Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers

Redução das internações por condições sensíveis à atenção primária no Brasil entre 1998-2009

OBJETIVO: Descrever a tendência de hospitalizações por condições sensíveis à atenção primária entre 1998 e 2009 no Brasil. MÉTODOS: Estudo ecológico de séries temporais com dados secundários referentes às internações hospitalares por condições sensíveis à atenção primária no Sistema Único de Saúde. Os dados foram obtidos do Sistema de Informações Hospitalares. As taxas de internações por 10.000 habitantes foram padronizadas por faixa etária e sexo, considerando a população brasileira masculina recenseada em 2000 como padrão. A análise de tendência da série histórica foi realizada por regressão linear generalizada pelo método de Prais-Winsten. RESULTADOS: Houve redução média anual de internações por condições sensíveis à atenção primária de 3,7% entre homens (IC95% -2,3;-5,1) e mulheres (IC95% -2,5;-5,6) entre 1998 e 2009. A tendência variou em cada unidade federativa, porém em nenhuma houve aumento das internações. No sexo masculino e feminino as maiores reduções foram observadas nas internações por úlceras gastrintestinais (-11,7% ao ano e -12,1%, respectivamente), condições evitáveis (-8,8% e -8,9%) e doenças das vias aéreas inferiores (-8,0% e -8,1%). Angina (homens), infecção no rim e trato urinário (homens e mulheres) e condições relacionadas ao pré-natal e parto (mulheres) apresentaram aumento nas internações. Os três grupos de doenças que mais ocasionaram internações foram gastrenterites infecciosas e complicações, internações por insuficiência cardíaca e asma. CONCLUSÕES: Houve redução substancial nas internações por condições sensíveis à atenção primária no Brasil entre 1998 e 2009, porém algumas doenças apresentaram estabilidade ou acréscimo, exigindo atenção do setor saúde.OBJECTIVE: To describe the trends in hospitalizations for ambulatory care sensitive conditions between 1998 and 2009 in Brazil. METHODS: The ecological time series study used secondary data on hospitalizations for ACSC in the Sistema Único de Saúde (SUS, National Unified Health System). Data were obtained from the Hospital Information System. Hospital admission rates per 10,000 inhabitants were standardized by age range and gender, using the 2000 census male Brazilian population as standard. Trend analysis of the historic series was performed through generalized linear regression using the Prais-Winsten method. RESULTS: Between 1998 and 2009, there was an average annual reduction in admissions for ambulatory care sensitive conditions of 3.7% in men (95%CI -2.3;-5.1) and women (95%CI -2.5; -5.6). The trend varied in each state, although no increase in admissions was observed in any state. In both men and women, the highest reductions were observed in hospitalizations for gastrointestinal ulcers (-11.7% a year and -12.1%, respectively), avoidable conditions (-8.8% and -8.9%) and lower respiratory diseases (-8.0% and -8.1%). Hospitalization increased only for angina (men), kidney infections and urinary tract infections (men and women) and conditions related to prenatal care and delivery (women). The three groups of illness which led to the most admissions were infectious gastroenteritis and its complications, cardiac insufficiency and asthma. CONCLUSIONS: Between 1998 and 2009, there was a substantial reduction in admissions for ambulatory care sensitive conditions in Brazil, although some illnesses presented stability or even an increase, which calls for attention from the health sector.OBJETIVO: Describir la tendencia de hospitalizaciones por condiciones susceptibles a atención primaria entre 1998 y 2009 en Brasil. MÉTODOS: Estudio ecológico de series temporales con datos secundarios relacionados con las Internaciones Hospitalarias por condiciones susceptibles a atención primaria en el Sistema Único de Salud de Brasil. Los datos fueron obtenidos del Sistema de Informaciones Hospitalarias. Las tasas de internaciones por 10.000 habitantes fueron estandarizadas por grupo etario y sexo, considerando la población brasileña masculina recensada en 2000 como patrón. El análisis de tendencia de la serie histórica fue realizado por regresión linear generalizado por el método de Prais-Winsten. RESULTADOS: Hubo reducción en el promedio anual de internaciones por condiciones susceptibles a atención primaria de 3,7% entre hombres (IC95% -2,3;-5,1) y mujeres (IC95% -2,5;-5,6) entre 1998 y 2009. La tendencia varió en cada unidad federativa, sin embargo, en ninguna hubo aumento de las internaciones. En el sexo masculino y femenino las mayores reducciones fueron observadas en las internaciones por úlceras gastrointestinales (-11,7% al año y -12,1%, respectivamente), condiciones evitables (-8,8% y -8,9%) y enfermedades de las vías aéreas inferiores (-8,0% y -8,1%). Angina (hombres), infección en el riñón y tracto urinario (hombres y mujeres) y condiciones relacionados al prenatal y parto (mujeres) presentaron aumento en las internaciones. Los tres grupos de enfermedades que más ocasionaron internaciones fueron gastroenteritis infecciosas y complicaciones, internaciones por insuficiencia cardíaca y asma. CONCLUSIONES: Hubo reducción sustancial en las internaciones por condiciones susceptibles a atención primaria en Brasil entre 1998 y 2009, sin embargo, algunas enfermedades presentaron estabilidad o aumento, exigiendo atención del sector salud

Spatial analysis of avoidable hospitalizations due to tuberculosis in Ribeirao Preto, SP, Brazil (2006-2012)

ABSTRACT OBJECTIVE To describe the spatial distribution of avoidable hospitalizations due to tuberculosis in the municipality of Ribeirao Preto, SP, Brazil, and to identify spatial and space-time clusters for the risk of occurrence of these events. METHODS This is a descriptive, ecological study that considered the hospitalizations records of the Hospital Information System of residents of Ribeirao Preto, SP, Southeastern Brazil, from 2006 to 2012. Only the cases with recorded addresses were considered for the spatial analyses, and they were also geocoded. We resorted to Kernel density estimation to identify the densest areas, local empirical Bayes rate as the method for smoothing the incidence rates of hospital admissions, and scan statistic for identifying clusters of risk. Softwares ArcGis 10.2, TerraView 4.2.2, and SaTScanTM were used in the analysis. RESULTS We identified 169 hospitalizations due to tuberculosis. Most were of men (n = 134; 79.2%), averagely aged 48 years (SD = 16.2). The predominant clinical form was the pulmonary one, which was confirmed through a microscopic examination of expectorated sputum (n = 66; 39.0%). We geocoded 159 cases (94.0%). We observed a non-random spatial distribution of avoidable hospitalizations due to tuberculosis concentrated in the northern and western regions of the municipality. Through the scan statistic, three spatial clusters for risk of hospitalizations due to tuberculosis were identified, one of them in the northern region of the municipality (relative risk [RR] = 3.4; 95%CI 2.7–4,4); the second in the central region, where there is a prison unit (RR = 28.6; 95%CI 22.4–36.6); and the last one in the southern region, and area of protection for hospitalizations (RR = 0.2; 95%CI 0.2–0.3). We did not identify any space-time clusters. CONCLUSIONS The investigation showed priority areas for the control and surveillance of tuberculosis, as well as the profile of the affected population, which shows important aspects to be considered in terms of management and organization of health care services targeting effectiveness in primary health care

Plasma concentrations of anserine, carnosine and pi-methylhistidine as biomarkers of habitual meat consumption

BACKGROUND/OBJECTIVES Dietary intake of red and processed meat has been associated with disease risk. Since dietary intake assessment methods are prone to measurement errors, identifying biomarkers of meat intake in bio-samples could provide more valid intake estimates. We examined associations of habitual red and processed meat, poultry, fish, and dairy products consumption with plasma concentrations of anserine, carnosine, pi-methylhistidine (Π-MH), tau-methylhistidine (T-MH), and the ratio of T-MH to Π-MH in a cross-sectional study. SUBJECTS/METHODS Plasma anserine, carnosine, Π-MH, and T-MH concentrations were measured using ion-pair LC-MS/MS in 294 participants in the second Bavarian Food Consumption Survey (BVS II). Habitual food consumption was assessed using three 24-h dietary recalls. Associations between plasma metabolites concentrations and meat, fish, eggs, and dairy products consumption were assessed by fitting generalized linear model, adjusted for age, sex, and BMI. RESULTS Total meat intake was associated with plasma concentrations of anserine, carnosine, Π-MH and, the ratio of T-MH to Π-MH. Red meat intake was related to carnosine (p-trend = 0.0028) and Π-MH plasma levels (p-trend = 0.0493). Poultry (p-trend = 0.0006) and chicken (p-trend = 0.0003) intake were associated with Π-MH. The highest anserine concentrations were observed in individuals consuming processed meat or turkey. For T-MH we did not observe any association with meat intake. CONCLUSIONS Our results indicate an association between habitual meat consumption and plasma concentrations of anserine, carnosine, Π-MH and the ratio of T-MH to Π-MH. Intervention studies should clarify whether the analyzed plasma metabolites are indicative for a specific type of meat before proposing them as biomarkers of habitual meat intake in epidemiologic studies

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications