulation of homozygous SNPs within the pig genome. 3' mRNA-seq on leg muscle, submandibular lymph node, and liver tissues was performed to identify differences in APA events between inbred and outbred Luchuan pigs. We revealed different tissue-specific APA usage caused by inbreeding, which were associated with different biological processes. Furthermore, we explored the role of polyadenylation signal (PAS) SNPs in APA regulation under inbreeding and identified key genes such as PUM1, SCARF1, RIPOR2, C1D, and LRRK2 that are involved in biological processes regulation. This study provides resources and sheds light on the impact of genomic homozygosity on APA regulation, offering insights into genetic characteristics and biological processes associated with inbreeding.
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Endogamia , Poliadenilação , Polimorfismo de Nucleotídeo Único , Animais , Poliadenilação/genética , Suínos/genética , Genoma , Homozigoto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade de Órgãos/genéticaRESUMO
The interaction between lifestyle--defined more specifically in health care as the personal exposome--and its implications on obesity and breast cancer development highlights the critical role of body composition and inflammation in these patients. There is clear evidence that the personal and internal exposome triggers biochemical, inflammatory, and metabolic reprogramming, which might favor ectopic lipid accumulation within the body, such as muscles. Additionally, the presence of excessive adipose tissue exacerbates these alterations in the internal exposome, resulting in cell damage and modifying body composition. Understanding the nexus between these lifestyle-induced exposome modifications, such as inflammation, and the resultant changes in body composition is crucial to assess the association with breast cancer progression and treatment responses. Various techniques can be used to evaluate body composition; one of those most used currently is bioelectrical impedance analysis. This analysis provides parameters, including phase angle (PhA), by which cellular health and metabolic activity can be assessed. In addition, PhA is a potential indicator of nutritional status and disease prognosis, as it has been linked to survival and quality of life in patients with cancer. Therefore, PhA might be used in daily oncology practice to implement an accurate nutritional intervention, reducing side effects and complications of oncology management, and improving quality of life during treatment and survival, even in patients with breast cancer with obesity or overweight. The aim of this review is to analyze the existing information on the current application of PhA in patients with breast cancer and its potential use as a tool to assess inflammatory response, identify malnutrition, and predict the deterioration of quality of life so that it could be proposed as an early indicator for nutritional interventions in this group of patients.
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Composição Corporal , Neoplasias da Mama , Inflamação , Estado Nutricional , Obesidade , Qualidade de Vida , Humanos , Neoplasias da Mama/complicações , Obesidade/complicações , Feminino , Impedância Elétrica , Estilo de Vida , Prognóstico , Tecido Adiposo/metabolismoRESUMO
Chronic hepatitis B virus infection (CHB) remains a global health concern, with currently available antiviral therapies demonstrating limited effectiveness in preventing hepatocellular carcinoma (HCC) development. Two primary challenges in CHB treatment include the persistence of the minichromosome, covalently closed circular DNA (cccDNA) of the hepatitis B virus (HBV), and the failure of the host immune response to eliminate cccDNA. Recent findings indicate several host and HBV proteins involved in the epigenetic regulation of cccDNA, including HBV core protein (HBc) and HBV x protein (HBx). Both proteins might contribute to the stability of the cccDNA minichromosome and interact with viral and host proteins to support transcription. One potential avenue for CHB treatment involves the utilization of therapeutic vaccines. This paper explores HBV antigens suitable for epigenetic manipulation of cccDNA, elucidates their mechanisms of action, and evaluates their potential as key components of epigenetically-driven vaccines for CHB therapy. Molecular targeted agents with therapeutic vaccines offer a promising strategy for addressing CHB by targeting the virus and enhancing the host's immunological response. Despite challenges, the development of these vaccines provides new hope for CHB patients by emphasizing the need for HBV antigens that induce effective immune responses without causing T cell exhaustion.
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BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1ß play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov under NCT06000514.
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The hypothalamus receives serotonergic projections from the raphe nucleus in a sex-specific manner. During systemic inflammation, hypothalamic levels of serotonin (5-hydroxytryptamine [5-HT]) decrease in male rats. The present study evaluated the involvement of endothelin-1 (ET-1) in the febrile response, hypolocomotion, and changes in hypothalamic 5-HT levels during systemic inflammation in male and female rats. An intraperitoneal injection of lipopolysaccharide (LPS) induced a febrile response and hypolocomotion in both male and female rats. However, although LPS reduced hypothalamic levels of 5-HT and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in male rats, it increased these levels in female rats. An intracerebroventricular injection of the endothelin-B receptor antagonist BQ788 significantly reduced LPS-induced fever and hypolocomotion and changes in hypothalamic 5-HT and 5-HIAA levels in both male and female rats. The i.c.v. administration of ET-1 induced a significant fever and hypolocomotion, but reduced the hypothalamic levels of 5-HT and 5-HIAA in both males and females. These results suggest an important sexual dimorphism during systemic inflammation regarding the release of 5-HT in the hypothalamus. Moreover, ET-1 arises as an important mediator involved in the changes in hypothalamic 5-HT levels in both male and female rats.
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Endotelina-1 , Hipotálamo , Inflamação , Piperidinas , Ratos Wistar , Serotonina , Caracteres Sexuais , Animais , Masculino , Feminino , Endotelina-1/metabolismo , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Ratos , Inflamação/metabolismo , Inflamação/induzido quimicamente , Serotonina/metabolismo , Piperidinas/farmacologia , Lipopolissacarídeos/toxicidade , Oligopeptídeos/farmacologia , Ácido Hidroxi-Indolacético/metabolismo , Antagonistas dos Receptores de Endotelina/farmacologia , Febre/metabolismo , Febre/induzido quimicamenteRESUMO
INTRODUCTION AND OBJECTIVES: Prostate apoptosis response protein-4 (PAR-4) is considered a tumor suppressor. However, the role of PAR-4 in hepatocellular carcinoma (HCC) has rarely been reported. The study explores the role of PAR-4 in the malignant behaviors of HCC cells. MATERIALS AND METHODS: TCGA database was applied to analyze the expression of PAR-4 in HCC. Evaluated PAR-4 relationship with clinical parameters and prognosis by tissue microarray; expression of STAT3, p-STAT3, Src and Ras was detected by Western blotting or laser confocal microscopy. Cell scratch and flow cytometry assays were used to observe IL-6 regulation of the malignant behaviors of HCC cells. The tumorigenic potential of HCC cells in vivo was evaluated in a nude mouse tumor model. RESULTS: Analysis indicated that the expression of PAR-4 in HCC tissues was significantly higher than that in normal liver tissues; and PAR-4 interacted with STAT3. KEGG analysis showed that PAR-4 plays a role in the Janus kinase (JAK)/STAT signaling pathway. The positive expression rate of PAR-4 in HCC tissues was significantly higher than that in adjacent tissues. Positive correlation between IL-6 and PAR-4 expression in the HCC tissues. Exogenous IL-6 significantly promoted the proliferation and migration of HCC cells and up-regulated the expression of PAR-4 and p-STAT3 in HCC cells. Interference of the expression of PAR-4 could reduce the malignant behaviors of HCC cells and inhibit tumorigenesis in a nude mouse tumor model. CONCLUSIONS: PAR-4 expression is positively correlated with HCC; PAR-4 promotes malignant behavior of HCC cells mediated by the IL-6/STAT3 signaling pathway.
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The extremotolerant red yeast Rhodotorula mucilaginosa displays resilience to diverse environmental stressors, including cold, osmolarity, salinity, and oligotrophic conditions. Particularly, this yeast exhibits a remarkable ability to accumulate lipids and carotenoids in response to stress conditions. However, research into lipid biosynthesis has been hampered by limited genetic tools and a scarcity of studies on adaptive responses to nutrient stressors stimulating lipogenesis. This study investigated the impact of nitrogen stress on the adaptive response in Antarctic yeast R. mucilaginosa M94C9. Varied nitrogen availability reveals a nitrogen-dependent modulation of biomass and lipid droplet production, accompanied by significant ultrastructural changes to withstand nitrogen starvation. In silico analysis identifies open reading frames of genes encoding key lipogenesis enzymes, including acetyl-CoA carboxylase (Acc1), fatty acid synthases 1 and 2 (Fas1/Fas2), and acyl-CoA diacylglycerol O-acyltransferase 1 (Dga1). Further investigation into the expression profiles of RmACC1, RmFAS1, RmFAS2, and RmDGA1 genes under nitrogen stress revealed that the prolonged up-regulation of the RmDGA1 gene is a molecular indicator of lipogenesis. Subsequent fatty acid profiling unveiled an accumulation of oleic and palmitic acids under nitrogen limitation during the stationary phase. This investigation enhances our understanding of nitrogen stress adaptation and lipid biosynthesis, offering valuable insights into R. mucilaginosa M94C9 for potential industrial applications in the future.