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Background Disordered mineral and bone metabolism is a common complication of chronic kidney disease (CKD). Bone biopsy remains the gold standard tool for evaluating renal osteodystrophy (ROD), but it is an invasive procedure. Despite a growing interest in the ability of newer bone biomarkers to discriminate between different forms of ROD, data on pre-dialysis patients are scarce. Methods A cross-sectional study was conducted in a cohort of 56 patients with CKD Stages 3 and 4. Participants underwent a transiliac bone biopsy after a course of double tetracycline labelling. Circulating levels of Wnt signalling inhibitors sclerostin and Dickkopf-1 (DKK1), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin were measured and correlated with histomorphometric analysis results. Results Most patients had abnormal bone histology and low-turnover bone disease was the predominant form of ROD. Characteristics associated with high bone turnover were worse renal function, lower serum calcium and higher intact parathyroid hormone and fibroblast growth factor-23 levels. Patients with low bone turnover, on the other hand, presented with higher sclerostin along with lower DKK1 and sRANKL levels. In the multivariable logistic regression analysis, sclerostin and DKK1 levels were independently associated with low-turnover bone disease. Conclusions Our results suggest that circulating levels of Wnt signalling inhibitors sclerostin and DKK1 are predictive of low-turnover bone disease in patients not yet on dialysis. Further research is needed to assess the performance of these bone turnover biomarkers, compared with histomorphometric analysis, in the diagnosis and treatment monitoring of ROD., Graphical Abstract Graphical Abstract

Background: Postmenopausal women have an elevated risk of developing cardiovascular diseases, which can be counteracted by conventional exercise regimes or recreational football. Less is known about the impact of exercise programmes based on other team sports. Thus, we examined the effects of recreational team handball on aerobic performance, cardiorespiratory fitness and cardiometabolic health in untrained postmenopausal women. Methods: Sixty-seven participants (age 68 ± 6 years, stature 157 ± 6 cm, body mass 67 ± 10 kg, fat mass 37 ± 7%, VO2peak 25.2 ± 3.6 mL/min/kg, Yo-Yo intermittent endurance level 1 test performance (YYIE1) 230 ± 103 m) with no previous experience of team handball were randomly allocated to either a team handball (THG, n = 41) or a control (CG, n = 26) group. THG performed 2-3 60-min training sessions per week for 16 weeks. YYIE1 performance and cardiometabolic markers were evaluated at baseline and post-intervention. Results: Average attendance during recreational team handball training was 1.9 ± 0.4 sessions per week, with mean heart rates of 76 ± 6%HRmax and 18 ± 9 min (44 ± 20% of total time) played at HR > 80%HRmax. A between-group effect was observed for YYIE1 performance, with a more pronounced improvement in aerobic exercise performance in THG compared to CG (70 ± 62 vs 15 ± 44%; p < 0.001). Within-group improvements (p < 0.05) were observed for THG with regard to VO2peak (7 ± 10%), incremental treadmill test time to exhaustion (TTE) (11 ± 14%), total cholesterol (-3 ± 9%) and low-density lipoprotein cholesterol (-2 ± 14%), with no significant changes in CG except an increase (p < 0.05) in TTE. Post-intervention values were higher for THG vs CG for YYIE1 performance (88%; 406 ± 216 vs 216 ± 75 m) and VO2peak (10%; 27.5 ± 3.8 vs 24.9 ± 3.6 mL/min/kg). Conclusions: Recreational team handball can be used to obtain moderate-to-vigorous aerobic intensities, and just 2 weekly 60-min team handball training sessions for 16 weeks can result in improvements in aerobic performance and in markers of cardiorespiratory fitness in postmenopausal women with no previous experience of the sport. RP is supported by a grant from the Portuguese Foundation for Science and Technology (SFRH/BD/136789/2018). This study is part of the Handball for Health project, which has the support of the Portuguese Handball Federation, the European Handball Federation and Gaia City Hall. We would like to thank all the participants for their committed participation. We would also like to express our gratitude to the students and technicians of the University Institute of Maia and Faculty of Sport, University of Porto, who collaborated in the data collection and provided technical assistance, and to Henrik Holm Andersen from Copenhagen Translation for the language editing.

Predictions of mortality may help in the selection of patients who benefit from intensive care. Endothelial dysfunction is partially responsible for many of the organic dysfunctions in critical illness. Reactive hyperaemia is a vascular response of the endothelium that can be measured by peripheral arterial tonometry (RH-PAT). We aimed to assess if reactive hyperaemia is affected by critical illness and if it correlates with outcomes. Prospective study with a cohort of consecutive patients admitted to an Intensive Care Unit. RH-PAT was accessed on admission and on the 7th day after admission. Early and late survivors were compared to non-survivors. The effect of RH-PAT variation on late mortality was studied by a logistic regression model. The association between RH-PAT and severity scores and biomarkers of organic dysfunction was investigated by multivariate analysis. 86 patients were enrolled. Mean ln(RHI) on admission was 0.580 and was significantly lower in patients with higher severity scores (p

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9–induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

Background Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet. Methods Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet. Results Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p

Background The Zika virus (ZIKV) is a flavivirus and the human disease caused by this virus has been described in the Americas in 2015. ZIKV has been identified as an etiological agent of acute exanthematous disease in Brazil. In the same year, an epidemic of microcephaly with images suggestive of congenital infection raised the suspicion of a relationship between these alterations and ZIKV infection. Epidemiological and histopathological studies point to a strong relationship between prenatal Zika virus infection and microcephaly. Newborns with microcephaly, may also present auditory and visual changes, seizures and severe neurodevelopmental impairment. In 2016, the World Health Organization (WHO) declared Zika virus (ZIKV) infection a public health emergency of international concern. Aims Clinical observation in the ambulatory school of ABRAH (Brazilian Association of Recycling and Homeopathy Assistance) of patients with encephalopathy of various origins, using the medicine Helleborus niger as equalizer of the NS (Nervous System), as described in the Complex Systems of Carillo, shows improvement in motor, cognitive and seizure disorders. Based on this observation, we propose to use this method in patients with ZIKV congenital infection. Methodology To evaluate 15 patients in follow-up at the AFR (Fluminense Rehabilitation Association), through homeopathic anamnesis, clinical, diathesic, biotypological and temperamental classification. The Gross Motor Function Classification System (GMFCS) will be used. All patients will receive Helleborus niger 6 Ch daily for 6 months. Results and discussion This study was forwarded to the research ethics committee and will begin in July 2019. Will be evaluated the use of Helleborus niger in patients with congenital infection by ZIKV, as equalizer of NS. The expected result is overall neurological improvement. Conclusion Helleborus niger, probably stimulating self-regulation through uninjured neurological pathways, will promote autopoiesis and construction of new programs of action, and will enable the improvement of patients with congenital ZIKV infection.

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this cross-sectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefficient: β = 0.45, P-value = ≤0.001, β = 0.60, P = ≤ 0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our findings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle.

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this crosssectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefcient: β=0.45, P-value= ≤0.001, β=0.60, P=≤0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our fndings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle., Portuguese Foundation for Science and Technology Sapiens 358007/99, Oeiras City Council, Becel Portugal, Roche Pharmaceuticals Portugal, Compal Portugal, University of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucia, European Union (EU) SOMM17/6107/UGR, Fundacion Carolina C.2016574961

Background: Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. Methods: PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. Results: The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. Conclusion: This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS. This work was supported by the Insulin Resistance Study Group of the Endocrinology, Diabetes and Metabolism Portuguese Society. Ana Cristina Santos holds a FCT Investigator contract IF/01060/2015.

To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness.A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection.Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m.Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica.Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção.Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção.A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.

Faecal calprotectin (FC) is a sensitive and non-invasive marker for gastrointestinal mucosal inflammation [1]. Since Calprotectin is a small calcium-binding protein released by neutrophils (S100 family) as a result of an inflammatory process [2], it is an excellent inflammatory marker to distinguish organic inflammatory bowel disease (IBD) - Crohn’s disease (CD) or Ulcerative Colitis (UC) from functional disease- Irritable Bowel Syndrome (IBS) [1,2]. In pediatric patients, FC is useful for an early diagnosis of IBD significantly reducing the number of invasive procedures in children with gastrointestinal symptoms. Endoscopic procedures are unpleasant for the patient, time-consuming and bear the risk of intestinal perforation. In addition, FC is more sensitive than C-reactive protein (CRP) in reflecting IBD activity [3], being for this reason also used to monitor IBD therapy and to predict relapse in these patients [1,3]. Because of its enormous potential as biomarker, many methods have been developed for its measurement. Although the quantitative enzyme-linked immune sorbent assay (ELISA) is considered the “gold” standard method to quantify FC, there are also immunochromatographic tests that are regularly used. More recently, automated immunoassays have been developed as an alternative, leading to an improved solution in the routine laboratory in view of an exponential increase in workload [4,5]. In our hospital, we have been using a rapid test to measure FC in pediatric samples. As the number of tests for these samples has been increasing in the last years, the possibility to automate this parameter was considered as worth to evaluate. The main purpose of this study was to determine FC levels with an immunoassay test adapted to an automated equipment and compare with a rapid routine test.

Background: Nurses are the largest professional group in healthcare and those who make more decisions. In 2014, the Committee on Bioethics of the Council of Europe launched the “Guide on the decision-making process regarding medical treatment in end-of-life situations” (hereinafter, Guide), aiming at improving decision-making processes and empowering professionals in making end-of-life decisions. The Guide does not mention nurses explicitly. Objectives: To analyze the ethical principles most valued by nurses working in palliative care when making end-of-life decisions and investigate if they are consistent with the framework and recommendations of the Guide; to identify what disputed/controversial issues are more frequent in these nurses’ current end-of-life care practices. Design: Qualitative secondary analysis. Participants/context: Three qualitative datasets including 32 interviews from previous studies with nurses working in palliative care in Portugal. Ethical consideration: Ethical approval was obtained from the Ethics Research Lab of the Instituto de Bioética (Ethics Research Lab of the Institute of Bioethics) (Ref.04.2015). Ethical procedures are thoroughly described. Findings: All participant nurses referred to autonomy as an ethical principle paramount in end-of-life decision-making. They were commonly involved in end-of-life decision-making. Palliative sedation and communication were the most mentioned disputed/controversial issues. Discussion: Autonomy was highly valued in end-of-life care and decision-making. Nurses expressed major concerns in assessing patients’ preferences, wishes, and promoting advance care planning. Nurses working in palliative care in Portugal were highly involved in end-of-life decision-making. These processes embraced a collective, inclusive approach. Palliative sedation was the most mentioned disputed issue, which is aligned with previous findings. Communication also emerged as a sensitive ethical issue; it is surprising, however, that only three nurses referred to it. Conclusion: While the Guide does not explicitly mention nurses in its content, this study shows that nurses working in palliative care in Portugal are involved in these processes. Further research is needed on nurses’ involvement and practices in end-of-life decision-making.

Background: Making palliative care accessible to all citizens who are in need of this type of care requires effective policies and education. Moreover, healthcare professionals have an ethical and legal responsibility to ensure quality palliative care. Nevertheless, palliative care has had traditionally a limited emphasis in healthcare professionals’ undergraduate education. Aim: To study the current status of palliative care education in nursing undergraduate curricula and compare 2005 and 2015 findings. Design: An online survey was sent to all state schools providing nursing undergraduate education in Portugal ( N = 21). The survey assessed if and how palliative care was included in the curricula, and whether or not national and international recommendations for palliative care nursing education were followed. Further analysis included the content of available curricula/syllabi. Setting/participants: A total of 19 schools completed the survey (90% of response rate). These institutions are geographically dispersed and representative of state nursing educational institutions in Portugal. Results: In 2015, all participant schools integrated palliative care in their curricula; nine schools had palliative care as an independent curricular unit (an 800% increase compared to 2005). While in 2005, only 14 out of 23 (61%) schools included palliative care explicitly in their curricula; in 2015, all 19 participant schools did so. National and international recommendations were followed. Conclusion: The inclusion of palliative care within nursing undergraduate curricula strongly increased from 2005 to 2015. Further research is needed to understand the contribution of education in the access, care provision, quality and development of palliative care in this country.

Background: Ethical decisions are part of contemporary practices in palliative care. The need of making such decisions is associated to higher burnout levels and other work related problems among healthcare professionals. Aims: As part of the project entitled “Decisions in End-of-Life Care in Spain and Portugal” (DELiCaSP), this study aims to (i) identify the most common ethical decisions made by Portuguese palliative care teams and (ii) understand how the making of such decisions relates to burnout. Methods: A mixed methods study was conducted with 9 palliative care teams, using (i) questionnaires of socio-demographic and professional variables, work-related experiences, (ii) the Maslach Burnout Inventory, (iii) interviews and (iv) observations. These teams were geographically dispersed across the country, covering the North, Centrum and South regions, and heterogeneous: Five palliative care units for inpatients; three home care teams; and one hospital support team. A total of 20 interviews and 240 hours of observations were completed until reaching saturation. Results: The most common ethical decisions were related to communication issues (information disclosure of the diagnosis and prognosis), forgoing treatment and sedation. Although perceived as stressful, emotionally demanding and challenging, ethical decisions were not significantly associated with burnout. Conclusions: Making ethical decisions is not associated with higher burnout levels among professionals working in Portuguese palliative care teams. This can be explained by the interprofessional decision-making process followed by these teams, which promotes a sense of shared-decision and team-based empowerment; and by the advanced level of interdisciplinary education in palliative care that these professionals have.

Objectives Depressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics. Methods A stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1–5 scale and categorised as 1=no, 2–3=mild/moderate and 4–5=severe/very severe. Results Depressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17–65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms. Conclusions More than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care.

The aim of this study was to analyze electroencephalographic (EEG) background activity in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) by means of multiscale spectral entropy (MSSE). To achieve this goal, five minutes of EEG activity were acquired from 18 cognitive healthy controls, 10 MCI subjects and 32 AD patients. Our results showed statistically significant differences (p-values < 0.05, Kruskal-Wallis test) in MSSE values for all scale factors. Additionally, a 3D receiver operating characteristic (ROC) curve was used to assess the discrimination ability of MSSE among the 3 groups, showing a good three-way discrimination power (volume under the surface of 0.6). These results suggest that MSSE can be a useful measure to characterize neural alterations in AD, even at early stages.

Background: Education sessions about palliative care among teenagers are uncommon in developed countries. However, very little is known either about the impact of this type of intervention or about how this age-group perceives its impact. The purpose of this study was therefore to (i) implement an education program about palliative care among teenagers and (ii) to investigate the impact of the program on the participants. Methods: An action-research study was conducted at a local community parish in Portugal in November 2015. An education programme was purposively built about palliative care, using active educational strategies adapted for teenagers. Quantitative and qualitative techniques and instruments were used for data collection: questionnaire; reflective diaries; interviews and written testimony. The program had three stages: preparation; intervention; and evaluation. Qualitative data were analysed using thematic content analysis; quantitative data were analysed descriptively. Results: 69 people (47 teenagers) participated in the education program. Findings show that the education program contributed to creating awareness about palliative care. Both the teenagers and other participants assessed the education program positively. At the end of the program, teenagers had a constructive message about palliative care. Conclusions: The education-intervention contributed to create awareness about palliative care among the participant teenagers, who ended the program with a positive message about palliative care. Based on our findings, the following policy implications can be drawn: (1) Further research is needed to evaluate the effect of education programs about palliative care among younger age groups (teenagers and children), particularly in relation to the changing of attitudes toward palliative care. (2) Education about palliative care should be promoted to local communities, involving all age groups, to foster involvement, participation and empowerment. (3) Compassionate communities should be promoted to enhance the health and wellbeing of all citizens at the end of their life.

This study aimed to analyze the associations between sedentary behavior, physical activity (PA), and cardiorespiratory fitness (CRF), with carotid intima-media thickness (cIMT), a marker of atherosclerosis already present at an early stage among obese adolescents. The associations between anthropometric measures, sedentary time, PA, CRF, and cIMT of 54 Caucasian obese adolescents were analyzed using partial correlations (controlling for age and sex) and multiple linear regressions. Differences between participants with and without a healthy CRF were also analyzed using independent sample t test. Sedentary time did not correlate with any of the variables. Light physical activity correlated positively with mean cIMT (r(38) = 0.36, p = 0.024). Moderate physical activity (MPA) correlated positively with both mean (r(38) = 0.37, p = 0.018) and maximum (r(38) = 0.33, p = 0.039) cIMT. CRF was inversely associated with mean cIMT (r(40) = −0.36, p = 0.019), even when controlling for sedentary time (r(37) = −0.35, p = 0.030). The best predictors of cIMT were MPA and weight. No significant differences in cIMT were found between participants with healthy and unhealthy CRF. Conclusion: Although we need to be cautious due to the limitations of the study, the results suggest that despite the importance of decreasing sedentary time, increasing PA intensity may be more effective in improving endothelial structural health among obese adolescents.

Background Activation of the immune system is one of the several pathways suggested as involved in Heart Failure (HF). The complement system is a key component of innate immunity. We hypothesized that complement proteins C3 and C4 can be an important predictor of death in patients with this condition. Methods 380 patients admitted with acute HF were recruited. They were followed up during 6 months. Serum C3c and C4c proteins were measured and groups were created and compared according to the 25th percentile cut-off value. A multivariate Cox-regression model was used to establish the prognostic value of both markers with the endpoints of HF and all-cause death. Results Median patients' age was 78 years and 49% of the patients were men. No major differences were observed in clinical characteristics of the groups. Patients with lower values of C3c and C4c had significantly higher values of BNP. During the 6 month period of follow up, 63 patients died, and 49 patients were due to HF. C4c showed univariate prognostic value, but not multivariate value. The multivariate-adjusted Hazard Ratios for the 6 month HF and all-cause death in patients with C3c values below 110.0 mg/dL were, respectively, 2.32 (95% CI: 1.25–4.28) and 2.52 (95% CI: 1.41–4.49). Conclusion Lower C3c levels are independently associated with higher risk of death. Our results reinforce the role of innate immunity in HF pathophysiology.

Thymidylate synthase (TYMS) has three polymorphisms that may modulate thymidylate synthase (TS) expression levels: (1) 28 base pairs (bp) variable number tandem repeat (VNTR) (rs34743033); (2) single nucleotide polymorphism (SNP) C>G at the twelfth nucleotide of the second repeat of 3R allele (rs2853542); and (3) 6 bp sequence deletion (1494del6, rs34489327). This study was conducted to evaluate the influence of TYMS polymorphisms on the survival of Portuguese patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. Our results showed no statistically significant differences between VNTR genotypes; although, considering the SNP C>G, homozygotes 3RG presented a better prognostic at 36 months (p = 0.004) and overall survival (p = 0.003) when compared to 2R3RG patients. Patients with “median/high expression genotypes” demonstrated a better survival at 12 months (p = 0.041) when compared to “low expression genotypes”. Furthermore, 6 bp− carriers (p = 0.006) showed a better survival at 12 months when compared to 6 bp+ homozygotes patients. When analyzing TYMS haplotypes, better survival at 12 months was observed for patients carrying haplotypes with the 6 bp− allele (2R6 bp−; p = 0.026 and 3RG6 bp−; p = 0.045). This is the first report that evaluates the three major TYMS polymorphisms in the therapeutic outcome of NSCLC in Portugal. According to our results, the TYMS polymorphisms may be useful tools to predict which advanced NSCLC patients could benefit more from platinum-based chemotherapy regimens.

Introduction: Professionals working in intensive and palliative care units, hence caring for patients at the end-of-life, are at risk of developing burnout. Workplace conditions are determinant factors to develop this syndrome among professionals providing end-of-life care. Objectives: To identify and compare burnout levels between professionals working in intensive and palliative care units; and to assess which workplace experiences are associated with burnout. Methods: A nationwide, multicentre quantitative comparative survey study was conducted in Portugal using the following instruments: Maslach Burnout Inventory–Human Services Survey, Questionnaire of workplace experiences and ethical decisions, and Questionnaire of socio-demographic and professional characteristics. A total of 355 professionals from 10 intensive care and 9 palliative care units participated in the survey. A series of univariate and multivariate logistic regression analyses were performed; odds ratio sidelong with 95% confidence intervals were calculated. Results: 27% of the professionals exhibited burnout. This was more frequent in intensive care units (OR = 2.525, 95% CI: 1.025–6.221, p = .006). Univariate regression analyses showed that higher burnout levels were significantly associated with conflicts, decisions to withhold/withdraw treatment, and implementing palliative sedation. When controlling for socio-demographic and educational characteristics, and setting (intensive care units versus palliative care units), higher burnout levels were significantly and positively associated with experiencing conflicts in the workplace. Having post-graduate education in intensive/palliative care was significantly but inversely associated to higher burnout levels. Conclusions: Compared to palliative care, working in intensive care units more than doubled the likelihood of exhibiting burnout. Experiencing conflicts (e.g., with patients and/or families, intra and/or inter-teams) was the most significant determinant of burnout and having post-graduate education in intensive/palliative care protected professionals from developing this syndrome. This highlights the need for promoting empowering workplace conditions, such as team empowerment and conflict management. Moreover, findings suggest the need for implementing quality improvement strategies and organizational redesign strategies aimed at integrating the philosophy, principles and practices of palliative care in intensive care units.

The objective was to compare measures from dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and anthropometry with a reference four-compartment model to estimate fat mass (FM) and fat-free mass (FFM) changes in overweight and obese women after a weight-loss programme. Forty-eight women (age 39.8 ± 5.8 years; weight 79·2 ± 11·8 kg; BMI 30·7 ± 3·6 kg/m2) were studied in an out-patient weight-loss programme, before and after the 16-month intervention. Women attended weekly meetings for the first 4 months, followed by monthly meetings from 4 to 12 months. Body composition variables were measured by the following techniques: DXA, anthropometry (waist circumference-based model; Antrform), BIA using Tanita (TBF-310) and Omron (BF300) and a reference four-compartment model. Body weight decreased significantly ( − 3·3 (sd3·1) kg) across the intervention. At baseline and after the intervention, FM, percentage FM and FFM assessed by Antrform, Tanita, BF300 and DXA differed significantly from the reference method (P ≤ 0·001), with the exception of FFM assessed by Tanita (baselineP = 0·071 and afterP = 0·007). DXA significantly overestimated the change in FM and percentage FM across weight loss ( − 4·5v. − 3·3 kg;P v. − 2·0 %;P v. − 3·3 kg;P = 0·043 and − 1·1v. − 2·0 %;P = 0·013) compared with the four-compartment model. Tanita and BF300 did not differ (P>0·05) from the reference model in any body composition variables. We conclude that these methods are widely used in clinical settings, but should not be applied interchangeably to detect changes in body composition. Furthermore, the several clinical methods were not accurate enough for tracking body composition changes in overweight and obese premenopausal women after a weight-loss programme.

This study was designed to compare measured and predicted thoracic gas volume (V (TG)) after weight loss and to analyze the effect of body composition confounders such as waist circumference (WC) on measured V (TG) changes.Prospective intervention study.Outpatient University Laboratory, Lisbon, Portugal.Eighty-five overweight and obese women (body mass index = 30.0+/-3.5 kg/m(2); age = 39.0+/-5.7 years) participating in a 16-month university-based weight control program designed to increase physical activity and improve diet.Body weight (Wb), body volume (Vb), body density (Db), fat mass (FM), percent fat mass (%FM) and fat-free mass (FFM) were assessed by air-displacement plethysmography (ADP) at baseline and at post-intervention (16 months). The ADP assessment included a protocol to measure V (TG) and a software-based predicted V (TG). Dual-energy X-ray absorptiometry (DXA) (Hologic QDR 1500) was also used to estimate FM, %FM and FFM. Maximal oxygen uptake (VO(2) max) was assessed with a modified Balke cardiopulmonary exercise testing protocol with a breath-by-breath gas analysis.Significant differences between the baseline and post-weight loss intervention were observed for body weight and composition (Vb, Db, %FM, FM and FFM), and measures of V (TG) (measured: Delta=0.2 l, P0.001; predicted: Delta=0.01 l, P0.010) variables. Measured V (TG) change was negatively associated with the change in the WC (P=0.008), controlling for VO(2) max and age (P=0.007, P=0.511 and P=0.331). Linear regression analysis results indicated that %FM and FM using the measured and predicted V (TG) explained 72 and 76%, and 86 and 90% respectively, of the variance in %FM and FM changes using dual-energy x-ray absorptiometry.After weight loss, measured V (TG) increased significantly, which was partially attributed to changes is an indicator of body fat distribution such as WC. Consequently, measured and predicted V (TG) should not be used interchangeably when tracking changes in body composition. The mechanisms relating the reduction of an upper body fat distribution with an increase measured V (TG) are worthy of future investigation.

The blood–brain barrier plays an important role in protecting the brain from injury and diseases, but also restrains the delivery of potential therapeutic drugs for the treatment of brain illnesses, such as tumors. Glioma is most common cancer type of central nervous system in adults and the most lethal in children. The treatment is normally poor and ineffective. To better understand the ability of drug delivery systems to permeate this barrier, a blood–brain barrier model using human brain endothelial cells and a glioma cell line is herein proposed. The consistent trans-endothelial electrical values, immunofluorescence and scanning electronic microscopy showed a confluent endothelial cell monolayer with high restrictiveness. Upon inclusion of glioma cell line, the trans-endothelial electrical resistance decreased, with consequent increase of apparent permeability of fluorescein isothiocyanate dextran used as model drug, revealing a reduction of the barrier robustness. In addition, it was demonstrated a cell shape modification in the co-culture, with loss of tight junctions. The microenvironment of co-cultured model presented significant increase of of CCL2/MCP-1 and IL-6 production, correlating with the modulation of permeation. The results encourage the use of the proposed in vitro model as a screening tool when performing drugs permeability for the treatment of disorders among the central nervous system.

Background:It is unclear how sedentary behavior (SED), physical activity (PA), and cardiorespiratory fitness (CRF) influence vascular structure in children of varying body size. This study examined whether associations between SED, PA, and CRF with intima-media thickness (IMT) added to that of abdominal fatness and IMT. Differences in physiological measures among waist circumference (WC) percentiles were tested.Methods:We assessed IMT of the carotid artery in 265 children aged 11 to 13 years (135 girls). Measures included IMT assessed with high-resolution ultrasonography, WC, body fat mass (BFM) from DXA, and CRF determined using a maximal cycle test. SED and PA were assessed by accelerometry. Association between IMT and CRF adjusted for PA variables, and body composition phenotypes were tested with multiple linear regression analysis.Results:CRF was related to IMT independently of moderate to vigorous PA (MVPA) and SED (P < .05). When WC was added to the model CRF was no longer associated with IMT (P > .05). Children in the higher WC group had increased mean values of BMI, BFM, WC, and IMT and lower MVPA and CRF (P < .05).Conclusion:Full modeling of SED, MVPA, CRF, and WC revealed that regional adiposity appears to have the biggest role in arterial structure of children.

Background: Adolescent obesity epidemic is one of the major health priorities as it tracks into adult life. There is widespread need for new creative strategies and lifestyle programs. This study was designed to investigate the possible impact of including peers on the weight management program and assess the long-run adherence to behaviour change, with a potential positive impact on body mass index, body composition, and physical activity. Peer influence is major at this age and it is expected that adolescents will be better motivated and engaged in the behaviour changes when they are accompanied by their friends. Methods/design: The study is a non-randomised, non-blinded controlled trial, including two groups: 1) Comparison group (n= 35), which will receive a 12 month standard treatment at the hospital setting plus a weekly interactive and physical activity session; 2) Experimental group (n=99), which will receive the standardized treatment at the hospital plus a weekly session together with a peer of their choice. The sample size calculations for the primary outcomes showed that we will have power to detect effect sizes of 0.25. Measures include: a) Dual-energy x-ray absorptiometry (for body composition assessment); b) Anthropometric evaluations; c) Assessment of physical activity levels by accelerometers; d) Psychosocial mediators (motivation and peer support) assessed with a package of psychometric questionnaires; and e) Outcomes (quality of life and well-being). Discussion: Adolescence is a crucial period for the development of a healthy lifestyle, especially among those who reach this age with an obesity condition. Obesity management programs directed to adolescents are often an adopted version of programs developed for children, most of them with a strong focus on the family, or an adopted version of adult programs, not recognizing the specificities of this age group. This study is designed taking into account the unique characteristics of this life-cycle stage, with the main objective of testing an innovative treatment for adolescent obesity. Trial registration: This trial is registered in the clinicaltrials.gov with the number NCT02024061

Early detection of impairment in vascular structure is an important clinical pursuit. However, it is unknown which measure of body composition best predicts vascular wall changes. We assess the differences in body composition among intima-media thickness (IMT) tertiles and determined which measures of body composition are associated with IMT in 385 children aged 11–13 years (196 girls). In this cross-sectional study, body mass index (BMI), waist circumference (WC), body fat mass (BFM), and trunk fat mass (TFM) from dual-energy radiographic absorptiometry and IMT through high-resolution ultrasonography were collected. Differences in body composition measures among IMT tertiles [low IMT (LIMT), ≤0.46 mm; middle IMT, 0.46–0.53 mm; higher IMT (HIMT), ≥0.53 mm] were assessed with ANOVA/ANCOVA after categorization. Regression analysis was used to assess the relationships between body composition and IMT. The groups were similar for sex, age, and maturity (p > 0.05). As compared with LIMT group, subjects with HIMT had higher mean values of BMI, BFM, TFM, and WC (p

Making decisions related to health care issues is a demanding task. These decisions are influenced by many combined factors related to the patient, their relatives, and the professional as an individual and as a team member, beyond other factors considering the team as a whole. When these decisions are concerned to palliative and end-of-life care, ethical dilemmas or problems may occur (e.g: decisions related to place of care and death, decisions regarding therapeutic interventions for symptom control, decisions about withholding and/or withdrawing treatments, decisions considering truth disclosure and communication, decisions considering patients’ autonomy and self-determination, decisions related to the justice and resource distribution). Beside these problems, even though palliative care principles reject any interventions in order to postpone or hasten death, issues such as medical futility, euthanasia and physician assisted suicide need to be reflected and discussed.

Objective To analyze the ataxin 2 ( ATXN2 ) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG) n alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. Design Case-control study. Setting France and Quebec, Canada. Participants A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. Results We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2–pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. Conclusions Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.

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This study reports on outcomes from a behavioral obesity treatment program, evaluating if treatment-related changes in body image and psychological well-being are predictors of weight change during treatment and after follow-up. Participants were 142 overweight/obese women (BMI=30.2+/-3.7kg/m(2); age=38.3+/-5.8 years) participants in a behavioral treatment program consisting of a 4-month treatment period and a 12-month follow-up. Psychosocial variables improved during treatment and these changes were correlated with 4-month weight reduction. Short-term changes in body size dissatisfaction (p=.002) and mood (p=.003) predicted long-term weight loss. Additional results suggest that there might be a predictive role of short-term changes in body size dissatisfaction and self-esteem on long-term weight loss after accounting for initial weight change (p

The aims were to identify whether there is burnout and the burnout levels of doctors and nurses working in ICUs (adult polyvalent units in northern Portugal). Also, to identify factors that may lead to the development of burnout in doctors and nurses working in the ICU.

Background In addition to the benefits on physical and mental health, cardiorespiratory fitness has shown to have positive effects on cognition. This study aimed to investigate the relationship between cardiorespiratory fitness and body weight status on academic performance among seventh-grade students. Methods Participants included 1531 grade 7 students (787 male, 744 female), ranging in age from 12 to 14 years (Mage = 12.3 ± 0.60), from 3 different cohorts. Academic performance was measured using the marks students had, at the end of their academic year, in mathematics, language (Portuguese), foreign language (English), and sciences. To assess cardiorespiratory fitness the Progressive Aerobic Cardiovascular Endurance Run, from Fitnessgram, was used as the test battery. The relationship between academic achievement and the independent and combined association of cardiorespiratory fitness/weight status was analysed, using multinomial logistic regression. Results Cardiorespiratory fitness and weight status were independently related with academic achievement. Fit students, compared with unfit students had significantly higher odds for having high academic achievement (OR = 2.29, 95% CI: 1.48-3.55, p