Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

NLC-Based Sunscreen Formulations with Optimized Proportion of Encapsulated and Free Filters Exhibit Enhanced UVA and UVB Photoprotection.

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs' particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122-135 nm), PdI (<0.3), encapsulation efficiency (>90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties.

Effects of post-exercise cold-water immersion on performance and perceptive outcomes of competitive adolescent swimmers.

PURPOSE: To evaluate the effects of repeated use of cold-water immersion (CWI) during a training week on performance and perceptive outcomes in competitive adolescent swimmers. METHODS: This randomized-crossover study included 20 athletes, who received each intervention [CWI (14 ± 1 °C), thermoneutral water immersion (TWI) (27 ± 1 °C) as placebo, and passive recovery (PAS)] three times a week between the land-based resistance training and swim training. The interventions were performed in a randomized order with a 1-week wash-out period. We tested athletes before and after each intervention week regarding swim (100 m freestyle sprints) and functional performance (flexibility, upper and lower body power, and shoulder proprioception). We monitored athlete's perceptions (well-being, heaviness, tiredness, discomfort and pain) during testing sessions using a 5-item questionnaire. Athlete preferences regarding the interventions were assessed at the end of the study. We used generalized linear mixed models and generalized estimating equations for continuous and categorical variables, respectively (intervention x time). RESULTS: We found a time effect for swim performance (p = .01) in which, regardless the intervention, all athletes improved sprint time at post-intervention compared to baseline. There was an intervention effect for pain (p = .04) and tiredness (p = .04), but with no significant post-hoc comparisons. We found no significant effects for other outcomes. All athletes reported a preference for CWI or TWI in relation to PAS. CONCLUSION: The repeated use of CWI throughout a training week did not impact functional or swim performance outcomes of competitive adolescent swimmers. Perceptive outcomes were also similar across interventions; however, athletes indicated a preference for both CWI and TWI.

ALCAM is a biomarker of tumor aggressiveness and worse prognosis in glottic laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most frequent head and neck tumor. Prognosis of patients with LSCC has not improved in recent decades, showing a need for the identification of prognostic biomarkers and new therapeutic targets. Recently, we showed that ALCAM overexpression was associated with glottic LSCC prognosis. OBJECTIVES AND METHODS: Aiming to validate the prognostic value of ALCAM, we evaluate the ALCAM protein levels by immunohistochemistry in 263 glottic LSCC surgically treated with neck dissection. RESULTS: ALCAM was expressed in 48.7% and overexpressed in 36.5% of glottic LSCC samples. ALCAM overexpression was associated with lymph node metastasis (p = 0.030), lymphovascular involvement (p = 0.0002), high-grade tumors (p = 0.025), and tumor relapse (p = 0.043). Multivariate survival analyses showed an overfitting between ALCAM overexpression and lymph node metastasis as a prognostic variable. CONCLUSIONS: High ALCAM expression was associated with an aggressive glottic LSCC profile.

Association between molar hypomineralization, genes involved in enamel development, and medication in early childhood: A preliminary study.

BACKGROUND: Molar hypomineralization (MH) is defined as a multifactorial condition, and thus, its presence may be defined by interactions between environmental and genetic factors. AIM: To evaluate the association between MH, genes involved in enamel development, and the use of medication during pregnancy in early childhood. DESIGN: One hundred and eighteen children, 54 with and 64 without MH, were studied. The data collected included demographics, socioeconomic data, and the medical history of mothers and children. Genomic DNA was collected from saliva. Genetic polymorphisms in ameloblastin (AMBN; rs4694075), enamelin (ENAM; rs3796704, rs7664896), and kallikrein (KLK4; rs2235091) were evaluated. These genes were analyzed by real-time polymerase chain reaction using TaqMan chemistry. The software PLINK was used to compare allele and genotype distributions of the groups and to assess the interaction between environmental variables and genotypes (p < .05). RESULTS: The variant allele KLK4 rs2235091 was associated with MH in some children (odds ratio [OR]: 3.75; 95% confidence interval [CI] = 1.65-7.81; p = .001). Taking medications in the first 4 years of life was also associated with MH (OR: 2.94; 95% CI = 1.02-6.04; p = .041) and specifically in association with polymorphisms in ENAM, AMBN, and KLK4 (p < .05). The use of medications during pregnancy was not associated with MH (OR: 1.37; 95% CI = 0.593-3.18; p = .458). CONCLUSION: The results of this study suggest that taking medication in the postnatal period appears to contribute to the etiology of MH in some evaluated children. There may be a possible genetic influence of polymorphisms in the KLK4 gene with this condition.

The effects of sleep deprivation, acute hypoxia, and exercise on cognitive performance: A multi-experiment combined stressors study.

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity.

Insulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous, however, this association remains controversial. The aim of this study was to perform an in-depth multifactorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active, n = 9), individuals with obesity (Obese, n = 9), and individuals with obesity, insulin resistance, and type 2 diabetes (T2D, n = 22). Mitochondrial capacity was assessed by ex vivo mitochondrial respiration with fatty-acid and glycolytic-supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity). Supercomplex assembly was measured by Blue Native (BN)-PAGE and immunoblot. Tricarboxylic (TCA) cycle intermediates were assessed with targeted metabolomics. Exploratory transcriptomics and DNA methylation analyses were performed to uncover molecular differences affecting mitochondrial function among the three groups. We reveal no discernable differences in skeletal muscle mitochondrial content, mitochondrial capacity, supercomplex assembly, TCA cycle intermediates, and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (body mass index, age, and aerobic capacity). We highlight that lean, active individuals have greater mitochondrial content, mitochondrial capacity, supercomplex assembly, and TCA cycle intermediates. These phenotypical changes are reflected at the level of DNA methylation and gene transcription. The collective observation of comparable muscle mitochondrial capacity in individuals with obesity and T2D (vs. individuals without T2D) underscores a dissociation from skeletal muscle insulin resistance. Clinical trial number: NCT01911104.NEW & NOTEWORTHY Whether impaired mitochondrial capacity contributes to skeletal muscle insulin resistance is debated. Our multifactorial analysis shows no differences in skeletal muscle mitochondrial content, mitochondrial capacity, and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity). We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription.

Genetic screening in a Brazilian cohort with inborn errors of immunity.

BACKGROUND: Inherited genetic defects in immune system-related genes can result in Inborn Errors of Immunity (IEI), also known as Primary Immunodeficiencies (PID). Diagnosis of IEI disorders is challenging due to overlapping clinical manifestations. Accurate identification of disease-causing germline variants is crucial for appropriate treatment, prognosis, and genetic counseling. However, genetic sequencing is challenging in low-income countries like Brazil. This study aimed to perform genetic screening on patients treated within Brazil's public Unified Health System to identify candidate genetic variants associated with the patient's phenotype. METHODS: Thirteen singleton unrelated patients from three hospitals in Rio de Janeiro were enrolled in this study. Genomic DNA was extracted from the peripheral blood lymphocytes of each patient, and whole exome sequencing (WES) analyses were conducted using Illumina NextSeq. Germline genetic variants in IEI-related genes were prioritized using a computational framework considering their molecular consequence in coding regions; minor allele frequency ≤ 0.01; pathogenicity classification based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines gathered from the VarSome clinical database; and IEI-related phenotype using the Franklin tool. The genes classification into IEI categories follows internationally recognized guidelines informed by the International Union of Immunological Societies Expert Committee. Additional methods for confirmation of the variant included Sanger sequencing, phasing analysis, and splice site prediction. RESULTS: A total of 16 disease-causing variants in nine genes, encompassing six different IEI categories, were identified. X-Linked Agammaglobulinemia, caused by BTK variations, emerged as the most prevalent IEI disorder in the cohort. However, pathogenic and likely pathogenic variants were also reported in other known IEI-related genes, namely CD40LG, CARD11, WAS, CYBB, C6, and LRBA. Interestingly, two patients with suspected IEI exhibited pathogenic variants in non-IEI-related genes, ABCA12 and SLC25A13, potentially explaining their phenotypes. CONCLUSIONS: Genetic screening through WES enabled the detection of potentially harmful variants associated with IEI disorders. These findings contribute to a better understanding of patients' clinical manifestations by elucidating the genetic basis underlying their phenotypes.

Social Representations of Hesitant Brazilians about Vaccination against COVID-19.

BACKGROUND: The control of the COVID-19 pandemic has been a great challenge. Understanding the thoughts and beliefs underlying vaccine hesitancy can help in the formulation of public policies. The present study aimed to analyze the social representations of hesitant Brazilians about vaccination against COVID-19. METHODS: Qualitative research guided by the Theory of Social Representations, carried out through an online survey among Brazilian adults living in Brazil. The data were analyzed using the IRaMuTeQ software. RESULTS: Of the 173,178 respondents, 10,928 were hesitant and declared reasons for vaccination hesitation. The analysis generated three classes: mistrust of the vaccine and underestimation of the severity of the pandemic; (dis)information and distrust of political involvement; and fear of adverse reactions to COVID-19 vaccines. CONCLUSIONS: Social knowledge, presented by the representations apprehended in this study, demonstrates difficulty in discerning the reliability of information and a social imagination full of doubts and uncertainties. Understanding the internal dynamics of these groups, with their representations of the world, is important to propose policies and actions that echo and cause changes in the understanding of the role of immunization. It is essential to shed light on the sociological imagination so that gaps filled with false information can be dismantled and confronted with scientific knowledge accessible to the population.

Repeated Massage Improves Swimmers' Perceptions during Training Sessions but Not Sprint and Functional Performance: A Randomized Controlled Trial.

This study aimed to investigate the effects of repeated massage adjusted for swimmers' training on the perceptive, functional, and performance outcomes of a sprint. We also investigated the effects of a single short massage on swimmers' self-reported perceptions after resistance training. This cross-over randomized controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis included 19 male and female competitive swimmers between 12 and 20 years old. Participants were subjected to three 12-min interventions over a week between resistance and swim training and monitored regarding training load and perceptions. After the intervention week we assessed: perceptive (well-being, heaviness, tiredness, discomfort, and pain), performance (sprint time, FINA points, and stroke characteristics), and functional outcomes (flexibility, squat jump, bench press, proprioception), in addition to athlete beliefs and preferences. A massage was defined as consisting of sliding movements on the arms, back, and anterior thigh, with metronomic rhythm control (1:1), and was divided into two protocols: superficial massage (SM) (light touch) and deep massage (DM) (light, moderate, intense effleurage) while the control (CON) rested. After repeated massage (SM and SM), participants had less chances to report tiredness, and they also maintained perceptions of well-being while CON got worse throughout the week. However, we found evidence of worsening of the perceptions of heaviness and pain at the main stages of the swim training for the massage groups. SM and DM had no effects over sprint and functional performance. Our results suggest that the swimmers were able to train harder with no harm to recovery.

Trustworthiness of information sources on vaccines for COVID-19 prevention among Brazilians.

OBJECTIVE: This study aims to assess the trustworthiness of information sources, perception of clear information about the vaccine, and strategies to increase adherence to vaccination to provide managers with information that helps establish effective communication with the population about vaccination. METHOD: This is an online survey conducted between January 22 and 29, 2021, preceded by an Informed Consent, that aims to assess vaccine hesitancy, which corresponded to the first week of vaccination initiation to prevent COVID-19 in Brazil. Data were obtained from a questionnaire made available through a free platform and stored in Google Forms and later exported to the SPSS statistical package for analysis. The sample consisted of all questionnaires from participants who self-declared as age 18 or older, Brazilian, and residing in Brazil at the time of the survey. Incomplete records with more than 50% of blank items and duplicates were excluded. All categorical variables were analyzed from their absolute and relative frequencies. Multivariate logistic regression was performed to verify the relationship between dependent variables and independent variables. RESULTS: The results show that trust in information sources diverges between hesitant and non-hesitant. They also showed that some participants show an overall distrust that seems to have deeper foundations than issues related only to the source of information. The high rejection of television and the WHO as sources of information among hesitant suggests that integrated actions with research institutes, public figures vaccinating, and religious leaders can help to combat vaccine hesitation. Two actors become particularly important in this dynamic, both for good and bad, and their anti-vaxxer behavior must be observed: the doctor and the Ministry of Health. CONCLUSION: This study contributes to gathering valuable information to help understand the behavior and thinking relevant to the adherence to vaccination recommendations.

What Parameters Influence the Effect of Cold-Water Immersion on Muscle Soreness? An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Our objective was to determine the efficacy of cold-water immersion (CWI) on the management of muscle soreness to identify the impact of immersion time, water temperature, CWI protocol, and type of exercise on this outcome. DESIGN: Intervention systematic review and meta-analysis. SETTING: MEDLINE/PubMed, Embase, Central, and SPORTDiscus databases were searched from their earliest record to July 30, 2020. Only randomized controlled trials that assessed muscle soreness comparing CWI and control were included. Studies were pooled in different subgroups regarding the used protocol: water temperature (severe or moderate cold), immersion time (short, medium, or longer time), CWI protocol (intermittent or continuous application), and type of exercise (endurance or resistance exercise). Data were pooled in a meta-analysis and described as weighted mean difference (95% confidence interval, P < 0.05). PARTICIPANTS: Athletes and nonathletes. INTERVENTIONS: Cold-water immersion and control condition. MAIN OUTCOME MEASURES: Muscle soreness. RESULTS: Forty-four studies were included. For immediate effects, CWI was superior to control regardless of water temperature and protocol, and for short and medium immersion times and endurance exercises. For delayed effects, CWI was superior to control in all subgroups except longer immersions time. CONCLUSIONS: This study suggests that CWI is better than control for the management of muscle soreness and water temperature and CWI protocol do not influence this result, but only short and medium immersions times presented positive effects. Aiming immediate effects, the best results suggest CWI application only after endurance exercises, while delayed effect CWI was superior both after endurance and resistance exercises.

Taurine and Exercise: Synergistic Effects on Adipose Tissue Metabolism and Inflammatory Process in Obesity.

Taurine has been investigated as a possible strategy for the treatment of obesity. The benefits of taurine supplementation and the importance of adipose tissue to the whole-body energy metabolism are undeniable; however, the impact of the association of taurine and exercise on adipose tissue dynamics remains unclear, especially in the context of obesity. The present investigation sought to explore the effects of taurine supplementation associated with physical exercise as an excellent strategy for treating and preventing obesity. We highlighted the main studies that support the effects of taurine associated with exercise on the modulation of energy and lipid metabolism and also its impacts on the adipose tissue metabolism and morphology in obese individuals and obese animal models, suggesting taurine as a promising strategy to combat obesity. However, more investigations are necessary to elucidate the safe and effective dose, the mechanisms, and the potential effects of taurine supplementation associated with exercise in the adipose tissue as a therapeutic strategy for preventing and treating obesity.

Untargeted lipidomic analysis of plasma from obese women submitted to combined physical exercise.

This study aimed to determine the changes of lipidome in obese women undergoing combined physical exercise training. Fourteen adult women with obesity (mean BMI and age, 33 kg/m2 and 34 ± 5 years), were submitted to combined physical training (aerobic and strength exercises, alternately, 55 min at 75-90% of the maximum heart rate, 3 times a week) for 8 weeks. All participants were evaluated before and after the training intervention for lipidome, anthropometric measurements, muscle strength, and maximum oxygen consumption (VO2max). Untargeted liquid chromatography-mass spectrometry analyses allowed the identification of 1252 variables, of which 160 were significant (p < 0.05), and 61 were identified as molecular species of lipids. Volcano plot analysis revealed LPC(16:0p), LPC(18:0p), LPC(20:2), and arachidonic acid upregulated and PC(38:1p), PC(40:4), PC(40:4p) downregulated after combined physical exercise. From the results of the overall Principal component analysis (PCA), the major finding was SM(d18:1/20:0), arachidonic acid, and PC(40:6) species. Other changes included a reduction in waist circumference (Δ = - 2 cm) (p < 0.05), with no weight loss. In conclusion, 8-week of combined exercise training in obese women brought changes in different classes of lipids. This study provides further information to understand the effect of combined physical exercise on lipids related to obesity.

Aerobic training increases mitochondrial respiratory capacity in human skeletal muscle stem cells from sedentary individuals.

The impact of aerobic training on human skeletal muscle cell (HSkMC) mitochondrial metabolism is a significant research gap, critical to understanding the mechanisms by which exercise augments skeletal muscle metabolism. We therefore assessed mitochondrial content and capacity in fully differentiated CD56+ HSkMCs from lean active (LA) and sedentary individuals with obesity (OS) at baseline, as well as lean/overweight sedentary individuals (LOS) at baseline and following an 18-day aerobic training intervention. Participants had in vivo skeletal muscle PCr recovery rate by 31P-MRS (mitochondrial oxidative kinetics) and cardiorespiratory fitness (V̇o2max) assessed at baseline. Biopsies of the vastus lateralis were performed for the isolation of skeletal muscle stem cells. LOS individuals repeated all assessments posttraining. HSkMCs were evaluated for mitochondrial respiratory capacity by high-resolution respirometry. Data were normalized to two indices of mitochondrial content (CS activity and OXPHOS protein expression) and a marker of total cell count (quantity of DNA). LA individuals had significantly higher V̇o2max than OS and LOS-Pre training; however, no differences were observed in skeletal muscle mitochondrial capacity, nor in carbohydrate- or fatty acid-supported HSkMC respiratory capacity. Aerobic training robustly increased in vivo skeletal muscle mitochondrial capacity of LOS individuals, as well as carbohydrate-supported HSkMC respiratory capacity. Indices of mitochondrial content and total cell count were similar among the groups and did not change with aerobic training. Our findings demonstrate that bioenergetic changes induced with aerobic training in skeletal muscle in vivo are retained in HSkMCs in vitro without impacting mitochondrial content, suggesting that training improves intrinsic skeletal muscle mitochondrial capacity.

Taurine as a possible antiaging therapy: A controlled clinical trial on taurine antioxidant activity in women ages 55 to 70.

OBJECTIVE: Based on the antioxidant effects of taurine, which are capable of controlling oxidative stress in the aging process, the aim of this study was to investigate the effects of taurine supplementation on biomarkers of oxidative stress in women 55 to 70 y of age. METHODS: A double-blind study was conducted with 24 women (61.4 ± 4.2 y, body mass index 31.4 ± 5.1 kg/m²). The participants were randomly assigned to either a control group (GC, n = 11), supplemented with placebo (1.5 g of starch); or a taurine group (GTAU, n = 13), supplemented with taurine (1.5 g), for 16 wk. As primary outcomes, taurine and oxidative stress marker levels were determined in plasma samples. Anthropometry, functional capacity testing, and plasma mineral levels were evaluated as secondary outcomes. The evaluations were performed pre- and postintervention. Food consumption was assessed before, during, and after the intervention. The results were analyzed by two-way repeated analysis of variance measures mixed model, with the Sidak post hoc (P < 0.05). RESULTS: Taurine and superoxide dismutase (SOD, antioxidant enzyme) plasma levels were increased in the GTAU group. SOD levels also were higher than in the GC group after supplementation. Glutathione reductase levels decreased regardless of the intervention. Malondialdehyde levels increased only in the GC participants. CONCLUSION: Taurine supplementation prevented the decrease in the antioxidant enzyme SOD, suggesting taurine as a strategy to control oxidative stress during the aging process.

Evaluation of methotrexate-loaded surfactants, ceramides and cholesterol-based lamellar phases as a topical treatment for psoriasis.

OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder. Oral or subcutaneous methotrexate (MTX) is a first-line antipsoriatic treatment, whose adverse effects can be observed even at low doses. To minimize systemic side effects, antipsoriatic drugs should be administered topically, since they could permeate the stratum corneum. As liquid crystals with lamellar phase (LP) can be helpful in promoting skin permeation, this work evaluated two MTX-loaded LPs (C1CH and C1CHCE), based on stearic acid, cholesterol and ceramides, like topical treatments for mice with imiquimod-induced psoriasis. METHODS: C1CH and C1CHCE were topically administered to mice with imiquimod-induced psoriasis. Dexamethasone cream was used as positive treatment control. Skin histology and inflammation biomarkers were assessed. KEY FINDINGS: C1CH and C1CHCE exhibited marked immunomodulatory effects and induced extensive microstructural skin remodelling on the epidermis and dermis. These formulations increased keratinization score, epidermis thickness, inflammatory infiltrate, hair follicle hypertrophy and vascular congestion in the dermis. C1CH and C1CHCE also attenuated IL-10 upregulation and upregulated IL-1, IFN-γ, TNF-α and prostaglandin E2 levels, as well as myeloperoxidase, N-acetyl-ß-d-glucosaminidase and cyclooxygenase 2 activity compared with untreated psoriatic animals. CONCLUSION: Although liquid crystals have been reported as good options for carrying topical drugs, they need to be carefully assessed on a case-by-case basis.

Photobiomodulation therapy applied during an exercise-training program does not promote additional effects in trained individuals: A randomized placebo-controlled trial.

BACKGROUND: Previous studies have shown positive results of photobiomodulation (PBM) for improving performance and accelerating post-exercise recovery. However, the effects of PBM in healthy individuals who underwent a neuromuscular adaptation training remain unclear. OBJECTIVE: To investigate the effects of PBM during a training program combining sprints and explosive squats exercises on clinical, functional, and systemic outcomes in trained healthy individuals compared to a placebo intervention and a control. METHODS: We conducted a randomized placebo-controlled trial. Healthy males were randomly assigned to three groups: active PBM (30 J per site), placebo, or control (passive recovery). The participants performed a six-week (12 sessions) of a training program consisting of a combination of sprints and squats with recovery applied between sprints and squats. To prevent the influence of the primary neuromuscular adaptation to exercise on the results, all participants had to participate in a period of six weeks of exercise training program. Functional, clinical, and psychological outcomes and vascular endothelial growth factor (VEGF) were assessed at baseline and after six weeks. Results are expressed as mean difference (MD) and 95% confidence intervals (CI). RESULTS: Thirty-nine healthy male volunteers (aged 18-30 years; body mass index 23.9 ±â€¯3 kg/m²) were recruited. There was no significant time by group interaction, and no significant effect of group, but there was a significant effect of time for maximal voluntary isometric contraction (primary outcome) (MD=22 Nm/kg; 95%CI: 3.9, 40) and for squat jump (MD=1.6 cm; 95CI%: 0.7, 2.5). There was no significant interaction (time*group), time, or group effect for the other outcomes. CONCLUSION: The addition of PBM to a combined training performed for six weeks in previously trained individuals did not result in additional benefits compared to placebo or no additional intervention.

Taurine upregulates insulin signaling and mitochondrial metabolism in vitro but not in adipocytes of obese women.

OBJECTIVES: Based on taurine's beneficial roles in metabolic diseases in rodents and obese individuals, we investigated the effects of taurine supplementation on adipose tissue using transcriptome analysis, 3T3-L1 adipocytes, and subcutaneous white adipose tissue (scWAT) of obese women. METHODS: First, we applied bioinformatics analysis to evaluate the effect of the taurine synthesis pathway on the adipose tissue of several BXD mice strains. After that, using 3T3-L1 adipocytes, we investigated the effects of different taurine doses in proteins related to insulin signaling, lipid oxidation, and mitochondrial function. Finally, we evaluated the effects of taurine supplementation (3 grams, 8 wk) on the same proteins in the scWAT of obese women. RESULTS: The transcriptome analysis showed that the taurine biosynthesis pathway was positively associated with insulin signaling and mitochondrial metabolism in the scWAT of BXD mice. The experiments using 3T3-L1 cells highlighted that the taurine dosage has an essential function in taurine synthesis, insulin, and mitochondrial markers. In contrast, the 8-wk taurine administration did not change the basal insulin, proteins of the taurine synthesis or insulin pathways, lipid oxidation, or mitochondrial metabolism in the scWAT of obese women. CONCLUSIONS: For the first time, to our knowledge, we showed that supplementation with 3 g of taurine for 8 wk promoted no effect in the insulin signaling pathway in the scWAT of obese women. These findings bring new perspectives to investigate different taurine doses and the intervention period for human studies owing to the potential antiobesity activity of taurine.