Modeling Methods and Influencing Factors for Age Estimation Based on DNA Methylation / 法医学杂志

Age estimation based on tissues or body fluids is an important task in forensic science. The changes of DNA methylation status with age have certain rules, which can be used to estimate the age of the individuals. Therefore, it is of great significance to discover specific DNA methylation sites and develop new age estimation models. At present, statistical models for age estimation have been developed based on the rule that DNA methylation status changes with age. The commonly used models include multiple linear regression model, multiple quantile regression model, support vector machine model, artificial neural network model, random forest model, etc. In addition, there are many factors that affect the level of DNA methylation, such as the tissue specificity of methylation. This paper reviews these modeling methods and influencing factors for age estimation based on DNA methylation, with a view to provide reference for the establishment of age estimation models.

Cross-Platform Application of DNA Methylation Age Estimation Model in Eastern Chinese Han Population / 法医学杂志

OBJECTIVES@#To evaluate the forensic application value of an age estimation model based on DNA methylation in eastern Chinese Han population, and to provide a theoretical basis for exploring age estimation models suitable for different detection platforms.@*METHODS@#According to the 6 age-related methylation sites in the published blood DNA methylation age estimation models of Chinese Han population, the DNA methylation level of 48 samples was detected by pyrosequencing and next-generation sequencing (NGS). After submitting DNA methylation levels to the age estimation model, the DNA methylation ages were predicted and compared with their real ages.@*RESULTS@#The 6 DNA methylation sites in both detection techniques were age-related, with an R2 of 0.85 and a median absolute deviation (MAD) of 4.81 years when using pyrosequencing；with an R2 of 0.84 and MAD of 4.41 years when using NGS.@*CONCLUSIONS@#The blood DNA methylation age estimation model can be used under pyrosequencing and multi-purpose regional methylation enrichment sequencing technology based on NGS and it can accurately estimate the age.

Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

Aging-associated prostate smooth muscle hypercontractility in rats

Abstract Benign prostatic hyperplasia (BPH) is a multifactorial disease, highly associated with aging and characterized by increased prostate smooth muscle (PSM) contractility. Animal models have been employed to explore the aging-associated PSM hypercontractility; however, studies have focused in old animals, neglecting the initial alterations in early ages. The determination of prostatic dysfunctions onset is crucial to understand the BPH pathophysiology and to propose new BPH treatments. Considering that PSM contractility in 10-month-old rats has already been explored, the aim of the present study was to characterize the PSM contractility in younger rats. Male Wistar control (3.5-month-old), 6- and 8-month-old rats were used. Concentration-response curves to phenylephrine and electrical-field stimulation (EFS) were conducted in prostate from all groups. For the first time, we showed that 6- and 8-month-old rats exhibit PSM hypercontractility. The increased prostate contractility to phenylephrine starts around at 6-month-old, worsening during the aging. The 8-month-old rats exhibited hypercontractility to phenylephrine and EFS compared to the control and 6-month-old groups. Reduced phenylephrine potency was observed in 8-month-old rats, indicating an increased age-dependent prostate sensibility to this agonist. Collectively, our findings support the use of 6- and 8-month-old aged rats as new models to explore prostate hypercontractility in BPH.

Quality of Life of Elderly People Living in Different Types of Long-term Care Facilities

Abstract Population aging is a worldwide occurrence that has become urgent in developing countries. Quality of life can be measured to identify functional capacity and determine the degree of impact on quality of life exerted on an individual. This study aimed to measure the quality of life of elderly people who have been living in different long-term care facilities for the elderly. Therefore, this research was developed with a qualitative and descriptive approach. Data were obtained from medical records and interviews, and were analyzed in R language interpreter software on the Ubuntu Linux operating system. Seventy-nine elderly people participated in the study. Eleven lived in Home Marista, and 68 lived in Home Jesus Maria José. A socioeconomic questionnaire was used to collect data on the socioeconomic characteristics of the participants. The Mini-Mental State Exam was used to measure degree of cognition. The Short Form-36 Questionnaire was used to measure quality of life. The present study suggests that the results found can clarify the individual vulnerability of the elderly in the age group studied regardless of the type of residence. Despite the discrepancy found regarding the care provided at the long-term care facilities, the scores, obtained with the quality of life assessment, did not show significant differences.

Telomere length: biological marker of cellular vitality, aging, and health-disease process

SUMMARY The aging process occurs due to the decline of vital physiological functions and adaptability of the body, being influenced by genetics and lifestyle. With advances in genetics, biological aging can be calculated by telomere length. Telomeres are regions at the ends of chromosomes that play a role in the maintenance and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular senescence. Several studies show that shorter telomeres are associated with acute and chronic diseases, stress, addictions, and intoxications. Even in the current COVID-19 pandemic, telomere shortening is proposed as a marker of severity in individuals infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On the other hand, healthy lifestyle habits increase telomere length and balance of various cellular functions, preventing diseases.

Advance in research on epigenetic clock/age and its implications / 中华医学遗传学杂志

The progress of epigenetic research has led to the discovery and confirmation of age-related markers based on DNA methylation. These DNA methylation indices are called "epigenetic clock/age". The concept of "epigenetic clock/age" and the establishment of its evaluation system are helpful to solve some of the long-standing problems in the field of life and medicine. When facing the current global aging, it is of great significance to refer to the comprehensive health parameters to determine the biological age and life span of an individual, and thus to design a plan to slow down the process of life cycle. This paper has summarized the concept and development of "epigenetic clock/age" in recent years.

Regulatory roles of microRNAs in sarcopenia and exercise intervention / 生理学报

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.

Research Progress on Age Estimation Based on DNA Methylation / 法医学杂志

Age estimation is of great significance in the fields of criminal investigation and forensic identification. It can provide the age information of individuals to judicial departments to facilitate the development of judicial work. In recent years, age estimation methods expanded from the morphological level to the molecular biology level. With the rapid development of epigenetics represented by DNA methylation, and the advancement of DNA methylation detection technology together with the detection platform, many age estimation methods based on DNA methylation biomarkers, or using several biological fluids, such as blood, blood stains, saliva, semen stains, etc. are developed. Currently, researches related to age estimation based on DNA methylation are relatively widely carried out. This paper summarizes the researches on age estimation based on DNA methylation, in order to provide references for related studies and forensic applications.

Genes related to maintenance of autophagy and successful aging / Genes relacionados à manutenção da autofagia e envelhecimento bem-sucedido

ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

RESUMO Considerando o envelhecimento como um fenômeno em que há um declínio nos processos essenciais a sobrevivência celular, investigamos as vias autofágica e proteassômica em três grupos: jovens, idosos e longevos. O perfil de expressão dos genes relacionados à via autofágica foi analisado em sangue periférico, e a quantificação do proteassoma realizada em plasma. Não foram encontradas alterações significativas nas concentrações plasmáticas de proteassoma ou na correlação entre as concentrações de proteassoma e as idades. No entanto, alguns genes relacionados a autofagia e / ou apoptose foram expressos diferencialmente. Além disso, as análises de rede e de enriquecimento mostraram uma interação entre quatro dos cinco genes diferencialmente expressos e a associação desses ao processo transcricional. Considerando que os indivíduos longevos mantiveram tanto a expressão de genes ligados à maquinaria autofágica, quanto os níveis de proteassoma quando comparados aos idosos, concluímos que esses fatores poderiam ser considerados cruciais para o envelhecimento bem-sucedido.

Estudo da prevalência de competições terapêuticas entre idosos com multimorbidades do estudo SABE (Saúde, Bem-estar e Envelhecimento) / Therapeutic competition in community-living elderly with multimorbidity (Health, Well-being and Aging - SABE study)

O envelhecimento da população implica em aumento da prevalência de doenças crônicas não transmissíveis (DCNT) e uso de polifarmácia (uso de 5 ou mais medicamentos concomitantemente). Porém, o uso de medicamentos pode ter um efeito negativo em pacientes com multimorbidade. Entende-se como competição terapêutica (CT) a interação medicamento-doença em que o tratamento recomendado para certa condição pode alterar negativamente (competir com) outra condição coexistente. Neste âmbito, o objetivo principal deste trabalho foi estimar a prevalência de CT e avaliar características associadas à CT em idosos da comunidade. O presente estudo usou como base o estudo populacional de idosos do município de São Paulo: Estudo Saúde, Bem-estar e Envelhecimento, onda 2015. As CTs foram definidas a partir de guias de prática clínica (GPCs) com alta qualidade, selecionados a partir de revisão sistemática e avaliação da qualidade. Somente cerca de um quarto dos GPC apresentaram alta qualidade e foram usados para extração das CTs. A média de idade dos 1.224 idosos do SABE foi 70,8, 56,2% eram mulheres, 84% viviam acompanhados, 27,5% estudaram 9 anos e mais, quase 50% declararam renda insuficiente para cobrir com as despesas diárias, metade autoavaliaram a saúde como regular ou ruim, cerca de 40% relataram polifarmácia. Estatinas, inibidores da enzima de recaptação de angiotensina e inibidores da bomba de próton foram as classes de medicamentos mais relatadas. Multimorbidade foi reportada por 61,7% dos idosos. A prevalência de CT foi de 13,2%. Entre idosos com multimorbidade, a prevalência de CT foi de 21,4%. No modelo final de regressão logística, CT foi associada com polifarmácia (OR: 4,70; IC 95% 3,00 7,36), hospitalização no último ano (OR: 1,75; IC 95% 1,07 2,87), queda no último ano (OR: 1,57; IC 95% 1,04 2,36) e pior autoavaliação de saúde (OR: 1,92; IC 95% 1,23 2,99). Profissionais de saúde devem ter cautela ao selecionar GPC e ao prescrever medicamentos a idosos com multimorbidade

Aging implies in an increasing prevalence of noncommunicable diseases (NCDs) and polypharmacy use (use of 5 or more medications concomitantly). However, medications may have a negative effect on patients with multimorbidity. Therapeutic competition (TC) is known as a drug-disease interaction in which the treatment recommended for a certain condition can negatively alter (compete with) another coexisting condition. In this context, the main objective of this study was to estimate the prevalence of TC and evaluate characteristics associated with TC in community dwelling older adults. The present study used the population-based study of older adults living in the city of São Paulo (SABE study, 2015 survey). TCs were identified by using clinical practice guidelines (CPGs) with high quality. A systematic review and critical appraisal of CPGs were conducted to identify high-quality CPGs. Only about a quarter of CPGs were of high quality and were used for CT extraction. A total of 80 CTs were identified from the high-quality CPGs. The mean age of the 1,224 SABE participants was 70.8, 56.2% were women, 84% did not live alone, 27.5% studied 9 years and over, almost 50% declared insufficient income to cover daily expenses, half self-assessed health, such as regular or poor, about 40% reported polypharmacy. Statins, angiotensin-reuptake enzyme inhibitors and proton pump inhibitors were the most commonly reported drug classes. Multimorbidity was reported by 61.7% seniors. The prevalence of TC was 13.2%. Among seniors with multimorbidity, the prevalence of TC was 21.4%. In the final logistic regression model, TC was associated with polypharmacy (OR: 4.70, 95% CI 3.00 - 7.36), hospitalization in the last year (OR: 1.75, 95% CI 1.07-2 , 95% CI 1.04 - 2.36) and worse health self - assessment (OR: 1.92, 95% CI 1.23 - 2.99), a decrease in the last year (OR: 1.57; Health professionals should be careful when selecting CPGs and prescribing medications to older adults with multimorbidity

Transcriptome differences between 20- and 3, 000-year-old Platycladus orientalis reveal that ROS are involved in senescence regulation

Background: Platycladus orientalis has an extremely long life span of several thousands of years, attracting great interests in the mechanisms involved in such successful senescence regulation and resistance at physiological and molecular levels. Results: The levels of reactive oxygen species (ROS) were higher in 3,000-year-old than in 20-year-old P. orientalis, and the activities of GR and GSH demonstrated the same trend. We produced and analyzed massive sequence information from pooled samples of P. orientalis through transcriptome sequencing, which generated 51,664 unigenes with an average length of 475 bp. We then used RNA-seq analysis to obtain a high-resolution age­course profile of gene expression in 20- and 3,000-year-old P. orientalis individuals. Totally, 106 differentially expressed genes were obtained, of which 47 genes were downregulated and 59 upregulated in the old tree. These genes were involved in transcription factors, hormone-related responses, ROS scavengers, senescence-related responses, stress response, and defense and possibly play crucial roles in tackling various stresses in the 3,000-year-old P. orientalis during its life time. The expression patterns of genes related to ROS homeostasis further indicated that the high ability of ROS scavenging could be helpful for the 3,000-year-old P. orientalis to resist senescence. Conclusions: This study provides a foundation for the elucidation of senescence resistance through molecular studies and the discovery of useful genes in P. orientalis.

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

Association of genetic polymorphisms with physical capacities and body composition in older women / Associação de polimorfismos genéticos com capacidades físicas e composição corporal em idosas

Abstract The elderly population has grown substantially, and the decline in physical capacities and increase in the body fat percentage are important characteristics of aging. Genetic factors may explain these declines and studies related to this issue are justified because they predict what physical capacities present larger declines in different individuals and enable the adoption of strategies to slow them. Thus, the aim of this study was to evaluate the effect of ACE I / D and ACTN3 R / X genetic polymorphisms on body fat, muscle strength and power levels, aerobic capacity, flexibility and agility in older women. Sixty-six older women were genotyped with respect to ACTN3 and ACE polymorphisms for the division of groups and submitted to anthropometric measurements, physical tests in the AAHPERD and RIKLI and JONES test batteries and IPAQ to determine the level of physical activity and the Food Consumption Marker Form. Older women with XX genotype in relation to ACTN3 genotype had lower levels of flexibility of upper and lower limbs and lower cardiorespiratory fitness. Moreover, in relation to the ACE genotype, ID individuals exhibited higher cardiorespiratory fitness and lower body fat percentages. In relation to the other variables, there was no statistical difference among groups. It was concluded that the genetic variants under study play a role in some of the physical capacities and body composition in elderly women. In the future, data of this nature will enable each individual to have specific health interventions directed to the variables showing higher genetic potential for decline.

Resumo A população idosa tem crescido de forma substancial e o declínio nas capacidades físicas, além do aumento na porcentagem de gordura corpórea, são características importantes do envelhecimento. Fatores genéticos podem explicar estes declínios e pesquisas relacionadas a essa temática se justificam porque predizer quais capacidades físicas apresentarão maiores declínios em cada indivíduo possibilita a adoção de estratégias para retardá-los. Assim objetivamos avaliar o efeito dos polimorfismos genéticos ECA I/D e ACTN3 R/X nos níveis de gordura corporal, força e potência muscular, capacidade aeróbia, flexibilidade e agilidade em idosas. 66 idosas foram genotipadas em relação aos polimorfismos da ACTN3 e da ECA para divisão dos grupos e submetidas a medidas antropométricas, testes físicos da bateria de testes da AAHPERD e RIKLI E JONES, IPAQ para determinar o nível de atividade física e o Formulário de Marcadores de Consumo Alimentar. Mulheres idosas com o genótipo XX em relação ao gene da ACTN3 apresentaram menores níveis de flexibilidade dos membros superiores e menor capacidade cardiorrespiratória. Por outro lado, em relação ao gene da ECA, os indivíduos ID apresentaram maior capacidade cardiorrespiratória e menor porcentagem de gordura. Em relação às outras variáveis não houve diferença estatística entre os grupos. Concluímos que as variantes genéticas estudadas têm influência em algumas das capacidades físicas e na composição corporal em idosas. No futuro dados desta natureza possibilitarão cada indivíduo ter suas intervenções em saúde direcionadas às variáveis que ele apresenta maior potencial genético para declínio.

Bone mineral density in independent elderly women with different physical and functional profiles and vitamin D receptor gene polymorphisms / Densidade mineral óssea de idosas independentes com diferentes perfis físico-funcionais e polimorfismos do gene do receptor da vitamina D

Abstract The aim of the study was to compare BMD among physically independent elderly women with different physical-functional profiles and vitamin D receptor gene (VDR) polymorphisms, as well as to analyze the effect of the interaction between these last two aspects on BMD. Overall, 165 elderly women had BMD assessed by bone densitometry. Handgrip and lower limb strength and functional exercise capacity (6MWT) were also assessed. VDR polymorphisms (TaqI, BsmI, ApaI and FokI) were analyzed by polymerase chain reaction. For analyses, elderly women were categorized according to their performance on physical-functional tests into low performance (LP; <25th percentile), normal performance (NP; 25th percentile ≤ NP ≤ 75th percentile) and high performance (HP;> 75th percentile). Regarding functional exercise capacity, LP group showed lower BMD compared to HP and NP groups (p=0,003). With respect to handgrip strength, there was a trend for LP group to have lower bone mineral density compared to NP group (p=0.08). No differences were observed in femur and lumbar BMD in comparisons among the different VDR genotypes (0.07≤p≤0.94); among different groups regarding lower limb strength (p=0.49) and in the interaction analysis among variables (0.17≤p≤0.77). It was concluded that physically independent elderly women with low functional exercise capacity have lower bone mineral density than those classified as normal and high performance. However, apparently, there is no effect of the interaction between VDR gene polymorphisms and physical and functional factors on BMD.

Resumo O objetivo do estudo foi comparar a DMO entre idosas fisicamente independentes com diferentes perfis físico-funcionais e polimorfismos do gene do receptor da vitamina D (VDR), assim como analisar a interação entre estes dois últimos aspectos sobre a DMO. Participaram do estudo 165 idosas, as quais tiveram a DMO avaliada por meio da densitometria óssea. Foram avaliadas também a força de preensão manual (FPM), força de membros inferiores (FMI) e a capacidade funcional de exercício (TC6min). Os polimorfismos do gene VDR (TaqI, BsmI, ApaI e FokI) foram analisados pela reação em cadeia da polimerase. Para as análises, as idosas foram categorizadas de acordo com seu desempenho físico-funcional em baixo desempenho (BD; <percentil 25), desempenho normal (DN; percentil 25 ≤ DN ≤ percentil 75) e alto desempenho (AD; > percentil 75). Para a capacidade funcional de exercício, o grupo BD apresentou menor DMO em comparação ao grupo AD e DN (p=0,003). Em relação à FPM, o grupo BD apresentou uma tendência a menor DMO quando comparado ao grupo DN (p=0,08). Não foram observadas diferenças na DMO do fêmur e da lombar na comparação entre os genótipos do gene VDR (0,07≤p≤0,94); entre os grupos em relação à FMI (p=0,24) e na análise de interação entre as variáveis (0,17≤p≤0,77). Pode-se concluir que as idosas fisicamente independentes com baixa capacidade funcional de exercício apresentam menor DMO que aquelas com desempenho normal e alto desempenho. No entanto, aparentemente não existe interação entre os polimorfismos do gene VDR e o desempenho físico-funcional sobre a DMO.

Genetic variants associated with neurodegenerative Alzheimer disease in natural models

The use of transgenic models for the study of neurodegenerative diseases has made valuable contributions to the field. However, some important limitations, including protein overexpression and general systemic compensation for the missing genes, has caused researchers to seek natural models that show the main biomarkers of neurodegenerative diseases during aging. Here we review some of these models-most of them rodents, focusing especially on the genetic variations in biomarkers for Alzheimer diseases, in order to explain their relationships with variants associated with the occurrence of the disease in humans.

Ventricular arrhythmias in Chagas disease

Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

EXPERIENCE WITH THE BRAZILIAN NETWORK FOR STUDIES IN REPRODUCTIVE AND PERINATAL HEALTH: THE POWER OF COLLABORATION IN POSTGRADUATE PROGRAMS / EXPERIÊNCIA COM A REDE BRASILEIRA DE ESTUDOS EM SAÚDE REPRODUTIVA E PERINATAL: O PODER DA COLABORAÇÃO NA PÓS-GRADUAÇÃO

The scientific collaboration in networks may be developed among countries, academic institutions and among peer researchers. Once established, they contribute for knowledge dissemination and a strong structure for research in health. Several advantages are attributed to working in networks: the inclusion of a higher number of subjects in the studies; generation of stronger evidence with a higher representativeness of the population (secondary generalization and external validity); higher likelihood of articles derived from these studies to be accepted in high impact journals with a wide coverage; a higher likelihood of obtaining budgets for sponsorship; easier data collection on rare conditions; inclusions of subjects from different ethnic groups and cultures, among others. In Brazil, the Brazilian Network for Studies on Reproductive and Perinatal Health was created in 2008 with the initial purpose of developing a national network of scientific cooperation for the surveillance of severe maternal morbidity. Since the establishment of this Network, five studies were developed, some of them already finished and others almost being completed, and two new ones being implemented. Results of the activities in this Network have been very productive and with a positive impact on not only the Postgraduate Program of Obstetrics and Gynecology from the University of Campinas, its coordinating center, but also on other participating centers. A considerable number of scientific articles was published, master´s dissertations and PhD theses were presented, and post-doctorate programs were performed, including students from several areas of health, from distinct regions and from several institutions of the whole country. This represents a high social impact taking into account the relevance of the studied topics for the country.

As colaborações científicas em rede podem ocorrer entre países, instituições acadêmicas e entre pares de pesquisadores e, uma vez estabelecidas, contribuem para a disseminação do conhecimento e estruturação da pesquisa em saúde. Diversas vantagens são atribuídas ao trabalho em rede como: a inclusão de maior número de participantes nos estudos; gerar evidências mais fortes e com maior representatividade da população (generalização secundária e validade externa); maior facilidade das publicações oriundas dos estudos serem aceitas em periódicos de impacto e abrangência; maior probabilidade de obtenção de verbas para financiamento; maior facilidade na coleta de dados sobre condições raras; inclusão de participantes de diferentes grupos étnicos e culturas, entre outras. No Brasil a Rede Brasileira de Estudos em Saúde Reprodutiva e Perinatal foi criada em 2008 com o objetivo inicial de desenvolver rede nacional de cooperação científica para vigilância da morbidade materna grave. Desde sua formação, cinco estudos foram desenvolvidos, alguns já encerrados e outros em fase de finalização, com outros dois em fase final de implantação. Os resultados das atividades desta Rede têm sido bastante produtivos e impactaram positivamente não apenas no Programa de Pós-Graduação em Tocoginecologia da Universidade Estadual de Campinas, seu centro coordenador, mas também o de outros centros participantes, uma vez que expressivo número de artigos científicos foi publicado, mestrados e doutorados foram defendidos e pós-doutorados finalizados, de alunos de diversas áreas da saúde, de diferentes regiões e de várias instituições de todo o país, com alto impacto social dada a relevância dos temas estudados para o país.