Obesity influences T CD4 lymphocytes subsets profiles in children and adolescent's immune response.

PURPOSE: Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation occurring in adults with the disease. Since the profile of these cells is poorly understood in the pediatric population, the present study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. METHODS: Using flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n=20) to those with eutrophy (EU group, n=16). Plasma levels of cytokines in both groups were determined by CBA. RESULTS: The OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared to the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, while CTLA-4 is decreased in all subpopulations compared to the EU group. Furthermore, Th2, Th17 and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. CONCLUSION: CD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

COVID-19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances.

In the 2 years since the COVID-19 pandemic was officially declared, science has made considerable strides in understanding the disease's pathophysiology, pharmacological treatments, immune response, and vaccination, but there is still much room for further advances, especially in comprehending its relationship with obesity. Science has not yet described the mechanisms that explain how obesity is directly associated with a poor prognosis. This paper gathers all published studies over the past 2 years that have described immune response, obesity, and COVID-19, a historical and chronological record for researchers and the general public alike. In summary, these studies describe how the cytokine/adipokine levels and inflammatory markers, such as the C-reactive protein, are associated with a higher body mass index in COVID-19-positive patients, suggesting that the inflammatory background and immune dysregulation in individuals with obesity may be expressed in the results and that adiposity may influence the immune response. The timeline presented here is a compilation of the results of 2 years of scientific inquiry, describing how the science has progressed, the principal findings, and the challenges ahead regarding SARS-CoV-2, COVID-19, and emerging variants, especially in patients with obesity.

Modulation of Regulatory T Cells Activity by Distinct CD80 and CD86 Interactions With CD28/CTLA-4 in Chagas Cardiomyopathy.

Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of the chronic phase of Chagas disease caused by Trypanosoma cruzi infection. It was described as the most fibrosing cardiomyopathies, affecting approximately 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, most patients who progress to the chronic form develop the indeterminate clinical form (IND), may remain asymptomatic for life, or develop some cardiac damage. Some mechanisms involved in the etiology of the clinical forms of Chagas disease have been investigated. To characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4+ (Th1, Th2, Th17, and Treg) and CD8+ T lymphocyte subsets, we used blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with T. cruzi antigens from non-infected (NI), IND, and CARD individuals. We demonstrated a higher frequency of CD8+ CD25+ T lymphocytes and CD8+ Treg cells after anti-CD80 antibody blockade only in the CARD group. In contrast, a lower frequency of CD4+ Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. A higher frequency of CD4+ Treg CD28+ lymphocytes, as well as an association between CD4+ Treg lymphocytes and CD28+ expression on CD4+ Treg cells in the CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade, was observed. We proposed that Treg cells from IND patients could be activated via CD86-CTLA-4 interaction, leading to modulation of the immune response only in asymptomatic patients with Chagas disease, while CD80 may be involved in the proliferation control of T CD8+ lymphocytes, as also in the modulation of regulatory cell activation via CD28 receptor. For the first time, our data highlight the role of CD80 in modulation of Treg lymphocytes activation in patients with CARD, highlighting a key molecule in the development of Chagas cardiomyopathy.

Effects of dipyrone and acetylsalicylic acid on contractions of distal cauda epididymis duct, serum testosterone and sperm count in rats.

The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 µM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1ß, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.

Fluoxetine and sertraline effects on rat distal cauda epididymis contraction, sperm count and sperm transit time trough epididymis.

Fluoxetine and sertraline are antidepressants drugs capable to impair male fertility by decreasing the number of sperm cells in the ejaculate. However, the mechanism underlying these effects is still not fully understood. It is also reported that alterations in epididymis contraction induced by different drugs affect the number of sperm cells, leading to male fertility alterations. Therefore, this study aimed to investigate if both fluoxetine and sertraline could affect the rat epididymis contraction, altering the sperm transit and/or sperm count trough rat epididymis. In vitro effects of fluoxetine and sertraline (1, 3 and 10 µM) were evaluated in isolated distal cauda epididymis of rats by pharmacological experiments. The effects of long-term treatment with fluoxetine and sertraline (20 mg/kg, i.p., 21 days) were also checked on distal cauda epididymis contractions, serum testosterone levels, sperm production, sperm reserves and sperm transit time trough rat epididymis. In vitro fluoxetine and sertraline (>3 µM) impaired the contractions induced by KCl, phenylephrine or carbachol although fluoxetine 1 µM potentiate the phenylephrine-induced contractions. Long-term in vivo treatment with fluoxetine and sertraline promoted: (a) an enhancement of rat distal cauda spontaneous contractions; (b) a potentiation of phenylephrine-induced contractions; (c) a decreased in serum testosterone levels; and (d) a diminished daily sperm production, sperm reserves trough epididymis and sperm transit time in rat cauda epididymis. In conclusion, the alteration in the motor activity of epididymis could be associated to the low sperm count in this organ and accelerated transit time trough epididymal cauda of rats.

Occurrence of Methylmercury in Rice-Based Infant Cereals and Estimation of Daily Dietary Intake of Methylmercury for Infants.

Recent reports of elevated levels of methylmercury (MeHg) in rice revealed the possible occurrence of MeHg in infant rice cereals, leading to potential MeHg exposure through cereal consumption. Total mercury (THg) and MeHg levels in 119 infant cereal samples commonly marketed in the United States and China and estimated daily intake of MeHg through cereal consumption were determined. Concentrations of THg and MeHg in the tested cereal samples ranged from 0.35 to 15.9 µg/kg and from 0.07 to 13.9 µg/kg with means of 2.86 and 1.61 µg/kg, respectively. Rice-based cereals contained MeHg levels significantly higher than those of nonrice cereals, indicating that MeHg in rice could be source of MeHg in cereals. Cereal consumption could be a potential pathway of MeHg exposure for infants, as the EDI through cereal consumption amounted to 4-122% of the MeHg reference dose, suggesting the necessity of further evaluation of the potential health risk of dietary MeHg exposure to infants.

Fatores associados a lesões de pele decorrentes do período intraoperatório / Factors associated with skin lesions resulting during the intraoperative period / Factores asociados a lesiones de piel resultantes del período intraoperatorio

Objetivo: Avaliar a ocorrência de lesões de pele no período intraoperatório decorrentes de procedimentos cirúrgicos realizados em um hospital universitário de grande porte. Método: Estudo transversal, descritivo, com abordagem quantitativa, realizado em um hospital universitário do Recife, Pernambuco, Brasil. A amostra foi constituída de 154 pacientes submetidos a cirurgias eletivas entre os meses de janeiro e abril de 2018, avaliados nos períodos pré e pós-operatório, por meio da aplicação da Escala de Avaliação de Risco para o Desenvolvimento de Lesões Decorrentes do Posicionamento Cirúrgico (ELPO), no intraoperatório. A coleta de dados ocorreu na visita pré-operatória e no primeiro dia de pós-operatório. Resultados: Dos 154 pacientes avaliados, sete apresentaram 11 lesões de pele, como lesões por pressão estágio I, estágio II e abrasão, predominantemente no glúteo e no tórax. As variáveis tempo do procedimento cirúrgico, tipo de anestesia e comorbidades foram os principais fatores de associados à ocorrência das lesões. Conclusão: Entre os pacientes que apresentaram lesões de pele devido ao posicionamento cirúrgico, a maioria foi classificada pela ELPO como alto risco, o que leva a crer que se trata de uma escala adequada para avaliação de risco de lesões de pele em pacientes cirúrgicos

Objective: To evaluate the occurrence of skin lesions in the intraoperative period due to surgical procedures performed at a large university hospital. Method: A cross-sectional, descriptive study with a quantitative approach, performed at a university hospital in Recife, Pernambuco, Brazil. The sample consisted of 154 patients undergoing elective surgeries between January and April 2018. They were evaluated in the pre and postoperative periods, through the application of the Risk Assessment Scale for the Development of Injuries due to Surgical Positioning (ELPO), during the intraoperative period. Data were collected at the preoperative visit and on the first postoperative day. Results: Of the 154 patients evaluated, seven presented 11 skin lesions, such as stage I, stage II and abrasion lesions, predominantly in the gluteus and thorax. The variables length of the surgical procedure, type of anesthesia and comorbidities were the main factors associated with the occurrence of lesions. Conclusion: Among patients who presented skin lesions due to surgical positioning, most were classified by the ELPO as high risk, which suggests that this is a suitable scale for assessing the risk of skin lesions in surgical patients.

Objetivo: Evaluar la ocurrencia de lesiones de piel en el período intraoperatorio resultantes de procedimientos quirúrgicos realizados en un hospital universitario de gran porte. Método: Estudio transversal, descriptivo, con abordaje cuantitativo, realizado en un hospital universitario de Recife, Pernambuco, Brasil. La muestra fue constituida de 154 pacientes sometidos a cirugías electivas entre los meses de enero y abril de 2018, valuados en los períodos pre y postoperatorio, por medio de la aplicación de la Escala de Evaluación de Riesgo para el Desarrollo de Lesiones Debidas al Posicionamiento Quirúrgico (ELPO), en el intraoperatorio. La recolección de datos ocurrió en la visita preoperatoria y en el primer día de postoperatorio. Resultados: De los 154 pacientes evaluados, siete presentaron 11 lesiones de piel, como lesiones por presión estadio I, II y abrasión, predominantemente en el glúteo y en el tórax. Las variables tiempo del procedimiento quirúrgico, tipo de anestesia y comorbilidades fueron los principales factores de asociados a la ocurrencia de las lesiones. Conclusión: Entre los pacientes que representaron lesiones de piel debido al posicionamiento quirúrgico, la mayoría fue clasificada por ELPO como alto riesgo, lo que lleva a creer que se trata de una escala adecuada para la evaluación del riesgo de lesiones de piel en pacientes quirúrgicos