Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice.

The sympathetic arm of the inflammatory reflex is the efferent pathway through which the central nervous system (CNS) can control peripheral immune responses. Diminazene aceturate (DIZE) is an antiparasitic drug that has been reported to exert protective effects on various experimental models of inflammation. However, the pathways by which DIZE promotes a protective immunomodulatory effects still need to be well established, and no studies demonstrate the capacity of DIZE to modulate a neural reflex to control inflammation. C57BL/6 male mice received intraperitoneal administration of DIZE (2 mg/Kg) followed by lipopolysaccharide (LPS, 5 mg/Kg, i.p.). Endotoxemic animals showed hyperresponsiveness to inflammatory signals, while those treated with DIZE promoted the activation of the inflammatory reflex to attenuate the inflammatory response during endotoxemia. The unilateral cervical vagotomy did not affect the anti-inflammatory effect of DIZE in the spleen and serum. At the same time, splenic denervation attenuated tumor necrosis factor (TNF) synthesis in the spleen and serum. Using broad-spectrum antibiotics for two weeks showed that LPS modulated the microbiota to induce a pro-inflammatory profile in the intestine and reduced the serum concentration of tryptophan and serotonin (5-HT), while DIZE restored serum tryptophan and increased the hypothalamic 5-HT levels. Furthermore, the treatment with 4-Chloro-DL-phenylalanine (pcpa, an inhibitor of 5-HT synthesis) abolished the anti-inflammatory effects of the DIZE in the spleen. Our results indicate that DIZE promotes microbiota modulation to increase central 5-HT levels and activates the efferent sympathetic arm of the inflammatory reflex to control splenic TNF production in endotoxemic mice.

Cuidados à pessoa em fim de vida e família no serviço de medicina intensiva / End-of-life care and the family in the intensive care unit

A Medicina Intensiva apresenta um desenvolvimento marcante nas últimas décadas. Atualmente, vive-se mais tempo, sendo esta longevidade acompanhada de morbilidades que aumentam o número de internamentos hospitalares, particularmente em Serviço de Medicina Intensiva. Estes dois aspetos, além da natureza crítica da própria doença, levam a que os Serviços de Medicina Intensiva a nível mundial apresentem taxas de mortalidade elevadas. Os enfermeiros especialistas em Enfermagem Médico-cirúrgica, na área de Enfermagem à Pessoa em Situação Crítica procuram cuidar da pessoa/família a vivenciar processos complexos de doença crítica, nomeadamente nas perturbações emocionais daí resultantes, tais como a dignificação da morte e os processos de luto. No âmbito do VIII Curso de Mestrado em Enfermagem Médico-Cirúrgica, da Escola Superior de Saúde do Instituto Politécnico de Viana do Castelo, realizou-se o Estágio de Natureza Profissional no Serviço de Medicina Intensiva Polivalente do Centro Hospitalar de Entre o Douro e Vouga, no período compreendido entre 3 de outubro de 2022 e 31 de março de 2023. Este estágio revelou-se uma oportunidade para desenvolver diversas atividades, principalmente: no âmbito da prestação de cuidados à pessoa em situação crítica e família; da gestão e supervisão dos cuidados, adequação dos recursos humanos e materiais através do acompanhamento e colaboração do enfermeiro tutor; no diagnóstico de necessidades de formação e intervenção enquanto formador, através da elaboração de um póster sobre a (não) utilização de heparina na manutenção do cateter venoso central, contribuindo para a inovação da prática clínica; e no desenvolvimento de um estudo de investigação com base nas necessidades do serviço. O trabalho de investigação realizado procurou conhecer a opinião dos enfermeiros do serviço acerca dos cuidados prestados à pessoa em fim de vida no Serviço de Medicina Intensiva Polivalente. Para tal, realizou-se um estudo qualitativo descritivo e exploratório, com recurso à entrevista semiestruturada a 10 enfermeiros deste serviço, cuja análise de conteúdo foi realizada segundo o referencial de Bardin. O desenvolvimento deste trabalho permitiu efetuar um diagnóstico de situação e identificar as intervenções realizadas pelos enfermeiros neste contexto, aspetos facilitadores e dificultadores na prestação de cuidados à pessoa em fim de vida e família e identificar os contributos para a melhoria no atendimento. A prestação de cuidados de conforto, assente numa comunicação eficaz, controlo adequado de sintomas e trabalho em equipa, foram considerados fundamentais na prestação de cuidados à pessoa em fim de vida e família. Os enfermeiros consideraram ainda que a prestação de cuidados pode ser otimizada, com a implementação de várias medidas, nomeadamente a tomada de decisão em equipa, a abordagem da temática dos cuidados em fim de vida nas discussões de equipa, envolvimento do psicólogo na equipa multidisciplinar e formação na área. Assim, considera-se que este estudo pode servir como um ponto de partida para a melhoria progressiva da qualidade dos cuidados prestados à pessoa em fim de vida e família no Serviço de Medicina Intensiva. A realização do estágio permitiu o desenvolvimento de dois níveis de competências: Competências comuns, nomeadamente no domínio da responsabilidade profissional, ética e legal, no domínio da melhoria contínua da qualidade, no domínio da gestão dos cuidados e no domínio do desenvolvimento das aprendizagens profissionais; e Competências especificas no âmbito do cuidar da pessoa em situação crítica e família e na maximização da prevenção, intervenção e controlo de infeção. Todo este desenvolvimento foi sustentado na observação, na prática baseada na evidência mais recente, na partilha de experiências e no aperfeiçoar do pensamento crítico-reflexivo.

Intensive Care Medicine has undergone remarkable development in recent decades. Currently, people are living longer and this lifespan is accompanied by morbidities that increase the number of hospital admissions, particularly in Intensive Care Units. In addition to the critical nature of the disease, these two aspects lead to high mortality rates in Intensive Care Units worldwide. The specialist nurses in Medical-Surgical Nursing, in the area of Nursing the Person in Critical Condition, seek to care for the person/family experiencing complex processes of critical illness, namely in the resulting emotional disturbances, such as the dignification of death and mourning processes. Within the scope of the VIII Master's Degree Course in Medical-Surgical Nursing of the School of Health of the Polytechnic Institute of Viana do Castelo, a Professional Training Course was carried out at the Polyvalent Intensive Care Unit of the Entre o Douro e Vouga Hospital Centre between October 3, 2022 and March 31, 2023. This internship proved to be an opportunity to develop several activities, mainly: the provision of care to critically-ill patients and their families; the management and supervision of care, and the suitability of human and material resources through the monitoring and collaboration of the nurse tutor; the diagnosis of training needs and intervention in the role of trainer through the development of a poster on the (non-)use of heparin in the maintenance of the central venous catheter, thus contributing to the innovation of clinical practice; and the development of a research study based on the service needs. The research study aimed to identify the nurses' opinion about the care provided to the person at the end-of-life in the Polyvalent Intensive Care Unit. To this end, a qualitative descriptive and exploratory study was conducted using semi-structured interviews with 10 nurses of this service, whose content analysis was performed according to Bardin's framework. The development of this study allowed diagnosing the situation and identifying the interventions performed by nurses in this context, facilitating and hindering aspects in the provision of care to the person at the end-of-life and the family, as well as identifying the contributions to improved care. The provision of comfort care, supported on effective communication, adequate symptom control and teamwork were considered essential in the provision of care to the end-of-life person and family. Nurses also considered that the provision of care can be optimised with the implementation of various measures, namely team decision-making, addressing the topic of end-of-life care in team discussions, involving the psychologist in the multidisciplinary team, and training in this area. Therefore, it is considered that this study may serve as a starting point for the progressive improvement of the quality of care provided to the end-of-life patient and family in the Intensive Care Unit. Carrying out the internship allowed the development of two levels of skills: Common skills, namely in the field of professional, ethical and legal responsibility, in the field of continuous quality improvement, in the field of care management and in the field of developing professional learning; and Specific skills based on caring for people in critical situations and their families and maximizing prevention, intervention and infection control. All this development was based on observation, practice based on the latest evidence, sharing of experiences and improvement of critical-reflective thinking.

Angiotensin-(1-7) improves tail skin heat loss and increases the survival of rats with polymicrobial sepsis.

Sepsis is a serious syndrome, characterized by the excessive release of inflammatory mediators and thermoregulatory changes, being fever the most common sign. However, despite the importance of Angiotensin (Ang)-(1-7) in controlling the inflammation, the role of the peptide in the febrile response and mortality in animals submitted to experimental model of sepsis is still not clear. In this way, we evaluate the effect of continuous infusion of Ang-(1-7) in inflammatory response, thermoregulation and in mortality of Wistar male rats submitted to colonic ligation puncture (CLP). Before CLP surgery, the infusion pumps (Ang-(1-7), 1.5 mg/mL or saline) were inserted into the abdominal cavity and maintained for 24 h. CLP rats showed a febrile response starting from 3 h after and persisted until the 24th hour of experiment. Continuous treatment with Ang-(1-7) attenuated the febrile response and reestablished the euthermia 11 h after CLP, until the end of experiment, which coincided with an increased heat loss index (HLI). This effect was associated with a decrease in production of pro-inflammatory mediators in liver, white adipose tissue (WAT) and hypothalamus. Moreover, an increase in norepinephrine (NE) content in interscapular brown adipose tissue (iBAT) was observed in CLP animals, which was attenuated with treatment with Ang-(1-7), and decreased mortality in CLP animals treated with Ang-(1-7). Taken together, the present study demonstrates that continuous infusion treatment with Ang-(1-7) can promote a global anti-inflammatory effect, reestablishing the tail skin heat loss as a key thermo-effector function, resulting in an increased survival of animals submitted to experimental sepsis.

Electronic and dynamical properties of non-covalent diatomic aggregates formed by He with neutral and ionic Li and Be.

CONTEXT AND RESULTS: This work aims to study the influence of the absence and presence of permanent charges on the electronic and dynamical properties of the non-covalent bound diatomic systems involving He and Li, Be as neutral and ionic partners. The charge displacement results suggest that in the formation of HeLi[Formula: see text], HeBe[Formula: see text], and HeBe[Formula: see text], the neutral He atom undergoes, in the electric field of the ion, a pronounced electronic polarization, and the natural bond order theoretical approach indicates that in the formation of the molecular orbital He acts as a weak electron donor. The energy decomposition analysis provides the dispersion and induction components as the attractive leading terms controlling the stability of all systems, confirming that the formed bond substantially maintains a non-covalent nature which is also supported by the Quantum Theory of Atoms in Molecules (QTAIM) analysis. Finally, it was found that the HeLi and HeBe neutral systems are unstable under any condition, HeLi[Formula: see text] and HeBe[Formula: see text] ionic systems are stable below 317K and 138K, respectively, while the HeBe[Formula: see text] system becomes unstable only after 3045K. COMPUTATIONAL AND THEORETICAL TECHNIQUES: The potential energy curves and interactions in all systems were studied theoretically based on coupled-cluster singles and doubles method with perturbative inclusion of triples CCSD(T) method with an aug-cc-pV5Z basis set. More precisely, it was determined the potential energy curves describing the stability of the HeLi, HeLi[Formula: see text], HeBe, HeBe[Formula: see text], and HeBe[Formula: see text] systems, the charge displacement within the formed adducts, the decomposition of their total interaction energy, the topological analysis of their bonds, their rovibrational energies, their spectroscopic constants and lifetimes.

Spatial modeling of homicide mortality in the Northeast region of Brazil.

OBJECTIVE: To analyze the spatiotemporal distribution of homicide mortality and association with social determinants of health in the Northeast Region of Brazil. METHODS: Ecological study with spatiotemporal modeling of homicide deaths between 2000 and 2019. Temporal trends were analyzed by segmented linear regression. Crude mortality was calculated and adjusted by smoothing the local empirical Bayesian method and analyzed by the Global/Local Moran Index and spatiotemporal scan statistics. The association between social determinants of health and homicide mortality was performed using multiple linear regression and autoregressive spatial models. RESULTS: 353,089 deaths were recorded. Mortality increased from 2000 to 2019, with an annual increase of 4.37 in males and 3.57 in females. High risk spatial and spatiotemporal clusters were identified in the coastal region of the states. The spatial regression model showed an association with socioeconomic inequalities. CONCLUSIONS: High risk areas for homicides associated with socioeconomic inequality, which should be considered as a priority for designing and investing in public health policies were investigated.

Spatial modeling of homicide mortality in the Northeast region of Brazil / Modelado espacial de la mortalidad por homicidios en la Región Noreste de Brasil / Modelagem espacial da mortalidade por homicídios na Região Nordeste do Brasil

ABSTRACT Objective: To analyze the spatiotemporal distribution of homicide mortality and association with social determinants of health in the Northeast Region of Brazil. Methods: Ecological study with spatiotemporal modeling of homicide deaths between 2000 and 2019. Temporal trends were analyzed by segmented linear regression. Crude mortality was calculated and adjusted by smoothing the local empirical Bayesian method and analyzed by the Global/Local Moran Index and spatiotemporal scan statistics. The association between social determinants of health and homicide mortality was performed using multiple linear regression and autoregressive spatial models. Results: 353,089 deaths were recorded. Mortality increased from 2000 to 2019, with an annual increase of 4.37 in males and 3.57 in females. High risk spatial and spatiotemporal clusters were identified in the coastal region of the states. The spatial regression model showed an association with socioeconomic inequalities. Conclusions: High risk areas for homicides associated with socioeconomic inequality, which should be considered as a priority for designing and investing in public health policies were investigated.

RESUMEN Objetivo: Analizar distribución espaciotemporal de mortalidad por homicidios y relación con determinantes sociales de salud en el Noreste brasileño. Métodos: Estudio ecológico con modelado espaciotemporal de óbitos por homicidios entre 2000 y 2019. Las tendencias temporales fueron analizadas por regresión lineal segmentada. La mortalidad brutal fue calculada y acordada por moderación del método bayesiano empírico local y analizadas por Índice de Moran Global/Local y estadística de barrido espaciotemporal. La relación entre determinantes sociales de salud y mortalidad por homicidios fue realizada mediante la regresión lineal múltiple y modelos espaciales autorregresivos. Resultados: Fueron registrados 353.089 óbitos. La mortalidad aumentó de 2000 para 2019, con un incremento anual de 4,37 en el sexo masculino y 3,57 y en el femenino. Aglomeraciones espaciales y espaciotemporales de alto riesgo fueron identificadas en la región costera de los estados. El modelo de regresión espacial demostró relación con las desigualdades socioeconómicas. Conclusiones: Identificamos áreas de alto riesgo para homicídios relacionadas con la desigualdad socioeconómica, debiendo ser consideradas como prioridad para el delineamiento e inversión en políticas públicas en salud.

RESUMO Objetivo: Analisar a distribuição espaçotemporal da mortalidade por homicídios e associação com determinantes sociais da saúde na Região Nordeste do Brasil. Métodos: Estudo ecológico com modelagem espaço temporal dos óbitos por homicídios entre 2000 e 2019. As tendências temporais foram analisadas por regressão linear segmentada. A mortalidade bruta foi calculada e ajustada pela suavização do método bayesiano empírico local e analisadas pelo Índice de Moran Global/Local e estatística de varredura espaço temporal. A associação entre os determinantes sociais da saúde e a mortalidade por homicídios foi realizada por meio da regressão linear múltipla e modelos espaciais autorregressivos. Resultados: Foram registrados 353.089 óbitos. A mortalidade aumentou de 2000 para 2019, com um acréscimo anual de 4,37 no sexo masculino e 3,57 no feminino. Aglomerações espaciais e espaçotemporais de alto risco foram identificadas na região costeira dos estados. O modelo de regressão espacial demonstrou associação com as desigualdades socioeconômicas. Conclusões: Identificamos áreas de alto risco para homicídios associadas com a desigualdade socioeconômica, devendo ser consideradas como prioridade para o delineamento e investimento em políticas públicas em saúde.

Sobrecarga dos cuidadores informais de pessoas com esclerose lateral amiotrófica / Burden of informal caregivers of people with amyotrophic lateral sclerosis / Sobrecarga de los cuidadores informales de personas con esclerosis amiotrófica lateral

Resumo Enquadramento: A esclerose lateral amiotrófica é uma doença neurodegenerativa, progressiva, incapacitante e sem cura, onde o cuidador assume um papel fundamental na resposta às necessidades. Objetivo: Analisar a associação entre caraterísticas sociodemográficas e profissionais do cuidador e sobrecarga; e entre caraterísticas sociodemográficas e clínicas da pessoa com ELA e a sobrecarga do cuidador. Metodologia: Estudo descritivo-correlacional. Amostra de disponíveis com 30 doentes e 30 cuidadores. Como instrumento utilizou-se o Questionário de Avaliação da Sobrecarga do Cuidador Informal. Análise estatística com testes paramétricos e não paramétricos. Resultados: Doentes com média de 66,4 ± 11,17 anos e distribuição homogénea quanto ao sexo. Cuidadores maioritariamente cônjuges, mulheres e com sobrecarga moderada (56,7%), sendo menos afetada a "reações a exigências" e mais afetada os "mecanismos de eficácia e de controlo" (média 25,67 ± 21,76 e média 66,39 ± 21,50). Caraterísticas sociodemográficas do cuidador, funcionalidade do doente, tempo de cuidados e ventilação não invasiva, relacionam-se com os níveis de sobrecarga (sig < 0,05). Conclusão: Os cuidadores apresentam níveis moderados de sobrecarga, tornando importante cuidados de proximidade.

Abstract Background: Amyotrophic lateral sclerosis (ALS) is an incurable and disabling progressive neurodegenerative disease, where the caregiver plays a key role in meeting the patient's needs. Objective: To analyze the association between caregivers' sociodemographic and professional characteristics and their burden and between the sociodemographic and clinical characteristics of individuals with ALS and caregivers' burden. Methodology: Descriptive-correlational study. Sample of 30 patients and 30 caregivers. The Informal Caregiver Burden Assessment Questionnaire was used. Parametric and non-parametric tests were used for data analysis. Results: The sample of patients had a mean age of 66.4 ± 11.17 years and homogeneous gender distribution. The majority of caregivers were women, spouses, with moderate levels of burden (56.7%), less affected by "reactions to demands" and more affected by "efficacy and control mechanisms" (mean 25.67 ± 21.76 and mean 66.39 ± 21.50). The caregiver's sociodemographic characteristics, the patient's functional status, the number of care hours, and the use of non-invasive ventilation were associated with burden levels (sig < 0.05). Conclusion: Caregivers have moderate levels of burden, highlighting the importance of proximity care.

Resumen Marco contextual: La esclerosis amiotrófica lateral es una enfermedad neurodegenerativa, progresiva, incapacitante e incurable, donde el cuidador informal asume un papel fundamental en la respuesta a las necesidades. Objetivos: Analizar la asociación entre características sociodemográficas y profesionales del cuidador y la sobrecarga; y entre las características sociodemográficas y clínicas de la persona con ELA y la sobrecarga del cuidador. Metodología: Estudio descriptivo-correlacional. Muestra de disponible con 30 pacientes y 30 cuidadores. Para la evaluación de la sobrecarga, se utilizó el Cuestionario de evaluación de la sobrecarga del cuidador informal. Análisis estadístico con pruebas paramétricas e no paramétricas. Resultados: Pacientes con una media de 66,4 ± 11,17 años y distribución homogénea por sexo. Cuidadores mayoritariamente cónyuges, mujeres y con sobrecarga moderada (56,7%), siendo menos afectada por "reacciones a demandas" y más afectada por "mecanismos de eficiencia y control" (media 25,67 ± 21,76 y media 66,39 ± 21,50). Las características sociodemográficas del cuidador, la funcionalidad del paciente, la duración del cuidado y la ventilación no invasiva están asociados con los niveles de sobrecarga (sig < 0,05). Conclusión: Los cuidadores tienen niveles de sobrecarga moderados, por lo que son importantes los cuidados de proximidad.

A Detailed Study of Electronic and Dynamic Properties of Noble Gas-Oxygen Molecule Adducts.

In this work, the binding features of adducts formed by a noble gas (Ng = He, Ne, Ar, Kr, Xe, and Rn) atom and the oxygen molecule (O2) in its ground Σg-3, in the past target of several experimental studies, have been characterized under different theoretical points of view to clarify fundamental aspects of the intermolecular bond. For the most stable configuration of all Ng-O2 systems, binding energy has been calculated at the theory's CCSD(T)/aug-cc-pVTZ level and compared with the experimental findings. Rovibrational energies, spectroscopic constants, and lifetime as a function of temperature were also evaluated by adopting properly formulated potential energy curves. The nature of the interaction involved was deeply investigated using charge displacement analysis, symmetry-adapted perturbation theory (SAPT), and natural bond orbital (NBO) methods. In all adducts, it was found that the charge transfer plays a minor role, although O2 is an open shell species exhibiting a positive electron affinity. Obtained results also indicate that the dispersion attraction contribution is the main responsible for the complex stability.

Comparison between low, moderate, and high intensity aerobic training with equalized loads on biomarkers and performance in rats.

This study investigated the physiological and molecular responses of Wistar Hannover rats, submitted to three 5-week chronic training models, with similar training loads. Twenty-four Wistar Hanover rats were randomly divided into four groups: control (n = 6), low-intensity training (Z1; n = 6), moderate-intensity training (Z2; n = 6) and high-intensity training (Z3; n = 6). The three exercise groups performed a 5-week running training three times a week, with the same prescribed workload but the intensity and the volume were different between groups. An increase in maximal speed was observed after four weeks of training for the three groups that trained, with no difference between groups. Higher rest glycogen was also observed in the soleus muscle after training for the exercise groups compared to the control group. We also found that the Z2 group had a higher protein content of total and phosphorylated GSK3-ß compared to the control group after five weeks of training. In conclusion, the present study shows that five weeks of treadmill training based on intensity zones 1, 2, and 3 improved performance and increased resting glycogen in the soleus muscle, therefore intensity modulation does not change the training program adaptation since the different program loads are equalized.

Glucocorticoids decrease thermogenic capacity and increase triacylglycerol synthesis by glycerokinase activation in the brown adipose tissue of rats.

Although it is well established that glucocorticoids inactivate thermogenesis and promote lipid accumulation in interscapular brown adipose tissue (IBAT), the underlying mechanisms remain unknown. We found that dexamethasone treatment (1 mg/kg) for 7 days in rats decreased the IBAT thermogenic activity, evidenced by its lower responsiveness to noradrenaline injection associated with reduced content of mitochondrial proteins, respiratory chain protein complexes, noradrenaline, and the ß3 -adrenergic receptor. In parallel, to understand better how dexamethasone increases IBAT lipid content, we also investigated the activity of the ATP citrate lyase (ACL), a key enzyme of de novo fatty acid synthesis, glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, and the three glycerol-3-P generating pathways: (1) glycolysis, estimated by 2-deoxyglucose uptake, (2) glyceroneogenesis, evaluated by phosphoenolpyruvate carboxykinase activity and pyruvate incorporation into triacylglycerol-glycerol, and (3) direct phosphorylation of glycerol, investigated by the content and activity of glycerokinase. Dexamethasone increased the mass and the lipid content of IBAT as well as plasma levels of glucose, insulin, non-esterified fatty acid, and glycerol. Furthermore, dexamethasone increased ACL and G6PD activities (79% and 48%, respectively). Despite promoting a decrease in the incorporation of U-[14 C]-glycerol into triacylglycerol (~54%), dexamethasone increased the content (~55%) and activity (~41%) of glycerokinase without affecting glucose uptake or glyceroneogenesis. Our data suggest that glucocorticoid administration reduces IBAT thermogenesis through sympathetic inactivation and stimulates glycerokinase activity and content, contributing to increased generation of glycerol-3-P, which is mostly used to esterify fatty acid and increase triacylglycerol content promoting IBAT whitening.

Phosphodiesterase 4 inhibition restrains muscle proteolysis in diabetic rats by activating PKA and EPAC/Akt effectors and inhibiting FoxO factors.

AIM: There is growing evidence about the ability of cyclic adenosine monophosphate (cAMP) signaling and nonselective phosphodiesterase (PDE) inhibitors on mitigate muscle atrophy. PDE4 accounts for the major cAMP hydrolyzing activity in skeletal muscles, therefore advances are necessary about the consequences of treatment with PDE4 inhibitors on protein breakdown in atrophied muscles. We postulated that rolipram (selective PDE4 inhibitor) may activate cAMP downstream effectors, inhibiting proteolytic systems in skeletal muscles of diabetic rats. MAIN METHODS: Streptozotocin-induced diabetic rats were treated with 2 mg/kg rolipram for 3 days. Changes in the levels of components belonging to the proteolytic machineries in soleus and extensor digitorum longus (EDL) muscles were investigated, as well as cAMP effectors. KEY FINDINGS: Treatment of diabetic rats with rolipram decreased the levels of atrogin-1 and MuRF-1 in soleus and EDL, and reduced the activities of calpains and caspase-3; these findings partially explains the low ubiquitin conjugates levels and the decreased proteasome activity. The inhibition of muscle proteolysis may be occurring due to phosphorylation and inhibition of forkhead box O (FoxO) factors, probably as a consequence of the increased cAMP levels, followed by the activation of PKA and Akt effectors. Akt activation may be associated with the increased levels of exchange protein directly activated by cAMP (EPAC). As a result, rolipram treatment spared muscle mass in diabetic rats. SIGNIFICANCE: The antiproteolytic responses associated with PDE4 inhibition may be helpful to motivate future investigations about the repositioning of PDE4 inhibitors for the treatment of muscle wasting conditions.

Risk of hospitalization and risk of death for healthcare workers with COVID-19 in nine European Union/European Economic Area countries, January 2020 - January 2021

We assessed the impact of COVID-19 on healthcare workers (HCWs) from data on 2.9 million cases reported from nine countries in the EU/EEA. Compared to non-HCWs, HCWs had a higher adjusted risk of hospitalization (IRR 3.0 [95% CI 2.2-4.0]), but not death (IRR 0.9, 95% CI 0.4-2.0). Article Summary LineHealthcare workers are hospitalized more frequently than non-healthcare workers when adjusting for age, sex, and comorbidities.

Rapid assessment of the impact of lockdown on the COVID-19 epidemic in Portugal

BackgroundPortugal took early action to control the COVID19 epidemic, imposing a lockdown on March 16 when it recorded only 62 cases of COVID-19 per million inhabitants and no reported deaths. The Portuguese people complied quickly, reducing their overall mobility by 80%. We estimate the impact of the lockdown in Portugal in terms of reducing burden on the health service. MethodsWe forecasted epidemic curves for: Cases, hospital inpatients (overall and in ICU), and deaths without lockdown, assuming that the impact of containment measures would start 14 days after lockdown was implemented. We used exponential smoothing models for deaths, intensive care (ICU) and hospitalizations and an ARIMA model for number of cases. Models were selected considering fitness to the observed data to the 31st of March 2020. We then compared observed(with intervention) and forecasted curves (without intervention). ResultsBetween April 1 and April 15, there were 146 fewer deaths(-25%), 5568 fewer cases (-23%) and, as of April 15, there were 519 fewer ICU inpatients(-69%) and 508 fewer overall hospital inpatients(-28%) than forecasted without lockdown. On April 15 the number of ICU inpatients could have reached 748, three times higher than the observed value (229) if the intervention had been delayed. ConclusionIf the lockdown had not been implemented in mid-March, Portugal ICU capacity (528 ICU beds) would likely have been breached in the first half of April. The lockdown seems to have been effective in reducing transmission of SARS-Cov-2, serious Covid-19 illness and associated mortality, thereby decreasing demand on health services. Early action allowed time for the National Health Service to acquire protective equipment, to increase capacity to test and cope with the surge in hospital and ICU demand caused by the pandemic.

COVID-19 :Determinants of Hospitalization, ICU and Death among 20,293 reported cases in Portugal

IntroductionDeterminants of hospitalization, intensive care unit (ICU) admission and death are still unclear for Covid-19 and only a few studies have adjusted for confounding for different clinical outcomes including all reported cases in a country. We used routine surveillance data from Portugal to identify risk factors for COVID-19 outcomes, in order to support risk stratification, clinical and public health interventions, and scenarios to plan health care resources. MethodsWe conducted a retrospective cohort study including 20,293 laboratory confirmed cases of COVID-19 in Portugal extracted in April 28 2020, electronically through the National Epidemic Surveillance System of the Directorate-General of Health(DGS). We calculated absolute risks, relative risks (RR) and adjusted relative risks (aRR) to identify demographic and clinical factors associated with hospitalization, admission to ICU and death using Poisson regressions. ResultsIncreasing age after 60 years was the greatest determinant for all outcomes. Assuming 0-50 years as reference, being aged 80-89 years was the strongest determinant of hospital admission (aRR-5.7), 70-79 years for ICU(aRR-10.4) and > 90 years for death(aRR-226.8) with an aRR of 112.7 in those 70-79. Among comorbidities, Immunodeficiency, cardiac disease, kidney disease, and neurologic disease were independent risk factors for hospitalization (aRR 1.83,1.79,1.56, 1.82), for ICU these were cardiac, Immunodeficiency, kidney and lung disease (aRR 4.33, 2.76, 2.43, 2.04), and for death they were kidney, cardiac and chronic neurological disease (aRR: 2.9, 2.6, 2.0) Male gender was a risk factor for all outcomes. There were small statistically significant differences for the 3 outcomes between regions. Discussion and ConclusionsOlder age stands out as the strongest risk factor for all outcomes specially for death as absolute is risk was small for those younger than 50. These findings have implications in terms of risk stratified public health measures that should prioritize protecting older people although preventive behavior is needed in all ages. Epidemiologic scenarios and clinical guidelines may consider these estimated risks, even though under-ascertainment of mild and asymptomatic cases should be considered.

Activation of adipose tissue glycerokinase contributes to increased white adipose tissue mass in mice fed a high-fat diet.

PURPOSE: Investigate the pathways of glycerol-3-P (G3P) generation for triacylglycerol (TAG) synthesis in retroperitoneal (RWAT) and epididymal (EWAT) white adipose tissues from high-fat diet (HFD)-fed mice. METHODS: Mice were fed for 8 weeks a HFD and glycolysis, glyceroneogenesis and direct phosphorylation of glycerol were evaluated, respectively, by 2-deoxyglucose uptake, phosphoenolpyruvate carboxykinase (PEPCK-C) activity and pyruvate incorporation into TAG-glycerol, and glycerokinase activity and glycerol incorporation into TAG-glycerol in both tissues. RESULTS: HFD increased body and adipose tissue mass and serum levels of glucose and insulin, which were accompanied by glucose intolerance. RWAT and EWAT from HFD-fed mice had increased rates of de novo fatty acid (FA) synthesis (52% and 255%, respectively). HFD increased lipoprotein lipase (LPL) activity and content in EWAT (107%), but decreased in RWAT (79%). HFD decreased the lipolytic response to norepinephrine (57%, RWAT and 25%, EWAT), ß3-adrenoceptor content (50%), which was accompanied by a decrease in phosphorylated-hormone-sensitive lipase (~80%) and phosphorylated-adipocyte triacylglycerol lipase (~60%) in both tissues. HFD decreased the in vitro rates of glucose uptake (3.5- and 6-fold), as well as in glyceride-glycerol synthesis from pyruvate (~3.5-fold) without changes in PEPCK-C activity and content in RWAT and EWAT, but increased glycerokinase activity(~3-fold) and content (90 and 40%) in both tissues. CONCLUSION: The data suggest that direct phosphorylation of glycerol by glycerokinase may be responsible for maintaining the supply of G3P for the existing rates of FA esterification and TAG synthesis in RWAT and EWAT from HFD-fed mice, contributing, along with a lower lipolytic response to norepinephrine, to higher adiposity.

Association between Single Nucleotide Polymorphisms and Glioma Risk: A Systematic Literature Review.

This study aimed to determine the main single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of the genes XRCC1, ERCC2, and EFEMP1, respectively.

Public health management: systemic analysis of social determinants of health in Brazilian municipalities.

The health sector is considered extremely important by governments and multilateral international organisms, due to its implication to life, as well as material and human struggling involved. This study adopts a systematical approach in order to question if the mortality outcomes in medium Brazilian cities explain or may be explained by factors considered external to the public health service, expressed by health social determinants. Therefore, this study aims to investigate health conditions in public health management in medium Brazilian cities. The scenario adopted contains 192 cities with a population contingent between 100 000 and 500 000 inhabitants, between the years 2007 and 2011. The database produced, containing 30 indicators representing conceptual models referenced, allowed the elaboration of an operational model of health social determinants from a Bayesian network. As result, we elaborated a model of health system formed by six factors, showing associations that allow a better comprehension about relations among health social determinants and health conditions, producing contextualized information, able to subsidize the formulation of strategies by managers of Sistema Único de Saúde.

Modelo conceitual aplicável a estudos sobre determinantes sociais da saúde em municípios brasileiros / A conceptual model for studies on social determinants of health in Brazilian municipalities

Resumo Os modelos conceituais de determinantes sociais da saúde (DSS) disponíveis na literatura, embora úteis para compreensão dos mecanismos que afetam os resultados do sistema de saúde sobre as condições de vida das populações, apresentam limitações quanto à sua aplicação em estudos empíricos e, consequentemente, na orientação da gestão de políticas públicas de saúde. Isso ocorre porque as categorias adotadas por esses modelos não são adequadamente representadas por indicadores ou variáveis homogêneas, sujeitas a manipulações matemáticas ou estatísticas em um sistema simples de relacionamentos. Este estudo tem por objetivo contribuir para o preenchimento dessa lacuna, ao propor um modelo conceitual de DSS passível de aplicação operacional, ou seja, de ser reproduzido em modelos matemáticos ou estatísticos, a fim de subsidiar estudos e definir estratégias de saúde pública. O esforço recorre à literatura para revisar modelos conceituais consagrados, identificar um conjunto de DSS e apresentar recomendações e critérios de escolha. Na sequência, identifica fontes de dados confiáveis que disponibilizem indicadores e variáveis dispostos em séries históricas e propõe o desenho de um modelo conceitual aplicável, cuja operacionalização requer métodos e ferramentas próprios de uma abordagem sistêmica.

Abstract The conceptual models of Social Determinants of Health (SDH) available in the literature, although useful for comprehending mechanisms that affect the results of the health system on the living conditions of the population, present limitations regarding their application in empirical studies and, consequently, in guiding public health policies. This occurs because the categories adopted by these models are not adequately represented by indicators of homogeneous variables subject to mathematical or statistical manipulations in a simple relation system. This study aims to help filling this gap by proposing an operationally applicable SDH conceptual model - reproducible as a mathematical or statistical model - to support studies and define strategies concerning public health. We resorted to the literature to review previously developed conceptual models, identifying a set of SDH and presenting recommendations and choice criteria. Then we located reliable data sources supplying indicators and variables listed in historic series and proposed an applicable conceptual model, which requires specific methods and tools for a systemic approach for operationalization.

Conhecimento de enfermeiros da Estratégia Saúde da Família sobre a tuberculose / Nurses' knowledge of the family health strategy on tuberculosis

Objetivo: analisar o conhecimento de enfermeiros da Estratégia Saúde da Família sobre a tuberculose. Método: trata-se de estudo quantitativo, descritivo e transversal, com 22 enfermeiras. Utilizou-se, como instrumento de coleta, um questionário estruturado e adaptado. Descreveram-se as variáveis numéricas como média e desvio padrão e sumarizaram-se as variáveis categóricas em frequências simples e porcentagens a partir de tabelas. Resultados: revelou-se, quanto ao recebimento de capacitação sobre a temática da tuberculose, que 77,27% referiram nunca ter sido capacitados. Alerta-se, em relação aos sinais e sintomas para um provável caso de tuberculose, que 68,18% não responderam de forma correta. Identificou-se que 86,36% acertaram sobre a duração do esquema terapêutico e os medicamentos utilizados no tratamento. Destacou-se, no tocante aos efeitos medicamentosos, que todas as participantes responderam de maneira inadequada. Conclusão: evidenciou-se um conhecimento superficial por parte das enfermeiras na atuação contra a tuberculose, o que dificulta a estratégia de controle da doença no município, fazendo-se necessária a realização de capacitação sobre os diferentes aspectos relacionados à tuberculose.(AU)

Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of pentoxifylline on skeletal muscles of diabetic rats.

Advances in the knowledge of the mechanisms controlling protein breakdown in skeletal muscles have allowed the exploration of new options for treating muscle-wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE) inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly via inhibiting protein breakdown. The aim of this study was to explore the mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of atrogin-1 and muscle RING finger-1 were decreased, as were the activities of caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX, which at least partly explains the drop in the ubiquitin conjugate (EDL) levels and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE activity and increased cAMP content in muscles of diabetic rats; moreover, it also increased both the protein levels of exchange protein directly activated by cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle mass was practically prevented in diabetic rats treated with PTX. These findings advance our understanding of the mechanisms underlying the antiproteolytic effects of PTX and suggest the use of PDE inhibitors as a strategy to activate cAMP signaling, which is emerging as a promising target for treating muscle mass loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in addition to ß2AR agonists, phosphodiesterase inhibitors such as pentoxifylline (PTX) can be an interesting option. This study advances the understanding of the mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of diabetic rats, which involve the activation of both exchange protein directly activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and calpain/caspase-3-proteolytic machinery.