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.

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.

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.

Enhanced choroid plexus segmentation with 3D UX-Net and its association with disease progression in multiple sclerosis.

BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.

Breakthroughs in road mapping IL-35 mediated immunotherapy for type-1 and autoimmune diabetes mellitus.

IL-35 is a recently discovered protein made up of IL-12α and IL-27ß chains. It is encoded by IL12A and EBI3 genes. Interest in researching IL-35 has significantly increased in recent years, as evidenced by numerous scientific publications. Diabetes is on the rise globally, causing more illness and death in developing countries. The International Diabetes Federation (IDF) reports that diabetes is increasingly affecting children and teenagers, with varying rates across different regions. Therefore, scientists seek new diabetes treatments despite the growth of drug research. Recent research aims to emphasize IL-35 as a critical regulator of diabetes, especially type 1 and autoimmune diabetes. This review provides an overview of recent research on IL-35 and its link to diabetes and its associated complications. Studies suggest that IL-35 can offer protection against type-1 diabetes and autoimmune diabetes by regulating macrophage polarization, T-cell-related cytokines, and regulatory B cells (Bregs). This review will hopefully assist biomedical scientists in exploring the potential role of IL-35-mediated immunotherapy in treating diabetes. However, further research is necessary to determine the exact mechanism and plan clinical trials.

Objective sleep enhancement in Parkinson's disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex.

INTRODUCTION: Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. METHODS: In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. RESULTS: The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5-2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. CONCLUSION: Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

Urine-derived renal epithelial cells isolated after kidney transplant are sensitive to neutrophil gelatinase-associated lipocalin exposure during in vitro culture.

Urine-derived renal epithelial cells (URECs) are highly voided after kidney transplant and express typical kidney markers, including markers of kidney epithelial progenitor cells. Recently URECs have shown promising immunomodulatory properties when cultured with Peripheral Blood Mononuclear Cells (PBMCs), promoting an increase in the T regulatory cells. In vivo, kidney cells are highly exposed to damage associated molecules during both acute and chronic kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most -known early marker of acute and chronic kidney damage. However, its role on the evolution of renal damage has not yet been fully described, nor has its impact on the characteristics of renal-derived cells during in vitro culture. The aim of this study is to investigate the effect of NGAL on the characteristics of URECs isolated after kidney transplant, by exposing these cells to the treatment with NGAL during in vitro culture and evaluating its effect on UREC viability, proliferation, and immunomodulatory potential. The exposure of URECs to NGAL reduced their viability and proliferative capacity, promoting the onset of apoptosis. The immunomodulatory properties of URECs were partially inhibited by NGAL, without affecting the increase of Treg cells observed during UREC-PBMCs coculture. These results suggest that the exposure to NGAL may compromise some features of kidney stem and specialized cell types, reducing their viability, increasing apoptosis, and partially altering their immunomodulatory properties. Thus, NGAL could represent a target for approaches acting on its inhibition or reduction to improve functional recovery.

Sleep disturbances and associated factors in patients with Parkinson's disease.

AIMS: This study aimed to describe clinical characteristics and sleep quality of Parkinson's Diseases (PD) patients and identify associated factors with sleep quality. METHODS: A cross-sectional study was conducted at the National Geriatric Hospital, Hanoi, Vietnam, from December 2022 to April 2023. A total of 130 Parkinson's disease patients undergoing treatment at the hospital were invited. Demographic and clinical characteristics were obtained. The diagnosis of sleep disorders was based on the standards outlined in the DSM-V. A multivariate logistic regression model was employed. RESULTS: 90.9 % experienced sleep disorder, with the significant types including insomnia (76.2 %) and restless legs syndrome (56.2 %). The majority of patients suffered two (33.1 %) and one kind of sleep disorder (32.3 %). Most patients experienced sleep disorders after diagnosis of PD (80.0 %). Only having shoulder and neck pain was positively associated with a likelihood of having sleep disturbances (OR=4.87, 95 %CI=1.18-20.15). CONCLUSION: This study found a high rate of sleep disorders among PD patients in our sample. Shoulder and neck pain was found to be associated with a risk of sleep disorders. Pain management should be performed to improve the sleep quality of PD patients.

A new strategy for the treatment of Parkinson's disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective.Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ("RP", the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established "shuffling" procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection.Approach.In a novel "residuals" method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the preceding nrmilliseconds. Finally, we compute the PSD of the model's residuals.Main results.We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey -- in which alpha-beta oscillations (8-30 Hz) were anticipated -- the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection.Significance.These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

Early growth response factor 3 regulates coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression.

AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r= 0.55, p < 0.001), IL-1ß levels (r=0.21, p=0.004) and the Gensini score (r=0.20, p=0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

Caloric restriction leading to attenuation of experimental Alzheimer's disease results from alterations in gut microbiome.

BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.

Autobiographical Storytelling in Patients with Mild Alzheimer's Disease: Focused, Reflected, and Entertaining; A Comparative Study.

OBJECTIVES: We assessed whether individuals with mild Alzheimer's disease (AD), despite some deficits in autobiographical memory, could effectively convey their personal experiences through storytelling. METHODS: We invited 37 individuals with mild AD and 37 control participants to share their personal experiences. We rated these narratives based on five characteristics of storytelling: focus, reflection, entertainment, structure, and specificity. RESULTS: Analyses demonstrated that individuals with AD conveyed more general than specific memories, and no significant differences were observed between structured and unstructured memories. Importantly, individuals with AD recounted more memories with focus than without, with reflection than without, and that were entertaining than were not. Compared with those of the control participants, the narratives of the individuals with AD were less focused, structured, and specific. However, no significant differences were observed between the two samples regarding reflection or entertainment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Individuals with mild AD can have difficulties in retrieving specific memories, but their storytelling of personal experience can be focused, exhibit reflection, and be entertaining. Individuals with mild AD can engage in reflective and entertaining autobiographical storytelling, potentially contributing to their sense of identity and connection with others.