Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC.

BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

Profiling early adopters of 'iSupport-Portugal': a country-specific version of a worldwide adapted digital support program for informal caregivers of people with dementia.

Introduction: Informal caregivers are the backbone of dementia care. iSupport is a World Health Organization digital support program for caregivers of people with dementia (PwD) that has been culturally adapted in several countries. iSupport was previously assessed for its feasibility in Portugal, and this country-specific version is now being utilized as a remote measurement tool (RMT). It constitutes the first internationally developed iSupport platform that is technically and scientifically enhanced to collect data on sociodemographic, clinical, and psychosocial variables of dementia care dyads. This paper characterizes the early adopters of iSupport-Portugal and discusses its exploration as a RMT. Methods: Cross-sectional data were collected between February and July 2023 from users registering on isupport-portugal.pt. To characterize caregivers and PwD, eligibility was limited to unpaid caregivers assisting community dwelling PwD (n = 173). Data were collected through self-administered instruments in users' accounts. Caregivers completed psychosocial measures on burden, anxiety, depression, quality of life, desire to institutionalize and usage of community services. Textual data on caregivers' needs underwent content analysis. Results: Among the early adopters of iSupport-Portugal (n = 365), 52.3% were informal caregivers, while 44.7% were health/social care professionals or others. Most caregivers were female (82.7%), middle-aged (M 51.7 years), highly educated (M 15.3 years) and supporting a parent (70.5%). Caregivers cared for a median of 24 h/week and 60.8% lived with the PwD. Neuropsychiatric symptoms were reported for 94.1% of PwD, who scored as moderately dependent (Barthel Index: M 14.0). Significant burden was reported by 88.4% of caregivers (≥21 on ZBI-22). Among caregivers scoring borderline or abnormal (≥8 on HADS) for anxiety, depression, or both (75.5%), 30.8% sought mental health counseling. Caregivers supporting a PwD not using community services scored higher on anxiety (p = 0.003), and depression (p = 0.009). Text data revealed unmet practical, emotional, and informational needs. Discussion: iSupport-Portugal has garnered fair initial interest from caregivers, particularly from those who are children, highly educated, and employed. Early adopters exhibited significant psychological distress, and both practical and emotional needs, which contrast with limited use of support services for themselves and the PwD. iSupport-Portugal shows promise for descriptive research on care dyads, particularly among newer generations of caregivers.

Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration.

Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.

Forecasted Dementia Prevalence in Portugal (2020-2080).

Dementia is a global public health challenge, and its impact on Portugal is yet unclear. This study forecasts dementia prevalence in Portugal until 2080. Using the Gonçalves-Pereira et al (2021) method, we estimated dementia cases among older adults (≥65 years) in the community. Applying age-sex specific prevalence rates of the Gonçalves-Pereira study to population projections for Portugal between 2020-2080, based on the 10/66 Dementia Research Group criteria (10/66 DRG) and the Diagnostic and Statistical Manual of Mental Disorders IV criteria (DSM-IV), to Portugal's population projections (2020-2080) under various growth scenarios (low, medium, and high). We anticipate a more than 2-fold increase in dementia prevalence from 2020 to 2080, both for 10/66 DRG [2.1%-5.0%] and DSM-IV [.8%-2.0%]. By 2080, those aged ≥80 years are projected to constitute 75.0% (vs 59.0% in 2020) of all dementia cases, particularly affecting women. Addressing dementia growth in Portugal calls for a comprehensive global response, while country-level estimates facilitate informed public health planning, policy-making, and resource allocation.

Biomonitoring of polycyclic aromatic hydrocarbons exposure and short-time health effects in wildland firefighters during real-life fire events.

Human biomonitoring data retrieved from real-life wildland firefighting in Europe and, also, worldwide are scarce. Thus, in this study, 176 Portuguese firefighters were biomonitored pre- and post- unsimulated wildfire combating (average:12-13 h; maximum: 55 h) to evaluate the impact on the levels of urinary polycyclic aromatic hydrocarbons hydroxylated metabolites (OHPAH; quantified by high-performance liquid chromatography with fluorescence detection) and the associated short-term health effects (symptoms, and total and differentiated white blood cells). Correlations between these variables and data retrieved from the self-reported questionnaires were also investigated. Firefighters were organized into four groups according to their exposure to wildfire emissions and their smoking habits: non-smoking non-exposed (NSNExp), non-smoking exposed (NSExp), smoking non-exposed (SNExp), and smoking and exposed (SExp). The most abundant metabolites were 1-hydroxynaphthalene and 1-hydroxyacenaphthene (1OHNaph + 1OHAce) (98-99 %), followed by 2-hydroxyfluorene (2OHFlu) (0.2-1.1 %), 1-hydroxyphenanthrene (1OHPhen) (0.2-0.4 %), and 1-hydroxypyrene (1OHPy) (0.1-0.2 %); urinary 3-hydroxybenzo(a)pyrene was not detected. The exposure to wildfire emissions significantly elevated the median concentrations of each individual and total OHPAH compounds in all groups, but this effect was more pronounced in non-smoking (1.7-4.2 times; p ≤ 0.006) than in smoking firefighters (1.3-1.6 times; p ≤ 0.03). The greatest discriminant of exposure to wildfire emissions was 1OHNaph + 1OHAce (increase of 4.2 times), while for tobacco smoke it was 2OHFlu (increase of 10 times). Post-exposure, white blood cells count significantly increased ranging from 1.4 (smokers, p = 0.025) to 3.7-fold (non-smokers, p < 0.001), which was accompanied by stronger significant correlations (0.480 < r < 0.882; p < 0.04) between individual and total OHPAH and total white blood cells (and lymphocytes > monocytes > neutrophils in non-smokers), evidencing the impact of PAH released from wildfire on immune cells. This study identifies Portuguese firefighters with high levels of biomarkers of exposure to PAH and points out the importance of adopting biomonitoring schemes, that include multiple biomarkers of exposure and biomarkers of effect, and implementing mitigations strategies.

Baseline data and associations between urinary biomarkers of polycyclic aromatic hydrocarbons, blood pressure, hemogram, and lifestyle among wildland firefighters.

Introduction: Available literature has found an association between firefighting and pathologic pathways leading to cardiorespiratory diseases, which have been linked with exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are highlighted as priority pollutants by the European Human Biomonitoring Initiative in occupational and non-occupational contexts. Methods: This cross-sectional study is the first to simultaneously characterize six creatinine-adjusted PAHs metabolites (OHPAHs) in urine, blood pressure, cardiac frequency, and hemogram parameters among wildland firefighters without occupational exposure to fire emissions (> 7 days), while exploring several variables retrieved via questionnaires. Results: Overall, baseline levels for total OHPAHs levels were 2 to 23-times superior to the general population, whereas individual metabolites remained below the general population median range (except for 1-hydroxynaphthalene+1-hydroxyacenaphtene). Exposure to gaseous pollutants and/or particulate matter during work-shift was associated with a 3.5-fold increase in total OHPAHs levels. Firefighters who smoke presented 3-times higher total concentration of OHPAHs than non-smokers (p < 0.001); non-smoker females presented 2-fold lower total OHPAHs (p = 0.049) than males. 1-hydroxypyrene was below the recommended occupational biological exposure value (2.5 µg/L), and the metabolite of carcinogenic PAH (benzo(a)pyrene) was not detected. Blood pressure was above 120/80 mmHg in 71% of subjects. Firefighters from the permanent intervention team presented significantly increased systolic pressure than those who performed other functions (p = 0.034). Tobacco consumption was significantly associated with higher basophils (p = 0.01-0.02) and hematocrit (p = 0.03). No association between OHPAHs and blood pressure was found. OHPAHs concentrations were positively correlated with monocyte, basophils, large immune cells, atypical lymphocytes, and mean corpuscular volume, which were stronger among smokers. Nevertheless, inverse associations were observed between fluorene and pyrene metabolites with neutrophils and eosinophils, respectively, in non-smokers. Hemogram was negatively affected by overworking and lower physical activity. Conclusion: This study suggests possible associations between urinary PAHs metabolites and health parameters in firefighters, that should be further assessed in larger groups.

Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.

Long noncoding RNA expression in acute lymphoblastic leukemia: A systematic review.

Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored current literature on lncRNA expression in ALL to identify lncRNAs consistently reported as differentially expressed (DE) either in ALL versus controls or between ALL subtypes. By comparing articles that provided global expression data for DE lncRNAs in the ETV6::RUNX1-positive ALL subtype, we identified four DE lncRNAs in three independent studies (two versus other subtypes and one versus controls), showing concordant expression of LINC01013, CRNDE and lnc-KLF7-1. Additionally, LINC01503 was consistently downregulated on ALL versus controls. Within RT-qPCR studies, twelve lncRNA were DE in more than one source. Thus, several lncRNAs were supported as DE in ALL by multiple sources, highlighting their potential role as candidate biomarkers or therapeutic targets. Finally, as lncRNA annotation is rapidly expanding, standardization of reporting and nomenclature is urgently needed to improve data verifiability and compilation.

Gynecologic Adnexal Tumors and Tumor-Like Lesions in Children and Adolescents: Experience at a Cancer Center.

Introduction. Tumors and tumor-like lesions of the uterine adnexa in children and adolescents are uncommon but may carry devastating consequences. Methods. We conducted an observational retrospective cohort study, to describe patients aged 0 to 19 years diagnosed with tumors and tumor-like lesions of the uterine adnexa at our institution between 2000 and 2018. Results. Eighty-nine patients with 105 adnexal lesions were included. Thirty-seven (42%) patients presented with benign tumors, 13 (15%) with borderline tumors, 25 (28%) with malignant tumors and 14 (16%) with tumor-like lesions. Germ cell tumors (n = 45|43%) were the most frequent, followed by epithelial tumors (n = 30|29%). No significant differences were found in the age distribution of the lesions by malignant potential or histologic group. Most patients (n = 80|90%) were treated primarily with conservative surgery, including cystectomy (n = 25|28%) and unilateral oophorectomy/adnexectomy (n = 54|61%). Thirty-four (38%) underwent surgical staging (partial omentectomy and peritoneal biopsies). Twenty (23%) patients with borderline and malignant tumors were submitted to chemotherapy. Four (5%) patients with borderline or malignant tumors relapsed, one of whom died from disease. Conclusion. Gynecological lesions in children and adolescents encompass a wide range of rare histological tumor subtypes, requiring evaluation by experienced pathologists. Most tumors were diagnosed at early stages, with low relapse and mortality rates. Conservative management, with fertility sparing surgery and limited use of adjuvant chemotherapy, is of utmost importance.

Current Nursing Education Considering Southern Europe's Reality and Legal Framework: A Two-Phased Research Approach.

Nursing education and formation is still heterogenous in spite of The Bologna Declaration in 1999. Apart from the existence of basic curriculum standards, universities have flexibility regarding its design. The objective of this study is to provide an overview of contemporary nursing education and contrast it with the legal frameworks in place in four Southern European countries: Portugal, Spain, Italy, and Greece. A scoping review was conducted in order to revise and obtain an up-to-date review of current nursing education and quality. Then, a content evaluation of the legal public framework was conducted. A total of nine articles were included in the review. Data analysis evoked three main themes from the results: nursing education heterogeneity owing to ECTS increased from 180 to 240 for the diversity of clinical practice hours; the nursing framework lacked a definition; and the evolution of nursing education, alongside quality improvement and more accurate guidelines were required. Regarding their legal framework, the main directives and legislation standards were assessed and compared with the current curriculum. To conclude, nursing heterogeneity education evokes competence inequality among students and future professionals as larger curricular programs (240 ECTS) offer more clinical practice. Nursing education uniformity could enhance international mobility and promote knowledge exchange and nursing competence framework definitions. These are facts that certainly bring nursing empowerment. This study was not registered.

Economic evaluation of biological treatments in patients with severe asthma: a systematic review.

BACKGROUND: Asthma is a highly prevalent disease, one of the chronic diseases with the highest economic costs; thus, it imposes a high economic burden on society, the healthcare system, patients, and third-party payers. Contrary to this study, until now, systematic reviews of economic evaluations (EEs) of treatments for severe asthma have not been exclusively focused on biological treatments, and have included a small number of studies and only model-based EEs. METHODS: This study systematically reviews EEs of biological therapies for severe asthma published until December 2022 using PRISMA guidelines. The review analyzes the cost-effectiveness of biologicals in comparison to SOC, or SOC plus OCS. The quality of the EEs is assessed using Consensus on Health Economics Checklist extended (CHEC-extended). RESULTS: Thirty-nine studies were eligible: 15 based on a Markov model, and 19 trial-based; eight adopting societal and NHS perspectives, and seven the payer's perspective. The reviewed EEs addressed cost-effectiveness, cost-utility, and incremental costs and outcomes comparison. Their findings were mainly expressed through ICER-incremental cost-effectiveness ratio (24 studies: 13 concluded that biological were cost-effective) and cost comparison analysis (14 studies: 6 concluded that biological were cost-effective), and were sensitive to a wide variety of factors (e.g. medication cost, treatment response, time horizon, utility benefits, mortality, exacerbation rate, discount rate, etc.). CONCLUSIONS: There has been some ambiguity concerning the EE of biological therapies due to variation in choice of study design and contradictory results. Nevertheless, it can be concluded that biological treatments improve health outcomes, in many contexts at a high cost.

Evaluation of a Dementia Training Course for Staff of a Center of Dementia Care.

INTRODUCTION: Literature shows poor dementia training and competencies among health and social professionals. Due to the growing prevalence of people with dementia and all the related care demands, specialized training is increasingly needed but must be effective in terms of impact on knowledge, behaviors, and attitudes. We aimed to analyze the impact of a first-level dementia training course for staff of a new specialized center for people with dementia, considering the first three levels of Kirkpatrick's evaluation framework, namely, staff reaction (satisfaction), skills and learning (knowledge and dementia attitudes), and behavior changes. METHODS: This is a single-center group pre-post design study of a 12-session online course. An online questionnaire was administered to measure satisfaction, expectations, knowledge/learning, attitudes (Dementia Attitude Scale), and new behaviors/practices. We compared perceived knowledge (Wilcoxon signed-rank test) and attitudes (paired t test). Thematic analysis explored new behaviors/practices. RESULTS: Eighty-five professionals and 1 volunteer were included (median age 31, 92% female). Satisfaction with the training was high (median 4/5). Perceived knowledge improved (median 3-4; p < 0.001). The knowledge test median score was 70.8%. After training, participants showed better attitudes toward dementia (mean 116.5, SD 10.3, to mean 122.2, SD 11.5; p < 0.001). Most (93%) said their behavior/practice changed. Thematic analysis yielded four new behavior/practice dimensions: care provision/interaction, communication, family/caregivers, and self-confidence. CONCLUSIONS: The course improved all dimensions evaluated, suggesting it effectively provides first-level dementia training. This may be transferable to similar settings.

Exploring Clinical Trials to Manage Firefighters' Sleep Quality: A PRISMA Compliant Systematic Review.

Sleep research has grown over the past decades and investigators are deeply involved in studying sleep and its impact on human health and body regulation. Despite the understanding that insufficient sleep is strongly linked to the development of several disorders, unsatisfactory sleep exposes health and safety to innumerous risks. The present study aims to review and analyze the main results of clinical trials, registered at ClinicalTrials.gov and ICTRT databases, and developed construct strategies to improve sleep quality on firefighters and enhance professionals' sleep and health conditions. The protocol was registered in PROSPERO under number CRD42022334719. Trials registered between first registry and 2022 were included. We retrieved 11 registered clinical trials; seven met eligibility criteria and were included in the review. A relation between sleep disorders, shift work, and occupational health problems was found, and retrieved trials showed that sleep education programs can improve sleep quality and sleep hygiene. Science has already recognized sleep's importance for metabolic functioning and survivorship. Nevertheless, it continues to play a major role in discovering methods to diminish the problems faced. Strategies contemplating sleep education, or intervention, should be presented to fire services to tackle this problem and promote healthier and safer environments.

The Psychological Science Accelerator's COVID-19 rapid-response dataset.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.

Effect of carbohydrate mouth rinse on muscle strength and muscular endurance: A systematic review with meta-analysis.

The present systematic review with meta-analysis summarized studies that investigated the effect of carbohydrate (CHO) mouth rinse on muscle strength and muscular endurance. The search was performed in six databases. Thirteen randomized clinical trials were selected and the standardized mean difference between CHO mouth rinse and placebo for maximal strength and muscular endurance was determined via a random-effects model using Review Manager 5.4 software. Meta-regression was also performed to explore the influence of load, number of sets, number of exercises, fasting time, CHO concentration, and number of mouth rinses on the main outcomes. There was no significant effect of CHO mouth rinse on maximal strength (mean difference= 0.25 kg, 95%CI - 1.81 to 2.32 kg, z = 0.24, p = 0.810). However, there was a significant positive effect of CHO mouth rinse on muscular endurance (mean difference = 1.24 repetitions, 95%CI 0.70 to 1.77 repetitions, z = 4.55, p < 0.001). Meta-regression identified that CHO mouth rinse has greater benefits on muscular endurance when using high workloads, multiple exercises, and a smaller number of mouth rinses (p = 0.001). In conclusion, CHO mouth rinse has no effect on maximal muscle strength but has a positive effect on muscular endurance and seems to optimize when fewer mouth rinses, high workloads and numbers of exercises are used.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2057417.

Willingness to institutionalize a relative with dementia: a web-platform assessment with the Portuguese adapted version of the Desire-to-Institutionalize Scale.

Introduction: Older persons with dementia (PwD) are more likely to be institutionalized than their counterparts without dementia. The caregiver's desire to institutionalize has been suggested as the most important predictor of actual institutionalization. This cross-sectional study aimed to culturally adapt the Desire to Institutionalize Scale (DIS) to a country with a high prevalence of dementia (Portugal) and examine its psychometric properties. Methods: The reliability, structural validity, and criterion validity of the DIS-PT were assessed by applying the scale using a remote measurement web platform. A sample of 105 dementia caregivers completed the DIS-PT and several psychosocial measures, including caregiver burden, anxiety, depression, quality of life, PwD functional independence, and neuropsychiatric symptoms. Results: The DIS-PT demonstrated good structural validity, with one factor explaining 75% of the total variance. The internal consistency of the scale was high (α = 0.802). Most caregivers (65.7%) endorsed at least one item on the DIS-PT (Mdn 2). The caregiver's desire to institutionalize was significantly associated with the caregiver, care recipient, and contextual variables previously known to affect institutional placement. These included the caregivers' occupational status, perceived burden, anxiety (but not depression), physical and psychological quality of life, care recipient education, severity of neuropsychiatric symptoms, and cohabitation with the caregiver. Discussion: This study offers preliminary support for the psychometric quality of the DIS-PT. The scale has practical applications in the early identification of caregivers considering nursing home placement, providing room for intervention in modifiable risk factors that may otherwise lead to the institutionalization of PwD. Remote measurement tools may hold value in assessing caregiving dyads non-intrusively and inexpensively.

Genetic Association and Differential RNA Expression of Histone (De)Acetylation-Related Genes in Pemphigus Foliaceus-A Possible Epigenetic Effect in the Autoimmune Response.

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4+ T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B, PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.

Ações educativas como possibilidade de repensar a sexualidade da pessoa idosa / Educational actions as a possibility of rethinking the sexuality of the elderly person / Acciones educativas como posibilidad para repensar la sexualidad de las personas mayores

Objetivo: descrever atividades educativas sobre a sexualidade desenvolvidas com os idosos. Método: Trata-se de a um estudo descritivo, com abordagem qualitativa, fundamentado nos pressupostos da pesquisa-ação, mediada pelo questionamento se as atividades podem possibilitar o repensar sobre a sexualidade da pessoa idosa. Resultados: As atividades desenvolvidas permitiram que os participantes pudessem ter uma visão diferenciada e uma compreensão maior sobre o que realmente significa sexualidade, e como ela está diretamente envolvida com o processo de envelhecimento, proporcionando a concepção de que a sexualidade pode ser vivida em qualquer fase da vida e de várias formas. Conclusão: Notou-se, após as atividades educativas desenvolvidas, não somente a melhor compreensão sobre a temática, mas a ruptura do receio de falar sobre um assunto permeado de tabus nesse segmento populacional (AU).

Objective: to describe educational activities about sexuality developed with the elderly. Method: This is a descriptive study, with a qualitative approach, based on the assumptions of action research, mediated by questioning whether the activities can enable rethinking about the sexuality of the elderly. Results: The activities developed allowed the participants to have a different view and a greater understanding of what sexuality really means, and how it is directly involved with the aging process, providing the conception that sexuality can be experienced at any stage of life and of shapes. Conclusion: It was noted, after the educational activities developed, not only a better understanding of the theme, but the fear of talking about a subject permeated by taboos in this population segment (AU).

Objetivo: describir actividades educativas sobre sexualidad desarrolladas con ancianos. Método: Se trata de un estudio descriptivo, con abordaje cualitativo, pautado en los supuestos de la investigación-acción, mediada por el cuestionamiento de si las actividades pueden posibilitar repensar la sexualidad de los ancianos. Resultados: Las actividades desarrolladas permitieron a los participantes tener una mirada diferente y una mayor comprensión de lo que realmente significa la sexualidad, y cómo ella está directamente involucrada con el proceso de envejecimiento, brindando la concepción de que la sexualidad puede ser experimentada en cualquier etapa de la vida y de formas. Conclusión: Se constató, después de las actividades educativas desarrolladas, no sólo una mejor comprensión del tema, sino el temor de hablar sobre un tema permeado por tabúes en este segmento de la población (AU).

Transition to bereavement: A prospective longitudinal study of health-related quality of life in informal caregivers of oldest-old individuals.

Introduction: Experiencing bereavement may be challenging. Despite the oldest-old population increase, a subgroup at greater risk of death, few studies focus on the grieving process of informal caregivers (ICs). This study analyzed the transition to bereavement of ICs of oldest-old individuals (≥80 years) over 1-year and compares the evolution of the health-related quality of life (HrQoL) between those experiencing bereavement and those who continued care through the study period. Materials and methods: A prospective longitudinal observational study was conducted enrolling 204 ICs of the Metropolitan Area of Porto (North Portugal), of which 36 experienced the death of care receiver (CR). ICs' health profile and burden were assessed. CRs' functional and cognitive status were also appraised. Results: Bereaving caregivers were mostly female, CRs' children, and had on average 60.4 years at baseline. Caregivers spent a mean of 10.1 h/day (SD = 7.7) caring, for 80.6 months (SD = 57.5). The time elapsed since CR's death was 6 months (SD = 3.5) from entering in the study. CRs who died had a mean age of 88.3 (SD = 5.4) years at baseline, and were very dependent. Over a 1-year follow-up, bereaving caregivers showed a significant decrease in mental health following CR's death; on the other hand, caregivers who continued caring improved mental health [F(1, 159) = 4.249, p = 0.041]. Discussion: Ending the caregiver career was marked by a decline in mental health whereas to continue caring was marked by an improvement in this outcome. While it is highly expected that the CR's death will be perceived as a relief considering both the caregiver's characteristics (e.g., medicines) and the CR condition (e.g., high dependence levels), the results suggest an opposite direction. CRs' death seems to arise an emotional burden for IC, at least during the first year, possibly triggering feelings of loneliness and a life without purpose that seems to aggravate mental health issues. Conclusion: The transition to bereavement among ICs seems to lead to a caregiver mental health decline while those who continued caring (and thereby, experiencing caregiving stressors) seems to improve in this outcome. Ceasing caregiving stressors does not seem to contribute better experiencing bereavement among ICs, suggesting the need for support throughout this phase.