Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis.

Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Ferritin heavy chain supports stability and function of the regulatory T cell lineage.

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.

A cross-sectional study in critically ill patients affected by COVID-19 in an intensive care unit: would Acinetobacter baumannii resistant to carbapenems be the biggest villain?

AIM: to describe cases of infection of Acinetobacter baumannii (A. baumannii) in critically ill patients affected by COVID-19, admitted to an intensive care unit (ICU), using dexamethasone. METHODOLOGY: cross-sectional study conducted on patients admitted to the intensive care unit COVID-19 survey among hospitalized patients from November 2020 to March 2021. SETTING: large hospital, reference for caring for patients with COVID-19 in Bahia (Brazil). PATIENTS: a convenience sample of 22 patients admitted to the COVID ICU signed the consent form agreeing to participate in the study. Three patients were excluded for having decided to participate without signing the form. RESULTS: of the 22 patients listed, 45 % (10) had blood infection or mechanical ventilation-associated pneumonia by A. baumannii in blood cultures and/or tracheal aspirate secretion. We observed that there is a moderate correlation between the length of stay and infection by A. baumannii (Spearman's ρ; 0.592; p-value<0.005) and a strong correlation between the number of days on mechanical ventilation and infection by these bacteria (Spearman's ρ; 0.740; p-value<0.001). This percentage is higher than the value of 0.62 % of infection by A. baumannii in this ICU in the same period of the year before COVID-19 (p-value<0.0001). CONCLUSIONS: hospitals that receive patients with COVID-19 may be vulnerable to outbreaks of multi-drug resistant organisms, such as A. baumannii . It is worth reflecting on the care and operational practices in handling these patients, especially in isolation and restriction measures for those from other nosocomial areas.

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.

Influence of excessive daytime sleepiness on the treatment adherence of obstructive sleep apnea.

OBJECTIVES: To compare positive airway pressure (PAP) adherence between patients with or without excessive daytime sleepiness (EDS) in mild, moderate and severe obstructive sleep apnea (OSA). METHODS: Patients ≥18 years diagnosed with OSA in 2018 and 2019, without previous history of PAP usage and with adherence registration in the first medical consultation after treatment initiation, were included. EDS was defined as a score of ≥10 on the Epworth Scale. Patients were divided into two groups according to the adherence to PAP: "Adherent" if using the device for ≥4 h for ≥70% of the nights and "Nonadherent" otherwise. Simple and multiple logistic regression models for adherence were determined. RESULTS: 321 patients were included, most male (64.2%), with mean age 56.56 years. Most patients had severe OSA (n = 159; 49.5%), and median AHI was 29.3/h [16.8; 47.5]. Being older or having a severe OSA resulted in an increased adherence (OR = 1.020, CI95% = [1.002; 1.039] and OR = 2.299, CI95% = [1.273; 4.191], respectively). In patients without EDS a statistically significant difference was found in adherence between those with severe OSA and both mild and moderate OSA categories (OR = 0.285, p = 0.023 and OR = 0.387, p = 0.026, respectively), with patients with severe OSA being adherent. There was no statistical difference in adherence between patients with or without EDS (OR 1.083; p = 0.876), nor in the different degrees of severity in those with EDS. CONCLUSION: In our study there were no differences in PAP therapy adherence between patients with or without excessive daytime sleepiness. Older age and higher OSA severity resulted in higher adherence rates.

Preventive measures for the progression of dysphagia in patients with cancer of head and neck subjected to radiotherapy: a systematic review with meta-analysis. / Medidas de prevenção da progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia: uma revisão sistemática com meta-análise.

PURPOSE: To identify the effects of prophylactic, non-pharmacological measures on the progression of dysphagia in patients with head and neck cancer undergoing radiotherapy. RESEARCH STRATEGIES: The search was performed in Medline (via PubMed), Scopus, and Embase databases, as well as in the gray literature. SELECTION CRITERIA: Randomized clinical trials were included, with adult patients (≥ 18 years old) and diagnosed with head and neck cancer, treated with radiotherapy (with or without surgery and chemotherapy), and submitted to non-pharmacological protocols for the prevention of dysphagia. DATA ANALYSIS: The risk of bias was assessed using the PEDRO scale and the overall quality of evidence was assessed using the GRADE instrument. RESULTS: Four studies were considered eligible, and of these, two were included in the meta-analysis. The result favored the intervention group, with a mean difference of 1.27 [95% CI: 0.74 to 1.80]. There was low heterogeneity and the mean score for risk of bias was 7.5 out of 11 points. The lack of detail in the care with selection, performance, detection, attrition, and reporting biases contributed to the judgment of the quality of the evidence, considered low. CONCLUSION: Prophylactic measures to contain dysphagia can promote important benefits on the oral intake of patients with head and neck cancer when compared to those who did not undergo such a therapeutic measure during radiotherapy.

OBJETIVO: Identificar os efeitos de medidas profiláticas, não farmacológicas, sobre a progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia. ESTRATÉGIA DE PESQUISA: A busca foi realizada nas bases de dados Medline (via PubMed), Scopus e Embase, assim como na literatura cinzenta. CRITÉRIOS DE SELEçÃO: Foram incluídos ensaios clínicos randomizados, com pacientes adultos (≥ 18 anos) e diagnóstico de câncer de cabeça e pescoço, tratados com radioterapia (associada ou não à cirurgia e quimioterapia) submetidos a protocolos não farmacológicos de prevenção da disfagia. ANÁLISE DOS DADOS: O risco de viés foi avaliado por meio da escala PEDRO e a qualidade global da evidência foi avaliada de acordo com o instrumento GRADE. RESULTADOS: Foram considerados elegíveis 4 estudos, e desses, dois foram incluídos na metanálise. O resultado favoreceu o grupo intervenção, com diferença média de 1,27 [IC 95%: 0,74 à 1,80]. Houve baixa heterogeneidade e a pontuação média para risco de viés foi de 7,5 de um total de 11 pontos. A falta de detalhamento nos cuidados com os vieses de seleção, performance, detecção, atrito e de relato contribuíram para o julgamento da qualidade da evidência, considerada baixa. CONCLUSÃO: Medidas profiláticas de contenção da disfagia podem promover importantes benefícios sobre a ingesta oral dos pacientes com câncer de cabeça e pescoço, quando comparados aqueles que não realizaram tal medida terapêutica ao longo da radioterapia.

Conciliação medicamentosa na admissão de pacientes transplantados renais em um hospital universitário / Medication reconciliation in the admission of kidney transplant patients to a university hospital

Introdução:O presente estudo considerou conciliações medicamentosas realizadas na admissão hospitalar de pacientes transplantados renais e intervenções farmacêuticas decorrentes desse processo.Métodos:Trata-se de um estudo transversal realizado no período de julho de 2018 a julho de 2019 no Hospital de Clínicas de Porto Alegre. Foram coletadas as características dos pacientes, as conciliações medicamentosas realizadas pelo farmacêutico clínico, as discrepâncias identificadas pelo mesmo (intencionais e não intencionais) e o resultado das intervenções. Os medicamentos foram classificados de acordo com a Anatomic Therapeutic Chemical (ATC).Resultados:Dos 719 pacientes acompanhados pelo farmacêutico clínico, 175 tiveram a conciliação medicamentosa de admissão realizada, desses, 56 apresentaram discrepâncias não intencionais. Encontramos a média de 2,2 medicamentos omissos por prescrição com desvio padrão de 1,3 medicamentos. No total, foram realizadas 122 intervenções farmacêuticas, sendo que em 61,5% houve adesão por parte da equipe médica. A classe terapêutica com maior ocorrência (43,4%) de discrepâncias não intencionais foi a que atuava sobre o aparelho cardiovascular. As variáveis observadas foram sexo, número de medicamentos nas intervenções (ambas com associação significativa com a adesão médica), idade, tempo de internação, número de medicamentos na internação e número de medicamentos de uso prévio (estas últimas sem associação significativa com a adesão médica). Conclusões:A conciliação medicamentosa previne possíveis erros de medicação, uma vez que a identificação das discrepâncias não intencionais na prescrição médica gera sinalizações que são levadas pelo farmacêutico clínico à equipe assistente, a fim garantir o uso seguro e correto dos medicamentos durante a internação hospitalar.

Introduction:This study considered medication reconciliations performed on hospital admission of kidney transplant patients and pharmaceutical interventions resulting from this process.Methods:This is a cross-sectional study carried out from July 2018 to July 2019 at Hospital de Clínicas de Porto Alegre. The characteristics of the patients, the medication reconciliations performed by the clinical pharmacist, the discrepancies identified by the same (intentional and unintentional) and the result of the interventions were collected. The drugs were classified according to the Anatomic Therapeutic Chemical (ATC). Results:Of the 719 patients monitored by the clinical pharmacist, 175 had medication reconciliation on admission performed, of which 56 had unintentional discrepancies. We found an average of 2.2 missing medications per prescription with a standard deviation of 1.3 medications. In total, 122 pharmaceutical interventions were performed, and in 61.5% there was adherence by the medical team. The therapeutic class with the highest occurrence (43.4%) of unintentional discrepancies was that which acted on the cardiovascular system. The variables observed were gender, number of medications in interventions (both with a significant association with medical adherence), age, length of stay, number of medications in hospitalization and number of medications previously used (the latter without a significant association with medical adherence).Conclusions:Medication reconciliation prevents possible medication errors, since the identification of unintentional discrepancies in the medical prescription generates signals that are taken by the clinical pharmacist to the assistant team, in order to guarantee the safe and correct use of medications during hospitalization.

Medidas de prevenção da progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia: uma revisão sistemática com meta-análise / Preventive measures for the progression of dysphagia in patients with cancer of head and neck subjected to radiotherapy: a systematic review with meta-analysis

RESUMO Objetivo Identificar os efeitos de medidas profiláticas, não farmacológicas, sobre a progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia. Estratégia de pesquisa A busca foi realizada nas bases de dados Medline (via PubMed), Scopus e Embase, assim como na literatura cinzenta. Critérios de seleção Foram incluídos ensaios clínicos randomizados, com pacientes adultos (≥ 18 anos) e diagnóstico de câncer de cabeça e pescoço, tratados com radioterapia (associada ou não à cirurgia e quimioterapia) submetidos a protocolos não farmacológicos de prevenção da disfagia. Análise dos dados O risco de viés foi avaliado por meio da escala PEDRO e a qualidade global da evidência foi avaliada de acordo com o instrumento GRADE. Resultados Foram considerados elegíveis 4 estudos, e desses, dois foram incluídos na metanálise. O resultado favoreceu o grupo intervenção, com diferença média de 1,27 [IC 95%: 0,74 à 1,80]. Houve baixa heterogeneidade e a pontuação média para risco de viés foi de 7,5 de um total de 11 pontos. A falta de detalhamento nos cuidados com os vieses de seleção, performance, detecção, atrito e de relato contribuíram para o julgamento da qualidade da evidência, considerada baixa. Conclusão Medidas profiláticas de contenção da disfagia podem promover importantes benefícios sobre a ingesta oral dos pacientes com câncer de cabeça e pescoço, quando comparados aqueles que não realizaram tal medida terapêutica ao longo da radioterapia.

ABSTRACT Purpose To identify the effects of prophylactic, non-pharmacological measures on the progression of dysphagia in patients with head and neck cancer undergoing radiotherapy. Research strategies The search was performed in Medline (via PubMed), Scopus, and Embase databases, as well as in the gray literature. Selection criteria Randomized clinical trials were included, with adult patients (≥ 18 years old) and diagnosed with head and neck cancer, treated with radiotherapy (with or without surgery and chemotherapy), and submitted to non-pharmacological protocols for the prevention of dysphagia. Data analysis The risk of bias was assessed using the PEDRO scale and the overall quality of evidence was assessed using the GRADE instrument. Results Four studies were considered eligible, and of these, two were included in the meta-analysis. The result favored the intervention group, with a mean difference of 1.27 [95% CI: 0.74 to 1.80]. There was low heterogeneity and the mean score for risk of bias was 7.5 out of 11 points. The lack of detail in the care with selection, performance, detection, attrition, and reporting biases contributed to the judgment of the quality of the evidence, considered low. Conclusion Prophylactic measures to contain dysphagia can promote important benefits on the oral intake of patients with head and neck cancer when compared to those who did not undergo such a therapeutic measure during radiotherapy.

Impact of COVID-19 pandemic on the mental health of healthcare workers during the first wave in Portugal: a cross-sectional and correlational study.

OBJECTIVES: The COVID-19 pandemic has had a negative impact on the mental health of healthcare workers (HCWs) worldwide. This study aims to identify the degree to which sociodemographic variables and indicators of subjective well-being and psychological resilience are associated, positively and negatively, with the outcomes of burnout, stress, depression and anxiety among Portuguese HCWs observed during the first wave. It also aims to evaluate the strength of association of these variables and indicators with each outcome. DESIGN: Cross-sectional quantitative study. The statistical methods used are simple logistic model, multiple logistic regression model and -2*log-likelihood statistic. SETTING: Portuguese HCWs living in Portugal and working in the Portuguese healthcare system. PARTICIPANTS: The study included 1535 professionals, with a mean age of 38 years. PRIMARY AND SECONDARY OUTCOMES MEASURES: Psychological variables were measured by Copenhagen Burnout Inventory, the Resilience Scale, the Depression, Anxiety and Stress Scales and the Satisfaction with Life Scale. RESULTS: High levels of personal (55%; n=844), work-related (55.1%; n=846) and client-related burnout (35.4%; n=543) were found. Additionally, participants expressed substantial levels of depression (28.7%; n=441), stress (36.4%; n=558) and anxiety (33.1%; n=508). About 1202 participants (78.3%) demonstrated moderate-to-high levels of resilience. Profession, work regime during the pandemic, having a health problem, resilience and satisfaction with life are independent variables significantly associated with the outcomes of burnout, stress, depression and anxiety. Satisfaction with life was the independent variable that had a major association with all outcomes. CONCLUSIONS: Governments and hospital administrations should take action to promote resilience and satisfaction with life as these variables are protective relating to mental health problems. Interventions as educational sessions, psychological support at work, programmes promoting resilience and coping mechanisms and better work conditions may improve mental health. The implementation of measures to protect healthcare students from developing prejudicial outcomes seams very adequate and important.

IL-7 Receptor Drives Early T Lineage Progenitor Expansion.

IL-7 and IL-7R are essential for T lymphocyte differentiation by driving proliferation and survival of specific developmental stages. Although early T lineage progenitors (ETPs), the most immature thymocyte population known, have a history of IL-7R expression, it is unclear whether IL-7R is required at this stage. In this study, we show that mice lacking IL-7 or IL-7R have a marked loss of ETPs that results mostly from a cell-autonomous defect in proliferation and survival, although no changes were detected in Bcl2 protein levels. Furthermore, a fraction of ETPs responded to IL-7 stimulation ex vivo by phosphorylating Stat5, and IL-7R was enriched in the most immature Flt3+Ccr9+ ETPs. Consistently, IL-7 promoted the expansion of Flt3+ but not Flt3- ETPs on OP9-DLL4 cocultures, without affecting differentiation at either stage. Taken together, our data show that IL-7/IL-7R is necessary following thymus seeding by promoting proliferation and survival of the most immature thymocytes.

Home-based transcranial direct current stimulation in dual active treatments for symptoms of depression and anxiety: A case series.

Transcranial direct current stimulation (tDCS) is a potential treatment strategy across some psychiatric conditions. However, there is high heterogeneity in tDCS efficacy as a stand-alone treatment. To increase its therapeutic potential, researchers have begun to explore the efficacy of combining tDCS with psychological and pharmacological interventions. The current case series details the effect of 6-10 weeks of self-administered tDCS paired with a behavioral therapy smartphone app (Flow™), on depressive and anxiety symptoms, in seven patients (26-51 years old; four female) presenting distinctive psychiatric disorders (major depression, dysthymia, illness anxiety disorder, obsessive-compulsive disorder, and anxiety disorders). tDCS protocol consisted of an acute phase of daily 30 min sessions, across 10 workdays (2 weeks Monday-to-Friday; Protocol 1) or 15 workdays (3 weeks Monday-to-Friday; Protocol 2). A maintenance phase followed, with twice-weekly sessions for 4 or 3 weeks, corresponding to 18 or 21 sessions in total (Protocol 1 or 2, respectively). The Flow tDCS device uses a 2 mA current intensity, targeting the bilateral dorsolateral prefrontal cortex. The Flow app offers virtually guided behavioral therapy courses to be completed during stimulation. We assessed depressive symptoms using MADRS-S and BDI-II, anxious symptoms using STAI-Trait, acceptability using ACCEPT-tDCS, and side effects using the Adverse Effects Questionnaire, at baseline and week 6 of treatment. Six patients underwent simultaneous cognitive-behavioral psychotherapy and two were on antidepressants and benzodiazepines. According to the Reliable Change Index (RCI), for depressive symptoms, we found clinically reliable improvement in five patients using MADRS-S (out of seven; RCI: -1.45, 80% CI; RCI: -2.17 to -4.82, 95% CI; percentage change: 37.9-66.7%) and in four patients using BDI-II (out of five; RCI: -3.61 to -6.70, 95% CI; percentage change: 57.1-100%). For anxiety symptoms, clinically reliable improvement was observed in five patients (out of six; RCI: -1.79, 90% CI; RCI: -2.55 to -8.64, 95% CI; percentage change: 12.3-46.4%). Stimulation was well-tolerated and accepted, with mild tingling sensation and scalp discomfort being the most common side effects. This case series highlights the applicability, acceptability, and promising results when combining home-based tDCS with psychotherapy and pharmacotherapy to manage depression and anxiety symptoms in clinical practice.

Educar para a bioética: desafio em enfermagem / Educating for bioethics: a challenge in nursing / Educar en bioética: desafío en la enfermería

Resumo Educar para a bioética é um desafio na atualidade. Ainda maior se torna este desafio, quando pensamos no ensino da bioética a estudantes de enfermagem, que irão desempenhar uma profissão que tem como expoente máximo o cuidar da outra pessoa. Tratando-se de uma profissão que implica a relação com o outro e a prestação de cuidados humanizados e adequados a cada situação específica, torna-se importante desenvolver ferramentas de ensino que promovam não só o desenvolvimento técnico e o conhecimento de como fazer, mas essencialmente o desenvolvimento de competências morais, pessoais e profissionais que conduzam a cuidados de saúde de excelência. Este artigo pretende apresentar uma reflexão sobre o ensino da bioética e a sua relação com o desenvolvimento da competência moral dos estudantes de enfermagem, assim como sugerir algumas estratégias no ensino da Bioética que potenciem a formação de enfermeiros cada vez mais competentes.

Abstract Educating for bioethics is a challenge today. This challenge is even greater when we think of the teaching of bioethics to nursing students, who will perform a profession that has as its maximum target the care of other people. Because it is a profession that implies the relationship with the other and the provision of humanized and appropriate care to each situation, it is important to develop teaching tools that promote not only technical improvement and knowledge of how to do a task, but also the development of moral, personal and professional skills that lead to excellent health care. This article presents a reflection on the teaching of bioethics and its relationship with the development of moral competence of nursing students, suggesting some strategies that enhance the teaching of bioethics and the education of increasingly competent nurses.

Resumen Educar en bioética es un desafío en la actualidad. Esto se vuelve más grande cuando pensamos en la enseñanza de bioética a estudiantes de enfermería, quienes desempeñarán una profesión que tiene la máxima expresión la asistencia a las personas. Por ser una profesión que involucra la relación con el otro y la prestación de una asistencia humanizada y adecuada a cada situación específica, es importante desarrollar herramientas didácticas que promuevan no solo el desarrollo técnico y el conocimiento de cómo hacerlo, sino fundamentalmente el desarrollo de competencias morales, personales y profesionales que promuevan una excelente atención en salud. Este artículo reflexiona sobre la enseñanza de la bioética y su relación con el desarrollo de la competencia moral de los estudiantes de enfermería, así como sugiere algunas estrategias para la enseñanza de la Bioética que promueva una formación de profesionales cada vez más competentes.

The mediating role of life satisfaction in the relationship between depression, anxiety, stress and burnout among Portuguese nurses during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic had a large consequence on healthcare systems, increasing the risks of psychological issues in health professionals. Nurses, in particular, have been exposed to multiple psychosocial stressors and struggled with intensive work, insufficiency of resources and uncertainty in the face of an unknown disease. Life satisfaction might protect nurses from the consequences of chronic stress. The aim of this study was to explore the mediating role of satisfaction with life in the relationship between depression, stress, anxiety and burnout (personal, work-related, and client-related). METHODS: A cross-sectional, descriptive, correlational study design was performed, using an online questionnaire distributed via social networks. A total of 379 nurses completed the survey, comprising standardized measures of satisfaction with life, resilience (Resilience Scale), depression, anxiety, stress (Depression Anxiety Stress Scales), and burnout (Copenhagen Burnout Inventory Scale). A hierarchical regression model was estimated for each burnout dimension. RESULTS: Participants showed high levels of work, personal and client-related burnout, 57.3%, 57%, and 35.1%, respectively. More than 70% of the respondents had a normal level of depressive symptoms, 66.8% presented normal level of anxiety and 33.5% of the respondents reported mild, moderate, severe or extremely severe symptoms of stress. The results revealed that life satisfaction partially mediated the association between stress and personal burnout, depression and work-related burnout, and the association between anxiety and client-related burnout in nurses. CONCLUSIONS: The COVID-19 pandemic brought added difficulties for nurses' work conditions, whereby it became necessary to develop adaptative measures that reduce stressors in work environment and promote nurses' life satisfaction.

Seasonal semen quality of a local and commercial taurine cattle breeds, raised in a subtropical climate: Relationship between external morphology of the animals and climate.

Livestock production is considered an important factor influencing global warming; however, climate change has also been considered one of the major factors affecting livestock production and reproduction. The present study was carried out in the Southern region of Brazil and aimed to assess the seasonal influence of climatic factors and external morphology of the animals on the semen quality. Three ejaculates were obtained from each bull (Crioulo Lageano and Angus) in summer and winter seasons. Motile cells, sperm vigor, sperm concentration, sperm membrane status, and sperm abnormalities were analyzed in fresh and post-thawed semen. In addition, the sperm kinetics using CASA was assessed on post-thawed semen. Environmental data such as air temperature (AT), relative humidity (RH), mean radiant temperature (MRT) and temperature-humidity index (THI) were measured. Furthermore, body and testicular metrics, as well as hair coat characteristics, were recorded in each season on all bulls. Environmental traits differed significantly between seasons. Results of the PLS regression and Spearman's correlations confirmed a negative relationship between climatic variables and sperm traits in both seasons. Semen quality between breeds and seasons was similar, satisfactory, and heat stress was not sufficient to impair spermatozoa viability. External morphological traits were considered non-important in the final model. The findings of this study suggest that AT, MRT, and THI were the most important factors that could affect seminal characteristics of bulls raised in a subtropical climate.

Professional Quality of Life Among Physicians and Nurses Working in Portuguese Hospitals During the Third Wave of the COVID-19 Pandemic.

BACKGROUND: In the last 2 weeks of January 2021, Portugal was the worst country in the world in incidence of infections and deaths due to COVID-19. As a result, the pressure on the healthcare system increased exponentially, exceeding its capacities and leaving hospitals in near collapse. This scenario caused multiple constraints, particularly for hospital medical staff. Previous studies conducted at different moments during the pandemic reported that COVID-19 has had significant negative impacts on healthcare workers' psychological health, including stress, anxiety, depression, burnout, post-traumatic stress symptoms, and sleep disturbances. However, there are many uncertainties regarding the professional quality of life of hospital nurses and physicians. To address gaps in previous research on secondary traumatic stress, we focused on healthcare workers working in hospitals affected by a major traumatic event: the third wave of COVID-19. OBJECTIVES: The aim of the present study was to identify the contribution of personal and work-related contextual variables (gender, age, parental status, occupation, years of experience, working with patients affected by COVID-19) on professional quality of life of healthcare workers. METHODS: Cross-sectional study with a web-based questionnaire given to physicians and nurses working in a hospital setting. A total of 853 healthcare professionals (276 physicians and 586 nurses; median age 37 years old) participated in the survey assessing professional quality of life compassion satisfaction, secondary traumatic stress, and burnout. Factors of professional quality of life were assessed using regression analysis. RESULTS: Most of the participants showed moderate (80%; n = 684) or high (18%; n = 155) levels of compassion satisfaction, whereas the majority of them experienced moderate levels of burnout (72%; n = 613) and secondary traumatic stress (69%; n = 592). The analyzed variables demonstrated no differences between professionals who were directly or not involved in the care of COVID-19 patients. Parental status was found to be a significant factor in compassion satisfaction. Female gender was significantly associated with more susceptibility to secondary traumatization. Factors that may potentially contribute to burnout include years of professional experience and the number of work hours per week. CONCLUSION: The COVID-19 pandemic has created a new challenge for the healthcare system. Burnout and secondary traumatic stress can lead to medical errors and impact standards of patient care, particularly compromising compassionate care. It is therefore recommended that hospitals develop psychoeducational initiatives to support professionals in dealing with barriers to compassion.

Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER+/HER2- Breast Cancer.

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER+/HER2- breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers. EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2- primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1. RESULTS: Higher baselines ER and PgR were significantly associated with a greater chance of complete cell-cycle arrest (CCCA: Ki67 <2.7%) at 14 weeks and higher baseline Ki67, c-PARP, and CCNE1 with a lower chance. The interaction with treatment was significant only for c-PARP. CCND1 levels were decreased c.20% by letrozole at 2 and 14 weeks but showed a tendency to increase with palbociclib. CCNE1 levels fell 82% (median) in tumors showing CCCA but were unchanged in those with no CCCA. Only 2/9 tumors showed CCCA 3-9 days after stopping palbociclib. ESR1 mutations were found in 2/4 tumors for which surgery took place ≥6 months after starting treatment. CONCLUSIONS: High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3-9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the "off" week of its schedule.

Atuação fonoaudiológica em pacientes com câncer de esôfago submetidos a tratamento radioterápico: Série de casos / Speech therapy performance in patients with esophagus cancer receiving radiotherapy treatment: A case series / Actuación fonoaudiológica en pacientes con cáncer de esófago en radioterapia: Serie de casos

Introdução: A atuação fonoaudiológica na disfagia decorrente do câncer de esôfago ainda é recente. Não foi encontrado até o momento, estudos que descrevam a atuação fonoaudiológica em pacientes com câncer de esôfago submetidos a radioterapia. Sendo assim, este trabalho teve como objetivo descrever a atuação fonoaudiológica em pacientes com câncer de esôfago, submetidos a tratamento radioterápico com queixa de disfagia. Métodos: Trata-se de uma série de cinco casos, que receberam acompanhamento fonoaudiológico ambulatorial. Os pacientes foram avaliados por meio de avaliação clínica da deglutição, classificação do grau de alteração de deglutição com aplicação de escala visual analógica e protocolos de qualidade de vida utilizados na área da oncologia. Foram submetidos ainda a uma abordagem terapêutica para deglutição. Resultados: Os pacientes obtiveram melhora da deglutição, apresentando, ao término do tratamento, diminuição dos sintomas de disfagia, possibilidade de ingesta de alimentos via oral e melhora da qualidade de vida. Conclusão: A fonoterapia, compreendendo a avaliação clínica da deglutição, seguida de treino da deglutição e exercício miofuncional para abertura do esfíncter esofágico superior (Shaker), auxiliou na reabilitação da disfagia esofágica.

Introduction: Speech therapy performance in dysphagia resulting from esophageal cancer is still a recent subject. To date, there are no studies describing the speech therapy performance of patients with esophageal cancer undergoing radiotherapy. For this reason, the aim of this study was to describe speech therapy performance in patients with esophageal cancer receiving radiotherapy treatment and with complaints of dysphagia. Methods: This is a series of five cases, with patients that received outpatient speech therapy. The patients were assessed using clinical swallowing evaluation, classification of the degree of swallowing alteration with application of visual analog scale and quality of life protocols used in oncology. They also underwent a therapeutic approach to swallowing. Results: The patients' swallowing was improved and, at the end of the treatment, there were reduced symptoms of dysphagia, possibility of oral intake of food and improved quality of life. Conclusions: Speech therapy, comprising the clinical assessment of the swallowing function, followed by swallowing training and myofunctional exercise to open the upper esophageal sphincter, supported the rehabilitation of esophageal dysphagia.

Introducción: La actuación fonoaudiológica en disfagia decurrente de cáncer del esófago es todavía reciente. Hasta ahora, no se han encontrado estudios que describan la actuación fonoaudiológica en pacientes con cáncer de esófago sometidos a radioterapia. De esta forma, este trabajo tuvo como objetivo describir la actuación del fonoaudiologo en pacientes con cáncer de esófago sometidos a tratamiento de radioterapia con queja de disfagia.Métodos: Esta es una serie de cinco casos, que recibieron terapia fonoaudiologica en ambulatorio. Los pacientes fueron evaluados mediante evaluación clínica de deglución, clasificación del nivel de alteración de la deglución con aplicación de escala visual analógica y protocolos de calidad de vida utilizados en el área de oncología. También fueron sometidos a un enfoque terapéutico para la deglución. Resultados: Los pacientes mejoraron su deglución, presentando, al final del tratamiento, una reducción en los síntomas de disfagia, la posibilidad de ingesta de alimentos por vía oral y una mejora en la calidad de vida. Conclusión: La terapia fonoaudiologica, que comprende la evaluación clínica de deglución, seguida del entrenamiento de deglución y ejercicio miofuncional para abrir el esfínter esofágico superior, ayudó en la rehabilitación de la disfagia esofágica.

Self-renewal of double-negative 3 early thymocytes enables thymus autonomy but compromises the ß-selection checkpoint.

T lymphocyte differentiation in the steady state is characterized by high cellular turnover whereby thymocytes do not self-renew. However, if deprived of competent progenitors, the thymus can temporarily maintain thymopoiesis autonomously. This bears a heavy cost, because prolongation of thymus autonomy causes leukemia. Here, we show that, at an early stage, thymus autonomy relies on double-negative 3 early (DN3e) thymocytes that acquire stem-cell-like properties. Following competent progenitor deprivation, DN3e thymocytes become long lived, are required for thymus autonomy, differentiate in vivo, and include DNA-label-retaining cells. At the single-cell level, the transcriptional programs of thymopoiesis in autonomy and the steady state are similar. However, a new cell population emerges in autonomy that expresses an aberrant Notch target gene signature and bypasses the ß-selection checkpoint. In summary, DN3e thymocytes have the potential to self-renew and differentiate in vivo if cell competition is impaired, but this generates atypical cells, probably the precursors of leukemia.

Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iNKT) differentiation in mice.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the endogenous locus by CRISPR/Cas9 and tested the requirement of Ppic in hematopoiesis. Several immune cell lineages covering BM progenitors, lymphocyte precursors, as well as mature cells at the periphery were analyzed. While most lineages were unaffected, invariant NKT (iNKT) cells were reduced in percentage and absolute cell numbers in the Ppic-deficient thymus. This affected the most mature stages in the thymus, S2 and S3, and the phenotype was maintained at the periphery. Additionally, immature transitional T1 and T2 B lymphocytes were increased in the Ppic-deficient spleen, but the phenotype was lost in mature B lymphocytes. In sum, our data show that Ppic is dispensable for myeloid cells, platelets, erythrocytes, αß, and γδ T lymphocytes in vivo in the steady state, while being involved in B- and iNKT cell differentiation.

Cell competition in hematopoietic cells: Quality control in homeostasis and its role in leukemia.

Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. In the thymus, cell competition was addressed in thymus transplantation experiments, and found to be a homeostatic process that contributes to thymus turnover. Cell competition in the thymus depends on the capacity of T lymphocyte precursors to respond to interleukin 7 (IL-7). Failed cell competition permitted thymocyte self-renewal and autonomous thymopoiesis for several weeks, that culminated with leukemia onset. Beyond the work addressing cell competition in these cells, we discuss current hypotheses and observations that could be explained by cell competition. These include the clonal dynamics of hematopoietic stem cells in the ageing organism and initiation of leukemia.