Examining the mediating role of muscle quantity in adolescents: associations with adiposity, cardiorespiratory fitness, muscular fitness, and cardiometabolic risk factors.

The aim of this study was to evaluate the mediation role of muscle quantity in the relationship between physical fitness and cardiometabolic risk factors (CMRF) in adolescents. This cross-sectional study conducted with 120 adolescents of both sexes, aged between 10 and 17 years. Body mass, height, fat mass (FM), lean mass, blood pressure, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, insulin, cardiorespiratory fitness (CRF) and 1 repetition maximum strength (1-RM) with evaluation of the leg press 45° (RM-leg), bench press (RM-bench) and arm curl (RM-arm). Body mass index z-score, appendicular skeletal muscle mass, appendicular skeletal muscle mass index, lean mass index (LMI), muscle-to-fat ratio (MFR), age at peak height velocity, and CMRF z-score were calculated. The direct relation between FM and CMRF was mediated by the LMI (26%) and inverse relation between CRF and CMRF was mediated by the LMI (26%). For girls, the direct relation between FM and CMRF was mediated by the LMI (32%); the inverse relation between CRF, RM-leg, RM-arm and CMRF was mediated by the LMI (32%, 33%, and 32%, respective). For boys, the indirect effect was not significant, indicating that LMI is not a mediator in the relation between FM, CRF, 1-RM with CMRF. The direct relation between RM-leg and CMRF was mediated by the MRF (16%). This finding evidenced the importance of promoting a healthy lifestyle to improve physical fitness levels and the quantity of muscle mass in adolescents.

Screening with urine Histoplasma antigen test in asymptomatic patients starting TNF-alpha inhibitor therapy: a cohort study.

Background: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals. Methods: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis. Results: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive. Conclusion: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.

Using a urine test for fungal infection to screen people without symptoms who are about to start taking immunobiologic medications This study looked at the prevalence of histoplasmosis, a fungal infection, in asymptomatic patients who were about to start treatment with TNF-α inhibitors, which are medications used for autoimmune diseases. The researchers tested urine samples for Histoplasma antigen before the patients started the treatment and followed them for 180 days after starting the medication to see if they developed any symptoms of histoplasmosis. The study included 54 patients in southern Brazil, and they found that 14.8% of the patients tested positive for the Histoplasma antigen before starting the treatment. However, none of the patients, including those who tested positive, developed histoplasmosis during the 6-month follow-up. The researchers concluded that histoplasmosis infection may be more common in these patients than previously thought, but it's still not clear if asymptomatic patients with a positive antigen test will develop the infection when starting TNF-α inhibitor treatment. The study did not find any specific risk factors for developing histoplasmosis in this group of patients, and based on their findings, they did not recommend routine screening or preventive therapy for histoplasmosis before starting TNF-α inhibitor treatment.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Serum metabolites associated with increased insulin resistance and low cardiorespiratory fitness in overweight adolescents.

BACKGROUND AND AIMS: Obesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of normal-weight and overweight adolescents and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. METHODS AND RESULTS: The sample was composed of 57 adolescents and divided into two groups: the normal-weight group (NWG, n = 24) and the overweight group (OWG, n = 33). They underwent blood collection and anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, and percentage of fat mass (%FM) and lower levels of peak oxygen consumption (VO2 peak) compared with the NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared with the NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with %FM; pyruvate and valerate positively correlated with IR; and glutamate, tyrosine, and valerate negatively correlated with CRF. CONCLUSION: Changes in the BC lead to changes in the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results indicate new targets for health monitoring and prevention of cardiovascular and metabolic diseases in adolescents.

Post-acute COVID-19 syndrome after reinfection and vaccine breakthrough by the SARS-CoV-2 Gamma variant in Brazil.

We describe a case of prolonged COVID-19 caused by the SARS-CoV-2 Gamma variant in a fully vaccinated healthcare worker, 387 days after an infection caused by lineage B.1.1.33. Infections were confirmed by whole-genome sequencing and corroborated by the detection of neutralizing antibodies in convalescent serum samples. Considering the permanent exposure of this healthcare worker to SARS-CoV-2, the waning immunity after the first infection, the low efficacy of the inactivated vaccine at preventing COVID-19, the immune escape of the Gamma variant (VOC), and the burden of post-COVID syndrome, this individual would have benefited from an additional dose of a heterologous vaccine.

Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines.

Cervical cancer is the third most common in Brazilian women. The chemotherapy used for the treatment of this disease can cause many side effects; then, to overcome this problem, new treatment options are necessary. Natural compounds represent one of the most promising sources for the development of new drugs. In this study, 13 different species of 6 families from the Brazilian Cerrado vegetation biome were screened against human cervical cancer cell lines (CCC). Some of these species were also evaluated in one normal keratinocyte cell line (HaCaT). The effect of crude extracts on cell viability was evaluated by a colorimetric method (MTS assay). Extracts from Annona crassiflora, Miconia albicans, Miconia chamissois, Stryphnodendron adstringens, Tapirira guianensis, Xylopia aromatica, and Achyrocline alata showed half-maximal inhibitory concentration (IC50) values < 30 µg/mL for at least one CCC. A. crassiflora and S. adstringens extracts were selective for CCC. Mass spectrometry (Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ESI FT-ICR MS)) of A. crassiflora identified fatty acids and flavonols as secondary compounds. One of the A. crassiflora fractions, 7C24 (from chloroform partition), increased H2AX phosphorylation (suggesting DNA damage), PARP cleavage, and cell cycle arrest in CCC. Kaempferol-3-O-rhamnoside and oleic acid were bioactive molecules identified in 7C24 fraction. These findings emphasize the importance of investigating bioactive molecules from natural sources for developing new anti-cancer drugs.

Phosphoenolpyruvate carboxykinase from T. cruzi magnetic beads affinity-based screening assays on crude plant extracts from Brazilian Cerrado.

In T. cruzi, a causative agent of Chagas disease, phosphoenolpyruvate carboxykinase (TcPEPCK) is associated with carbohydrate catabolism. Due to its importance in the metabolism of the parasite, it has become a promising target for the development of new drugs against Chagas disease. Aiming to investigate different approaches for ligands screening, TcPEPCK was immobilized on amine-terminated magnetic beads (TcPEPCK-MB) and kinetically characterized by liquid chromatography tandem mass spectrometry activity assay with a KMapp value of 10 ± 1 µM to oxaloacetate as substrate. Natural products library affords highly diverse molecular frameworks through their secondary metabolites, herein a ligand fishing TcPEPCK-MB assay is described for prospecting ligands in four ethanolic extracts of Brazilian Cerrado plants: Qualea grandiflora (Vochysiaceae), Diospyros burchellii (Ebenaceae), Anadenanthera falcata (Fabaceae) and Byrsonima coccolobifolia (Malpighiaceae). The chemical characterization of eleven identified ligands was carried out by liquid chromatography tandem high-resolution mass spectrometry experiments. Senecic acid, syneilesinolide A, phytosphingosine and vanillic acid 4-glucopyranoside are herein reported for the first time for Q. grandiflora, D. burchellii, A. falcata, respectively. In addition, the specificity of the assay was observed since only catechin was fished out from the ethanolic extract of B. coccolobifolia leaves, despite the presence of epicatechin epimer.

Altered metabolomic profiling of overweight and obese adolescents after combined training is associated with reduced insulin resistance.

Exercise training and a healthy diet are the main non-pharmacological strategies for treating chronic conditions, such as obesity and insulin resistance (IR), in adolescents. However, the isolated metabolic changes caused by exercise training without dietary intervention have not yet been established. We investigated how combined training (CT) without dietary intervention altered the concentrations of serum metabolites, biochemical, anthropometric and functional parameters in overweight and obese adolescents. Thirty-seven adolescents (14.6 ± 1.05 years), of both sexes, were randomly assigned to the control group (CG, n = 19) or the training group (TG, n = 18). The CT was composed by resistance training and aerobic training performed in the same session (~ 60 min), three times a week, for 12 weeks. All assessments were performed pre and post-intervention. Metabolomics analyses were conducted using nuclear magnetic resonance spectroscopy (1H NMR) in a 600 MHz spectrometer. There was a decrease in body weight (BW), body mass index (BMI), waist circumference (WC), % body fat (%BF), fasting glucose, insulin levels, and insulin resistance (IR), by HOMA-IR, in the TG. An increase in fat-free mass (FFM) was also observed in the CG. The metabolic changes were given mainly by changes in the levels of metabolites 2-oxoisocaproate (↓TG), 3-hydroxyisobutyrate (↑CG and ↓TG), glucose (↓TG), glutamine (↓CG and ↑TG) and pyruvate (↓TG). These findings demonstrate the positive effects of CT program without dietary intervention on metabolomic profile, body composition, biochemical markers, and glucose metabolism in overweight and obese adolescents.

Hexane partition from Annona crassiflora Mart. promotes cytotoxity and apoptosis on human cervical cancer cell lines.

Cervical cancer is the third most commonly diagnosed tumor type and the fourth cause of cancer-related death in females. Therapeutic options for cervical cancer patients remain very limited. Annona crassiflora Mart. is used in traditional medicine as antimicrobial and antineoplastic agent. However, little is known about its antitumoral properties. In this study the antineoplastic effect of crude extract and derived partitions from A. crassiflora Mart in cervical cancer cell lines was evaluated. The crude extract significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration, and induces cell death in SiHa cells. Yet, the combination of the crude extract with cisplatin leads to antagonistic effect. Importantly, the hexane partition derived from the crude extract presented cytotoxic effect both in vitro and in vivo, and initiates cell responses, such as DNA damage (H2AX activity), apoptosis via intrinsic pathway (cleavage of caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and mitochondrial membrane depolarization) and decreased p21 expression by ubiquitin proteasome pathway. Concluding, this work shows that hexane partition triggers several biological responses such as DNA damage and apoptosis, by intrinsic pathways, and was also able to promote a direct decrease in tumor perimeter in vivo providing a basis for further investigation on its antineoplastic activity on cervical cancer.

Effects of polymorphisms in APOB, APOE, HSD11ß1, PLIN4, and ADIPOQ genes on lipid profile and anthropometric variables related to obesity in children and adolescents.

Genes can influence lipid profile and anthropometric variables related to obesity. The present study aimed to verify if variants of the APOE, APOB, ADIPOQ, HSD11ß1, and PLIN4 genes are associated with lipid levels or anthropometric variables in a sample comprised of 393 Euro-Brazilian children and adolescents. DNA was genotyped by TaqMan allelic discrimination assay. The ε4 and ε2 alleles of the APOE gene were associated respectively with lower high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.015 and p=0.012, respectively), while the ε3 allele was associated with higher abdominal circumference (p=0.0416) and excess weight (p=0.0001). The G allele (rs846910) of the HSD11ß1 gene was also associated with excess weight (p=0.039). No other association was found. Our results indicate that the ε4 and ε2 alleles could contribute to lower HDL-C and LDL-C levels, respectively, furthermore, the ε3 allele and the G allele (rs846910) of HSD11ß1 gene may be risk factors for excess of weight.These findings are very important because we observed that some genetic variants influence the lipid profile and anthropometric variables early in life.

High frequency of trypanosomatids in gallery forest bats of a Neotropical savanna.

Bats are well-known hosts of trypanosomatids, though information about their role as reservoirs of these protozoans in the Brazilian savanna is poorly known. We aimed to analyze the occurrence of trypanosomatid species in bats occurring in remnants of gallery forests of Brasília, Federal District of Brazil. We sampled bats using mist nets in six sites, and we collected blood, wing fragments and oral swab samples from all captured individuals. Trypanosomatids were identified in the captured bats through sequencing of the SSUrRNA region and kDNA qPCR. We found no parasite in blood smears of 146 individuals of 14 species captured, but blood cultures were positive for nine bats. We detected trypanosomatids molecularly in 111 (76%) specimens of all bat species in the studied areas. Most of the infected bats had Leishmania-like DNA detected in blood and swab samples of the oral mucosa. We distinguished three species of Trypanosoma (Trypanosoma dionisii, T. rangeli and T. cruzi) in Carollia perspicillata. SSUrRNA PCR of oral samples is a non-invasive and practical method for identification of trypanosomatid species in bats. Our results support our belief that bats could be potential reservoirs for Trypanosoma and Leishmania-like species in the enzootic cycle of these parasites in gallery forests of the Brazilian Cerrado biome.

Endothelial wall thickness, cardiorespiratory fitness and inflammatory markers in obese and non-obese adolescents.

BACKGROUND: Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated. OBJECTIVE: To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents. METHOD: Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound. RESULTS: The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max. CONCLUSIONS: Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents.

Endothelial wall thickness, cardiorespiratory fitness and inflammatory markers in obese and non-obese adolescents

Background: Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated. Objective : To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents. Method : Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound. Results: The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max. Conclusions : Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents. .

Aterosclerose subclínica e marcadores inflamatórios em crianças e adolescentes obesos e não obesos / Atherosclerosis subclinical and inflammatory markers in obese and nonobese children and adolescents

OBJETIVO: Realizou-se revisão sistemática sobre espessamento médio-intimal (EMI) e marcadores inflamatórios, comparou-se EMI por metanálise e analisou-se a correlação entre EMI e variáveis inflamatórias em crianças e adolescentes obesos e não obesos. FONTES DOS DADOS: Buscaram-se artigos nas bases de dados Pubmed, Bireme e Science Direct, nos anos de 2000 a 2010, com as seguintes palavras-chave em inglês: "obesity", "adolescents", "atherosclerosis" e "child", sendo utilizados em duas combinações: obesity+adolescents+atherosclerosis e obesity+child+atherosclerosis. Utilizou-se meta-análise para comparar EMI entre obesos e não obesos. SINTESE DOS DADOS: Selecionou-se criteriosamente 16 artigos para análise final. Houve diferença da espessura de EMI entre obesos e não obesos em 12 estudos, confirmada pela meta-análise. Os obesos apresentaram concentrações de proteína C-reativa mais elevada em 13 artigos analisados (p < 0,05) e menores de adiponectina em 4 (p < 0,05). Em geral, os obesos apresentaram concentrações menores de adiponectina e maiores valores de EMI e Proteina C-reativa do que os não-obesos, evidenciando relação entre obesidade e início de processo inflamatório. CONCLUSÕES: Conclui-se que há relação da obesidade com aumento do EMI e alterações nas concentrações dos marcadores inflamatórios nesta fase.

We conducted a systematic review of intima-media thickness(IMT) and inflammatory markers, compared IMT and identified by meta-analysis related to EMI and inflammatory variables in obese and non-obese children and adolescents. We searched for articles in databases Pubmed, Bireme and Science Direct, during years 2000 to 2010, with the following key words in English: "obesity", "adolescents", "atherosclerosis" and "child ", They were used in two combinations: obesity + adolescents + atherosclerosis + child + obesity and atherosclerosis. We used meta-analysis to compare IMT between obese and non-obese patients. We carefully selected 16 articles for final analysis. There were differences in the thickness of IMT between obese and non-obese patients in 12 studies, confirmed by meta-analysis. Obese patients had concentrations of C-reactive protein higher in 13 articles analyzed (p < 0.05) and lower adiponectin levels in 4 (p < 0.05). In general, obese men had lower concentrations of adiponectin and higher values of IMT and C-reactive protein than non-obese men, showing the relationship between obesity and early inflammatory process. We concluded that there is a relationship of obesity with increased IMT and changes in concentrations of inflammatory markers in this phase.

Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and V.

Cathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in many pathological conditions. This report describes the synthesis and evaluation of a series of N-arylanthranilic acids, acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics revealed that compounds of the classes of acridones are reversible competitive inhibitors of the target enzyme with affinities in the low micromolar range. They represent promising lead candidates for the discovery of novel competitive cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4-quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were uncompetitive inhibitors.

Atherosclerosis subclinical and inflammatory markers in obese and nonobese children and adolescents.

We conducted a systematic review of intima-media thickness(IMT) and inflammatory markers, compared IMT and identified by meta-analysis related to EMI and inflammatory variables in obese and non-obese children and adolescents. We searched for articles in databases Pubmed, Bireme and Science Direct, during years 2000 to 2010, with the following key words in English: "obesity", "adolescents", "atherosclerosis" and "child ", They were used in two combinations: obesity + adolescents + atherosclerosis + child + obesity and atherosclerosis. We used meta-analysis to compare IMT between obese and non-obese patients. We carefully selected 16 articles for final analysis. There were differences in the thickness of IMT between obese and non-obese patients in 12 studies, confirmed by meta-analysis. Obese patients had concentrations of C-reactive protein higher in 13 articles analyzed (p < 0.05) and lower adiponectin levels in 4 (p < 0.05). In general, obese men had lower concentrations of adiponectin and higher values of IMT and C-reactive protein than non-obese men, showing the relationship between obesity and early inflammatory process. We concluded that there is a relationship of obesity with increased IMT and changes in concentrations of inflammatory markers in this phase.