Epigenetic alterations in urothelial bladder cancer associated with disease outcomes.

OBJECTIVES: Bladder cancer (BLCA) is a molecular heterogeneous disease with known genetic distinctive signatures. However, DNA methylation is highly prevalent across a wide range of tumors, suggesting its potential in oncogenesis. Here, we aimed to interrogate the role of nine epigenetic alterations as diagnostic and prognostic markers in BLCA. METHODS: DNA methylation, gene expression, and clinicopathological information were retrieved from The Cancer Genome Atlas data portal. Methylation values and gene expression were assessed to determine their association with normal and malignant tissue. Additionally, we studied the association between methylation values and clinicopathological variables. For the prognostic model, Kaplan-Meier Survival curves were generated. Lastly, univariate and multivariate analysis were performed to evaluate the simultaneous impact of methylation and clinicopathological variables on the risk of tumor progression and survival. RESULTS: Nine CpG sites' methylation ß -values involved in our study demonstrated different methylation signatures between normal and malignant urothelium. Hypermethylated CpGs were overrepresented in tumor tissue (p < 0.0001). Opposingly, 4 CpG sites showed lower methylation values in tumor samples (p < 0.0001). Cg12743248high and cg17192862low are risk factors for progression-free survival, whereas cg12374721high (HR:3.003 (1.283-7.030)) also demonstrated to be the most valuable independent risk factor for disease progression and a risk factor for overall survival. CONCLUSIONS: We have identified that methylated cg12374721 shows promise as a diagnostic and independent prognostic marker in BLCA progression.

Increased Galactosidase Beta 1 Expression as a Senescent Key Factor in ß-Cells Function Modulation at the Early Steps of Type 2 Diabetes.

BACKGROUND: In type 2 diabetes, insulin resistance is observed, and ß-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of ß-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic ß-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. METHODS: C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. RESULTS: The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased ß-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1ß and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic ß-cells. CONCLUSION: The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes.

The Contribution of the Sheep and the Goat Model to the Study of Ovarian Ageing.

Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells has been identified in the ovaries of reproductively aged mice. These cells have been considered hallmarks of ovarian ageing. However, up to date multinucleated giant cells have only been described in the ovaries of the mice. Therefore, the aim of the present work was to evaluate and characterize the presence of such hallmarks of ovarian ageing in the sheep and the goat. In this study, ovaries from juvenile (6 months) and mature animals (18-24 months) were used. The hematoxylin and eosin technique was performed to describe the ovarian morphology and evaluate the ovarian follicle reserve pool. Sudan black B staining and the detection of autofluorescence emission were used to identify and characterize the presence of multinucleated giant cells. Statistical analyses were performed with GraphPad Prism 9.0.0. A decrease in the follicle reserve pool and the presence of multinucleated giant cells, with lipofuscin accumulation and the emission of autofluorescence, were observed in the ovaries of the mature animals of both species. Our results support the interest in the use of the ovine and the caprine model, that share physiological and pathophysiological characteristics with humans, in future studies addressing ovarian ageing.

Prevalence and Management of Incidental Testicular Masses-A Systematic Review.

Management of incidentally diagnosed small testicular masses (STM) is controversial. Although there is the risk of malignancy, it might be realistic to safely seek preservation of testicles bearing benign masses. This study aims to systematically evaluate the evidence regarding prevalence of STMs, their benign or malignant histology and their management. We conducted a systematic literature search for studies reporting small or incidental testicular masses and their management by radical orchiectomy, testis sparing surgery (TSS) or ultrasound (US) surveillance. We initially screened 2126 abstracts and from these, 57 studies met the inclusion criteria. Testicular masses were detected in 1.74% of patients undergoing US examination. Regarding STMs removed by surgery, 41.12% were benign. Intraoperative frozen section examination (FSE) is a reliable tool to discriminate between benign and malignant testicular masses (average 93.05% accuracy), supporting TSS. Benign lesions were associated with smaller diameter (<1 cm 68.78% benign), were often hypoechoic and exhibited regular margins on US. Conclusions: Small testicular masses are often benign. Clinical and US patterns are not accurate enough for including patients in surveillance protocols and TSS paired with FSE is pivotal for precluding the removal of testicles bearing benign lesions. Future research might unveil new imaging tools or biomarkers to support clinical management.

Experience with direct oral anticoagulants in pregnancy - a systematic review.

OBJECTIVES: The experience and use of the new direct oral anti coagulants (DOACs) in pregnancy is limited, but as they offer many practical advantages compared to low molecular weight heparin (LMWH), the pursue of their safety is challenging. METHODS: Systematic review of studies in which DOACs were used during pregnancy and the puerperal period (PROSPERO registry-CRD42021237688). Searches were performed on MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library databases, until July 2021 and secondary sources using the MeSH terms 'pregnancy', 'pregnancy complications', 'venous thrombosis', 'congenital abnormalities', 'Factor Xa Inhibitors,' and names of specific DOACs. Search was limited to human studies, with English or French as languages of report. RESULTS: Literature search yielded 1,989 results which, after duplicate exclusion, resulted in 672 publications. Studies were then screened using the specified eligibility criteria described and studies that did not meet the criteria were excluded, resulting in 21 full text studies to an in-depth analysis and data extraction. Overall, 339 cases of DOACs usage during pregnancy were reported until now. The data demonstrated 56% live births but a miscarriage rate of 22.2% and an elective termination of pregnancy in 21.8%; fetal abnormalities related to DOACs occurred in 3.6%. Our meta-analysis displayed a higher rate of fetal loss and fetal abnormalities with DOACs use compared to LMWH, notwithstanding similar bleeding complications. CONCLUSIONS: The current information available for the 339 cases herein reported does not allow a conclusion that DOACs can be safely used in pregnancy.

A multi-staged neuropeptide response to traumatic brain injury.

PURPOSE: As the most abundant neuropeptides in Central Nervous System, Substance P and Neuropeptide Y are arguably involved in the response to brain trauma. This study aims to characterize a new concept of multi-staged neuropeptide response to TBI. METHODS: This study assessed Substance P, Neuropeptide Y, S100B, standard inflammatory parameters and ionic disturbance in TBI victims, with and without intracranial lesions, and healthy controls. In the group with intracranial lesions, blood samples were drawn until 6 h after initial trauma, at 48 h and 7 days post-TBI. RESULTS: An early increase in Substance P (mean 613.463 ± 49.055 SE 6 h post-TBI with brain contusions vs. 441.441 ± 22.572 SE pg/dL control group) is evident. Concerning TBI without intraparenchymatous lesions, an increase in substance P is also present (825.60 ± 23.690 SE pg/dL). Following an initial increase and subsequent fall in NPY levels (45.997 ± 4.96 SE 6 h post-TBI vs. 32.395 ± 4.056 SE 48 h post-TBI vs. 19.700 ± 1.462 SE pg/mL control group), a late increase in NPY is obvious (43.268 ± 6.260 SE pg/mL 7 day post-TBI). Post-traumatic hypomagnesemia (0.754 ± 0.015 SE 6 h post-TBI vs. 0.897 ± 0.021 SE mmol/L control group) and a peak in S100B (95.668 ± 14.102 SE 6 h post-TBI vs. 30.187 ± 3.347 SE pg/mL control group) are also present. CONCLUSION: A multi-staged neuropeptide response to TBI is obvious and represents a potential therapeutic strategy for the treatment of intraparenchymal lesions and cerebral edema following TBI.

Unhealthy lifestyles, environment, well-being and health capability in rural neighbourhoods: a community-based cross-sectional study.

BACKGROUND: Non-communicable diseases are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults, which may be amplified by wider determinants of health. Changes in rural environments reflect the need of better understanding the factors affecting the self-ability for making balanced decisions. We assessed whether unhealthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability. METHODS: We conducted a community-based cross-sectional study in 15 Portuguese rural neighbourhoods to describe individuals' health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design to gather information about evidence-based data, lifestyles and neighbourhood satisfaction (incorporated in eVida technology), within a random sample of 270 individuals, and in-depth interviews to 107 individuals, to uncover whether environment influence the ability for improving or pursuing heath and well-being. RESULTS: Men showed to have a 75% higher probability of being overweight than women (p-value = 0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value = 0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value = 0.293) and aged over 75 years (RR: 1.78; p-value = 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits). Overall, metabolic risk linked to BMI was higher in small villages than in municipalities. Seven dimensions, economic development, built (and natural) environment, social network, health care, demography, active lifestyles, and mobility, reflected the self-perceptions in place affecting the individual ability to make healthy choices. Qualitative data exposed asymmetries in surrounding environments among neighbourhoods and uncovered the natural environment and natural resources specifies as the main value of rural well-being. CONCLUSIONS: Metabolic risk factors reflect unhealthy lifestyles and can be associated with environment contextual-dependent circumstances. People-centred approaches highlight wider socioeconomic and (natural) environmental determinants reflecting health needs, health expectations and health capability. Our community-based program and cross-disciplinary research provides insights that may improve health-promoting changes in rural neighbourhoods.

Type 2 and type 3 innate lymphoid cells at the maternal-fetal interface: implications in preterm birth.

BACKGROUND: Preterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies. The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth. METHODS: We analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor. RESULTS: We observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor. CONCLUSION: Our results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

Qualidade de vida de idosos brasileiros e portugueses: uma análise comparativa / Análisis comparativo de la calidad de vida de los adultos mayores de Brasil y Portugal / Quality of Life in Older Adults in Brazil and Portugal: A Comparative Analysis

Introdução: A longevidade tornou-se uma das maiores conquistas da segunda metade do século XX. Objetivo: Comparar a qualidade de vida de idosos brasileiros e portugueses usuários da atenção primária à saúde. Materiais e Métodos: Estudo quantitativo, transversal e comparativo, aplicado a amostra probabilística englobando 294 idosos acompanhados pela Saúde da Família divididos em dois grupos: 130 idosos em Benevides/Brasil, e 164 em Coimbra/Portugal, no período de 2015-2017. A caracterização sociodemográfica e avaliação da qualidade de vida foram obtidos pelo instrumento World Health Organization Questionnaire of Quality of Life (WHOQOL-bref), consta de 26 questões divididas em quatro domínios: físico, psicológico, relações sociais e meio ambiente. Aplicado o Teste U de Mann-Whitney para análise estatística comparativa. Resultados: Nos grupos verificou-se predomínio do sexo feminino, casados, aposentados e com baixo grau de escolaridade (1 a 4 anos). A média da distribuição etária foi 70 anos para brasileiros e 76 anos para portugueses; na comparação da qualidade de vida, os idosos brasileiros obtiveram os melhores escores no domínio psicológico (79,1) enquanto portugueses tiveram melhor escore no domínio meio ambiente (65,6). Em Benevides o escore mais baixo foi o domínio meio ambiente (56,3) e, em Coimbra, o domínio com escore mais baixo foi o físico (60,7). Discussão: A qualidade de vida no envelhecimento é importante preditor para a preservação da autonomia do idoso. Conclusões: Estes resultados ampliam a concepção da importância da atenção integral no processo de envelhecimento com vista a proporcionar melhor qualidade de vida contribuindo para satisfazer as necessidades especificas da população idosa.

Introduction: Longevity is one of the greatest achievements in the last half of the 20th century. Objective: To compare the quality of life in older adults in Brazil and Portugal receiving primary health care. Materials and Methods: A comparative cross-sectional quantitative study was conducted with a probability sample of 294 older adults, who had been assisted with the Family Health strategy, being divided into two groups: 130 older adults living in Benevides, Brazil and 164 in Coimbra, Portugal during 2015 and 2017. The sociodemographic characterization and the quality of life assessment were determined through the WHO Quality of Life-BREF (WHOQOL-BREF), which consists of 26 questions assessing four domains: physical health, psychological health, social relationships and environment. The Mann-Whitney U test was applied for comparative statistical analysis. Results: There was a prevalence of married, retired women with a lower level of education (1 to 4 years) in the groups. The average age was 70 years in Brazil and 76 years in Portugal. In terms of quality of life, Brazilian older adults got better scores in the psychological health domain (79.1%) while Portuguese older adults scored best in the environmental domain (65.6%). The lowest scores were found in the environmental domain in Benevides (56.3%) and in the physical health domain in Coimbra (60.7%). Discussion: Quality of life in aging is a major predictor for the preservation of autonomy in older adults. Conclusion: These results help to broaden the importance of comprehensive care in the aging process to provide a better quality of life, which contributes to meeting the specific needs of older population.

Introducción: La longevidad se ha convertido en uno los mayores logros de la segunda mitad del siglo XX. Objetivo: Comparar la calidad de vida de los adultos mayores de Brasil y Portugal que reciben atención primaria de salud. Materiales y métodos: Se realizó un estudio cuantitativo transversal comparativo con una muestra probabilística de 294 adultos mayores que fueron acompañados por la estrategia de Salud Familiar y divididos en dos grupos: 130 adultos mayores ubicados en Benevides, Brasil y 164 en Coímbra, Portugal durante 2015 y 2017. La caracterización sociodemográfica y la evaluación de la calidad de vida se obtuvieron mediante el Cuestionario de Calidad de Vida de la Organización Mundial de la Salud (WHOQOL-BREF), que consta de 26 preguntas divididas en cuatro áreas: salud física, salud psicológica, relaciones sociales y ambiente. Se aplicó la prueba U de Mann-Whitney para el análisis estadístico comparativo. Resultados: En los grupos se observó el predominio de las mujeres casadas, jubiladas y con baja escolaridad (entre 1 y 4 años). La edad media fue de 70 años en Brasil y 76 años en Portugal. En cuanto a la calidad de vida, los adultos mayores brasileños obtuvieron mejores puntuaciones en el área de salud psicológica (79.1%) mientras que los adultos mayores portugueses tuvieron la mejor puntuación en el área ambiental (65.6%). Las puntuaciones más bajas se presentaron en el área ambiental en Benevides (56.3%) y en la salud física (60.7%) en Coímbra. Discusión: La calidad de vida en el proceso de envejecimiento es un importante predictor para la preservación de la autonomía de los adultos mayores. Conclusiones: Estos resultados amplían la concepción de la importancia de la atención integral en el proceso de envejecimiento para brindar una mejor calidad de vida, lo que contribuye a satisfacer las necesidades específicas de la población de edad avanzada.

Procalcitonin in preterm rupture of membranes: a systematic review and meta-analysis.

PURPOSE: Early detection of infection is of supreme importance in obstetrics; however, during pregnancy it is not reliably predicted by standard laboratory tests. We aimed to determine if procalcitonin (PCT) is a reliable predictor of chorioamnionitis (CA) in women with premature rupture of membranes (PPROM). METHODS: An electronic search of Scopus, ISI, Medline, Embase, ClinicalTrials.gov and the Cochrane Library databases was performed using specified key words. We examined all English and French reports on PCT measurement after admission for PPROM and considered: human studies published between 1990 and 2019; observational studies; and randomized controlled trials. A protocol was determined previously, registered at PROSPERO as CRD42019145464. The eligibility was independently assessed by two researchers and literature search yielded 590 studies; after revision of the titles and abstracts, 46 articles were identified as potentially eligible; eight studies were included in the meta-analysis. Primary data synthesis was performed in Review Manager Version 5.3 and average sensitivity and specificity was calculated using Midas, Stata. RESULTS: From the eight studies included, 335 participants with PPROM were enrolled. Our meta-analysis disclosed that PCT has a poor sensitivity (0.50; 95% CI 0.28-0.73) and a modest specificity (0.72; 95% CI 0.51-0.87) in diagnosing CA. C-reactive protein (CRP) not only has better sensitivity (0.71; 95% CI 0.53-0.84), but also better specificity (0.75; 95% CI 0.55-0.88), compared with the other inflammatory parameters analyzed. Procalcitonin does not seems to be better than CRP in preterm rupture of membranes for chorioamnionitis diagnosis.

Innate Lymphoid Cells in Human Pregnancy.

Innate lymphoid cells (ILCs) are a new set of cells considered to be a part of the innate immune system. ILCs are classified into five subsets (according to their transcription factors and cytokine profile) as natural killer cells (NK cells), group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Functionally, these cells resemble the T helper population but lack the expression of recombinant genes, which is essential for the formation of T cell receptors. In this work, the authors address the distinction between peripheral and decidual NK cells, highlighting their diversity in ILC biology and its relevance to human pregnancy. ILCs are effector cells that are important in promoting immunity, inflammation, and tissue repair. Recent studies have directed their attention to ILC actions in pregnancy. Dysregulation or expansion of pro-inflammatory ILC populations as well as abnormal tolerogenic responses may directly interfere with pregnancy, ultimately resulting in pregnancy loss or adverse outcomes. In this review, we characterize these cells, considering recent findings and addressing knowledge gaps in perinatal medicine in the context of ILC biology. Moreover, we discuss the relevance of these cells not only to the process of immune tolerance, but also in disease.

Can immunity during pregnancy influence SARS-CoV-2 infection? - A systematic review.

BACKGROUND: During pregnancy, the maternal immune system must create and sustain tolerance to the allogeneic fetus while maintaining the ability to protect against microbial assaults. OBJECTIVES: Ascertain the immunological differences in immune cells of pregnant women that may influence SARS-CoV-2 infection. STUDY DESIGN: Systematic review conducted in accordance with PRISMA guidelines and registered within PROSPERO CRD42020189735. A systematic search was undertaken across ISI, PubMed, Scopus, Embase, Cochrane Library and clinical trials.gov from January 2019 up until June 2020. Eligibility criteria included COVID-19 infection, pregnancy, and availability of immune characteristics for the pregnant women. Two authors independently screened for the suitability of inclusion. MAIN OUTCOME MEASURES: Information was manually extracted from full-text articles and efforts were made to identify overlapping data. Variables extracted and analysed included the quantification of white blood cells (WBC), lymphocytes, and C-reactive protein (CRP). RESULTS: The literature search yielded 162 studies, of which 11 were considered appropriate for selection. Only four were used in this systematic review. Our research showed that pregnant women with COVID-19 only differ from other pregnant women in their lower WBC count. The proportion of reduced lymphocyte cases is similar in both groups, as is the case of C-reactive protein levels. CONCLUSIONS: In line with previous coronavirus infections, severe maternal morbidity and perinatal death with COVID-19 infection were more likely to be expected in pregnancy. Our research showed that pregnant women with COVID-19 in terms of immunity only differ from other pregnant women in their lower WBC count.

The role of innate immunity in spontaneous preterm labor: A systematic review.

BACKGROUND: Immunoinflammatory response by innate immunity components is a field with increasing interest in understanding the mechanisms behind preterm labor (PTL). OBJECTIVES: Systematic review of the role of innate immunity in spontaneous PTL. STUDY DESIGN: PubMed, Scopus, ClinicalTrials.gov and Web of Science were searched using pregnancy AND innate OR toll-like OR natural-killer OR dendritic AND delivery OR premature OR rupture of membranes. MAIN OUTCOME MEASURES: All article titles and abstracts were evaluated by two individuals, based in strict predefined inclusion criteria. For relevant studies, title, abstract, and full text were assessed to identify PTL and innate immunity studies, excluding multiple pregnancies, cervical insufficiency and indicated PTL. RESULTS: From 894 articles evaluated, 101 full texts articles were assessed independently. For this systematic review 44 studies were finally included. Toll-like receptors 2 and 4 mediated immune dysfunction and inflammation can result in PTL. Moreover, PTL is linked to high levels of CD14+ monocytes; neutrophils seem important in inflammation-associated PTL and in pathological preterm premature rupture of membranes. Besides, decidual natural-killer cells and premature activation of dendritic cells may also participate in the etiology of PTL. Finally, dysregulation of maternal complement might increase the risk of PTL, characterized by high levels of innate lymphoid cells 2 and 3. CONCLUSIONS: Further research is warranted to ascertain the precise role of innate immunity in PTL. Nonetheless, our results indicate that Toll-like receptors, monocytes, natural-killer cells, dendritic cells and complement have significant roles in PTL.

Assessing Functional Capacity and Factors Determining Functional Decline in the Elderly: A Cross-Sectional Study.

INTRODUCTION: The aim of this study is to assess functional capacity and determine the factors associated with functional decline in the elderly in adult day care centres and home care support in the County of Coimbra, Portugal. MATERIAL AND METHODS: Cross-sectional study. A total of 115 participants of both genders, aged between 65 and 98, were enrolled in the home care support and adult day care system of the County of Coimbra, Portugal. Functional capacity was assessed using the Barthel index and the Lawton index. Another questionnaire gathered social, demographic and health status information. RESULTS: The basic activities of daily living were significantly associated with age, cohabitation, medication usage, falls and multiple morbidity. Analysis of the study's variables and the instrumental activities of daily living found significant associations between age, institutional affiliation, perceived health status, hospitalizations, medication usage, physical exercise, multiple morbidities, falls, and fall prevention. DISCUSSION: The results demonstrate that no statistically observable differences were found between gender and functional dependence. A significant association between the Barthel index and cohabitation was also found. We should also highlight that this sample revealed the extremely important role of families in determining the protection of highly dependent older people. Likewise, a significant association was observed between instrumental activities of daily living and levels of physical activity in which greater independence was found in those seniors who practiced physical exercise three or more times per week. CONCLUSION: The results of this study allow us to identify factors that may be associated with the functional decline in the elderly. Useful evidence for the adoption of intervention strategies in the elderly population was added, focused on the prevention of functional decline and maintenance of the functional capacities of the elderly.

Introdução: Foi objectivo este estudo avaliar a capacidade funcional e determinar os fatores associados ao declínio funcional dos idosos num centro de dia e apoio domiciliário no Concelho de Coimbra, Portugal. Material e Métodos: Estudo transversal. Participaram no estudo 115 indivíduos de ambos os géneros, com idades entre os 65 ­ 98 anos, que utilizaram os serviços de apoio domiciliário e centro de dia no Concelho de Coimbra, Portugal. A capacidade funcional foi avaliada através dos questionários: índice de Barthel e índice de Lawton. Foi utilizado um questionário para caracterização sociodemográfica e do estado de saúde dos participantes. Resultados: Na análise, as atividades básicas da vida diária tiveram associação significativa com idade, coabitação, uso de medicamentos, quedas e presença de multimorbilidade. Na análise entre as variáveis de estudo e as atividades instrumentais da vida diária, houve associação significativa com idade, vínculo com instituição, perceção do estado de saúde, internamento hospitalar, uso de medicamento, prática de atividades física, presença de multimorbilidade, quedas e prevenção de quedas. Discussão: Os resultados demonstram que não foram encontradas diferenças estatisticamente observáveis entre género e dependência funcional. Quando a relação entre as habilidades funcionais e a coabitação foi analisada, houve uma relação significativa entre o índice de Barthel e a coabitação. Sublinha-se que essa amostra revelou o papel altamente importante das famílias na determinação da proteção de pessoas idosas muito dependentes, bem como foi observada uma relação significativa entre as atividades instrumentais da vida diária e os níveis de atividade física, em que maior independência foi encontrada nos idosos que praticavam exercício físico três ou mais vezes por semana. Conclusão: Os resultados deste estudo permitem identificar fatores que podem estar associados ao declínio funcional dos idosos. Acrescentam evidências úteis para a adoção de estratégias de intervenção nesta população, focadas na prevenção do declínio funcional e na manutenção das capacidades funcionais dos idosos.

Development of a Healthy Lifestyle Assessment Toolkit for the General Public.

The prevalence of age-related non-communicable chronic diseases has increased worldwide, being the leading causes of morbidity and death in many world regions, including in Europe. Innovative models and strategies focused on preventive care, including early identification of risk factors underlying disease onset and progression, and proper modification of lifestyle habits and behaviors, might contribute to promote quality of life, healthy living and active aging. Healthy Lifestyle Innovative Quarters for Cities and Citizens (HeaLIQs4cities) is an EIT Health-funded project aiming to engage, empower and educate citizens toward healthy lifestyles. One of the major objectives of this project was to develop a toolkit for a rapid and informal assessment of healthy lifestyles, to be used at different levels of care pathways, including in informal public environments. In this paper, we describe the methodology underlying the development of the toolkit, which resulted from the collaboration of an interdisciplinary focus group of academic experts, from medicine, sport sciences, psychology, health economics, and innovative technologies applied to health. The following eight components were included in the toolkit: (1) anthropometric assessment and cardiometabolic parameters; (2) physical activity and exercise; (3) well-being, social cohesion, and functional independence; (4) nutrition; (5) mental health; (6) smoking, drinking, and use of illicit substances; (7) sleep habits and quality; and (8) health and disease. A traffic light rating system indicating the risk score was used (low: green; moderate: yellow; and relevant: orange) for each of the 8 components, together with recommendations for the toolkit users. After completing the reduced version of the toolkit, individuals showing moderate or relevant risk in one or more of the 8 dimensions, were invited to participate in a more detailed assessment (toolkit long version), based on deeper and scientifically validated tools. The toolkit was incorporated in eVida, a web-based platform that focuses on delivering services to personalized health and well-being. The validation of the current toolkit has been applied in wide-ranging public events in three different European Regions. Large scale deployment of the toolkit is expected to profit from the Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Aging (EIP on AHA).

Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis.

INTRODUCTION: The risks of pregnancy in women of advanced maternal age are not consensual amongst studies. The aim of this metaanalysis  was to determine whether women of advanced maternal age (≥ 35 years old) had worse obstetrical and perinatal outcomes than non- advanced maternal age women (20 - 34 years old) in singleton, naturally-conceived pregnancies. MATERIAL AND METHODS: We searched PubMed/ MEDLINE, IndexRMP and the Cochrane Database of Systematic Reviews. Ten studies were included according to the following criteria: population of > 1000 nulliparous and/or multiparous women with singleton gestations who did not undergo any type of infertility treatment. Using Review Manager v. 5.3, two meta-analysis were performed: one comparing the outcomes of 20 - 34-year-old vs 35 - 40-year-old women, and another comparing the outcomes of 35 - 40-year-old women vs > 40-year-old women. RESULTS: Women aged 35 - 40 years old were more likely to have > 12 years of education than 20 - 34 years old and > 40 years old women. Advanced maternal age women (35 - 40 and > 40 years old) were more likely to be overweight and having gestational diabetes and gestational hypertension. They were also more likely to undergo induced labour and elective caesarean deliveries. Furthermore, they had worse perinatal outcomes such as preterm delivery, low birthweight babies, higher rates of Neonatal Intensive Care Unit admission and worse Apgar scores. Advanced maternal age women had higher rates of perinatal mortality and stillbirth. DISCUSSION: Most authors present similar results to our study. Although the majority of adverse outcomes can be explained through the physio-pathological changes regarding the female reproductive apparatus that come with aging and its inherent comorbidities, according to the existing literature advanced maternal age can be an independent risk factor per se. In older pregnant women without comorbidities such as gestational hypertension or diabetes there are still worse obstetric and perinatal outcomes, which indicate that advanced maternal age is an independent strong risk factor alone. CONCLUSION: Advanced maternal age women are at a higher risk of adverse obstetrical and perinatal outcomes. In both comparisons, worse outcomes were more prevalent in the older group, suggesting that poorer outcomes are more prevalent with increasing age.

Introdução: Não há consenso na literatura sobre os riscos da gravidez em mulheres com idade materna avançada. O objetivo desta meta-análise consistiu em determinar se as mulheres com idade materna avançada (≥ 35) tiveram piores desfechos obstétricos e perinatais, comparativamente com as mulheres não-idade materna avançada (20 - 34 anos), em gestações de feto único e por conceção natural. Material e Métodos: A pesquisa bibliográfica foi feita na PubMed/MEDLINE, IndexRMP e na Cochrane Database of Systematic Reviews. Foram incluídos dez estudos segundo os seguintes critérios: população-estudo > 1000 mulheres, nulíparas e/ou multíparas, com gestações de feto único sem recurso a tecnologias de reprodução medicamente assistida. Duas meta-análises foram feitas com o programa Review Manager v. 5.3: uma comparando os desfechos da gravidez do grupo 20 - 34 anos com o grupo 35 - 40 anos e outra comparando os grupos de idades 35 - 40 e > 40 anos. Resultados: As mulheres com 35 - 40 anos tiveram mais probabilidade de ter > 12 anos de escolaridade, comparativamente ao grupo 20 - 34 e > 40 anos. Mulheres com idade materna avançada (35 - 40 e > 40 anos) tiveram maior probabilidade de ter excesso de peso e comorbilidades como diabetes gestacional e hipertensão gestacional. Tiveram também maior frequência de partos induzidos e de cesarianas eletivas. As mulheres mais velhas tiveram mais partos pré-termo e recém-nascidos com baixo peso. Os bebés das mães com idade materna avançada foram mais vezes admitidos na Unidade de Cuidados Intensivos Neonatais e tiveram piores índices de Apgar. De igual forma, as mulheres com idade materna avançada tiveram maiores taxas de mortalidade perinatal e morte in utero. Discussão: A maioria dos autores descreve resultados semelhantes àqueles que estão descritos na meta-análise. Embora os resultados desfavoráveis sejam em grande parte explicados pela fisiopatologia do envelhecimento do sistema reprodutor da mulher e comorbilidades inerentes ao avançar da idade, a bibliografia admite a idade materna avançada um fator de risco per se. Mesmo em mulheres com idade materna avançada sem comorbilidades como diabetes ou hipertensão gestacional, esta acaba por ser um fator de risco independente e significativo para desfechos adversos. Conclusão: Mulheres com idade materna avançada têm um maior risco de desfechos obstétricos e perinatais adversos. Em ambas as comparações os piores desfechos foram mais prevalentes no grupo de mulheres com maior idade, sugerindo maior expressão com o avançar da idade.

Aging Hallmarks: The Benefits of Physical Exercise.

World population has been continuously increasing and progressively aging. Aging is characterized by a complex and intraindividual process associated with nine major cellular and molecular hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, a loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This review exposes the positive antiaging impact of physical exercise at the cellular level, highlighting its specific role in attenuating the aging effects of each hallmark. Exercise should be seen as a polypill, which improves the health-related quality of life and functional capabilities while mitigating physiological changes and comorbidities associated with aging. To achieve a framework of effective physical exercise interventions on aging, further research on its benefits and the most effective strategies is encouraged.

The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens.

The Role of Moderate Aerobic Exercise as Determined by Cardiopulmonary Exercise Testing in ALS.

INTRODUCTION: The efficacy of cardiopulmonary exercise testing (CPET) to determining exercise intensity has not been established in Amyotrophic Lateral Sclerosis (ALS). We studied this intervention. METHODS: We included 48 ALS patients randomized in 2 groups: G1 (n = 24), exercise intensity leveled by CPET; G2 (n = 24), standard care limited by fatigue, during 6 months. ALS functional scale (ALSFRS-R) and forced vital capacity (FVC) were performed every 3 months; CPET was done at admission (T1) and 6 months later (T2). We registered oxygen uptake, carbon dioxide output, and ventilation at anaerobic threshold and at peak effort. Primary outcome was functional change. We used parametric statistics for comparisons and multiple regression analyses to identify independent predictors of functional decline. RESULTS: At T1 both groups were identical, except for higher FVC in G1 (p = 0.02). At T2, ALSFRS-R was higher (p = 0.035) in G1. Gas exchange variables at T2 did not change in G1 but had significant differences in G2 (p < 0.05). Multiregression analyses showed the Spinal ALSFRS-R slope and Intervention group (p < 0.001) as significant predictors of ALSFRS-R at T2. CONCLUSION: Aerobic exercise defined by CPET is feasible and can improve functional outcome in ALS. This trial is registered with Clinical trials.gov ID: NCT03326622.