Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Informação e prevenção não farmacológica da COVID-19 no território de uma unidade de saúde da família em Pernambuco / Information and non-pharmacological prevention of COVID-19 in the territory of a family health unit in Pernambuco / Información y prevención no farmacológica del COVID-19 en el territorio de una unidad de salud de la familia en Pernambuco

Introdução: O conhecimento da magnitude em que a população implementa medidas de proteção emitidas pelas autoridades de saúde pública é essencial na prevenção da doença do novo coronavírus (COVID-19). A eficácia de medidas não farmacológicas de prevenção e das políticas públicas destinadas a reduzir o contágio pela COVID-19 depende de quão bem os indivíduos são informados sobre as consequências da infecção e as medidas que devem adotar para reduzir sua propagação. O entendimento, as atitudes e as práticas das pessoas em relação à COVID-19 e sua prevenção são basilares para a compreensão da dinâmica epidemiológica, demandando a realização de pesquisas sobre o cumprimento de medidas não farmacológicas de prevenção do contágio em diversos territórios. Para isso, em 2020, medidas não farmacológicas contra a COVID-19 foram divulgadas por fontes diversas, estatais e privadas, para a maior parte da população brasileira, com a finalidade de orientar comportamentos para conter a crise sanitária. As equipes da Estratégia Saúde da Família têm um papel fundamental neste processo de educação em saúde, pois compreendem elementos socioculturais das suas comunidades, alcançando-as tanto em capilaridade quanto em adequação local da informação técnico-científica. Este artigo abrange uma pesquisa de campo, parte de um projeto multicêntrico nacional. Objetivo: Avaliar se a população do território de uma unidade da Estratégia Saúde da Família da cidade de Condado-PE entende e aplica as informações que recebeu sobre medidas não farmacológicas de prevenção em suas práticas de proteção contra a COVID-19. Mais especificamente, a pesquisa visou determinar que informações foram recebidas pelos respondentes, quais as suas fontes, o grau de confiabilidade atribuído a estas, além da adesão deles às medidas não farmacológicas e sua relação com variáveis sociodemográficas. Métodos: O modelo do estudo foi observacional e descritivo, com abordagem quantitativa, a partir da coleta de dados primários com 70 usuários por entrevista presencial com questionário estruturado. Resultados: Os resultados mostraram que a população recebeu vasta informação sobre prevenção da doença. Conclusão: Com níveis variados de confiabilidade das fontes, atribuindo importância relevante às medidas de prevenção e adotou a maioria delas, com exceção do isolamento social total.

Introduction: Knowledge of the magnitude to which the population implements protective measures issued by public health authorities is essential in preventing coronavirus disease 2019 (COVID-19). The effectiveness of non-pharmacological prevention measures (NPM) and public policies aimed at reducing the spread of COVID-19 depends on how well individuals are informed about the consequences of the infection and the measures they must adopt to reduce its spread. The understanding, attitudes, and practices of people in relation to COVID-19 and its prevention are fundamental for understanding the epidemiological dynamics, demanding research on compliance with NPM to prevent contagion in different territories. To this end, in 2020, NPM against COVID-19 were released by various sources, state and private, for most of the Brazilian population, with the aim of guiding behaviors to contain the health crisis. The Family Health Strategy (FHS) teams play a key role in this health education process, as they comprise sociocultural elements of their communities, reaching them both in capillarity and in local adequacy of technical-scientific information. This article covers field research, part of a national multicenter project. Objective: To evaluate whether the population of the territory of an FHS unit in the city of Condado, Pernambuco, understands and applies the information it received about NPM prevention in their practices to protect against COVID-19. More specifically, the research aimed to determine what information was received by the respondents, what are their sources, the degree of reliability attributed to these, in addition to their adherence to the NPM and their relationship with sociodemographic variables. Methods: The study model was observational and descriptive, with a quantitative approach, based on the collection of primary data with 70 users through face-to-face interviews with a structured questionnaire. Results: The results showed that the population received extensive information on disease prevention. Conclusion: With varying levels of reliability of the sources, attributing relevant importance to prevention measures and adopted most of them, with the exception of total social isolation.

El conocimiento de la magnitud con la que la población implementa las medidas de protección emitidas por las autoridades de salud pública es fundamental en la prevención de la enfermedad por coronavirus 2019 (COVID-19). La efectividad de las medidas de prevención no farmacológicas (MFN) y de las políticas públicas dirigidas a reducir la propagación de la COVID-19 depende de qué tan bien se informe a las personas sobre las consecuencias de la infección y las medidas que deben adoptar para reducir su propagación. La comprensión, actitudes y prácticas de las personas con relación al COVID-19 y su prevención son fundamentales para comprender la dinámica epidemiológica, exigiendo investigaciones sobre el cumplimiento de las MNF para prevenir el contagio en diferentes territorios. Con ese fin, en 2020, MNF contra el COVID-19 fueron divulgados por diversas fuentes, estatales y privadas, para la mayoría de la población brasileña, con el objetivo de orientar comportamientos para contener la crisis sanitaria. Los equipos de la Estrategia de Salud de la Familia (ESF) juegan un papel fundamental en este proceso de educación en salud, ya que integran elementos socioculturales de sus comunidades, alcanzándolas tanto en la capilaridad como en la adecuación local de la información técnico-científica. Este artículo aborda una investigación de campo, parte de un proyecto multicéntrico nacional, con el objetivo de evaluar si la población del territorio de una unidad de la ESF en la ciudad de Condado-PE comprende y aplica la información recibida sobre la prevención de MNF en sus prácticas de protección contra el COVID -19. Más específicamente, la investigación tuvo como objetivo determinar qué información recibieron los encuestados, cuáles son sus fuentes, el grado de confiabilidad atribuido a estas, además de su adherencia al MNF y su relación con variables sociodemográficas. El modelo de estudio fue observacional y descriptivo, con enfoque cuantitativo, basado en la recolección de datos primarios con 70 usuarios a través de entrevistas cara a cara con un cuestionario estructurado. Los resultados mostraron que la población recibió amplia información sobre prevención de la enfermedad, con diversos niveles de confiabilidad de las fuentes, atribuyendo importancia relevante a las medidas de prevención y adoptando la mayoría de ellas, con excepción del aislamiento social total.

Fatores intervenientes na gerência do cuidado de enfermagem à criança hospitalizada com cardiopatia reumática / Intervening factors in the management of nursing care for children hospitalized with rheumatic heart disease / Factores que intervienen en la gestión del cuidado de enfermería al niño hospitalizado con cardiopatía reumática

Objetivo: analisar os fatores intervenientes na gerência do cuidado de enfermagem à criança hospitalizada com cardiopatia reumática. Método: estudo descritivo-exploratório com abordagem qualitativa, que utilizou a Teoria Fundamentada em Dados e o Interacionismo Simbólico, respectivamente, como referencial metodológico e teórico. A coleta de dados foi realizada em uma instituição especializada em atendimento cardiológico, no munícipio do Rio de Janeiro. Foram entrevistados 19 profissionais de enfermagem através de um roteiro semiestruturado. Resultado: emergiram os seguintes fatores intervenientes na prática da gerência do cuidado: condição socioeconômica da família, comportamento da criança, condições de trabalho, comunicação ineficaz, educação permanente, trabalho em equipe e experiência profissional. Conclusão: os resultados apontam para a necessidade de proposição de estratégias de ação e interação que facilitem a prática gerencial de cuidado à criança com cardiopatia reumática e sua família face aos fatores intervenientes identificados.

Objective: to analyze the factors involved in the management of nursing care for children hospitalized with rheumatic heart disease. Method: this is a descriptive-exploratory study with a qualitative approach, which used Data-Based Theory and Symbolic Interactionism, respectively, as methodological, and theoretical references. Data was collected in an institution specializing in cardiac care in the city of Rio de Janeiro. Nineteen nursing professionals were interviewed using a semi-structured script. Result: the following intervening factors in the practice of care management emerged: the family's socioeconomic status, the child's behavior, working conditions, ineffective communication, continuing education, teamwork, and professional experience. Conclusion: the results point to the need to propose strategies for action and interaction that facilitate management practice in caring for children with rheumatic heart disease and their families, given the intervening factors identified.

Objetivo: analizar los factores que intervienen en la gestión del cuidado de enfermería al niño hospitalizado con cardiopatía reumática. Método: estudio descriptivo-exploratorio con enfoque cualitativo, cuyos marcos metodológico y teórico fueron la Teoría Fundamentada y el Interaccionismo Simbólico, respectivamente. La recolección de datos se realizó en una institución especializada en atención cardiológica, en la ciudad de Río de Janeiro. Fueron entrevistados 19 profesionales de enfermería mediante un cuestionario semiestructurado. Resultado: surgieron los siguientes factores intervinientes en la práctica de la gestión del cuidado: condición socioeconómica de la familia, comportamiento del niño, condiciones de trabajo, comunicación ineficaz, educación continua, trabajo en equipo y experiencia profesional. Conclusión: los resultados indican que es necesario proponer estrategias de acción e interacción que faciliten la práctica de la gestión del cuidado al niño con cardiopatía reumática y a sus familiares, con respecto a los factores intervinientes identificados.

COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Caracterización de la situación problémica en un estudio psicosocial con pacientes con enfermedad renal crónica

Introducción: La enfermedad renal crónica es un problema de salud a nivel mundial, su manifestación más grave, la insuficiencia renal crónica, incide en el contexto cubano y determina el crecimiento de pacientes en hemodiálisis. El objetivo del texto es valorar los principales resultados del diagnóstico y caracterización de la situación problémica en un estudio de carácter psicosocial con pacientes con Insuficiencia Renal Crónica en la sala de Hemodiálisis del municipio Florida, de la provincia de Camagüey. Método: Es una investigación-acción participativa de corte experimental, que se desarrolla entre enero 2023 y diciembre del 2024 la cual constituye salida del proyecto de investigación Sistema de acciones psicosociales para el perfeccionamiento de la atención integral a los pacientes con enfermedades no transmisibles. El universo está constituido por 56 pacientes y la muestra por 22, que reciben tratamiento depurador y conservador, 22 familiares y 12 profesionales del servicio. El instrumento de investigación por excelencia fue la encuesta a participantes. Resultados: La edad de los pacientes no es definitiva de un grupo etario; predominan los hombres; se constata un elevado por ciento de pacientes con poca tolerancia a la adherencia al tratamiento e insuficiente desarrollo de las habilidades psicosociales y declaran la necesidad de poseer conocimientos para lograr estados de salud que conlleven a la sobrevida. Discusión: No existe coincidencia con lo constatado en la determinación de los grupos etarios de prevalencia para la enfermedad, pero los especialistas insisten en que la enfermedad no es privativa de un período de vida específico; reconocen la importancia del conocimiento de los factores de riesgo por el paciente para la prevención, promoción y educación en salud y resaltan la necesidad de la comunicación y la empatía entre el personal de salud y el paciente, para lograr resultados y estados emocionales favorables ante la enfermedad y el tratamiento.

Introduction: Chronic kidney disease is a global health problem. Its most serious manifestation, chronic kidney failure, affects the Cuban context and determines the growth of patients on hemodialysis. The objective of the text is to evaluate the main results of the diagnosis and characterization of the problematic situation in a psychosocial study with patients with Chronic Renal Failure in the Hemodialysis room of the Florida municipality, of the county of Camagüey. Method: It is an experimental participatory action research, which takes place between January 2023 and December 2024, which constitutes the output of the research project System of psychosocial actions for the improvement of comprehensive care for patients with non-communicable diseases. The universe is made up of 56 patients and the sample is made up of 22, who receive purifying and conservative treatment, 22 family members and 12 service professionals. The research instrument par excellence was the participant survey. Results: The age of the patients is not definitive of an age group; men predominate; A high percentage of patients are found to have low tolerance for adherence to treatment and insufficient development of psychosocial skills and declare the need to possess knowledge to achieve health states that lead to survival. Discussion: There is no coincidence with what was found in the determination of the prevalence age groups for the disease, but specialists insist that the disease is not exclusive to a specific period of life; recognize the importance of the patient's knowledge of risk factors for prevention, promotion and health education and highlight the need for communication and empathy between health personnel and the patient, to achieve favorable results and emotional states in the face of the disease and treatment.

BI1 Activates Autophagy and Mediates TDP43 to Regulate ALS Pathogenesis.

Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease in adults. Currently, there are no known drugs or clinical approaches that have demonstrated efficacy in treating ALS. Mitochondrial function and autophagy have been identified as crucial mechanisms in the development of ALS. While Bax inhibitor 1 (BI1) has been implicated in neurodegenerative diseases, its exact mechanism remains unknown. This study investigates the therapeutic impact of BI1 overexpression on ALS both in vivo and in vitro, revealing its ability to mitigate SOD1G93A-induced apoptosis, nuclear damage, mitochondrial dysfunction, and axonal degeneration of motor neurons. At the same time, BI1 prolongs onset time and lifespan of ALS mice, improves motor function, and alleviates neuronal damage, muscle damage, neuromuscular junction damage among other aspects. The findings indicate that BI1 can inhibit pathological TDP43 morphology and initially stimulate autophagy through interaction with TDP43. This study establishes a solid theoretical foundation for understanding the regulation of autophagy by BI1 and TDP43 while shedding light on the pathogenesis of ALS through their interaction - offering new concepts and targets for clinical implementation and drug development.

Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease.

Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.

Association between serum magnesium levels and cognitive function in patients undergoing hemodialysis.

BACKGROUND: The relationship between chronic kidney disease-mineral and bone disorder (CKD-MBD) and cognitive function remains largely unknown. This cross-sectional study aimed to explore the association between CKD-MBD and cognitive function in patients on hemodialysis. METHODS: Hemodialysis patients aged ≥ 65 years without diagnosed dementia were included. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). CKD-MBD markers, serum magnesium, intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), fibroblast growth factor (FGF)-23, and soluble α-klotho were measured. RESULTS: Overall, 390 patients with a median age of 74 (interquartile range, 70-80) years, mean serum magnesium level of 2.4 ± 0.3 mg/dL, and median MoCA and MMSE scores of 25 (22-26) and 28 (26-29), respectively, were analyzed. MoCA and MMSE scores were significantly higher (preserved cognitive function) in the high-magnesium group than in the low-magnesium group according to the unadjusted linear regression analysis (ß coefficient [95% confidence interval (CI)] 1.05 [0.19, 1.92], P = 0.017 for MoCA; 1.2 [0.46, 1.94], P = 0.002 for MMSE) and adjusted multivariate analysis with risk factors for dementia (ß coefficient [95% CI] 1.12 [0.22, 2.02], P = 0.015 for MoCA; 0.92 [0.19, 1.65], P = 0.014 for MMSE). CONCLUSIONS: Higher serum magnesium levels might be associated with preserved cognitive function in hemodialysis patients. Conversely, significant associations were not observed between cognitive function and intact PTH, 25-OHD, FGF-23, or soluble α-klotho levels.

BRD7 as key factor in PBAF complex assembly and CD8+ T cell differentiation.

Upon infection, naïve CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodel system in this process remains largely unknown. Here we showed that BRD7, a component of the polybromo-associated BRG1-associated factor complex (PBAF), was required for naïve CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7-deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicated that the expression of BRD7 significantly turned to high from naïve CD8+ T cells to effector cells, bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and up-regulated its expression, leading to the maturation of effector T cells. Our research confirms BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.

Do pregnant persons want influenza vaccines? Knowledge, attitudes, perceptions, and practices toward influenza vaccines in 8 low- and middle-income countries.

BACKGROUND: While vaccination is the most effective way to prevent influenza infection and adverse outcomes, and despite WHO recommendations to vaccinate pregnant persons, access to seasonal influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons about seasonal influenza vaccines to inform actions to improve vaccine uptake among this priority population. METHODS: We pooled individual-level data from cross-sectional surveys assessing pregnant persons' attitudes toward seasonal influenza vaccines in eight low- and middle-income countries during 2018-2019. The eight countries used a standard protocol and questionnaire to measure attitudes and intents toward influenza vaccination. We stratified by country-level (presence/absence of a national influenza vaccination program, country income group, geographic region) and individual-level factors. FINDINGS: Our analysis included 8,556 pregnant persons from eight low- and middle-income countries with and without seasonal influenza vaccination programs. Most pregnant persons (6,323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without influenza vaccination programs (2,383, 89%) than in those with such programs (3,940, 67%, p < 0.001). INTERPRETATION: Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs may be well-received by pregnant persons, leading to averted illness both in pregnant persons themselves and in their newborn babies. FUNDING: US Centers for Disease Control and Prevention.

Drug Evaluation of Parkinson's Disease Patient-Derived Midbrain Organoids Using Mesoporous Au Nanodot-Patterned 3D Concave Electrode.

Brain organoids are being recognized as valuable tools for drug evaluation in neurodegenerative diseases due to their similarity to the human brain's structure and function. However, a critical challenge is the lack of selective and sensitive electrochemical sensing platforms to detect the response of brain organoids, particularly changes in the neurotransmitter concentration upon drug treatment. This study introduces a 3D concave electrode patterned with a mesoporous Au nanodot for the detection of electrochemical signals of dopamine in response to drugs in brain organoids for the first time. The mesoporous Au nanodot-patterned film was fabricated using laser interference lithography and electrochemical deposition. Then, the film was attached to a polymer-based 3D concave mold to obtain a 3D concave electrode. Midbrain organoids generated from Parkinson's disease (PD) patient-derived iPSCs with gene mutations (named as PD midbrain organoid) or normal midbrain organoids were positioned on the developed 3D concave electrode. The 3D concave electrode showed a 1.4 times higher electrochemical signal of dopamine compared to the bare gold electrode. And the dopamine secreted from normal midbrain organoids or PD midbrain organoids on the 3D concave electrode could be detected electrochemically. After the treatment of PD midbrain organoids with levodopa, the drug for PD, the increase in dopamine level was detected due to the activation of dopaminergic neurons by the drug. The results suggest the potential of the proposed 3D concave electrode combined with brain organoids as a useful tool for assessing drug efficacy. This sensing system can be applied to a variety of organoids for a comprehensive drug evaluation.

Mechanical Stress-induced Connective Tissue Growth Factor Plays a Critical Role in Intestinal Fibrosis in Crohn's-like Colitis.

Crohn's disease (CD) is an inflammatory bowel disease characterized by transmural inflammation and intestinal fibrosis. Mechanisms of fibrosis in CD are not well understood. Transmural inflammation is associated with inflammatory cell infiltration, stenosis, and distention, which present mechanical stress (MS) to the bowel wall. We hypothesize that MS induces gene expression of pro-fibrotic mediators such as connective tissue growth factor (CTGF), which may contribute to fibrosis in CD. A rodent model of CD was induced by intracolonic instillation of TNBS to the distal colon. TNBS instillation induced a localized transmural inflammation (site I), with a distended colon segment (site P) proximal to site I. We detected significant fibrosis and collagen content not only in site I, but also in site P in CD rats by day 7. CTGF expression increased significantly in sites P and I, but not in the segment distal to the inflammation site. Increased CTGF expression was detected mainly in the smooth muscle cells (SMC). When rats were fed exclusively with clear liquid diet to prevent mechanical distention in colitis, expression of CTGF in sites P and I was blocked. Direct stretch led to robust expression of CTGF in colonic SMC. Treatment of CD rats with anti-CTGF antibody FG-3149 reduced fibrosis and collagen content in both sites P and I and exhibited consistent trends towards normalizing expression of collagen mRNAs. In conclusion, our studies suggest that mechanical stress, by up-regulating pro-fibrotic mediators i.e. CTGF, may play a critical role in fibrosis in CD.

Prenatal exposure to an environmentally relevant phthalate mixture alters serum cytokine levels and inflammatory markers in the F1 mouse ovary.

Phthalates are used as plasticizers and solvents in consumer products. Virtually 100% of the U.S. population has measurable exposure levels to phthalates, however, the mechanisms by which prenatal exposure to phthalate mixtures affects reproductive health in the offspring remain unclear. Thus, this study tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture promotes inflammation in F1 ovarian tissue. Pregnant CD-1 dams were dosed orally with vehicle control (corn oil) or phthalate mixture (20 µg/kg/day, 200 µg/kg/day, 200 mg/kg/day, 500 mg/kg/day). Pregnant dams delivered pups naturally and ovaries and sera from the F1 females were collected at postnatal day (PND) 21, PND 60, 3 months, and 6 months. Sera were used to measure levels of C-reactive protein (CRP). Ovaries and sera were used for cytokine array analysis. RNA was isolated from F1 ovaries and used to quantify expression of selected cytokine genes. Prenatal exposure to the mixture significantly increased the levels of CRP at 200 µg/kg/day on PND 21 compared to controls. The mixture altered 6 immune factors in sera at PND 21 and 33 immune factors in the ovary and sera at 6 months compared to controls. The mixture increased ovarian expression of cytokines at PND 21 and decreased ovarian expression of cytokines at 6 months compared to controls. These data suggest that prenatal exposure to a phthalate mixture interferes with the immune response in F1 female mice long after initial exposure.

Mortality due to visceral leishmaniasis in Brazil by municipalities, 2001-2018: a spatial-temporal analysis of estimates from the Global Burden of Disease study.

OBJECTIVES: In the American regions, Brazil accounts for 97% of visceral leishmaniasis (VL) cases, with a case fatality rate of approximately 10%. This study aimed to investigate the VL mortality distribution in Brazil and identify high-priority and high-risk areas for intervention strategies. STUDY DESIGN: This was an ecological study that analysed the spatial-temporal patterns of VL mortality in Brazilian municipalities. METHODS: Age-standardised VL mortality rates from the Global Burden of Disease study from 2001 to 2018 were used. The distribution of mortality in the municipalities was assessed, and subsequently the Local Index of Spatial Autocorrelation (LISA) analysis was conducted to identify contiguous areas with high mortality rates. Scan analysis identified clusters of high spatial-temporal risks. RESULTS: The highest mortality rates and clusters were in municipalities located in the Northeast region and in the states of Tocantins and Roraima (North region), Mato Grosso do Sul (Central-West region), and Minas Gerais (Southeast region). According to LISA, there was an increase in the number of municipalities classified as high priority from the first 3-year period (n = 434) to the last 3-year period (n = 644). The spatio-temporal analysis identified 21 high-risk clusters for VL mortality. CONCLUSION: Areas with a high risk of VL mortality should prioritise preventing transmission, invest in early diagnosis and treatment, and promote the training of healthcare professionals.

Siamese Graph Convolutional Network quantifies increasing structure-function discrepancy over the cognitive decline continuum.

BACKGROUND AND OBJECTIVE: Alzheimer's disease dementia (ADD) is well known to induce alterations in both structural and functional brain connectivity. However, reported changes in connectivity are mostly limited to global/local network features, which have poor specificity for diagnostic purposes. Following recent advances in machine learning, deep neural networks, particularly Graph Neural Network (GNN) based approaches, have found applications in brain research as well. The majority of existing applications of GNNs employ a single network (uni-modal or structure/function unified), despite the widely accepted view that there is a nontrivial interdependence between the brain's structural connectivity and the neural activity patterns, which is hypothesized to be disrupted in ADD. This disruption is quantified as a discrepancy score by the proposed "structure-function discrepancy learning network" (sfDLN) and its distribution is studied over the spectrum of clinical cognitive decline. The measured discrepancy score is utilized as a diagnostic biomarker and is compared with state-of-the-art diagnostic classifiers. METHODS: sfDLN is a GNN with a siamese architecture built on the hypothesis that the mismatch between structural and functional connectivity patterns increases over the cognitive decline spectrum, starting from subjective cognitive impairment (SCI), passing through a mid-stage mild cognitive impairment (MCI), and ending up with ADD. The structural brain connectome (sNET) built using diffusion MRI-based tractography and the novel, sparse (lean) functional brain connectome (ℓNET) built using fMRI are input to sfDLN. The siamese sfDLN is trained to extract connectome representations and a discrepancy (dissimilarity) score that complies with the proposed hypothesis and is blindly tested on an MCI group. RESULTS: The sfDLN generated structure-function discrepancy scores show high disparity between ADD and SCI subjects. Leave-one-out experiments of SCI-ADD classification over a cohort of 42 subjects reach 88% accuracy, surpassing state-of-the-art GNN-based classifiers in the literature. Furthermore, a blind assessment over a cohort of 46 MCI subjects confirmed that it captures the intermediary character of the MCI group. GNNExplainer module employed to investigate the anatomical determinants of the observed discrepancy confirms that sfDLN attends to cortical regions neurologically relevant to ADD. CONCLUSION: In support of our hypothesis, the harmony between the structural and functional organization of the brain degrades with increasing cognitive decline. This discrepancy, shown to be rooted in brain regions neurologically relevant to ADD, can be quantified by sfDLN and outperforms state-of-the-art GNN-based ADD classification methods when used as a biomarker.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.