Abstract The COVID-19 pandemic has been the largest pandemic of the past century, and various genetic factors have played a significant role in this context. This study aimed to analyze the frequency and association between specific SNPs rs3806268 (NLRP3), rs4925543 (NLRP3), rs12150220 (NLRP1), rs455060 (NLRC4), rs699 (AGT), rs1137101 (LEPR), and rs1801133 (MTHFR) and severe/critical outcomes in Brazilian patients with COVID-19. A total of 100 patients were included in the study, comprising 66 cases and 34 controls. DNA was extracted, sequenced, and genotyped via next-generation sequencing (NGS). For non-parametric data, the Mann-Whitney and Kruskal-Wallis tests were used. Fisher’s test and multivariate logistic regression, considering AIC and BIC criteria, were employed for risk analysis. Odds Ratios (OR) were calculated, with significance set at p<0.05. Among the seven evaluated SNPs, only rs699-GG (AGT) (OR=8.07; p=0.04) was significantly associated with an increased risk of developing severe/critical COVID-19. Moreover, a borderline protective association was noted between rs1801133-GA (MTHFR) and the disease, although lacking statistical significance. In conclusion, the SNP rs699-GG (AGT) was associated with an increased risk of severe/critical COVID-19. COVID19 COVID 19 COVID-1 century context rs rs380626 NLRP3, NLRP3 NLRP , (NLRP3) rs492554 rs1215022 NLRP1, NLRP1 (NLRP1) rs45506 NLRC4, NLRC4 NLRC (NLRC4) rs69 AGT, AGT rs113710 LEPR, LEPR (LEPR) rs180113 MTHFR (MTHFR severecritical severe critical COVID19. 19. 10 6 3 controls extracted sequenced nextgeneration next generation NGS. NGS . (NGS) nonparametric non parametric data MannWhitney Mann Whitney KruskalWallis Kruskal Wallis used Fishers Fisher s regression criteria analysis OR (OR calculated p005 p 0 05 p<0.05 rs699GG rsGG GG (AGT OR=8.07 OR807 8 07 (OR=8.07 p=0.04 p004 04 Moreover rs1801133GA rsGA GA disease conclusion COVID1 1 COVID- rs38062 (NLRP3 rs49255 rs121502 (NLRP1 rs4550 (NLRC4 rs6 rs11371 (LEPR rs18011 (NGS p00 p<0.0 OR=8.0 OR80 (OR=8.0 p=0.0 rs3806 (NLRP rs4925 rs12150 rs455 (NLRC rs1137 rs1801 p0 p<0. OR=8. OR8 (OR=8. p=0. rs380 rs492 rs1215 rs45 rs113 rs180 p<0 OR=8 (OR=8 p=0 rs38 rs49 rs121 rs4 rs11 rs18 p< OR= (OR= p= rs3 rs12 rs1

RESUMO Este estudo objetivou comparar os efeitos agudos entre uma sessão de treinamento de força de alta versus moderada intensidade sobre marcadores inflamatórios em mulheres com obesidade severa. Estudo experimental do tipo cross-over, realizado com mulheres adultas com obesidade severa (IMC ≥ 40,0 kg/m²; idade ≥ 18 anos). Cada participante realizou uma sessão de treinamento de força de alta e de moderada intensidade (HIRT e MIRT, respectivamente) com intervalo de 7 dias entre as sessões. Quatro exercícios foram realizados em ambos os protocolos, com volume total de treino equalizado. O MIRT consistiu em 3 séries de 8 repetições cada, com intensidade de 75% de 1RM, enquanto o HIRT consistiu em 2 séries de 6 repetições, seguidas de um descanso de 20 segundos, com nova execução de 2 a 3 repetições, com mais um descanso de 20s e finalização com mais 2 a 3 repetições, com intensidade de 85% de 1RM. Amostras de sangue foram coletadas antes, 15 minutos após e 24 horas após ambos os protocolos de treino. Os marcadores inflamatórios analisados foram IL-2, IL-4, IL-6, IL-10, TNF-α e IFN-γ. Nove participantes completaram a intervenção (n=9; 35,2 ± 10,93 anos; IMC = 48,3 ± 5,06 kg/m²). O teste U de Mann-Whitney mostrou que não houve diferença significativa entre HIRT e MIRT na concentração dos marcadores. O teste de Friedman não mostrou diferenças significativas entre as medidas intragrupo para HIRT e MIRT. Esta pesquisa sugere que uma única sessão de treinamento de força de alta ou moderada intensidade não altera o estado inflamatório de mulheres com obesidade severa.

ABSTRACT This study objective to compare the acute effects between one resistance training bout with high versus moderate intensities on inflammatory markers in women with severe obesity. Experimental crossover study, performed with adult women with severe obesity (BMI ≥ 40.0 kg/m²; age ≥ 18 years old). Each participant performed a high and moderate intensity resistance training (HIRT and MIRT, respectively) with an interval of 7 days between bouts. Four exercises were performed in the both protocols, with total training volume equalized. MIRT consisted of 3 sets of 8 repetitions each, with an intensity of 75% of 1RM, while HIRT consisted of 2 sets of 6 repetitions, followed by a 20-second rest, with a new performance of 2 to 3 repetitions, with one more rest of 20s and finishing with 2 to 3 more repetitions, at an intensity of 85% of 1RM. Blood samples were collected before, 15 minutes after and 24 hours after both training protocols. The inflammatory markers analyzed were IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ. Nine participants have completed the intervention (n=9; 35.2 ± 10.93 years old; BMI = 48.3 ± 5.06 kg/m²). The Mann-Whitney U test showed that there was no significant difference between the HIRT and MIRT in the concentration of markers. Friedman's test did not report significant differences between intragroup measures for the HIRT as well as MIRT. This research suggests that a single session of high or moderate intensity resistance training does not change the inflammatory status of women with severe obesity.

RESUMO Objetivo O objetivo deste estudo foi avaliar a cinética diafragmática, a função respiratória e a dosagem sérica de leptina e citocinas inflamatórias (IL-6 e TNF-α) em três grupos clínicos: obeso, asmático e saudável. Métodos Estudo clínico-exploratório realizado com 73 jovens (12-24 anos, sendo 42,5% do sexo masculino) alocados em três grupos: obesidade (GO, n = 33), índice de massa corporal (IMC z-score) ≥ + 2 e asmáticos leves controlados (GA, n = 26), classificados pela GINA, e grupo controle saudável (GC, n = 14). Os participantes foram submetidos à ultrassonografia diafragmática, espirometria, pressão respiratória máxima, níveis séricos de leptina e níveis de IL-6 e TNF-α em hemocultura total. Resultados A espessura do diafragma foi maior no GO em comparação ao GA e GC (2,0 ± 0,4 vs 1,7 ± 0,5 e 1,6 ± 0,2, respectivamente, com p < 0,05). A ventilação voluntária máxima (VVM) foi significativamente menor no GO e GA em relação ao GC (82,8 ± 21,4 e 72,5 ± 21,2 vs 102,8 ± 27,3, respectivamente, com p < 0,05). O GO tem a maior taxa de leptina entre todos os grupos (com os outros dois grupos, p < 0,05). Os três grupos tinham níveis semelhantes de TNF-α e IL-6. Conclusão A hipertrofia muscular encontrada no diafragma de indivíduos obesos pode ser justificada pelo aumento do trabalho respiratório imposto pela condição crônica da doença. Esse aumento de espessura não ocorreu em asmáticos leves controlados. Os marcadores IL-6 e TNF-α não detectaram evidências de inflamação muscular, embora fosse esperado que a leptina estivesse alterada em indivíduos obesos. Pacientes obesos e asmáticos apresentaram menor resistência pulmonar do que os saudáveis.

ABSTRACT Objective The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-α) in three clinical groups: obese, asthmatic, and healthy. Methods This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) ≥ +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-α whole blood cell culture levels. Results Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-α and IL-6 levels. Conclusion The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-α markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.

Resumo Fundamento: As pessoas que vivem com HIV têm um risco aumentado de doença cardiovascular e espessamento da carótida, devido à inflamação causada pelo vírus, à terapia antirretroviral e a outros fatores de risco. No entanto, poucos estudos observaram a ocorrência de doenças cardiovasculares e espessamento carotídeo na população soropositiva com baixo risco cardiovascular e carga viral indetectável. Objetivos: Avaliar a associação entre níveis de marcadores inflamatórios e espessura da carótida em pessoas vivendo com HIV, sob terapia antirretroviral e com baixo risco cardiovascular. Métodos: Para determinar o baixo risco cardiovascular em ambos os grupos (indivíduos infectados e não-infectados pelo HIV), foi utilizado o Escore de Risco de Framingham. Os marcadores inflamatórios (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1 e sICAM-1) foram avaliados por citometria de fluxo. A espessura da carótida (mm) foi mensurada por meio de ultrassom com Doppler. O nível de significância foi de p < 0,05. Resultados: Em pessoas vivendo com HIV, a idade e o tabagismo foram associados a alterações da espessura da carótida. No grupo não-HIV, idade e níveis mais altos de colesterol total e LDL foram associados ao aumento da espessura da carótida. Utilizando a análise multivariada, observou-se associação significativa entre os níveis de TNF-α e IL-1β e maior chance de desenvolvimento de aterosclerose no grupo com HIV. Conclusão: Ambos os grupos têm risco semelhante de desenvolver doença cardiovascular, portanto, nosso estudo demonstra que indivíduos HIV-positivos com carga viral indetectável em terapia antirretroviral sem inibidores de protease e com baixo risco cardiovascular não apresentam diferenças na espessura da carótida em relação aos indivíduos não-infectados.

Abstract Background: People living with HIV are at increased risk of cardiovascular disease and carotid thickness, due to the inflammation caused by the virus, the antiretroviral therapy, and other risk factors. However, few studies have observed the occurrence of cardiovascular diseases and carotid thickness in HIV-positive population at low cardiovascular risk and with undetectable viral load. Objectives: To evaluate the association between levels of inflammatory markers and carotid thickness in people living with HIV, under antiretroviral therapy and at low cardiovascular risk. Methods: To determine low cardiovascular risk in both groups (HIV infected and non-infected individuals), the Framingham Risk Score was used. Inflammatory markers (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1, and sICAM-1) were assessed using flow cytometry. Carotid thickness (mm) was measured using Doppler ultrasound. Level of significance was p < 0.05. Results: In People living with HIV, age and smoking status were associated with carotid thickness alterations. In the non-HIV group, age, higher total cholesterol, and LDL levels were associated with increased carotid thickness. Using the multivariate analysis, a significant association between TNF-α and IL- 1( levels, and a higher chance of atherosclerosis development in HIV group were observed. Conclusions: Both groups have a similar risk for developing cardiovascular disease, therefore our study demonstrates that HIV-positive individuals with undetectable viral load in antiretroviral therapy without protease inhibitors and with low cardiovascular risk do not present differences in carotid thickness in relation to uninfected individuals.

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined.

BACKGROUND The severity of chronic chagasic cardiomyopathy (CCC), the most frequent clinical outcome of Chagas disease (CD), has been associated with cytokine-enriched heart tissue inflammation, and high serum levels of transforming growth factor (TGFβ), interferon-gamma (IFNγ), and tumour necrosis factor (TNF). Conversely, increased interleukin (IL)-10 serum concentrations have been associated with asymptomatic CD. Cytokines and cytokine-related gene polymorphisms may control cytokine expression and have been proposed to contribute to CCC outcomes. OBJECTIVES We evaluated the association of 13 cytokine-related genes (TGFB: rs8179181, rs8105161, rs1800469; IL10: rs1800890, rs1800871, rs1800896; IFNG: rs2430561; TNF: rs1800629; BAT1: rs3853601; LTA: rs909253, rs2239704; TNFR1: rs767455; TNFR2: rs1061624) with risk and progression of CCC. FINDINGS Four hundred and six seropositive patients from CD endemic areas in the state of Pernambuco, north-eastern Brazil, were classified as non-cardiopathic (A, 110) or cardiopathic (mild, B1, 163; severe, C, 133). We found no evidence of TGFB, IL10, TNF, or TNFR1/2 gene polymorphisms associated with CCC risk or progression. Only BAT1 rs3853601 −22G carriers (B1 vs. C: OR = 0.5; p-value = 0.03) and IFNG rs2430561 +874AT (A vs. C: OR = 0.7; p-value = 0.03; A vs. B1+C: OR = 0.8; p-value = 0.02) showed a significant association with protection from cardiopathy in a logistic regression analysis with adjustment for gender and ethnicity; however, the association disappeared after performing adjustment for multiple testing. A systematic review of TNF rs1800629 −308G>A publications included five studies for meta-analysis (534 CCC and 472 asymptomatic patients) and showed no consensus in pooled odds ratio (OR) estimates for A allele or A carriers (OR = 1.4 and 1.5; p-values = 0.14 and 0.15, respectively). In CD patients, TNF serum levels were increased, but not affected by the TNF rs1800629 −308A allele. MAIN CONCLUSIONS Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes.

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

O uso dos inibidores do fator de necrose tumoral no tratamento de pacientes com psoríase vem sendo relacionado a uma maior incidência de tuberculose, particularmente, nas suas formas extrapulmonar e disseminada. Apesar de sua indiscutível eficácia, essas drogas elevam o risco da reativação de infecção tuberculosa latente (ITBL), tornando obrigatório o diagnóstico da referida condição antes da sua administração. A investigação da infecção tuberculosa latente pelo teste cutâneo da tuberculina é falha, dada sua baixa especificidade, além de apresentar resultados duvidosos em pacientes com psoríase. Ensaios baseados na detecção da produção de interferon-gama in vitro por células monoclonais periféricas, estimuladas por antígenos específicos (Esat-6 e CFP-10), parecem oferecer maior acurácia quando comparados ao teste de Mantoux na identificação de infecção tuberculosa latente. Essa ferramenta diagnóstica tem oferecido maior especificidade, já que não apresenta correlação com medidas indiretas de exposição ao M. tuberculosis, como a vacinação por BCG, e com infecções por outras micobactérias