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.

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.

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.

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.

Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.

The Neurofibromatosis Type 1 (NF1) RASopathy is associated with persistent fibrotic nonunions (pseudarthrosis) in human and mouse skeletal tissue. Here, we first performed spatial transcriptomics to define the molecular signatures across normal endochondral healing following fracture in mice. Within the control fracture callus, we observed spatially restricted activation of morphogenetic pathways, such as TGF-ß, WNT, and BMP. To investigate the molecular mechanisms contributing to Nf1-deficient delayed fracture healing, we performed spatial transcriptomic analysis on a Postn-cre;Nf1flox/- (Nf1Postn) fracture callus. Transcriptional analyses, subsequently confirmed through p-SMAD1/5/8 immunohistochemistry, demonstrated a lack of BMP pathway induction in Nf1Postn mice. To further inform the human disease, we performed spatial transcriptomic analysis of fracture pseudarthrosis tissue from a NF1 patient. Analyses detected increased MAPK signaling at the fibrocartilaginous-osseus junction. Similar to the Nf1Postn fracture, BMP pathway activation was absent within the pseudarthrosis tissue. Our results demonstrate the feasibility to delineate the molecular and tissue-specific heterogeneity inherent in complex regenerative processes, such as fracture healing, and to reconstruct phase transitions representing endochondral bone formation in vivo. Furthermore, our results provide in situ molecular evidence of impaired BMP signaling underlying NF1 pseudarthrosis, potentially informing the clinical relevance of off-label BMP2 as a therapeutic intervention.

Bacteria are a major determinant of Orsay virus transmission and infection in Caenorhabditis elegans.

The microbiota is a key determinant of the physiology and immunity of animal hosts. The factors governing the transmissibility of viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans and represent an integral part of the natural environment of C. elegans. We determined the effects of bacteria isolated with C. elegans from its natural environment on the transmission of Orsay virus in C. elegans using quantitative virus transmission and host susceptibility assays. We observed that Ochrobactrum species promoted Orsay virus transmission, whereas Pseudomonas lurida MYb11 attenuated virus transmission relative to the standard laboratory bacterial food Escherichia coli OP50. We found that pathogenic Pseudomonas aeruginosa strains PA01 and PA14 further attenuated virus transmission. We determined that the amount of Orsay virus required to infect 50% of a C. elegans population on P. lurida MYb11 compared with Ochrobactrum vermis MYb71 was dramatically increased, over three orders of magnitude. Host susceptibility was attenuated even further in the presence of P. aeruginosa PA14. Genetic analysis of the determinants of P. aeruginosa required for attenuation of C. elegans susceptibility to Orsay virus infection revealed a role for regulators of quorum sensing. Our data suggest that distinct constituents of the C. elegans microbiota and potential pathogens can have widely divergent effects on Orsay virus transmission, such that associated bacteria can effectively determine host susceptibility versus resistance to viral infection. Our study provides quantitative evidence for a critical role for tripartite host-virus-bacteria interactions in determining the transmissibility of viruses among susceptible hosts.

The target of rapamycin signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity in Aspergillus flavus.

The target of rapamycin (TOR) signaling pathway is highly conserved and plays a crucial role in diverse biological processes in eukaryotes. Despite its significance, the underlying mechanism of the TOR pathway in Aspergillus flavus remains elusive. In this study, we comprehensively analyzed the TOR signaling pathway in A. flavus by identifying and characterizing nine genes that encode distinct components of this pathway. The FK506-binding protein Fkbp3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The TorA kinase plays a pivotal role in the regulation of growth, spore production, aflatoxin biosynthesis, and responses to rapamycin and cell membrane stress. As a significant downstream effector molecule of the TorA kinase, the Sch9 kinase regulates aflatoxin B1 (AFB1) synthesis, osmotic and calcium stress response in A. flavus, and this regulation is mediated through its S_TKc, S_TK_X domains, and the ATP-binding site at K340. We also showed that the Sch9 kinase may have a regulatory impact on the high osmolarity glycerol (HOG) signaling pathway. TapA and TipA, the other downstream components of the TorA kinase, play a significant role in regulating cell wall stress response in A. flavus. Moreover, the members of the TapA-phosphatase complexes, SitA and Ppg1, are important for various biological processes in A. flavus, including vegetative growth, sclerotia formation, AFB1 biosynthesis, and pathogenicity. We also demonstrated that SitA and Ppg1 are involved in regulating lipid droplets (LDs) biogenesis and cell wall integrity (CWI) signaling pathways. In addition, another phosphatase complex, Nem1/Spo7, plays critical roles in hyphal development, conidiation, aflatoxin production, and LDs biogenesis. Collectively, our study has provided important insight into the regulatory network of the TOR signaling pathway and has elucidated the underlying molecular mechanisms of aflatoxin biosynthesis in A. flavus.

Epileptic activity on foramen ovale electrodes is associated with sleep and tau pathology in Alzheimer's disease.

Both sleep alterations and epileptiform activity are associated with the accumulation of amyloid-ß and tau pathology and are currently investigated for potential therapeutic interventions in Alzheimer's disease (AD). However, a bidirectional intertwining relation between sleep and neuronal hyperexcitability might modulate the effects of AD pathology on the corresponding associations. To investigate this, we performed multiple day simultaneous foramen ovale (FO) plus scalp EEG and polysomnography (PSG) recordings and acquired 18F-MK6240 tau PET-MR in three patients in the prodromal stage of AD and in two patients with mild and moderate dementia due to AD, respectively. As an eligibility criterion for the present study, subjects either had a history of a recent seizure (n = 2) or subclinical epileptiform activity (SEA) on a previous scalp EEG taken in a research context (n = 3). The 18F-MK6240 standard uptake value ratio (SUVR) and asymmetry index (AI) were calculated in a priori defined volumes of interest (VOIs). Linear mixed effects models were used to study associations between interictal epileptiform discharges (IEDs), PSG parameters and 18F-MK6240 SUVR. Epileptiform activity was bilateral but asymmetrically present on FO electrodes in all patients and ≥ 95% of IEDs were not visible on scalp EEG. In one patient two focal seizures were detected on FO electrodes, both without visual scalp EEG correlate. We observed lateralized periodic discharges, brief potentially ictal rhythmic discharges and lateralized rhythmic delta activity on FO electrodes in four patients. Unlike scalp EEG, intracranial electrodes showed a lateralization of epileptiform activity. Although the amount of IEDs on intracranial electrodes was not associated to the 18F-MK6240 SUVR binding in different VOIs, there was a congruent asymmetry of the 18F-MK6240 binding towards the most epileptic hemisphere for the mesial (P = 0.007) and lateral temporal cortex (P = 0.006). IEDs on intracranial electrodes were most abundant during slow wave sleep (SWS) (92/h) and N2 (81/h), followed by N1 (33/h) and least frequent during wakefulness (17/h) and REM sleep (9/h). The extent of IEDs during sleep was not reflected in the relative time in each sleep stage spent (REM% (P = 0.415), N1% (P = 0.668), N2% (P = 0.442), SWS% (P = 0.988)), and not associated with the arousal index (P = 0.317), apnea-hypopnea index (P = 0.846) or oxygen desaturation index (P = 0.746). Together, our observations suggest a multi-directional interaction between sleep, epileptiform activity and tau pathology in AD.

Extensive mycetoma in forearm, chest and neck due to Nocardia mexicana.

INTRODUCTION: Mycetoma is a chronic granulomatous inflammatory disease of the subcutaneous tissue, which affects deep structures and bone. Most cases of actinomycetoma are caused by members of the genus Nocardia. CASE PRESENTATION: Here we report the case of a 43-year-old male who presented a disseminated mycetoma on the forearm, chest and neck, characterized by enlarged and erythematous lesions through which seropurulent material drains, and numerous atrophic scars. Molecular identification was performed by 16S gene amplification and sequencing. Nocardia mexicana was identified with 100% identity. Trimethoprim-sulfamethoxazole, diaminodiphenyl sulfone and amikacin was a successful treatment after 6 months. CONCLUSIONS: Nocardia mexicana is a rare organism that causes mycetoma. We report a case of extensive mycetoma on the forearm with spread to the neck and thorax associated with manipulation of the mouth of a calf.

Associations between TLRs 2 and 4, and ß-lactam antibiotics in COPD patients complicated with pulmonary infections.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. We aimed to investigate the associations between toll-like receptors 2 and 4 (TLR-2 and TLR-4) and ß-lactam antibiotics in COPD patients complicated with pulmonary infections. METHODOLOGY: A total of 156 COPD patients complicated with pulmonary infections were included. Their blood gas, airway resistance, health status, expression levels of TLR-2 and TLR-4, and pulmonary function were analyzed after treatment with ß-lactam antibiotics. RESULTS: Blood gas indices oxygen saturation, partial pressure of oxygen, and partial pressure of carbon dioxide at one day before treatment, on the fifteenth day of treatment, and on the first day after the end of treatment showed significant differences (p < 0.01). Significant differences were also detected in airway resistance indices (p < 0.01). The differences in the mRNA expression levels of TLR-2 and TLR-4 were significant (p < 0.05). Downward trends were observed in the clinical pulmonary infection score and acute physiology and chronic health evaluation II score, which indicated alleviation of the disease. Pulmonary function indices recorded vital capacity (VC)/predicted VC (%), recorded forced vital capacity at 1 s (FEV1)/predicted FEV1 (%), and residual volume/total lung capacity were significantly different (p < 0.05). CONCLUSIONS: ß-Lactam antibiotics had obvious therapeutic effects on COPD patients complicated with pulmonary infections, probably by suppressing or attenuating TLR-2- and TLR-4-mediated inflammatory responses. It is necessary to comprehensively evaluate and choose appropriate antibiotics, aiming for maximum relief of the pain to help patients recover quickly.

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher risk of dementia, and, consequently, be not rarely misdiagnosed. In this review, we summarize the state-of-the-art on LBD-AD by discussing the synergistic effects between AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment in LBD-AD and their possible diagnostic and prognostic value. AD pathology can be suspected in vivo by means of CSF, MRI and PET markers, whereas α-synuclein seed amplification assays (SAAs) represent to date the most promising technique to identify Lewy pathology in different biological tissues. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity like in pure AD. The implementation of blood-based biomarkers of AD might allow the fast screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account for the differential diagnosis of dementia syndromes, for the prognostic evaluation on an individual level and for guiding symptomatic and disease-modifying therapies.

Analyzing the infertility burden of polycystic ovarian syndrome in China: A comprehensive age-period-cohort analysis with future burden prediction (1990-2030).

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common but complex endocrine disorder widely linked to infertility and miscarriage. This study assessed the correlation between PCOS and infertility. METHODS: Using the latest data from the Global Burden of Disease 2019 database, we conducted an in-depth assessment of the disease burden attributed to PCOS in China. This analysis was performed using the joinpoint regression, age-period-cohort, and autoregressive integrated moving average (ARIMA) models. RESULTS: Between 1990-2019, an upward trend was observed in the age-standardized prevalence of PCOS-related female infertility in China. Joinpoint regression analysis revealed an increasing trend in the age-standardized prevalence of PCOS-related female infertility burden indicators as well as the average annual percentage change and annual percentage change across all age groups in China. In terms of the cohort effect, the period rate ratios associated with the age-standardized prevalence of PCOS-related infertility increased steadily over time. The ARIMA model predicted a relatively swift upward trend in the age-standardized prevalence of PCOS-related infertility in China from 2020-2030. CONCLUSION: The age-standardized prevalence of PCOS-related female infertility in China has increased between 1990-2019. The ARIMA model predicted that the age-standardized prevalence of this disease may continue to increase over the next decade. This study can increase the public's attention, improve women's health awareness, and have a certain significance for reducing female infertility related to PCOS.

Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease.

The escalating prevalence of Parkinson's disease (PD) underscores the need for innovative therapeutic interventions since current palliative measures, including the standard l-Dopa formulations, face challenges of tolerance and side effects while failing to address the underlying neurodegenerative processes. Here, we introduce DAD9, a novel conjugate molecule that aims to combine symptomatic relief with disease-modifying strategies for PD. Crafted through knowledge-guided chemistry, the molecule combines a nonantibiotic doxycycline derivative with dopamine, preserving neuroprotective attributes while maintaining dopaminergic agonism. This compound exhibited no off-target effects on PD-relevant cell functions and sustained antioxidant and anti-inflammatory properties of the tetracycline precursor. Furthermore, it effectively interfered with the formation and seeding of toxic α-synuclein aggregates without producing detrimental oxidative species. In addition, DAD9 was able to activate dopamine receptors, and docking simulations shed light onto the molecular details of this interaction. These findings position DAD9 as a potential neuroprotective dopaminergic agonist, promising advancements in PD therapeutics.

Long-term exposure to air pollution, road traffic noise and greenness, and incidence of myocardial infarction in women.

BACKGROUND: Emerging evidence shows that long-term exposure to air pollution, road traffic noise, and greenness can each be associated with cardiovascular disease, but only few studies combined these exposures. In this study, we assessed associations of multiple environmental exposures and incidence of myocardial infarction using annual time-varying predictors. MATERIALS AND METHODS: In a population-based cohort of 20,407 women in Sweden, we estimated a five-year moving average of residential exposure to air pollution (PM2.5, PM10 and NO2), road traffic noise (Lden), and greenness (normalized difference vegetation index, NDVI in 500 m buffers), from 1998 to 2017 based on annually varying exposures and address history. We used adjusted time-varying Cox proportional hazards regressions to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) of myocardial infarction per interquartile range (IQR). Furthermore, we investigated interactions between the exposures and explored potential vulnerable subgroups. RESULTS: In multi-exposure models, long-term exposure to greenness was inversely associated with incidence of myocardial infarction (HR 0.89; 95 % CI 0.80, 0.99 per IQR NDVI increase). Stronger associations were observed in some subgroups, e.g. among women with low attained education and in overweight (BMI ≥ 25 kg/m2) compared to their counterparts. For air pollution, we observed a tendency of an increased risk of myocardial infarction in relation to PM2.5 (HR 1.07; 95 % CI 0.93, 1.23) and the association appeared stronger in women with low attained education (HR 1.30; 95 % CI 1.06, 1.58). No associations were observed for PM10, NO2 or road traffic noise. Furthermore, there were no clear interaction patterns between the exposures. CONCLUSION: Over a 20-year follow-up period, in multi-exposure models, we found an inverse association between residential greenness and risk of myocardial infarction among women. Furthermore, we observed an increased risk of myocardial infarction in relation to PM2.5 among women with low attained education. Road traffic noise was not associated with myocardial infarction.

Evaluation of the coping attitudes of Alzheimer patients' relatives from the perspectives of depression, anxiety and guilt.

This study aims to assess coping attitudes in primary caregivers of individuals diagnosed with Alzheimer's disease residing in an institution, and to evaluate the association between coping attitudes and levels of guilt, depression, and anxiety among caregivers. The sample of this study consists of 150 individuals with relatives diagnosed with Alzheimer. The Beck Anxiety Inventory, the Coping Attitudes Scale, the Guilt Inventory, and the Beck Depression Inventory were used in the present study. It was determined that the participants' coping levels were below the average score and that they frequently used problem focus coping attitudes. A positive relationship was found between the emotion focused, nonfunctional coping levels of the participants and their continuous guilt, anxiety and depression levels. Depression and guilt has a strong effect on coping attitudes, while anxiety was determined to be a moderate predictive variable. Findings show that caregivers with depression, anxiety and continuous guilt use non-functional and emotional coping more frequently.