A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics

It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP) test) to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51ºC and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 µg/paw) and mice (125-500 µg/paw) with carrageen an led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, ip) inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 µg/paw) also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals

Nutritional Profile of Patients in Hemodialysis of the Hospital Universitário Ciências Médicas - Minas Gerais

Objectives: To evaluate the nutritional status of hemodialysis (HD) patients. Methods: A cross-sectional study was performed in all patients on HD at a single center. Results: We studied 72 patients, male (57%) and 45.8% between 45 and 64 years old. The most frequent etiology was systemic arterial hypertension (50.0%) and diabetes (20.8%). KT/V  > 1.2 was found in 88.8% of the patients, and phosphorus level > 5.5 mg/dL in 25%. The malnourished patients classified by body mass index (BMI) < 25 kg/m2 (66.67%), arm muscle circumference (WBC) index (84.72%) and albumin (≤ 4.0 g/dL) (28,8%), and 22,22% use a specific oral nutritional supplement for hypercaloric hyperproteic dialytic patients, provided by the hemodialysis service. The mean interdialytic weight gain (GPIDm) was < 2.5kg in 58.3% and the relative interdialytic weight gain (GPIDr) was < 4.5% in 75.0% of the patients. There was a significant association between GPIDm and CMB, patients with lower GPIDm (≤ 2.5 kg) tended to have more mild or moderate malnutrition (p = 0.003). No differences were observed by time in hemodialysis in relation to age, interdialytic weight gain, laboratory and anthropometric measurements. Conclusion: The nutritional assessment by BMI was in agreement with the Brazilian literature. By CMB, most were classified as malnourished, which differs from albumin, in that only ∼ 30% were malnourished. The results show the importance of supplementation for this population. We have seen that > 75% of the patients are within the ideal GPIDr (< 4.5% of the dry weight). The dialysis time did not affect the nutritional evaluation parameters

Gold nanoparticles inhibit steroid-insensitive asthma in mice preserving histone deacetylase 2 and NRF2 pathways

Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GCresistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2

Evaluation of comprehensive care for older adults in primary care services

OBJECTIVE: To evaluate the performance of comprehensive care for older adults in primary care services in the Brazilian Unified Health System in the state of Sao Paulo, Brazil. METHODS: A total of 157 primary care services from five health regions in midwestern Sao Paulo responded, from October to December 2014, the pre-validated 2014 questionnaire for primary care services assessment and monitoring. We selected 155 questions, based on national policies and guidelines on this theme. The responses indicate the service performance in older adults' care, clustered into three areas of analysis: health care for active and healthy aging (45 indicators, d1), chronic noncommunicable diseases care (89 indicators, d2), and support network in aging care (21 indicators, d3). Performance was measured by the sum of positive (value 1) or negative (value 0) responses for each indicator. Services were clustered according to k-means of the performance scores of each domain. After weighting the domains (Z tests), we estimated the associations between the scores of each domain and independent management variables (typology, planning and evaluation of services), with simple and multiple linear regression. RESULTS: Chronic noncommunicable diseases care (d2) showed, for all clusters, better average performance (55.7) than domains d1 (35.4) and d3 (39.2). Service performance in the general area of planning and evaluation associates with the performance of older adults' care. CONCLUSIONS: The evaluated services had incipient implementation of comprehensive care for older adults. The evaluation framework can contribute to processes to improve the quality of primary health care. OBJETIVO: Avaliar o desempenho da atenção integral ao idoso em serviços de atenção primária do Sistema Único de Saúde no estado de São Paulo, Brasil. MÉTODOS: Um total de 157 serviços de atenção primária de cinco regiões de saúde do centro-oeste paulista respondeu, de outubro a dezembro de 2014, o instrumento pré-validado Questionário de Avaliação e Monitoramento de Serviços de Atenção Básica 2014. Foram selecionadas 155 questões, com base nas políticas e diretrizes nacionais sobre essa temática. As respostas indicam o desempenho do serviço na atenção ao idoso, agrupadas em três domínios de análise: atenção à saúde para o envelhecimento ativo e saudável (45 indicadores, d1), atenção às doenças crônicas não transmissíveis (89 indicadores, d2) e rede de apoio na atenção ao envelhecimento (21 indicadores, d3). A medida de desempenho foi a soma de respostas positivas (valor 1) ou negativas (valor 0) para cada indicador. Os serviços foram agrupados segundo k-médias dos escores de desempenho de cada um dos domínios. Após a ponderação dos domínios (testes Z), foram estimadas as associações entre os escores de cada domínio e variáveis independentes de gestão (tipologia, planejamento e avaliação dos serviços), por meio de regressão linear simples e múltipla. RESULTADOS: A atenção às doenças crônicas não transmissíveis (d2) mostrou, para todos os agrupamentos, melhor desempenho médio (55,7) do que os domínios d1 (35,4) e d3 (39,2). O desempenho do serviço na área geral de planejamento e avaliação esteve associado ao desempenho da atenção ao idoso. CONCLUSÕES: Os serviços avaliados apresentaram implementação incipiente da atenção integral ao idoso. O quadro avaliativo pode contribuir para processos de melhoria da qualidade da atenção primária à saúde.publishersversionpublishe

Avaliação da atenção integral ao idoso em serviços de atenção primária

OBJECTIVE: To evaluate the performance of comprehensive care for older adults in primary care services in the Brazilian Unified Health System in the state of São Paulo, Brazil. METHODS: A total of 157 primary care services from five health regions in midwestern São Paulo responded, from October to December 2014, the pre-validated 2014 questionnaire for primary care services assessment and monitoring. We selected 155 questions, based on national policies and guidelines on this theme. The responses indicate the service performance in older adults’ care, clustered into three areas of analysis: health care for active and healthy aging (45 indicators, d1), chronic noncommunicable diseases care (89 indicators, d2), and support network in aging care (21 indicators, d3). Performance was measured by the sum of positive (value 1) or negative (value 0) responses for each indicator. Services were clustered according to k-means of the performance scores of each domain. After weighting the domains (Z tests), we estimated the associations between the scores of each domain and independent management variables (typology, planning and evaluation of services), with simple and multiple linear regression. RESULTS: Chronic noncommunicable diseases care (d2) showed, for all clusters, better average performance (55.7) than domains d1 (35.4) and d3 (39.2). Service performance in the general area of planning and evaluation associates with the performance of older adults’ care. CONCLUSIONS: The evaluated services had incipient implementation of comprehensive care for older adults. The evaluation framework can contribute to processes to improve the quality of primary health care.OBJETIVO: Avaliar o desempenho da atenção integral ao idoso em serviços de atenção primária do Sistema Único de Saúde no estado de São Paulo, Brasil. MÉTODOS: Um total de 157 serviços de atenção primária de cinco regiões de saúde do centro-oeste paulista respondeu, de outubro a dezembro de 2014, o instrumento pré-validado Questionário de Avaliação e Monitoramento de Serviços de Atenção Básica 2014. Foram selecionadas 155 questões, com base nas políticas e diretrizes nacionais sobre essa temática. As respostas indicam o desempenho do serviço na atenção ao idoso, agrupadas em três domínios de análise: atenção à saúde para o envelhecimento ativo e saudável (45 indicadores, d1), atenção às doenças crônicas não transmissíveis (89 indicadores, d2) e rede de apoio na atenção ao envelhecimento (21 indicadores, d3). A medida de desempenho foi a soma de respostas positivas (valor 1) ou negativas (valor 0) para cada indicador. Os serviços foram agrupados segundo k-médias dos escores de desempenho de cada um dos domínios. Após a ponderação dos domínios (testes Z), foram estimadas as associações entre os escores de cada domínio e variáveis independentes de gestão (tipologia, planejamento e avaliação dos serviços), por meio de regressão linear simples e múltipla. RESULTADOS: A atenção às doenças crônicas não transmissíveis (d2) mostrou, para todos os agrupamentos, melhor desempenho médio (55,7) do que os domínios d1 (35,4) e d3 (39,2). O desempenho do serviço na área geral de planejamento e avaliação esteve associado ao desempenho da atenção ao idoso. CONCLUSÕES: Os serviços avaliados apresentaram implementação incipiente da atenção integral ao idoso. O quadro avaliativo pode contribuir para processos de melhoria da qualidade da atenção primária à saúde

COVID-19 infodemic and impacts on the mental health of older people : cross-sectional multicenter survey study

Background: The COVID-19 pandemic received widespread media coverage due to its novelty, an early lack of data, and the rapid rise in deaths and cases. This excessive coverage created a secondary “infodemic” that was considered to be a serious public and mental health problem by the World Health Organization and the international scientific community. The infodemic particularly affected older individuals, specifically those who are vulnerable to misinformation due to political positions, low interpretive and critical analysis capacity, and limited technical-scientific knowledge. Thus, it is important to understand older people’s reaction to COVID-19 information disseminated by the media and the effect on their lives and mental health. Objective: We aimed to describe the profile of exposure to COVID-19 information among older Brazilian individuals and the impact on their mental health, perceived stress, and the presence of generalized anxiety disorder (GAD). Methods: This cross-sectional, exploratory study surveyed 3307 older Brazilians via the web, social networks, and email between July 2020 and March 2021. Descriptive analysis and bivariate analysis were performed to estimate associations of interest. Results: Major proportions of the 3307 participants were aged 60 to 64 years (n=1285, 38.9%), female (n=2250, 68.4%), and married (n=1835, 55.5%) and self-identified as White (n=2364, 71.5%). Only 295 (8.9%) had never started or completed a basic education. COVID-19 information was mainly accessed on television (n=2680, 81.1%) and social networks (n=1943, 58.8%). Television exposure was ≥3 hours in 1301 (39.3%) participants, social network use was 2 to 5 hours in 1084 (32.8%) participants, and radio exposure was ≥1 hour in 1223 (37%) participants. Frequency of exposure to social networks was significantly associated with perceived stress (P=.04) and GAD (P=.01). A Bonferroni post hoc test revealed significantly different perceived stress in participants who were exposed to social networks for 1 hour (P=.04) and those who had no exposure (P=.04). A crude linear regression showed that “some” social media use (P=.02) and 1 hour of exposure to social media (P<.001) were associated with perceived stress. Adjusting for sociodemographic variables revealed no associations with this outcome variable. In a crude logistic regression, some social media use (P<.001) and 2 to 5 hours of exposure to social media (P=.03) were associated with GAD. Adjusting for the indicated variables showed that some social network use (P<.001) and 1 hour (P=.04) and 2 to 5 hours (P=.03) of exposure to social media were associated with GAD. Conclusions: Older people, especially women, were often exposed to COVID-19–related information through television and social networks; this affected their mental health, specifically GAD and stress. Thus, the impact of the infodemic should be considered during anamnesis for older people, so that they can share their feelings about it and receive appropriate psychosocial care

Differential regulation of lung homeostasis and silicosis by the TAM receptors MerTk and Axl

IntroductionTAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the in vivo function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma.MethodsWe employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 μL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-β and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk-/- and WT AMs, confirming its importance during inflammation.ConclusionThis study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy

Potential of PEGylated toll-like receptor 7 ligands for controlling inflammation and functional changes in mouse models of asthma and silicosis

Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions. In vitro approaches and translation to murine models of obstructive and restrictive lung diseases were explored. In vitro studies with human PBMCs showed that both TMX-302 and TMX-306 marginally affects cytokine production as compared with equivalent concentrations of the TLR7 full agonist, TMX-202. The PEGylated compounds did not induce monocyte-derived DC maturation or B cell proliferation, differently from what observed after stimulation with TMX-202. Impact of PEGylated ligands on lung function and inflammatory changes was studied in animal models of acute lung injury, asthma, and silicosis following Lipopolysaccharide (LPS), allergen (ovalbumin), and silica inhalation, respectively. Subcutaneous injection of TMX- 302 prevented LPS- and allergen-induced airway hyper-reactivity (AHR), leukocyte infiltration, and production of pro-inflammatory cytokines in the lung. However, intranasal instillation of TMX-302 led to neutrophil infiltration and failed to prevent allergen-induced AHR, despite inhibiting leukocyte counts in the BAL. Aerosolized TMX-306 given prophylactically, but not therapeutically, inhibited pivotal asthma features. Interventional treatment with intranasal instillation of TMX-306 significantly reduced the pulmonary fibrogranulomatous response and the number of silica particles in lung interstitial space in silicotic mice. These findings highlight the potential of TMX-306, emphasizing its value in drug development for lung diseases, and particularly silicosis

Ansiedade em universitários iniciantes de cursos da área da saúde / Anxiety in university beginners of health courses

O transtorno de ansiedade é considerado uma associação de sentimentos, como o medo, a angústia e a preocupação. Esse transtorno vem sendo considerado o mal do último século, dadas as mudanças significativas ocorridas na atual sociedade moderna, tecnológica e competitiva. A entrada do estudante no ensino superior é cercada de muita expectativa, nesse contexto, o ambiente universitário gera um cenário desgastante que pode provocar transtornos ansiosos nos estudantes. Dessa forma, objetivou-se investigar os níveis de ansiedade em alunos universitários de 1º período nos cursos da área da saúde da UniFacema. Esse estudo trata-se de uma pesquisa de campo, exploratória, descritiva, de corte transversal, com abordagem quantitativa. A amostra desse estudo foi constituída por 199 acadêmicos de ambos os sexos, dos primeiros períodos de cursos na área da saúde. Utilizou-se como instrumentos de coleta de dados um questionário sociodemográfico e a Escala de Ansiedade de Zung. Como resultados constatou-se que ser do sexo feminino, ser divorciado, mudar da sua localidade para estudar, cursar Odontologia ou Educação Física configuraram-se como fator de risco para ansiedade. Conclui-se que o início da graduação é um momento novo e que muitas vezes podem deixar o sujeito ansioso, diante disso, foram observados níveis normais de ansiedade e ainda, ansiedade leve. Neste ponto, observa-se a importância de uma abordagem multidisciplinar a estes acadêmicos, com ênfase nos cuidados psicológicos, destacando o papel do psicólogo para a prevenção de quadros de ansiedade patológica