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.

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.

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.

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.

[Relevant Factors on Cognitive Evaluation of the Portuguese Population]. / Fatores Relevantes na Avaliação Cognitiva da População Portuguesa.

INTRODUCTION: Aging is an inevitable process that has a social impact in the forecoming decades, and it will present a great challenge regarding public health. An efficient health system requires a reflection on the preventive measures to be implemented. MATERIAL AND METHODS: The study population comprised a total number of 2672 individuals of both genders, aged 55 years and over, residents in continental Portugal, to whom a questionnaire was applied that included the following sections: Social network; Locomotion; Physical autonomy; Instrumental autonomy; Cognitive assessment; Physical activity. RESULTS: The study of aging in the Portuguese population found that physical autonomy for tasks related to daily life are associated with better cognitive evaluation. A statistically significant association was found between performance in cognitive assessment and gender, age, schooling, the fact of living alone, the number of hours being alone, autonomy to walk in the street, washing, dressing, eating, preparing meals, doing shopping, managing money and taking medications and washer / treat clothing. DISCUSSION: Cognitive evaluation is negatively influenced by the number of hours that an individual is alone. CONCLUSION: Activities of daily life must be valued, since they require the ability to plan and carry out tasks and their preservation is a key component in successful aging.

Introdução: O envelhecimento é um processo inevitável que tem um impacto social e será nas próximas décadas o grande desafio em termos de saúde pública. Um sistema de saúde eficiente requer uma reflexão sobre as medidas preventivas a aplicar. Material e Métodos: A amostra em estudo englobou 2672 indivíduos de ambos os géneros, com idade igual ou superior a 55 anos, residentes em Portugal continental, ao qual foi aplicado um questionário que incluiu as seguintes secções: Rede social; Locomoção; Autonomia física; Autonomia instrumental; Avaliação cognitiva; Atividade física. Resultados: O estudo do perfil de envelhecimento da população Portuguesa revelou que a autonomia física para tarefas relacionadas com o quotidiano, se associam a um melhor desempenho cognitivo. Verificámos uma associação estatisticamente significativa entre o desempenho na avaliação cognitiva e o género, a idade, a escolaridade, o facto de a pessoa viver sozinha, o número de horas que está sozinha, a autonomia a andar na rua, lavar-se, vestir-se, comer, preparar refeições, fazer compras, gerir dinheiro, tomar medicamentos e lavar/tratar a roupa. Discussão: A avaliação cognitiva é influenciada negativamente pelo número de horas que um indivíduo vive sozinho. Conclusão: As atividades da vida diária devem ser valorizadas, uma vez que requerem capacidade para planear e realizar tarefas e a sua preservação é uma componente chave num envelhecimento de sucesso.

Association between obesity and asthma - epidemiology, pathophysiology and clinical profile.

Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesity-induced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

A Standardized Classification for Subdural Hematomas- I.

Subdural hematomas are a frequent and highly heterogeneous traumatic disorder, with significant clinical and socioeconomic consequences. In clinical and medicolegal practice, subdural hematomas are classified according to its apparent age, which significantly influences its intrinsic pathogenic behavior, forensic implications, clinical management, and outcome. Although practical, this empirical classification is somewhat arbitrary and scarcely informative, considering the remarkable heterogeneity of this entity. The current research project aims at implementing a comprehensive multifactorial classification of subdural hematomas, allowing a more standardized and coherent assessment and management of this condition. This new method of classification of subdural hematomas takes into account its intrinsic and extrinsic features, using imaging data and histopathological elements, to provide an easily apprehensible and intuitive nomenclature. The proposed classification unifies and organizes all relevant details concerning subdural hematomas, hopefully improving surgical care and forensic systematization.

MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors.

Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

Can membrane progesterone receptor α on T regulatory cells explain the ensuing human labour?

Progesterone acts as an immunosteroid by contributing to the establishment of a pregnancy-protective milieu. It seems that it is the responsibility of progesterone to evade the inflammatory events that lead to parturition. T regulatory lymphocytes (Treg cells) could further explain the inhibition of the inflammatory mechanisms that lead to labour through the rapid action of progesterone on this cell subset. We investigated Treg cells and the membrane progesterone receptor α (mPRα) in these immune cells with in relationship to human parturition. This pilot cohort study was conducted in a single-centre tertiary obstetrical unit with 20 normal pregnant women. Variation in the absolute and relative frequency of CD4(+) T cells, Treg cells, and of mPR(α+) Treg cells was calculated by flow cytometry on three occasions (second and third trimesters; delivery day). Our results show that during normal pregnancy there is a generalised increase in Treg cells and mPR(α+) Treg cells, from the second to the third trimesters (23.4% vs. 52.3% and 4.3% vs. 8.3%, respectively). On the contrary, on delivery day, compared with the values in the third trimester, there is a sudden decrease in both Treg cells (52.3% vs. 17.4%) and mPR(α+) Treg cells (8.3% vs. 6.1%). Our findings suggest that human labour may develop as a consequence of a decline in mPR(α+) Treg cells, which reduces progesterone anti-inflammatory action through Treg cells.

Does progesterone administration in preterm labor influence Treg cells?

OBJECTIVES: The aim of this study was to determine if the actions of progesterone on preterm labor are accomplished through modulation of the percentage of regulatory T-cells (Treg). METHODS: The study was a cohort pilot study made in a single center tertiary obstetrical unit with women in preterm labor arrested with tocolytic treatment. Variation of the number and percentage of Treg cells obtained from peripheral blood samples of women with preterm labor were calculated by flow cytometry, before and after progesterone administration. RESULTS: In the paired samples for each patient, there was a significant difference in the Treg cell pool after progesterone treatment, with an increase in both their percentage (48.9 vs. 53; P=0.07) and absolute number (14.8 vs. 56.5 cells/µL; P=0.046). CONCLUSIONS: This research demonstrated a considerable increase in the Treg cell pool after progesterone treatment. This indicates a possible mechanism for progesterone treatment benefits in preterm labor, potentially increasing its more rational use.