Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE: To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS: A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS: History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION: The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.

ANTECEDENTES: O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental. OBJETIVO: Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS: Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual. RESULTADOS: Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO: Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.

SARS-CoV-2 Research in Dogs (Canis lupus familiaris) and Felines (Felis silvestris catus) Domiciled in an International Border Region (Paraguay and Brazil).

Introduction: COVID-19 is an infectious disease caused by SARS-CoV-2 that has become a serious threat to public health owing to its rapid spread from aerosols from infected people. Despite being considered a strictly human disease, there are reports in the literature about animals with confirmed presence of the virus. Aim: Owing to the scarcity of scientific literature on the potential for infection of animals and their importance for One Health, the objective of this work was to research SARS-CoV-2 RNA in felines (Felis silvestris catus) and dogs (Canis lupus familiaris) domiciled. Materials and Methods: Oropharyngeal swabs were collected from domestic dogs and cats belonging to patients diagnosed with COVID-19 from August to October 2021 and residents of the northwest and west regions of Paraná, Brazil. Results: Of the 34 samples collected, 14 were from dogs and 20 from cats. Three of these samples tested positive in real-time PCR, and two of them were also positive in the immunochromatographic test. After testing positive in real-time PCR, the samples underwent genetic sequencing using the Illumina COVIDSeq test. Of the 34 samples collected, three (9%), all of them female and from the feline species, tested positive in real-time PCR, with two of these (67%) also testing positive in the immunochromatographic test. Regarding sequencing, it was possible to sequence the three samples aligned with the AY.101 lineage, corresponding to the Delta variant. Conclusion: The occurrence of SARS-CoV-2 infection in dogs and cats is seen as an unintended event with significant implications for public health, including its potential transmission to other animal species. Further research is required to enhance our understanding of how this disease spreads among these animals and its broader impact on One Health initiatives.

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Double tendon transfer for massive rotator cuff tear: A case report.

INTRODUCTION AND IMPORTANCE: Repairing massive rotator cuff tears (MRCTs) can often be technically challenging due to tendon retraction, bursal fibrosis, and muscular fatty infiltration that usually occurs, often resulting in poor outcomes and an unpredictable prognosis. Although some other surgical management options have been reported, there is a lack of literature supporting tendon transfers in the presence of combined anterior and posterior-superior irreparable rotator cuff tears. We describe a case where a combined transfer of the latissimus dorsi and lower trapezius tendons was employed to treat an MRCT affecting the anterior and posterior superior portions of the rotator cuff. CASE PRESENTATION: A 64-year-old male presented significant pain and limited range of motion in the right shoulder following a traumatic anterior shoulder dislocation seven months prior. MRI showed retracted tears (> 5 cm) of the supraspinatus, infraspinatus, and subscapularis tendons with significant fatty infiltration (Goutallier IV). The patient underwent an open transfer of the lower trapezius tendon to the greater tuberosity and the latissimus dorsi to the lesser tuberosity. At the final follow-up, 2.5 years postoperatively, the patient exhibited a painless functional range of motion and could resume daily activities. CLINICAL DISCUSSION: Although there are alternative surgical options available, the positive outcomes observed in the presented case may be attributed to the restoration of rotational strength and the re-establishment of force coupling across the shoulder. CONCLUSION: This report describes the successful implementation of a surgical treatment option for managing MRCT affecting the anterior and posterior superior portions of the rotator cuff.

Oral health-related quality of life in the LGBTIQ+ population: a cross-sectional study.

The aim of this cross-sectional study was to investigate the associations between oral health-related quality of life (OHRQoL) and socioeconomic and demographic variables, suicidal ideation, self-perception of oral health, and experiences of dental care in the Brazilian adult LGBTIQ+ population. A sample of 464 participants completed self-administered online questionnaires and provided information for OHRQoL assessment, using the OHIP-14 instrument at three hierarchical levels of explanatory variables: LGBTIQ+ identities; socioeconomic and demographic data and existential suffering; and self-perception of oral health and experience of dental care. The collected data were fitted to hierarchical multiple logistic regression models, in which the associations between each independent variable with the OHIP-14 prevalence outcome were analyzed. The OHIP-14-prevalence index showed that 33.2% of the participants answered 'frequently' or 'always', and the highest frequencies were obtained for the psychological discomfort (27.8%), psychological disability (18.3%), and physical pain (17.5%) domains. According to the adjusted final model, LGBTIQ+ individuals who were more likely to have their OHRQoL affected were those who were indifferent (OR=3.21; 95% CI: 1.26-8.20), dissatisfied (OR=10.45; 95% CI: 3.86-28.26), or very dissatisfied (OR=53.93; 95% CI: 12.12-239.93) with their oral health status, and also those who had or have difficulty accessing dental treatment (OR=2.06; 95% CI: 1.24-3.41) (p<0.05). It may be concluded that the OHRQoL of the investigated Brazilian LGBTIQ+ population showed associations with individual aspects and with access to dental services.

Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes.

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.

A dermatological assessment of pediatric patients with tuberous sclerosis complex (TSC).

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing. OBJECTIVE: To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations. METHODS: Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months. RESULTS: The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas. STUDY LIMITATIONS: Small sample and a limited number of patients with TSC1 pathogenic variants. CONCLUSION: Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described.

Complications and clinical outcomes with minimally invasive plate osteosynthesis (MIPO) technique for midshaft clavicle fractures: a systematic review and meta-analysis.

Background: Clavicle fractures are among the most common upper limb fractures in adults, with the midshaft region being the most frequently affected site. Minimally invasive plate osteosynthesis (MIPO) has emerged as an alternative to the traditional open reduction and internal fixation (ORIF) technique, offering potential advantages. The purpose of this study was to conduct a systematic review to explore the results of this technique in the existing literature, with emphasis on the occurrence of surgical complications and functional outcomes and also to provide a comprehensive comparison of MIPO and ORIF in the management of midshaft clavicle fractures. Methods: We conducted a systematic review to evaluate the complication incidence and clinical outcomes of MIPO for midshaft clavicle fractures. We searched PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, the Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews databases without language or date restrictions. Studies focusing on midshaft clavicle fractures treated with MIPO were included, while other clavicle fractures and nonclinical studies were excluded. The risk of bias was assessed using the Methodological Index for Nonrandomized Studies criteria and the Risk of Bias Tool 2 Cochrane tool. Data synthesis included qualitative analysis, and if applicable, quantitative analysis and meta-analysis. Adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines ensured reporting quality. Results: A total of 107 studies were initially identified, after applying inclusion and exclusion criteria, 22 studies were included for data extraction. These studies involved the evaluation of 714 clavicles treated with the MIPO technique. Of the 714 MIPO cases, 11 cases of implant failure, 5 nonunions, 2 infections, and 28 cases with neurological impairment were observed. Quantitative analysis comparing MIPO with ORIF revealed that MIPO had significantly shorter surgery time (mean difference -12.95, 95% confidence interval [-25.27 to -0.63], P = .04) and lower occurrence of numbness (odds ratio 0.29, 95% CI [0.15-0.56], P = .0002) compared to ORIF. Time to bone union, functional outcomes, and other complications were similar between MIPO and ORIF at the final follow-up. An overall moderate risk of bias was found across the studies. Conclusion: The MIPO technique yields good and comparable results to ORIF for midshaft clavicle fractures. Additionally, the MIPO technique may offer advantages such as reduced surgical time and lower chances of neurological impairment.

LGBTQ+ related curricular activities in Brazilian Dental Schools: Do institutional and/or deans' profiles matter?

PURPOSE: The aim of this cross-sectional study was to investigate whether the characteristics of dental schools and the profiles of their deans were associated with curricular activities related to LGBTQ+ in Brazilian dental schools. METHODS: A survey was mailed to the deans of all Brazilian dental schools for the purpose of assessing the development of pedagogical activities focused on the topic of oral health of the LGBTQ+ population, and the characteristics of the institutions and profiles of their deans. The data collected were analyzed with hierarchical multiple logistic regression models in order to analyze associations between variables of interest. RESULTS: Of the deans approached, 156 (response rate of approximately 32.4%) completed and returned the survey. The majority of dental schools (67.3%) of the sample were private institutions and 39% of them developed pedagogical activities directed toward the LGBTQ+. This percentage was much lower in public institutions (18%). The results of the hierarchical multiple logistic regression demonstrated that deans who attributed high relevance to the theme "oral health of the LGBTQ+ population" were more likely to develop pedagogical activities directed toward the LGBTQ+ population (odds ratio = 4.74; 95% confidence interval: 1.65-13.48), than those who attributed low or little importance to this topic (p < 0.05). CONCLUSION: A low percentage of activities aimed at the LGBTQ+ population was observed in the sample of Brazilian dental schools. Deans must be aware of the importance of the topic and be motivated to implement pedagogical activities for this population.

Long-term maintenance treatment of rosacea: experts' opinion.

BACKGROUND: Rosacea is a chronic inflammatory dermatosis characterized by remissions and flares. Although the rosacea active treatment phase is well established, the long-term maintenance phase is still challenging. OBJECTIVE: To discuss and make recommendations on how to treat patients during the long-term maintenance phase for the main rosacea phenotypes. METHODS: A panel of six board-certified Brazilian dermatologists and one American dermatologist gathered to compose a consensus based upon an initial statement on how to treat rosacea during the long-term maintenance phase based on the methodology Nominal Group Technique. The experts discussed each factor based upon an initial statement on how to treat rosacea patients in the long-term maintenance phase. A sequence of comprehensive narrative reviews was performed; a questionnaire preparation about the definition of the maintenance phase and its management was presented; an interpersonal discussion and ranking of the ideas were conducted. Recommendations were made if the specialists had 75% agreement. RESULTS: The maintenance treatment phase, which starts by achieving IGA 0 or 1 grades at the active phase, should be considered at least during the 9-month period after remission. The recommendations of all treatments target this period. Daily skincare regimen and sunscreen are crucial. Active treatment phase should be recommended if signs or symptoms reappear or worsen. CONCLUSION: Maintenance phase success depends on patient's adherence to daily skin care, appropriate treatments, continued follow-up with dermatologist, and self-assessment to identify new signs and symptoms indicating disease relapse.

Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting.

INTRODUCTION: Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGS to detect copy number variants (CNVs) in clinical cytogenetics. MATERIALS AND METHODS: DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75 kb to 90.3 Mb, including aneuploidies and two cases of mosaicism. RESULTS: All CNVs were successfully detected by LP-WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP-WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP-WGS approach are at least similar to those provided by CMA. DISCUSSION: Our data show the potential use of LP-WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP-WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.

Oral health-related quality of life in the LGBTIQ+ population: a cross-sectional study

Abstract The aim of this cross-sectional study was to investigate the associations between oral health-related quality of life (OHRQoL) and socioeconomic and demographic variables, suicidal ideation, self-perception of oral health, and experiences of dental care in the Brazilian adult LGBTIQ+ population. A sample of 464 participants completed self-administered online questionnaires and provided information for OHRQoL assessment, using the OHIP-14 instrument at three hierarchical levels of explanatory variables: LGBTIQ+ identities; socioeconomic and demographic data and existential suffering; and self-perception of oral health and experience of dental care. The collected data were fitted to hierarchical multiple logistic regression models, in which the associations between each independent variable with the OHIP-14 prevalence outcome were analyzed. The OHIP-14-prevalence index showed that 33.2% of the participants answered 'frequently' or 'always', and the highest frequencies were obtained for the psychological discomfort (27.8%), psychological disability (18.3%), and physical pain (17.5%) domains. According to the adjusted final model, LGBTIQ+ individuals who were more likely to have their OHRQoL affected were those who were indifferent (OR=3.21; 95% CI: 1.26-8.20), dissatisfied (OR=10.45; 95% CI: 3.86-28.26), or very dissatisfied (OR=53.93; 95% CI: 12.12-239.93) with their oral health status, and also those who had or have difficulty accessing dental treatment (OR=2.06; 95% CI: 1.24-3.41) (p<0.05). It may be concluded that the OHRQoL of the investigated Brazilian LGBTIQ+ population showed associations with individual aspects and with access to dental services.

A Benchmark of In-House Homologous Recombination Repair Deficiency Testing Solutions for High-Grade Serous Ovarian Cancer Diagnosis.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients' treatment options and has been progressively incorporated into diagnostic laboratories. Here, we assessed the performance of an in-house HRD testing system deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx® (HRD Focus Panel)) with the reference assay from Myriad MyChoice® (CDx). A total of 85 ovarian cancer samples were subject to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R = 0.87, p-value = 3.39 × 10-19). The comparison of the assigned HRD status to the reference Myriad's test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA's test, while AmoyDx's test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data shows that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, making it an ideal alternative to offer to a broader number of patients while maintaining high-quality standards at more accessible price tiers.

Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.

Association between Arterial Hypertension and Laboratory Markers, Body Composition, Obstructive Sleep Apnea and Autonomic Parameters in Obese Patients. / Associação entre Hipertensão Arterial Sistêmica com Marcadores Laboratoriais, Composição Corporal, Apneia Obstrutiva do Sono e Variabilidade da Frequência Cardíaca em Adultos Obesos.

BACKGROUND: Systemic arterial hypertension (SAH) is a multifactorial disease, highly prevalent and associated with health risks. OBJECTIVE: The purpose of this study was to investigate the association between SAH and laboratory, anthropometric, heart rate variability (HRV), and obstructive sleep apnea markers and, secondarily, to analyze the sensitivity and specificity of the variables that are independent factors in the association. METHODS: Cross-sectional study with 95 obese patients treated at an obesity referral clinic in Salvador, BA, Brazil. SAH data were obtained from electronic medical records. The sample was stratified in the Normotensive Group (NG) and the Hypertensive Group (HG), and laboratory markers, body composition, polysomnography, and HRV were measured to evaluate the association of SAH with the predictor variables. For the analysis, p<0.05 was adopted. RESULTS: The average age of the NG was 36.3 ± 10.1 and HG 40.4 ± 10.6 years; 73.7% were women in the NG and 57.9% in HG; 82.4% in HG had insulin resistance. In the multivarious logistics regression model with adjustments in age, sex, height, and oxyhemoglobin saturation, SAH was inversely associated with fasting plasma glucose mg/dL (odds ratio [OR] = 0.96; 95% confidence interval [CI] = 0.92-0.99) and visceral fat area (VFA) cm2(OR = 0.98; 95% CI = 0.97-0.99). The area under the VFA curve was 0.728; CI 95% (0.620-0.836); fasting plasma glucose 0.693;CI 95% (0.582-0.804). CONCLUSIONS: Lower VFA and fasting plasma glucose concentrations were inversely associated with SAH. In addition, fasting plasma glucose and VFA showed a high sensitivity for SAH screening.

FUNDAMENTO: A hipertensão arterial sistêmica (HAS) é uma doença multifatorial, altamente prevalente e associada a riscos à saúde. OBJETIVO: O objetivo deste estudo foi investigar a associação entre HAS e marcadores laboratoriais, antropométricos, de variabilidade da frequência cardíaca (VFC) e de apneia obstrutiva do sono e, em segundo plano, analisar a sensibilidade e especificidade das variáveis que são fatores independentes na associação. MÉTODOS: Estudo transversal com 95 pacientes obesos atendidos em um ambulatório de referência em obesidade em Salvador, BA, Brasil. Os dados da HAS foram obtidos dos prontuários eletrônicos. A amostra foi estratificada em Grupo Normotenso (GN) e Grupo Hipertenso (GH), sendo medidos marcadores laboratoriais, composição corporal, polissonografia e VFC para avaliar a associação da HAS com as variáveis preditoras. Para as análises, adotou-se p<0,05. RESULTADOS: A média da idade do GN foi de 36,3 ± 10,1 e GH 40,4 ± 10,6 anos, 73,7% eram mulheres no GN e 57,9% no GH; 82,4% no GH apresentavam resistência à insulina. No modelo de regressão logística multivariado com ajustes para idade, sexo, altura e saturação de oxi-hemoglobina, a HAS foi inversamente associada à glicose plasmática em jejum mg/dL (odds ratio [OR] = 0,96; intervalo de confiança de 95% [IC] = 0,92-0,99) e área de gordura visceral (AGV) cm2 (OR = 0,98; IC 95% = 0,97-0,99). A área sob a curva AGV foi de 0,728; IC 95% (0,620-0,836) e glicemia de jejum 0,693; IC 95% (0,582-0,804). CONCLUSÃO: Menores concentrações de AGV e glicemia de jejum foram inversamente associadas à HAS. Além disso, tanto a glicemia de jejum quanto o AGV mostraram alta sensibilidade para triagem de HAS.

Acne characteristics in Latin American patients and the potential role of trifarotene.

BACKGROUND: Individualization of treatment based on acne type and severity, location, disease burden, and patient preference is required to maximize efficacy, safety, and adherence to therapy. Latin American populations have unique attributes that must be considered as part of this process to improve clinical success and achieve patient goals. Acne is more common among patients with darker skin phototypes, in whom it is often associated with postinflammatory hyperpigmentation and scarring-the most important acne sequelae-potentially due to more frequent and more severe underlying inflammatory processes in this population. DISCUSSION: These data argue for an early and proactive approach to managing acne in these patients with agents that target the inflammatory processes that underlie acne and its sequelae. As a class, retinoids offer a spectrum of activity that may be useful in addressing the unique needs of Latin American populations. CONCLUSION: Trifarotene, a novel, selective retinoid, has been evaluated in relevant patient populations.

The First Brazilian Cardiovascular Registry of Atrial Fibrillation: Primary Results of the RECALL Study.

BACKGROUND: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry. METHODS: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models. RESULTS: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA2DS2-VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death. CONCLUSIONS: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients.

The Omicron Lineages BA.1 and BA.2 (Betacoronavirus SARS-CoV-2) Have Repeatedly Entered Brazil through a Single Dispersal Hub.

Brazil currently ranks second in absolute deaths by COVID-19, even though most of its population has completed the vaccination protocol. With the introduction of Omicron in late 2021, the number of COVID-19 cases soared once again in the country. We investigated in this work how lineages BA.1 and BA.2 entered and spread in the country by sequencing 2173 new SARS-CoV-2 genomes collected between October 2021 and April 2022 and analyzing them in addition to more than 18,000 publicly available sequences with phylodynamic methods. We registered that Omicron was present in Brazil as early as 16 November 2021 and by January 2022 was already more than 99% of samples. More importantly, we detected that Omicron has been mostly imported through the state of São Paulo, which in turn dispersed the lineages to other states and regions of Brazil. This knowledge can be used to implement more efficient non-pharmaceutical interventions against the introduction of new SARS-CoV variants focused on surveillance of airports and ground transportation.

Tryptase ß regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis.

PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase ß cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, -4, and -5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase ß and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase ß and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase ß as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4.

Molecular aspects of COVID-19 and its relationship with obesity and physical activity: a narrative review

Abstract BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has several mechanisms of action related to inflammatory responses, especially in individuals diagnosed with obesity. This hyperinflammatory clinical profile resulting from the association between obesity and coronavirus disease 2019 (COVID-19) may be attenuated by regular physical activity. OBJECTIVE: The aim of this study was to review the evidence on the consequences of physical inactivity and physical activity on COVID-19 in patients with obesity. DESIGN AND SETTING: Narrative review at the Bahiana School of Medicine and Public Health in Salvador, Brazil. METHODS: We searched evidence on the association of COVID-19 with physical activity and obesity using the following keywords: "covid-19," "physical activity," and "obesity". The databases used were MEDLINE (PubMed), ScienceDirect, and Virtual Health Library. Studies published from 2019 to 2021 and available in Portuguese, English, and Spanish were included. The final search was conducted on September 26, 2021. RESULTS: We identified 661 studies in the database, among which 71 were considered for inclusion in the narrative review of the molecular aspects of COVID-19 and its relationship with physical activity and obesity. CONCLUSION: This literature review enabled the perception of the relationship between the molecular mechanisms of COVID-19 and obesity. Regular physical activity had various benefits for the inflammatory condition of the studied population, highlighting moderate-intensity.