Combined exercise on fatigue, quality of life and physical functioning in people under chemotherapy with oxaliplatin: Systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of combined exercise on fatigue, anxiety, depression, quality of life and physical functioning in gastroinstestinal neoplasm in people under chemotherapy with oxaliplatin treatment. METHODS: We searched pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (until Nov 2023) for randomized controlled trials that investigated the effects of combined exercise in gastroinstestinal neoplasm people under chemotherapy with oxaliplatin treatment. Two comparisons were made: combined exercise versus usual care, combined aerobic and versus usual care (follow up). The main outcomes were muscle strength, aerobic capacity, fatigue, anxiety, depression and quality of life. Mean differences (MD) with 95% confidence interval (CI) were calculated. RESULTS: Seven randomized controlled trials met the eligibility criteria, which included 464 people. Compared to usual care, combined aerobic and resistance resulted in decrease of general fatigue (-2.82; IC: 4.92 to -0.69, N = 48), physical fatigue (-5.08; IC: 8.41 to -1.74, N = 48) and improvement of domain physical functioning of quality of life (9.40; IC: 2.74 to 16.06, N = 48). Compared to usual care, combined aerobic and resistance - Follow up resulted in decrease of general fatigue (-2.32; IC: 4.41 to - 0.28, N = 48), physical fatigue (-0.92; IC: 3.31 to -1.47, N = 48) and improvement ofdomain physical functioning of (9.83; IC: 0.66 to 19.01, N = 48). CONCLUSIONS: Our results demonstrate that combined exercises improves fatigue (general; physical), domain physical functioning of quality of life in gastrointestinal neoplasm people under chemotherapy treatment when compared to usual care.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Decellularized Bovine Skeletal Muscle Scaffolds: Structural Characterization and Preliminary Cytocompatibility Evaluation.

Skeletal muscle degeneration is responsible for major mobility complications, and this muscle type has little regenerative capacity. Several biomaterials have been proposed to induce muscle regeneration and function restoration. Decellularized scaffolds present biological properties that allow efficient cell culture, providing a suitable microenvironment for artificial construct development and being an alternative for in vitro muscle culture. For translational purposes, biomaterials derived from large animals are an interesting and unexplored source for muscle scaffold production. Therefore, this study aimed to produce and characterize bovine muscle scaffolds to be applied to muscle cell 3D cultures. Bovine muscle fragments were immersed in decellularizing solutions for 7 days. Decellularization efficiency, structure, composition, and three-dimensionality were evaluated. Bovine fetal myoblasts were cultured on the scaffolds for 10 days to attest cytocompatibility. Decellularization was confirmed by DAPI staining and DNA quantification. Histological and immunohistochemical analysis attested to the preservation of main ECM components. SEM analysis demonstrated that the 3D structure was maintained. In addition, after 10 days, fetal myoblasts were able to adhere and proliferate on the scaffolds, attesting to their cytocompatibility. These data, even preliminary, infer that generated bovine muscular scaffolds were well structured, with preserved composition and allowed cell culture. This study demonstrated that biomaterials derived from bovine muscle could be used in tissue engineering.

New Trends to Treat Muscular Atrophy: A Systematic Review of Epicatechin.

Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several studies present contradictory results of treatment protocols and therapeutic effects. Therefore, the objective of this systematic review was to investigate the current literature showing the molecular mechanism and clinical protocol of epicatechin in muscle atrophy in humans, animals, and myoblast cell-line. The search was conducted in Embase, PubMed/MEDLINE, Cochrane Library, and Web of Science. The qualitative analysis demonstrated that there is a commonness of epicatechin inhibitory action in myostatin expression and atrogenes MAFbx, FOXO, and MuRF1. Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin). Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise. Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.

Unraveling the rationale and conducting a comprehensive assessment of KD025 (Belumosudil) as a candidate drug for inhibiting adipogenic differentiation-a systematic review.

Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.

Comparing Single-Item and Multi-Item Trust Scales: Insights for Assessing Trust in Project Leaders.

The purpose of this research is to provide researchers and leaders with a reliable and up-to-date comparison between a single-item and a multi-item trust scale, enabling effective assessment of team members' trust in their leaders. The aim of the study is to investigate whether a single-question scale is as reliable as a multi-item questionnaire in measuring trust. An additional goal is to provide researchers with insights and conditions for effectively using single or multiple measures to assess trust in leaders, considering factors like reliability and effectiveness. After conducting a comprehensive literature review, data were collected from 101 project members in Brazil using a survey methodology. The respondents were asked to provide feedback regarding their leaders, specifically project managers, and factor analysis was then employed to test the single-item and multi-item measures of trust. The advantages and disadvantages of each approach are discussed. The findings of our study demonstrate that both single-item and multi-item scales of trust should be utilized to gain a more comprehensive understanding of the trust construct. Single-item questionnaires can reduce survey length, improve respondent friendliness, and increase participant willingness. On the other hand, multi-item questionnaires enable researchers to analyze latent variables that contribute to an overall variable, but they cannot isolate data for each of those constructs. The results show that both measures are reliable, providing researchers and professionals with insights into the benefits and drawbacks associated with each method. Consequently, this research equips researchers and project professionals with valuable information for selecting the appropriate measurement tool.

Temporal response of post-activation performance enhancement induced by a plyometric conditioning activity.

Introduction: To better understand the post-activation performance enhancement (PAPE) effect promoted by a plyometric conditioning activity (CA), the aim of this study was to investigate the temporal response of PAPE after a plyometric CA. Methods: Fourteen healthy and active adults visited the laboratory 3 times, with an interval of 7 days between each visit. On the first day they were familiarized with the countermovement jump (CMJ) test and plyometric CA. In the second and third visits, participants performed either plyometric CA or control (remaining seated) in a crossover design. The CMJ test was performed pre and 1-, 3-, 6-, and 9-min post the plyometric CA or control. The comparisons were performed using the repeated measure two-factor ANOVA and Bonferroni adjustment (significance level adopted P ≤ 0.05). Results: Time (P < 0.01), condition (P < 0.01), and interaction (P < 0.01) effects were reported for CMJ comparisons. For the control condition, CMJ increased at 3 min compared to pre (P = 0.03) and at 3 min compared to 1 min (P = 0.03). For the plyometric CA, CMJ increased at 1- (P < 0.01), 3- (P < 0.01), and 6-min (P = 0.02) compared to pre. For condition comparisons, CMJ was different at 1- (P < 0.01), 3- (P < 0.01), 6- (P < 0.01), and 9-min (P = 0.02). The Effect size of the comparisons of all moments compared to pre was null (d < 0.20) for control and small (d < 0.50) for plyometric CA. Discussion: It is possible to conclude that the plyometric CA promoted a PAPE effect for up to 9-min. Strength and conditioning coaches and practitioners may consider multiple sets of plyometric CA to produce immediate enhancement of power in the lower limbs.

Effect of Combined Training on Body Image, Body Composition and Functional Capacity in Patients with Breast Cancer: Controlled Clinical Trial.

OBJECTIVE: Evaluate the effect of combined training on body image (BI), body composition and functional capacity in patients with breast cancer. As also the relationship of BI with body composition and functional capacity. METHODS: This was a Controlled Clinical Trial study, this study including 26 patients with breast cancer (30 to 59 years). The training group (n = 13) underwent 12 weeks of training, including three 60-min sessions of aerobic exercise and resistance training, and two sessions of flexibility training per week; each flexibility exercise lasted 20s. The Control Group (n = 13) received only the standard hospital treatment. Participants were evaluated at baseline and after 12 weeks. BI (primary outcomes) was assessed using the Body Image After Breast Cancer Questionnaire; Body composition was estimated with the indicators: Body mass index; Weight, Waist hip Ratio; Waist height ratio; Conicity index; Reciprocal ponderal index; Percentage of fat; Circumference of the abdomen and waist; Functional capacity by cardiorespiratory fitness (cycle ergometer) and strength (manual dynamometer). The statistic was performed in the Biostatistics and Stata 14.0 (α = 5%). RESULTS: The patients in the training group showed a reduction in the limitation dimension (p = 0.036) on BI, However, an increase in waist circumference was observed in both groups. In addition an increase in VO2max (p < 0.001) and strength in the right (p = 0.005) and left arms (p = 0.033). CONCLUSION: Combined training demonstrates to be an effective and non-pharmacological strategy to patients with breast cancer, with improvement on BI and functional capacity, changing related variables negatively when there is no physical training.

OBJETIVO: Avaliar o efeito do treinamento combinado na imagem corporal (IB), composição corporal e capacidade funcional em pacientes com câncer de mama. Assim como a relação do IB com a composição corporal e capacidade funcional. MéTODOS:: Este foi um estudo de Ensaio Clínico Controlado, este estudo incluiu 26 pacientes com câncer de mama (30 a 59 anos). O grupo de treinamento (n = 13) foi submetido a 12 semanas de treinamento, incluindo três sessões de 60 min de exercício aeróbio e treinamento de resistência, e duas sessões de treinamento de flexibilidade por semana; cada exercício de flexibilidade durou 20s. O Grupo Controle (n = 13) recebeu apenas o tratamento hospitalar padrão. Os participantes foram avaliados no início e após 12 semanas. O IB (desfechos primários) foi avaliado por meio do Body Image After Breast Cancer Questionnaire; A composição corporal foi estimada com os indicadores: índice de massa corporal; Peso, relação cintura-quadril; Relação da altura da cintura; Índice de conicidade; Índice ponderal recíproco; Porcentagem de gordura; Circunferência do abdômen e cintura; Capacidade funcional por aptidão cardiorrespiratória (cicloergômetro) e força (dinamômetro manual). A estatística foi realizada na Bioestatística e no Stata 14.0 (α = 5%). RESULTADOS: Os pacientes do grupo de treinamento apresentaram redução da dimensão da limitação (p = 0,036) no IB, porém, foi observado aumento da circunferência da cintura em ambos os grupos. Além disso, um aumento do VO2máx (p <0,001) e da força nos braços direito (p = 0,005) e esquerdo (p = 0,033). CONCLUSãO:: O treinamento combinado demonstra ser uma estratégia eficaz e não farmacológica para pacientes com câncer de mama, com melhora do IB e da capacidade funcional, alterando variáveis relacionadas negativamente quando não há treinamento físico.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

Effect of Combined Training on Body Image, Body Composition and Functional Capacity in Patients with Breast Cancer: Controlled Clinical Trial / Efeito do treinamento combinado na imagem corporal, composição corporal e capacidade funcional em pacientes com câncer de mama: ensaio clínico controlado

Abstract Objective Evaluate the effect of combined training on body image (BI), body composition and functional capacity in patients with breast cancer. As also the relationship of BI with body composition and functional capacity. Methods This was a Controlled Clinical Trial study, this study including 26 patients with breast cancer (30 to 59 years). The training group (n = 13) underwent 12 weeks of training, including three 60-min sessions of aerobic exercise and resistance training, and two sessions of flexibility training per week; each flexibility exercise lasted 20s. The Control Group (n = 13) received only the standard hospital treatment. Participants were evaluated at baseline and after 12 weeks. BI (primary outcomes) was assessed using the Body Image After Breast Cancer Questionnaire; Body composition was estimated with the indicators: Body mass index; Weight, Waist hip Ratio; Waist height ratio; Conicity index; Reciprocal ponderal index; Percentage of fat; Circumference of the abdomen and waist; Functional capacity by cardiorespiratory fitness (cycle ergometer) and strength (manual dynamometer). The statistic was performed in the Biostatistics and Stata 14.0 (α = 5%). Results The patients in the training group showed a reduction in the limitation dimension (p = 0.036) on BI, However, an increase in waist circumference was observed in both groups. In addition an increase in VO2max (p < 0.001) and strength in the right (p = 0.005) and left arms (p = 0.033). Conclusion Combined training demonstrates to be an effective and non-pharmacological strategy to patients with breast cancer, with improvement on BI and functional capacity, changing related variables negatively when there is no physical training.

Resumo Objetivo Avaliar o efeito do treinamento combinado na imagem corporal (IB), composição corporal e capacidade funcional em pacientes com câncer de mama. Assim como a relação do IB com a composição corporal e capacidade funcional. Métodos Este foi um estudo de Ensaio Clínico Controlado, este estudo incluiu 26 pacientes com câncer de mama (30 a 59 anos). O grupo de treinamento (n = 13) foi submetido a 12 semanas de treinamento, incluindo três sessões de 60 min de exercício aeróbio e treinamento de resistência, e duas sessões de treinamento de flexibilidade por semana; cada exercício de flexibilidade durou 20s. O Grupo Controle (n = 13) recebeu apenas o tratamento hospitalar padrão. Os participantes foram avaliados no início e após 12 semanas. O IB (desfechos primários) foi avaliado por meio do Body Image After Breast Cancer Questionnaire; A composição corporal foi estimada com os indicadores: índice de massa corporal; Peso, relação cintura-quadril; Relação da altura da cintura; Índice de conicidade; Índice ponderal recíproco; Porcentagem de gordura; Circunferência do abdômen e cintura; Capacidade funcional por aptidão cardiorrespiratória (cicloergômetro) e força (dinamômetro manual). A estatística foi realizada na Bioestatística e no Stata 14.0 (α = 5%). Resultados Os pacientes do grupo de treinamento apresentaram redução da dimensão da limitação (p = 0,036) no IB, porém, foi observado aumento da circunferência da cintura em ambos os grupos. Além disso, um aumento do VO2máx (p <0,001) e da força nos braços direito (p = 0,005) e esquerdo (p = 0,033). Conclusão O treinamento combinado demonstra ser uma estratégia eficaz e não farmacológica para pacientes com câncer de mama, com melhora do IB e da capacidade funcional, alterando variáveis relacionadas negativamente quando não há treinamento físico.

A Specific Pattern and Dynamics of Circulating Cytokines Are Associated with the Extension of Lung Injury and Mortality in Colombian Adults with Coronavirus Disease-19.

Increased systemic levels of inflammatory cytokines have been associated with the development of pathophysiologic events during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To further explore differences in the pattern and dynamics of plasma cytokines in individuals with coronavirus disease-19 (COVID-19), and the relationship with disease mortality, here we evaluated the plasma levels of proinflammatory and regulatory cytokines in Colombian patient survivors and nonsurvivors of SARS-CoV-2 infection. Individuals with confirmed COVID-19, with other respiratory diseases requiring hospitalization, and healthy controls, were included. Plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-γ, IL-10, soluble tumor necrosis factor receptor I (sTNFRI), and transforming growth factor-ß1 were measured by a bead-based assay or enzyme-linked immunosorbent assay and clinical, laboratory, and tomographic parameters were registered during hospitalization. The levels of most of the evaluated cytokines were increased in COVID-19 individuals relative to healthy controls. The levels of IL-6, IL-10, and sTNFRI were directly associated with the development of respiratory failure, immune dysregulation, and coagulopathy, as well as with COVID-19 mortality. Particularly, the early, robust, and persistent increase of circulating IL-6 characterized COVID-19 nonsurvivors, while survivors were able to counteract the inflammatory cytokine response. In addition, IL-6 systemic levels positively correlated with the tomographic extension of lung damage in individuals with COVID-19. Thus, an exacerbated inflammatory cytokine response, particularly mediated by IL-6 added to the inefficiency of regulatory cytokines, distinguishes COVID-19-associated tissue disturbances, severity, and mortality in Colombian adults.

Alternative culture medium design for biomass production of autochthonous meat starter Latilactobacillus sakei sp. sakei ACU-2.

The autochthonous strain Latilactobacillus sakei sp. sakei ACU-2 was selected as a meat starter culture for dry sausage production. Transferring this strain from laboratory scale to industry requires an increase in biomass production, while lowering process costs. In this study, a combination of techniques was applied in order to optimize the culture medium composition to enhance biomass production of L. sakei ACU-2. One variable at a time experiments, Plackett-Burman design, and mixture design were performed to fulfill the strain nutritional requirements. Eventually, the optimized formulation contained 19.46 g/L yeast extract; 8.28 g/L whey protein concentrate; 2.26 g/L soy peptone; 30 g/L cerelose; 1 g/L Tween 80; 5 g/L sodium acetate; 0.2 g/L magnesium sulfate and 0.05 g/L manganese sulfate. When L. sakei ACU-2 was cultivated in a bioreactor using the alternative medium, an enhancement of 75.5% of biomass production was achieved, in comparison to its growth in the commercial de Man, Rogosa, and Sharpe medium. Furthermore, a reduction of 62-86% of the cost was also attained. These results support a promising large-scale application of the designed medium for high biomass yields of the starter culture at minor costs.

A systematic review on physical function, activities of daily living and health-related quality of life in COVID-19 survivors.

OBJECTIVE: To analyze the published studies that investigated the physical function, activities of daily living and health-related quality of life in COVID-19 survivors. DESIGN: Systematic review. METHODS: We searched MEDLINE/PubMed, Scopus, SciELO, and Cochrane Library for studies that evaluated the physical function, activities of daily living and health-related quality of life after COVID-19 from the earliest date available to July 2021. Two independent reviewers screened and selected the studies. The Newcastle Ottawa Scale was used to evaluate methodological quality. RESULTS: We included 35 studies in this systematic review. Of the 35 studies included, 28 were cohort, and 7 cross-sectional studies The studies demonstrated that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Furthermore, incomplete recovery of physical function, and performance in activities of daily living were observed 1 to 6 months post-infection. DISCUSSION: Physical disability and reduction in health-related quality of life is a common condition in post-COVID-19 and impairments may persist up to 1 to 6 months. Researchers and clinicians can use these findings to understand the potential disabilities and rehabilitation needs of people recovering from the COVID-19.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados "respondedores verdadeiros". No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression.

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as a significant contributing factor. It involves the activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and chemokines and the infiltration of peripheral leukocytes into the central nervous system (CNS). These instances result in neuronal damage and neurodegeneration through activated nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa B (NF-kB) pathways and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Due to limited effectiveness regarding the inhibition of neuroinflammatory targets using conventional drugs, there is challenging growth in the search for innovative therapies for alleviating neuroinflammation in CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling and Expression, Cold Exposure, and Fibrin-Targeted strategies significantly promise to mitigate neuroinflammatory processes. These approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such as Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson's Disease, and Alzheimer's Disease. While the findings are promising, immunomodulatory therapies often face limitations due to Immune-Related Adverse Events. Therefore, the conduction of randomized clinical trials in this matter is mandatory, and will pave the way for a promising future in the development of new medicines with specific therapeutic targets.

Neurohumoral response and stress hyperglycemia in myocardial infarction.

Background: Hyperglycemia is associated with an increased risk for death in acute coronary syndromes. This could be related to underlying glucose metabolism abnormalities or be caused by a counter-regulatory stress response. However, there is a paucity of data on the relationship between stress hormones, hyperglycemia, and clinical outcomes in myocardial infarction. Methods: Single-center, prospective, observational study. Patients admitted to the coronary care unit with a diagnosis of myocardial infarction were included. On admission, blood samples were obtained to measure serum glucose, cortisol, and catecholamines. A second sample was obtained at 8 AM after 48 h from admission. Results: There was a mild and positive correlation between serum cortisol and glucose (Spearman's rho = 0.24, p = 0.005), and no significant correlation was found between glucose and catecholamines. A similar correlation between cortisol and glucose among diabetics and non-diabetics was observed. Significantly higher serum cortisol and glucose levels were present in patients who developed heart failure or died during hospitalization. The association between glycemia and mortality lost significance in multivariate analysis, with a significant interaction term with cortisol (p = 0.003). Conclusion: Cortisol is a key responsible for stress hyperglycemia, and its deleterious effects on the cardiovascular system could be the cause for worst outcomes associated with hyperglycemia in ACS. Further research is warranted to ascertain this relationship and to investigate potential therapeutic targets.

First molecular detection of canine herpesvirus 1 (CaHV-1) in the Eastern Brazilian Amazon.

BACKGROUND: Canine herpesvirus type 1 (CaHV-1) infects dogs and is associated with neonatal deaths and reproductive, ocular, neurological, and respiratory problems. In Brazil, reports of CaHV-1 have been restricted to the southeast and south regions, particularly in municipalities in the state of Rio Grande do Sul. OBJECTIVES: To assess the presence and variability of CaHV-1 in canine populations in the state of Pará, North Brazil. METHODS: Biological samples from 159 dogs from 4 municipalities in the State of Pará were evaluated using polymerase chain reaction and phylogenetic analyses, with the target being the viral enzyme, thymidine kinase. RESULTS: CaHV-1 was detected in 13 dogs (8.2%), with 2 animals being from the municipality of Santa Bárbara do Pará, 8 from Algodoal Island, 2 from Salinópolis, and one from Capanema. The study sequences revealed 100% identity among themselves and 64% to 100% identity with the other nucleotide sequences from Australia, Brazil, United Kingdom, and United States, including 100% identity with the 2002 isolate from Australia. The 1996 isolate from France was grouped in a branch that was different from the sequence of this study. CONCLUSIONS: This study presents the first molecular detection of CaHV-1 in dogs from the Amazon region in northern Brazil. The nucleotide identity between the strains and cytosine insertion in the sequences isolated in this study suggests at least 2 strains of CaHV-1 circulating in Brazil (Pará and BTU-1).

Atualização no Tratamento da Hipertensão Arterial Pulmonar / Update on the Treatment of Pulmonary Arterial Hypertension

Resumo Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Abstract In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

"Inflammatory peritonitis in a child with COVID-19″.

COVID-19 is the disease caused by SARS-COV-2 coronavirus infection (Severe acute respiratory syndrome coronavirus 2). Although its most prevalent symptoms are respiratory, there are descriptions of gastrointestinal manifestations in children, but the presentation as an acute abdomen is rare. We report the case of a 6-month-old infant who was admitted with a diagnosis of intestinal obstruction and generalized peritonitis with no apparent cause, in whom a SARS-CoV-2 rt-PCR search was positive. We have not found descriptions of similar cases in the literature so far.