Melatonin and Vascular Function.

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer's disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology.

Time as a consequence of internal coherence.

Time has been an elusive concept to grasp. Although we do not yet understand it properly, there have been advances made in regard to how we can explain it. One such advance is the Page-Wootters mechanism. In this mechanism, time is seen as an inaccessible coordinate and the apparent passage of time arises as a consequence of correlations between the subsystems of a global state. Here we propose a measure that captures the relational character of the mechanism, showing that the internal coherence is the necessary ingredient for the emergence of time in the Page-Wootters model. Also, we connect it to results in quantum thermodynamics, showing that it is directly related to the extractable work from quantum coherence.

Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies.

In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.

Controlled attenuation parameter for steatosis grading in chronic hepatitis C compared with digital morphometric analysis of liver biopsy: impact of individual elastography measurement quality.

BACKGROUND AND OBJECTIVE: Controlled attenuation parameter (CAP) diagnostic performance for steatosis grading has been controversial and considerable observer-related variability in liver biopsy has been reported. This is a subanalysis of a larger chronic hepatitis C study on noninvasive fibrosis staging. MATERIALS AND METHODS: Patients were prospectively enrolled for paired liver biopsy and transient elastography. Biopsy fragments were subjected to digital morphometric steatosis quantification. Associated patient and technical factors, including a newly described elastogram quality score, were evaluated. RESULTS: A total of 312 patients were included in the final analysis. The mean liver stiffness was 8.7±2.1 kPa. Morphometry showed S0 in 19.2% of patients, S1 in 28.5%, S2 in 31.1%, and S3 in 21.2%. CAP showed S0 in 11.2% of patients, S1 in 26.6%, S2 in 56.7%, and S3 in 5.4%. Spearman coefficient showed a positive and independent correlation between CAP and morphometric analysis (r=0.48, P<0.05), except for distinguishing S1 and S2 (P=0.11). Area under the receiver operating characteristic curves for the presence or absence of steatosis was 0.944; differentiation between levels I, II, and III were 0.776, 0.812, and 0.879. Elastogram quality independently predicted accuracy [odds ratio (OR): 6.95, 95% confidence interval (95%CI): 4.45-9.06 as well as CAP interquartile range OR: 2.81, 95%CI: 1.67-3.99] and liver stiffness (OR: 0.78, 95%CI: 0.51-0.80). CONCLUSION: We present an external validation for CAP against the objective steatosis quantification provided by digital morphometry. Fairly good performance indicators were found, except for S1 versus S2 differentiation. Variability and higher liver stiffness were associated with lower performance. Achieving higher quality measurements, however, overcame such limitations with excellent accuracy.

All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response.

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). PATIENTS AND METHODS: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. RESULTS: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. CONCLUSION: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.

Predictors of early discontinuation of interferon-free direct antiviral agents in patients with hepatitis C virus and advanced liver fibrosis: results of a real-life cohort.

AIM: The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. PATIENTS AND METHODS: We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors. RESULTS: In total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason [8 (42.1%)]. Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio: 1.1, 95% confidence interval: 1.02-1.19) and higher model for end-stage liver disease (odds ratio: 1.27, 95% confidence interval: 1.03-1.56) were associated with premature treatment interruption. CONCLUSION: Older age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.

Chronic hepatitis C virus infection: it is not only about the liver.

BACKGROUND AND AIMS: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are both hepatotropic and quite similar in terms of clinical manifestations and histopathology, their respective infections are distinct in terms of epidemiology and prognosis. Recognizing the differences between patients with HBV and HCV infection with respect to demographic characteristics, prevalence of comorbidities, and presence of lifestyle factors aids the proper treatment of these patients. We aimed to compare two populations with chronic viral liver disease (chronic HCV and chronic HBV), each of them with resolved hepatitis C. PATIENTS AND METHODS: We included patients referred to a municipal reference clinic from March 2009 through May 2012. Patient data were collected using standardized questionnaires at the patients' first visit to clinic. Questionnaires included epidemiological information, presence of comorbidities, and lifestyle. RESULTS: A total of 756 patients were included in the study, 348 (46.0%) with chronic HCV infection, 176 (23.3%) with chronic HBV infection, and 232 (30.7%) with resolved HCV infection. Multivariate analysis including patients with chronic HCV infection and chronic HBV infection indicated that age [adjusted odds ratio (AOR)=1.06; 95% confidence interval (CI): 1.03-1.08], alcohol abuse (AOR=1.58; 95% CI: 1.01-2.49), smoking (AOR=1.64; 95% CI: 1.00-2.17), and illicit drug (AOR=2.92; 95% CI: 1.69-5.02) use were associated independently with chronic HCV infection. Multivariate analyses including patients with chronic HCV infection and those patients with resolved HCV infection, presence of at least one comorbidity (AOR=1.94; 95% CI: 1.12-3.3), illicit drug use (AOR=3.24; 95% CI: 1.90-5.54), and age (AOR=1.03; 95% CI: 1.01-1.05) were independently associated with chronic HCV infection. Age (AOR=0.98; 95% CI: 0.96-0.99) and male sex (AOR=1.93; 95% CI: 1.26-2.95) were the only variables associated significantly with chronic HBV infection in the multivariate analysis between patients with chronic HBV infection and resolved HCV infection. CONCLUSION: Our results highlight that patients with chronic HCV infection are complex and require a multidisciplinary approach during patient follow-up and clinical management.

A Universidade colaborando na construção de um projeto de promoção da saúde: relato de experiência de um grupo de alunos de Medicina da Unicamp, Campinas, SP, Brasil / The university collaborating in the construction of a health promotion project: report on an experience of a group of Medical Students at Unicamp, Campinas, SP, Brazil

Este trabalho foi realizado com o objetivo de oferecer aos estudantes de graduação em Medicina da Universidade Estadual de Campinas (Unicamp) a vivência de ações de saúde pública, segundo princípios do Sistema Unico de Saúde (SUS), por meio da elaboração de um projeto coletivo de promoção da saúde ocular de crianças de 0 a 7 anos. Para isto, foi aplicado um questionário para levantar as necessidades em relação à saúde ocular em uma amostra da população usuária do Centro de Saúde Jardim Santa Mônica em Campinas (SP), em 2003. Nele, percebeu-se a falta de informações sobre cuidados básicos com os olhos e de recursos e qualificação profissional para diagnóstico e tratamento, bem como o desconhecimento dos direitos à saúde e a ausência de medidas preventivas, principalmente para crianças. Foi desenvolvido, então, um projeto de ação e aprendizado com alunos, professores, agentes comunitários de saúde e auxiliares de uma creche do bairro, formando uma equipe de trabalho. Foram realizadas oficinas com essa equipe, na perspectiva da promoção e proteção da saúde ocular. Para a sustentabilidade do projeto, o planejamento previu a criação de um banco de óculos para a doação de armações e garantia da confecção para as pessoas com dificuldades financeiras. A experiência da construção e da aplicação do projeto permitiu o conhecimento, na prática, da organização dos serviços e a dinâmica do sistema de saúde, inclusive para compreender alguns limites e sugerir políticas públicas de saúde ocular que correspondam às necessidades da população, apontando-se o papel do médico no desencadeamento de um trabalho coletivo de compartilhamento de saberes e responsabilidades.

The goal of this project was to promote eye health and provide eye care to children from 0 to 7 years of age and to offer to medical students of Unicamp the possibility of participating in practice in a public health action carried out according to the principles of the Brazilian Unified Health System (SUS - Sistema Unico de Saúde). In 2003, a questionnaire was applied to a sample of users of the Jardim Santa Mônica Health Care Center in Campinas, SP. Analysis of the data there obtained revealed some deficiencies in the promotion of eye health such as lack of information about basic eye care, lack of resources for treatment, lack of information about the right to care by the Unified Health System and the absence of any preventive measures, mainly for children. Thus, a project was developed offering workshops for students, teachers, community health agents and personnel from a neighborhood nurser y-school to enable them to act as multipliers of the obtained knowledge and to initiate a process of awareness building. A spectacle bank was created in order to grant the sustainability of the project, offering the confection of eye glasses with frames donated by the population and lenses offered by the city government and some optic stores to needed persons. Through this experience the medical students could obtain some practical knowledge about the organization of health services and the dynamics of the health system, enabling them to understand some limitations and to suggest public eye health policies meeting the needs of the population. A closer study of this project shows not only how important this kind of action is for the most needed segments of society but also the role a doctor can play as someone able to convince people to go for their rights.

Acidentes de punçäo em estudantes de medicina: um alerta / Needlestick injuries in medical students: a word of advice

A incidência dos acidentes por punção entre estudantes de Medicina, bem como suas causas e consequências reprepresentam um tema bastante controverso. Existem poucos estudos que avaliam os riscos de contaminação a que estão sujeitos os estudantes ao manipularem sanguee outros fluidos corpóreos durante seus estágios...

Prevalência de doenças esofágicas como etiologia de dor torácica não cardíaca / Prevalence of esophageal diseases as etiology of non-cardiac chest pain

A dor torácica é um sintoma muito frequente, uma vez afastada a etiologia cardíaca, o esôfago é o principal órgão a ser investigado. Os autores avaliam prospectivamente 100 pacientes com dor torácica não cardíaca, através de entrevista clínica e da realização de manometria esofágica e de pHmetria de 24h. Em 38 pacientes (38por cento) foi diagnosticada doença do refluxo gastroesofágico e 56 (56por cento) apresentaram alteração motora esófagica, sendo a hipotonia do esfíncter esofágico inferior (29por cento) e o esôfago "em quebra-nozes" (16por cento) as mais comuns. Ao analisar em conjunto, 63 pacientes (63por cento) apresentaram doença esofágica que pode ser associada com a dor torácica. Dessa forma, a investigação esofágica é muito importante para determinar um provável fator etiológico para a dor torácica, assim permitindo uma proposta terapêutica.

Processo expansivo criptocócico do SNC: relato de caso / Cryptococus expansive process of the SNC: report of two cases

Em decorrência da baixa incidência de abscessos e granulomas criptocócicos do SNC, os autores relatam dois casos de processo expansivo cerebral causados por esta micose. Foram analisados sintomatologia, métodos de investigaçao, de diagnóstico e conduta, com dados bibliográficos dos últimos anos.

Angiodisplasia de delgado: relato de caso / Angiodysplasia os small intestine: case report

Os autores apresentam um caso de angiodisplasia da porçao alta do intestino delgado. Fazem uma revisao da literatura médica nessa entidade, ressaltando sua raridade e sua complexidade diagnóstica e terapêutica. A angiodisplasia é a causa mais freqüente de hemorragia gastrintestinal sem etiologia conhecida. Um desafio diagnóstico, uma vez que a enteroscopia, técnica de escolha, nao se encontra disponível no Brasil. Será apreciado o resultado obtido com o colonoscópio introduzido por via oral e o tratamento clínico, com o uso de fármacos, como a hormonioterapia e o octreotide.