Evolução temporal da via de parto e os fatores maternos associados no Brasil (2011-2021) / Temporal evolution of the way of delivery and associated maternal factors in Brazil (2011-2021) / Evolución temporal de la vía del parto y factores maternos asociados en Brasil (2011-2021)

O processo de parto é um evento fisiológico fundamental na vida reprodutiva das mulheres. No entanto, o parto cirúrgico tem se tornado cada vez mais comum, tanto no Brasil como em outros países, resultando em preocupações com a medicalização excessiva do parto. O estudo visa fornecer informações abrangentes sobre o tema, considerando diferentes regiões geográficas do Brasil. Trata-se de estudo é ecológico e retrospectivo, utilizando dados do Sistema de Informações sobre Nascidos Vivos (SINASC) disponíveis no Departamento de Informática do Sistema Único de Saúde (DATASUS). Foram analisados dados de 2011 a 2021, com ênfase nas taxas de parto vaginal e cesariano, fatores sociodemográficos e obstétricos. Durante o período analisado, foram registrados 31.702.562 nascimentos no Brasil. Dos registros válidos, 43,9% foram partos vaginais e 56,1% foram cesarianos. Houve um aumento geral nas taxas de cesariana em todas as regiões brasileiras. A região Norte teve o maior percentual de partos vaginais (53,5%) e o menor de cesarianas (46,5%), enquanto as regiões Sul, Sudeste e Centro-Oeste apresentaram as maiores taxas de cesárea. O estudo revela um aumento nas taxas de cesariana ao longo da última década no Brasil, com diferenças regionais significativas. A prevalência de cesarianas nas regiões Sul, Sudeste e Centro-Oeste levanta preocupações sobre a medicalização do parto. Essas informações podem subsidiar ações de melhoria da qualidade da assistência ao parto e nascimento, com o objetivo de reduzir intervenções desnecessárias e promover melhores desfechos materno-fetais.

The childbirth process is a fundamental physiological event in the reproductive life of women. However, surgical delivery has become increasingly common, both in Brazil and in other countries, resulting in concerns about the excessive medicalization of childbirth. The study aims to provide comprehensive information on the subject, considering different geographic regions of Brazil. This is an ecological and retrospective study, using data from the Information System on Live Births (SINASC) available at the Department of Informatics of the Unified Health System (DATASUS). Data from 2011 to 2021 were analyzed, with emphasis on vaginal and cesarean delivery rates, sociodemographic and obstetric factors. During the analyzed period, 31,702,562 births were registered in Brazil. Of the valid records, 43.9% were vaginal deliveries and 56.1% were cesarean sections. There was a general increase in cesarean section rates in all Brazilian regions. The North region had the highest percentage of vaginal deliveries (53.5%) and the lowest of cesarean sections (46.5%), while the South, Southeast and Midwest regions had the highest cesarean rates. The study reveals an increase in cesarean rates over the last decade in Brazil, with significant regional differences. The prevalence of cesarean sections in the South, Southeast and Midwest regions raises concerns about the medicalization of childbirth. This information can support actions to improve the quality of delivery and birth care, with the aim of reducing unnecessary interventions and promoting better maternal-fetal outcomes.

El proceso del parto es un evento fisiológico fundamental en la vida reproductiva de la mujer. Sin embargo, el parto quirúrgico se ha vuelto cada vez más común, tanto en Brasil como en otros países, lo que genera preocupaciones sobre la excesiva medicalización del parto. El estudio tiene como objetivo proporcionar información completa sobre el tema, considerando diferentes regiones geográficas de Brasil. Se trata de un estudio ecológico y retrospectivo, utilizando datos del Sistema de Información de Nacidos Vivos (SINASC) disponible en el Departamento de Informática del Sistema Único de Salud (DATASUS). Se analizaron datos de 2011 a 2021, con énfasis en las tasas de parto vaginal y por cesárea, factores sociodemográficos y obstétricos. Durante el período analizado, se registraron 31.702.562 nacimientos en Brasil. De los registros válidos, 43,9% fueron partos vaginales y 56,1% cesáreas. Hubo un aumento general en las tasas de cesáreas en todas las regiones brasileñas. La región Norte tuvo el porcentaje más alto de partos vaginales (53,5%) y el más bajo de cesáreas (46,5%), mientras que las regiones Sur, Sudeste y Centro-Oeste presentaron las tasas más altas de cesáreas. El estudio revela un aumento en las tasas de cesáreas durante la última década en Brasil, con diferencias regionales significativas. La prevalencia de cesáreas en las regiones Sur, Sudeste y Centro-Oeste plantea preocupaciones sobre la medicalización del parto. Esta información puede apoyar acciones para mejorar la calidad de la atención del parto y nacimiento, con el objetivo de reducir las intervenciones innecesarias y promover mejores resultados materno-fetales.

Occupational Health: Physical Activity, Musculoskeletal Symptoms and Quality of Life in Computer Workers: A Narrative Review.

Computer work has assumed a very important role for many companies, but specific occupational and health symptoms associated with the use of computers can appear. According to the literature, physical activity is considered a key player in the prevention and control of work-related musculoskeletal symptoms, contributing to a better quality of life in computer workers. The principal aims of this review are to contribute to a better understanding of the relationship among sedentary behavior, physical activity and quality of life of computer workers; to outline the importance of promoting the development of an educational program for Occupational Health directed at computer workers at the level of quality of life, musculoskeletal symptoms, and physical activity; and to call for attention to the factors needed to initiate and maintain a health program that involves the active participation of workers who must be concerned about their health. This review demonstrates the important role of workplaces in health promotion and the opportunities that workplaces provide to establish and continue successful health-promotion programs for computer workers, generating important benefits for the health and quality of life of individuals and groups.

The Effects of COVID-19 Lockdown on the Perception of Physical Activity and on the Perception of Musculoskeletal Symptoms in Computer Workers: Comparative Longitudinal Study Design.

Lockdown resulting from the pandemic led to a change in the health habits of the computer workers community. Sedentary work, together with less active lifestyles, aggravated by the COVID-19 pandemic leads to impacts on physical activity (PA) and can contribute to the development of musculoskeletal symptoms (MSS). Aim(s): Understand the effects of lockdown on the perception of physical activity levels and on the perception of frequency of musculoskeletal symptoms, over periods of 12 months and 7 days, in computer workers. Methods: Longitudinal comparative study between 2019 (M1) and 2021 (M2), over 18 months, in 40 volunteer participants. The inclusion criteria were full-time workers aged between 18 and 65 and the exclusion criteria included diagnosis of non-work-related medical conditions. In addition to a socio-demographic questionnaire, the Nordic musculoskeletal questionnaire (NMQ) was used to evaluate the MSS and the International Physical Activity Questionnaire (IPAQ), was used to analyse the perception of the level of PA. These questionnaires were used in two assessment stages (M1 and M2). McNemar test and Wilcoxon paired test were used to evaluate the effect of lockdown on the perception of PA, and on the perception of frequency of musculoskeletal symptoms. Results: The MSS prevalence in the previous 12 months increased significantly in the neck (M1: 45.0%, M2: 62.5%, p = 0.046), in the shoulders (M1: 37.5%, M2: 55.0%, p = 0.033), and in the hands/wrists (M1: 25.0%, M2: 45.0%, p = 0.019). The mean pain score increased in the shoulders (1.43 ± 2.24, 2.35 ± 2.55, p = 0.003) and in the elbows (0.18 ± 0.59, 0.60 ± 1.34, p = 0.015). No differences were found in the PA between M1 and M2, but the weekly mean sitting time increased from 4.75 ± 2.26 to 6.26 ± 2.65 (p < 0.001). Conclusion: After 18 months it became clear that MSS perception increased mainly in the neck, shoulders and hands/wrists with a significant increase in pain intensity in the shoulder and elbow regions. The weekly sitting time increased significantly. Further studies are needed in order to determine the impact of teleworking in a pandemic context. But multifactor behind these results should be taken into account by health institutions and those responsible for the Prevention of Occupational Risks in Computer Workers in order to adopt educational strategies for the promotion of Physical activity (PA), in these workers.

Positive Effects of an Online Workplace Exercise Intervention during the COVID-19 Pandemic on Quality of Life Perception in Computer Workers: A Quasi-Experimental Study Design.

Computer workers' sedentary work, together with less active lifestyles, aggravated by the COVID-19 pandemic, represents a high risk for many chronic diseases, leading to a decrease in health-related quality of life (QoL). Workplace exercises consist of a set of physical exercises, implemented during work breaks, that have multiple benefits for workers' health. AIM: To assess the impact of online workplace exercises on computer workers' perception of quality of life. METHODS: Quasi-experimental study with two groups: a control group (n = 26) and an intervention group (n = 13). The inclusion criteria were that participants must be aged between 18 and 65 years old and the exclusion criteria included diagnosis of non-work-related medical conditions. The interventions consisted of workplace exercises, which were applied for 17 consecutive weeks, each session lasting 15 min, three times a week. The exercise programme, performed online and guided by a physiotherapist, consisted of mobility exercises, flexibility and strength exercises, with the help of a TheraBand® for elastic resistance. The control group were not subjected to any intervention. A socio-demographic questionnaire and the Health Survey Questionnaire (SF-36v2) were used in two assessment stages (M0-baseline and M1-final of intervention). A mixed ANOVA with interaction time*group was used to evaluate the effect of the exercise programme. RESULTS: A good perception of the QoL was obtained in both stages. The exercise programme had a positive effect in the domains of Pain (ptime*group = 0.012, η2p = 0.158), Physical Function (ptime*group = 0.078, η2p = 0.082), Physical Performance (ptime*group = 0.052, η2p = 0.098), and Emotional Performance (ptime*group = 0.128, η2p = 0.061). CONCLUSION: After 17 weeks of workplace exercises, it became clear that the intervention group positively increased their QoL perception, with this improvement being significant in the Pain domain, which resulted in an improvement in their health condition. Therefore, further studies are needed to determine the optimal exercise for CWs, with detailed exercise types, different intensities and focused on various health conditions.

[Communication in Clinical Practice, the Perspective of Patients with Cancer: Translation of the PACE (Patient Assessment of Cancer Communication Experiences) Questionnaire to European Portuguese]. / Comunicação na Prática Clínica, a Perspetiva dos Doentes com Cancro: Tradução do Questionário PACE (Patient Assessment Of Cancer Communication Experiences) para Português.

INTRODUCTION: Communication in clinical practice is essential to healthcare quality, especially in Oncology. The Patient Assessment of Communication Experiences questionnaire evaluates the perspective of cancer patients towards communication and identifies areas that can be improved. This study consists in its translation and validation to European Portuguese, to identify these areas. MATERIAL AND METHODS: We performed a descriptive, observational, cross-sectional study. The translation was conducted according to the World Health Organization's guidelines. We applied the questionnaires to a convenience sample, in patients under systemic antineoplastic treatment at the Day Hospital of Centro Hospitalar Universitário do Porto, between January and March 2020. We calculated the Cronbach's Alpha for each phase of care, the bivariate and multiple correlations and, for each question, the percentage of "non applicable" and most positive answers. RESULTS: We had 100 participants. The instrument we obtained ha good internal consistency, but the classification of some questions does not correlate sufficiently with the global opinion about the experiences with communication in the respective phase. The diagnosis phase revealed a lower proportion of positive experiences, particularly in terms of receiving the bad news. CONCLUSION: This study translates and validates part of the communication assessment instrument PACE to the Portuguese language and elicits the necessity to invest in the phase of diagnosis and disclosure of bad news.

Introdução: A comunicação na prática clínica é essencial para a qualidade dos cuidados de saúde, com particular importância na Oncologia. O questionário Patient Assessment of Cancer Communication Experiences avalia a perspetiva dos doentes oncológicos sobre a comunicação e identifica áreas a melhorar. Este estudo consiste na sua tradução e validação para português, para identificar essas áreas.Material e Métodos: Realizámos um estudo descritivo, observacional e transversal. O processo de tradução seguiu as normas da Organização Mundial de Saúde. Aplicámos os questionários numa amostra de conveniência, em doentes sob tratamento antineoplásico sistémico no Hospital de Dia do Centro Hospitalar Universitário do Porto, entre janeiro e março de 2020. Calculámos o coeficiente de Cronbach para cada fase dos cuidados, as correlações bivariadas e múltiplas e, para cada questão, a percentagem de respostas "não aplicável" e de resposta mais positiva.Resultados: Participaram 100 doentes. O instrumento obtido possui boa consistência interna, mas tem questões cuja classificação não se correlaciona satisfatoriamente com a opinião global das experiências com comunicação na respetiva fase. O diagnóstico foi a fase que revelou menos experiências positivas, especificamente na transmissão da notícia.Conclusão: Este estudo traduziu e validou uma parte do instrumento de avaliação de comunicação PACE, adaptando-o à realidade portuguesa, e demonstra a necessidade de investir na fase de diagnóstico, nomeadamente na transmissão de más notícias.

Occupational Health: Does Compliance with Physical Activity Recommendations Have a Preventive Effect on Musculoskeletal Symptoms in Computer Workers? A Cross-Sectional Study.

A lack of physical activity in computer workers (CW) can contribute to the development of musculoskeletal symptoms (MSS). Aim: (i) Evaluate MSS over a 12 month and 7 days period, (ii) determine physical activity (PA) levels and compliance with World Health Organization (WHO) PA recommendations, and (iii) assess the relationship between compliance with WHO PA recommendations and MSS. Methods: A cross-sectional observational study comprising 119 computer workers. The Nordic Musculoskeletal Questionnaire (NMQ) was used to evaluate the MSS and the International Physical Activity Questionnaire (IPAQ) was used to analyse the perception of the level of PA. Results: MSS occurred in the lumbar region (56.3%), neck (43.7%), and shoulders (39.5%). 44.7% of the participants reported a low level of PA. The percentage of compliance was similar among women and men (62.2% vs. 58.5%, respectively). Negative correlations were found between pain intensity and metabolic equivalent values. The participants who followed the WHO PA recommendations reported a lower frequency of MSS compared to those who did not, but the differences were not statistically significant. Conclusion: It was possible to conclude that computer workers presented a higher frequency of MSS in the lower back, neck, and shoulders. Regarding the level of PA, participants were mostly classified as low. Participants who followed the WHO PA recommendations reported lower MSS than those who did not. This finding could be important in obtaining successful programs that promote health-oriented physical activity in this group of workers.

Adenocarcinoma of the jejunum: management of a rare small bowel neoplasm.

Small bowel adenocarcinomas are rare malignant tumors that account for less than 2% of gastrointestinal tumors. Despite a thorough history, physical examination and complete diagnostic workup, the correct diagnosis of small intestinal neoplasm has been established preoperatively in only 50% of cases. Due to the rarity of this disease, there are very few established guidelines for its management and it has been primarily treated the same way as colorectal cancer, even though patient's prognostic outcome is worse. With new guidelines in 2020, we review a clinical case of a 64-year-old male patient with adenocarcinoma of the jejunum treated in our institution.

Permeability evaluation of gemcitabine-CPP6 conjugates in Caco-2 cells.

Cancer is one of the most alarming diseases due to its high mortality and still increasing incidence rate. Currently available treatments for this condition present several shortcomings and new options are continuously being developed and evaluated, aiming at increasing the overall treatment efficiency and reducing associated adverse side effects. Gemcitabine has proven activity and is used in chemotherapy. However, its therapeutic efficiency is limited by its low bioavailability as a result of rapid enzymatic inactivation. Additionally, tumor cells often develop drug resistance after initial tumor regression related to transporter deficiency. We have previously developed three gemcitabine conjugates with cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug while also preventing enzymatic deamination. The bioactivity of these new prodrugs was evaluated in different cell lines and showed promising results. Here, we assessed the absorption and permeability across Caco-2 monolayers of these conjugates in comparison with gemcitabine and the respective isolated cell-penetrating peptides (CPPs). CPP6-2 (KLPVMW) and respective Gem-CPP6-2 conjugate showed the highest permeability in Caco-2 cells.

Urinary Sodium Excretion and Adherence to the Mediterranean Diet in Older Adults.

Despite the well-known benefits of the Mediterranean Diet (MedDiet), data on the sodium intake is scarce. This study aimed to quantify the association between sodium excretion and the adherence to the MedDiet in the elderly. A representative sample of 1500 Portuguese adults (≥65 years) was assessed (1321 were eligible for the present analysis). A 24 h urine sample was collected and analysed for creatinine and sodium. Excessive sodium intake was defined as above 2000 mg/day. The adherence to the MedDiet was assessed by the PREDIMED. A binary logistic regression model was conducted to evaluate the association between urinary sodium excretion and the adherence to the MedDiet. Odds Ratios (OR) and respective 95% Confidence Intervals (95% CI) were calculated. Excessive sodium excretion was observed in 80.0% of men and 91.5% of women whereas a high adherence to the MedDiet was reported by 42.2% of women and 46.4% of men. After adjusting for confounders, excessive sodium excretion was associated with a high adherence to the MedDiet in men (OR = 1.94; 95% CI: 1.03-3.65) but not in women. These results show that the MedDiet can be an important source of sodium and highlight the need for implementing strategies to reduce sodium intake when following a MedDiet.

Food Networks As Urban Commons: Case Study of a Portuguese "Prosumers" Group.

In many parts of the world, people are coming together to experiment with ways to collectively take care of their livelihoods and create practical solutions to their needs. Guided by principles of solidarity, these grassroots initiatives represent rich contexts for research on the urban commons: what qualifies them as commons, and how do they emerge, develop, sustain and dissolve - or transform over time? This research dissects the commons character of a food network which emerged from Porto's solidarity economy movement in a post-crisis context. Following an action-research approach and methodological triangulation, we develop a qualitative analysis of a "prosumers" group, where both production and distribution were performed weekly by consumers themselves. We first analyze how the initiative emerged and then look at how its principles and democratic qualities relate to commons theories and frameworks. We then delve into the main dilemmas of its commoning practices and reflect about its transformative character and liminal role as a temporary urban commons. Despite ceasing its activities, there was a lived-experience and a knowledge commons which allowed it to be appropriated in new terms, and thus food networks as urban commons persist.

Diagnosis, treatment, and work impact of iron deficiency anemia in a Portuguese urban community.

INTRODUCTION: Little is known about iron deficiency anemia (IDA)'s treatment in Portugal. We aim to estimate the proportion of anemia, IDA, and iron deficiency without anemia; characterize the diagnostic procedures and prescription patterns; assess anemia's impact over work absenteeism, in a Local Health Unit. MATERIAL AND METHODS: Cross-sectional study that evaluated complete blood counts, iron-containing prescriptions, comorbidities, economic failure, and disability certificates issued in 2015 at the Local Health Unit. RESULTS: We evaluated 62,794 complete blood count. The proportion of anemia was 16.5%, higher in patients with economic failure, pregnant women, and patients with congestive heart failure. Of the patients with anemia 87.8% had not serum iron and/or ferritin dosing, and of those with serum iron/ferritin levels tested 50.6% had IDA. IDA was higher in pregnant women, women aged ≥15 years and in patients with congestive heart failure. Approximately 56.2% of patients with IDA did not receive iron-containing medication, and in 38% of the cases the prescribed dose was subtherapeutic. Of the total iron prescriptions 44.1% were association therapies. Anemia accounted for 5.2% of the disability certificates issued in 2015 (1749 workdays lost). DISCUSSION: Most patients with anemia are not being adequately evaluated and a major proportion does not undergo treatment or has subtherapeutic doses of iron. These results may explain the anemia's impact on work capacity. CONCLUSION: This is one of the largest studies on anemia in Portugal. An effort to adapt to the established recommendations is urged, to minimize the consequences of this disease.

Brief emotional screening in oncology: Specificity and sensitivity of the emotion thermometers in the Portuguese cancer population.

OBJECTIVE: This study aimed to determine the cutoff and the specificity and sensitivity of the Emotion Thermometers (ET) in a Portuguese sample of cancer patients. METHOD: A total of 147 patients (mean age = 49.2; SD = 12.6) completed the ET, the Brief Symptom Inventory (BSI), and the Subjective Experiences of Illness Suffering Inventory. Data were collected in a cancer support institution and in a major hospital in the North of Portugal. RESULT: The optimal cutoff for the Anxiety Thermometer was 5v6 (until 5 and 6 or more), which identified 74% of the BSI-anxiety cases and 70% of noncases. The Depression Thermometer cutoff was 4v5 (until 4 and 5 or more), which identified 85% of BSI-depression cases and 82% of noncases. Cutoff for the Anger Thermometer was 4v5 (until 4 and 5 or more), which identified 83% of BSI-hostility cases and 73% of noncases; for the Distress Thermometer, the optimal cutoff was 4v5 (until 4 and 5 or more), which identified 84% of the suffering cases and 73% of noncases. Finally, for the Help Thermometer, it was 3v4 (until 3 and 4 or more), which helped to identify 93% of the suffering cases and 64% of noncases. SIGNIFICANCE OF RESULTS: Results supported the Portuguese version of the ET as an important screening tool for identifying the emotional distress in cancer patients.

DNA-membrane complex formation during electroporation is DNA size-dependent.

Size of DNA molecules governs their interaction with the cell membrane during electroporation and their subsequent transport inside the cell. In order to investigate the effect of DNA size on DNA-membrane interaction during electroporation, cells are electro-pulsed with DNA molecules; 15 bp, 25 bp, 50 bp, 100 bp and 1000 bp (bp = base pairs). Within the experimental parameter space, DNA-membrane complexes or DNA aggregates are observed at the cell membrane for DNA molecules containing 25 or more base pairs. No aggregates are observed for DNA molecules containing 15 bp. For all DNA sizes, direct access to the cytoplasm is observed, however the amount translocated decays with the size. The observed dependency of DNA aggregate formation on the size of the DNA molecules is consistent with the Onsager's theory of condensation of anisotropic rod-like molecules.

Development of potent CPP6-gemcitabine conjugates against human prostate cancer cell line (PC-3).

Gemcitabine (dFdC) is a nucleoside analogue used in the treatment of various cancers, being a standard treatment for advanced pancreatic cancer. The effect of gemcitabine is severely compromised due to its rapid plasma degradation, systemic toxicity and drug resistance, which restricts its therapeutic efficacy. Our main goal was to develop new active conjugates of dFdC with novel cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug. All new peptides were prepared by solid phase peptide synthesis (SPPS), purified and characterized by HPLC and LC-MS. Cell-penetrating peptides (CPP) contain a considerably high ratio of positively charged amino acids, imparting them with cationic character. Tumor cells are characterized by an increased anionic nature of their membrane surface, a property that could be used by CPP to target these cells. The BxPC-3, MCF-7 and PC-3 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that conjugating dFdC with CPP6 significantly enhanced cell growth inhibitory activity on PC-3 cells, with IC50 between 14 and 15 nM. These new conjugates have potential to become new therapeutic tools for cancer therapy.

Novel insights into the antioxidant role of tauroursodeoxycholic acid in experimental models of Parkinson's disease.

Impaired mitochondrial function and generation of reactive oxygen species are deeply implicated in Parkinson's disease progression. Indeed, mutations in genes that affect mitochondrial function account for most of the familial cases of the disease, and post mortem studies in sporadic PD patients brains revealed increased signs of oxidative stress. Moreover, exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I inhibitor, leads to clinical symptoms similar to sporadic PD. The bile acid tauroursodeoxycholic acid (TUDCA) is an anti-apoptotic molecule shown to protect against MPTP-induced neurodegeneration in mice, but the mechanisms involved are still incompletely identified. Herein we used MPTP-treated mice, as well as primary cultures of mice cortical neurons and SH-SY5Y cells treated with MPP+ to investigate the modulation of mitochondrial dysfunction by TUDCA in PD models. We show that TUDCA exerts its neuroprotective role in a parkin-dependent manner. Overall, our results point to the pharmacological up-regulation of mitochondrial turnover by TUDCA as a novel neuroprotective mechanism of this molecule, and contribute to the validation of TUDCA clinical application in PD.

Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the cause of PD remains elusive, mitochondrial dysfunction and severe oxidative stress are strongly implicated in the cell death that characterizes the disease. Under oxidative stress, the master regulator of cellular redox status, nuclear factor erythroid 2 related factor 2 (Nrf2), is responsible for activating the transcription of several cytoprotective enzymes, namely glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1). Nrf2 is a promising target to limit reactive oxygen species (ROS)-mediated damage in PD. Here, we show that tauroursodeoxycholic acid (TUDCA) prevents both 1-methyl-4-phenylpyridinium (MPP+)- and α-synuclein-induced oxidative stress, through Nrf2 activation, in SH-SY5Y cells. Additionally, we used C57BL/6 male mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to elucidate the effect of TUDCA in this in vivo model of PD. In vivo, TUDCA treatment increases the expression of Nrf2, Nrf2 stabilizer DJ-1, and Nrf2 downstream target antioxidant enzymes HO-1 and GPx. Moreover, we found that TUDCA enhances GPx activity in the brain. Altogether, our results suggest that TUDCA is a promising agent to limit ROS-mediated damage, in different models of PD acting, at least in part, through modulation of the Nrf2 signaling pathway. Therefore, TUDCA should be considered a promising therapeutic agent to be implemented in PD.

Tauroursodeoxycholic Acid Protects Against Mitochondrial Dysfunction and Cell Death via Mitophagy in Human Neuroblastoma Cells.

Mitochondrial dysfunction has been deeply implicated in the pathogenesis of several neurodegenerative diseases. Thus, to keep a healthy mitochondrial population, a balanced mitochondrial turnover must be achieved. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in various neurodegenerative disease models; however, the mechanisms involved are still incompletely characterized. In this study, we investigated the neuroprotective role of TUDCA against mitochondrial damage triggered by the mitochondrial uncoupler carbonyl cyanide m-chlorophelyhydrazone (CCCP). Herein, we show that TUDCA significantly prevents CCCP-induced cell death, ROS generation, and mitochondrial damage. Our results indicate that the neuroprotective role of TUDCA in this cell model is mediated by parkin and depends on mitophagy. The demonstration that pharmacological up-regulation of mitophagy by TUDCA prevents neurodegeneration provides new insights for the use of TUDCA as a modulator of mitochondrial activity and turnover, with implications in neurodegenerative diseases.

Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokine receptors to assess the influence of polymorphic variants on the stage of liver damage in Brazilian patients chronically infected with HCV genotype 1 only. 141 unrelated patients were grouped according to their stage of fibrosis: absence of fibrosis or patients in the initial stages of fibrosis (F0-F2, n = 84), patients with advanced stages of fibrosis or cirrhosis (F3-F4, n = 57), without cirrhosis (F0-F3, n = 103), and with cirrhosis (F4, n = 38). The comparison of frequencies in each sub-sample was performed by 2 × 2 contingency tables using the chi-square or Fisher's exact test. Stepwise logistic regression was also used to assess independent associations between cirrhosis or fibrosis with polymorphic variants. The TNFA-308G:A genotype conferred increased risk of fibrosis and cirrhosis. The TNFA-238G:G genotype was associated with protection from cirrhosis. The IL10-819C:T genotype conferred protection from fibrosis and the IL1B-511C:T genotype conferred increased risk of cirrhosis. Some of these genotypes showed results on the borderline of statistical significance in the bivariate analysis. We conclude that gene variants of cytokines/receptors may influence liver damage in patients chronically infected by HCV genotype 1.

Alexithymia and psychopathology in patients with acute myocardial infarction.

OBJECTIVES: The purpose of this study was to investigate alexithymia in acute myocardial infarction (AMI) patients and its relationship with associated anxious-depressive co-morbidity. METHODS: We studied 71 participants: 30 consecutive patients with cardiac biomarkers and electrocardiographic criteria for acute myocardial infarction (AMI) in a coronary care unit, with a mean age of 65.23 ± 11.95 years (80% male) and a control group of 41 healthy subjects with a mean age of 62.85 ± 7.83 (46% male). We used the Identification Form (sociodemographic data) and clinical diagnostic, the 20-item Toronto Alexithymia Scale (TAS-20), the Symptom Check List ­ 90 Revised (SCL-90R) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Results show that patients with acute myocardial infarction had alexithymia scores significantly higher (P = 0.000) than the control group (60.0 ± 12.8 vs 49.9 ± 8.91) and also higher scores in psychopathological traits screened by the SCL-90R, namely high levels of somatization and depression. We also observed a positive correlation between psychopathological symptoms and alexithymia. A significant prevalence of alexithymia was found in patients with AMI suggesting that psychopathological symptoms have a significant relation with alexithymia. CONCLUSIONS: In this clinical setting the deficit of emotion expression points to the need of psychotherapeutic intervention in patients after an AMI event occurs, to improve prognosis and well-being.