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.

A 3D bioreactor model to study osteocyte differentiation and mechanobiology under perfusion and compressive mechanical loading.

Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (ß-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5% strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network. STATEMENT OF SIGNIFICANCE: This study highlights the importance of creating a three-dimensional (3D) in vitro model to study osteocyte differentiation and mechanobiology, as cellular functions are limited in two-dimensional (2D) models lacking in vivo tissue organization. By using a perfusion bioreactor platform, physiological conditions of fluid flow and compressive loading were mimicked to which osteocytes are exposed in vivo. Microporous poly(L-lactide-co-trimethylene carbonate) lactide (LTMC) scaffolds in 3D are identified as a valuable tool to create a favorable environment for osteocyte differentiation and to enable mechanical stimulation of osteocytes by perfusion and compressive loading. The LTMC platform imitates the mechanical bone environment of osteocytes, allowing the analysis of the interaction with other cell types in bone under in vivo biophysical stimuli.

Lemierre Syndrome: Clinical Challenges And The Anticoagulation Dilemma In Adolescent Care.

Lemierre syndrome is a rare, life-threatening condition characterized by an acute otorhinolaryngologic infection with septic thrombophlebitis of the internal jugular vein and septic embolism, particularly to the lungs. We describe a case of a previously healthy 15-year-old female patient who initially presents fever and odynophagia but quickly develops neck and pleuritic chest pain. Computed tomography was performed and the radiological findings confirmed the diagnosis of a Lemierre syndrome. She was managed with antibiotics, anticoagulant for three days and symptomatic treatment, with a gradually improving condition. After 17 days of hospitalisation, due to reappearance of pleuritic pain, a new imaging assessment was performed and showed additional septic emboli in the lungs, which prompted the reintroduction of anticoagulant therapy. Awareness of the existence of this syndrome is essential to ensure a radiological evaluation with computed tomography and thus timely diagnosis and treatment.

Development, validation and implementation of an augmented multi-well, multi-target quantitative PCR-HPV genotyping analysis through software automation, data science and artificial intelligence.

The value of HPV testing for cervical cancer screening is well established, where its use as primary screening option or as reflex test after atypical cytology results has recently gained wide acceptance. The importance of full genotyping and viral load determination has been demonstrated to enhance the clinical understanding of the viral infection progression during follow-up or after treatment, thereby providing clinicians with supplementary tools for optimized patient management. In this study a new analysis method for the RIATOL quantitative PCR assay was developed, validated and implemented in the laboratory of clinical molecular pathology at A.M.L. (Sonic Healthcare, Belgium), under national accreditation and following the international ISO guidelines. It presents the successful validation of a high throughput, multi-target HPV analysis method, with enhanced accuracy on both qualitative and quantitative end-results. This is achieved by software standardization and automation of PCR curve analysis and interpretation, using data science and artificial intelligence (DS/AI). Moreover, the user-centric functionality of the platform was demonstrated to enhance both staff training and routine analysis workflows, thereby saving time and laboratory personnel resources. Overall, the integration of the FastFinder plugin semi-automatic analysis algorithm with the RIATOL qPCR assay proved to be a remarkable advancement in high throughput HPV quantification, with demonstrated capability to provide highly accurate clinical-grade results and to reduce manual variability and analysis time.

Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024).

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.

Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat's claw) extracts: A systematic review and meta-analysis of in vivo studies.

Background: Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of U. tomentosa for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. Methods: We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of U. tomentosa on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869). Results: Twenty-four of 523 studies were included. U. tomentosa extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, p = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, p = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, p = 0.80), or tumor necrosis factor-alpha (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, p = 0.41). Conclusion: Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450869, Identifier CRD42023450869.

The effects of methylparaben exposure on biofilm tolerance to chlorine disinfection.

Parabens are emerging contaminants that have been detected in drinking water. Their presence in DW distribution systems (DWDS) can alter bacterial behaviour, characteristics, and structure, which may compromise DW disinfection. This work provides insights into the impact of methylparaben (MP) on the tolerance to chlorine disinfection and antibiotics from dual-species biofilms formed by Acinetobacter calcoaceticus and Stenotrophomonas maltophilia isolated from DW and grown on high-density polyethylene (HDPE) and polypropylene (PPL). Results showed that dual-species biofilms grown on PPL were more tolerant to chlorine disinfection, expressing a decrease of over 50 % in logarithmic reduction values of culturable cells in relation to non-exposed biofilms. However, bacterial tolerance to antibiotics was not affected by MP presence. Although MP-exposed dual-species biofilms grown on HDPE and PPL were metabolically more active than non-exposed counterparts, HDPE seems to be the material with lower impact on DW risk management and disinfection, if MP is present. Overall, results suggest that MP presence in DW may compromise chlorine disinfection, and consequently affect DW quality and stability, raising potential public health issues.

Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.

Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10-57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10-17) and European (b = 0.28; p = 1.14 × 10-23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10-12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.

POF-based biosensors for cortisol detection in seawater as a tool for aquaculture systems.

A surface plasmon resonance (SPR) phenomenon implemented via D-shaped polymer optical fiber (POF) is exploited to realize cortisol biosensors. In this work, two immonosensors are designed and developed for the qualitative as well as quantitative measurement of cortisol in artificial and real samples. The performances of the POF-based biosensors in cortisol recognition are achieved using different functionalization protocols to make the same antibody receptor layer over the SPR surface via cysteamine and lipoic acid, achieving a limit of detection (LOD) of 0.8 pg/mL and 0.2 pg/mL, respectively. More specifically, the use of cysteamine or lipoic acid changes the distance between the receptor layer and the SPR surface, improving the sensitivity at low concentrations of about one order of magnitude in the configuration based on lipoic acid. The LODs of both cortisol biosensors are achieved well competitively with other sensor systems but without the need for amplification or sample treatments. In order to obtain the selectivity tests, cholesterol and testosterone were used as interfering substances. Moreover, tests in simulated seawater were performed for the same cortisol concentration range achieved in buffer solution to assess the immunosensor response to the complex matrix. Finally, the developed cortisol biosensor was used in a real seawater sample to estimate the cortisol concentration value. The gold standard method has confirmed the estimated cortisol concentration value in real seawater samples. Liquid-liquid extraction was implemented to maximize the response of cortisol in liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis.

Effect of Cantilever Extension on Bone Loss in Mandibular Complete-Arch Implant-Supported Fixed Prostheses with Three and Four Implants.

PURPOSE: To compare the peri-implant bone loss of mandibular complete-arch implant-supported fixed prostheses (FPSs) supported by three and four implants and to correlate with the size of the horizontal and vertical distal cantilever at prosthesis placement (T1) and after 1 year (T2). MATERIALS AND METHODS: A total of 72 external hexagon (EH) type implants were placed in 20 participants. Of these, 24 supported an FPS with three implants (G3I) and 48 with four implants (G4I). The mandibular implants were named 1, 2, 3, and 4 according to their location in the arch, in a clockwise direction. Digital periapical radiographs were taken at times T1 and T2 for analysis and measurement of peri-implant bone loss. The horizontal and vertical distal cantilevers were measured with a digital caliper and correlated with peri-implant bone loss. RESULTS: The survival rate of implants in G3I was 91.66%, and in G4I it was 97.91%. The mean bone loss in G3I was 0.88 ± 0.89 mm, and in G4I it was 0.58 ± 0.78 mm (P = .225). There was no correlation between distal horizontal cantilevers and bone loss in the studied groups, with G3I being -0.25 (P = .197) and G4I -0.22 (P = .129). Larger vertical cantilevers of implants 1 (P = .018), 3 (P =.015), and 4 (P = .045) correlated with greater bone loss in G4I. CONCLUSIONS: The number of implants in an FPS did not influence peri-implant bone loss after 1 year of follow-up. Larger vertical cantilevers influenced greater bone loss in complete-arch implant-supported fixed prostheses supported by four implants.

Blended Psychological Interventions for Emotional Disorders in Youth: Acceptability and Intention to Use in a Sample of Portuguese Psychologists.

INTRODUCTION: The rise of mental health problems in youth highlights the need for accessible and cost-effective psychological interventions. Blended interventions, which combine face-to-face and online sessions, can be an adequate response to the increase in demands for youth mental health services. Although this can be a promising approach, effective dissemination depends on the professionals´ acceptance. OBJECTIVES: This study aimed to explore the acceptability of and intention to use blended interventions by psychologists working with children with emotional disorders and to examine their predictors, including previous knowledge, expectancies (i.e., performance expectancy, effort expectancy, social influence, and facilitating conditions), and attitudes toward evidence-based practices. METHODS: The sample consisted of 76 Portuguese psychologists (Mage = 37.26 years, SD = 10.47; 92.1% female) working in youth mental health services. The participants completed an online protocol to evaluate the different dimensions included in the study. RESULTS: The results showed that most participants demonstrated moderate to high acceptability of blended psychological interventions for emotional disorders in youth and intend to use them in the future. Regression analysis showed that performance expectancy and positive attitudes toward evidence-based practices were significant predictors of acceptance of blended interventions and that social influence was a significant predictor of both acceptance of and intention to use blended interventions. CONCLUSION: These results emphasize the importance of sharing the findings of blended interventions, changing professionals' attitudes toward evidencebased practices, and collaborating more closely with organizations and institutions to advance standards that encourage the adoption of this intervention format.

MR Imaging Findings in Anti-Leucine-Rich Glioma Inactivated Protein 1 Encephalitis: A Systematic Review and Meta-analysis.

BACKGROUND: Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable. PURPOSE: We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas. DATA SOURCES: PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022. STUDY SELECTION: Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included. DATA ANALYSIS: Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models. DATA SYNTHESIS: Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus. LIMITATIONS: Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity. CONCLUSIONS: T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein.

The impact of a physical exercise program on quality of life, fatigue, physical performance, and level of physical activity in patients with cancer.

OBJECTIVE: Increasing evidence suggests that exercise programs are of great value in the rehabilitation and survivorship of patients with cancer. However, challenges remain regarding maintaining patients more physically active. This study aimed to evaluate the impact of a supervised exercise program on quality of life, fatigue, physical performance, and levels of physical activity of patients with cancer. METHODS: An observational longitudinal study, with a 1-year prospective follow-up, was developed. SETTING: This is a university-based outpatient rehabilitation program in a high-complexity cancer care center in Sao Paulo. RESULTS: After the program, patients showed a significant gain in quality of life (p<0.0001), physical performance (p<0.0001), and improvement in fatigue (p<0.0001). After 12 months, 81.1% of the patients remained active, and only 4.5% declared themselves to be sedentary. CONCLUSION: The results of this study confirm that exercise programs are an important tool in the rehabilitation of patients with cancer and that an initial supervised exercise program, in combination with follow-ups, can help increase the levels of physical activity of this population. CLINICAL REHABILITATION IMPACT: This study provides additional information on the outcomes that are expected with the provision of a supervised physical exercise program in the rehabilitation care of patients with cancer and that additional follow-ups could further benefit this population.

Current applications, procedural and 1-year outcomes of Rotatripsy for the treatment of calcified coronary lesions.

BACKGROUND: Intravascular lithotripsy (IVL) combined with rotational atherectomy (RA), known as Rotatripsy, is used to treat severe coronary artery calcification (CAC), though data on efficacy, midterm safety and use sequence is limited. We aimed to identify indicators for Rotatripsy use and to assess its safety and success rates, both acutely and at 1-year follow-up. METHODS: Patients undergoing Rotatripsy for severe CAC across six centers from May 2019 to December 2023 were included. Demographic, clinical, procedural and follow-up data were collected. Efficacy endpoints included device success (delivery of the RA-burr and IVL-balloon across the target lesion and administration of therapy without related complications), technical success (TIMI 3 flow and residual stenosis <30% by quantitative coronary analysis) and procedural success [composite of technical success with absence of in-hospital major adverse cardiovascular events (MACE: cardiac death, myocardial infarction or target vessel revascularization). Safety endpoints comprised Rotatripsy-related complications and MACE at 1-year follow-up. RESULTS: A total of 114 patients (75 ± 9 years, 78% male) underwent Rotatripsy for 120 lesions. In the majority of procedures RA was followed by IVL, mostly electively (n = 68, 57%) but also for balloon underexpansion (n = 37, 31%) and stent crossing failure (n = 1, 1%). Diverse and complex target lesions were addressed with an average SYNTAX score of 24.6 ± 13.0. Device, technical and procedural success were 97%, 94% and 93%, respectively. Therapy-related complications included two (2%) coronary perforations, one (1%) coronary dissection and one (1%) burr entrapment. At 1-year follow-up(present in 77(67%) patients), MACE occurred in 7(9%) cases. CONCLUSIONS: Over a 1-year follow-up period, Rotatripsy was safe and effective, predominantly using RA electively before IVL.

COVID-19 e a incidência de AVC isquêmico pós-infecção: uma revisão integrativa da literatura / COVID-19 and the incidence of post-infection ischemic stroke: an integrative literature review

O SARS-CoV-2 é um vírus que surgiu em 2019, sendo responsável por causar uma síndrome respiratória que foi denominada COVID-19. O vírus possui uma proteína, chamada proteína Spike, que interage com as ACE2, estando presente no trato respiratório e nas células endoteliais, causando inflamação, apoptose e efeitos pró-trombóticos que ativam a via de coagulação. Dessa maneira, presume-se que o estado de hipercoagulabilidade do vírus e a inflamação endotelial estejam relacionados à fisiopatologia do AVC isquêmico pós-infecção. O objetivo desta revisão foi analisar a fisiopatologia e a etiologia dos AVCs associados à infecção pelo vírus SARS-CoV-2 e seus fatores de risco. Foi realizada uma busca por trabalhos prévios nas plataformas PubMed e BVS, e um total de 26 artigos científicos foram incluídos após a aplicação de critérios de inclusão e exclusão. Através dos estudos analisados, observou-se a correlação do aumento da incidência do AVC pós-infecção pelo SARS-CoV-2, e os fatores de risco presentes principais foram hipertensão arterial, fibrilação atrial, diabetes mellitus, dislipidemia e insuficiência cardíaca. Em conclusão, a infecção por SARS-CoV-2 possui relação com o aumento da incidência de AVC, possivelmente por seu mecanismo trombótico e inflamatório dos endotélios.

SARS-CoV-2 is a virus that emerged in 2019, being responsible for causing a respiratory syndrome that was named COVID-19. The virus has a protein, called Spike protein, which interacts with ACE2, which are present in the respiratory tract and endothelial cells, causing inflammation, apoptosis and prothrombotic effects that activate the coagulation pathway. Thus, it is presumed that the hypercoagulable state of the virus and endothelial inflammation are related to the pathophysiology of postinfection ischemic stroke. The aim of this review was to analyze the pathophysiology and etiology of strokes associated with SARSCoV-2 virus infection and their risk factors. A search for previous works was carried out on PubMed and VHL platforms, and a total of 26 scientific articles were included after applying inclusion and exclusion criteria. Through the studies analyzed, a correlation was observed between the increased incidence of stroke after infection with SARS-CoV-2, and the main risk factors present were arterial hypertension, atrial fibrillation, diabetes mellitus, dyslipidemia and heart failure. In conclusion, SARS-CoV-2 infection is related to the increased incidence of stroke, possibly due to its thrombotic and endothelial inflammatory mechanism.

Effects of gallic acid and physical training on liver damage, force, and anxiety in obese mice: Hepatic modulation of Sestrin 2 (SESN2) and PGC-α expression.

Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α.

Beyond Restrictive: Sleeve Gastrectomy to Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy as a Spectrum of One Single Procedure.

INTRODUCTION: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be split into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and post-prandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or SG as the first step of SADI-S. METHODS: Subjects submitted to SADI-S (n = 7) or SG (n = 7) at a tertiary referral public academic hospital underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively. RESULTS: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate, and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up. CONCLUSIONS: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. These data provide support for surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes.

Metatranscriptome and Resistome of the Endodontic Microbiome.

INTRODUCTION: In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression in endodontic infections. METHODS: Root canal samples were collected from ten teeth, including five primary and five persistent/secondary endodontic infections. RNA from endodontic samples was extracted, and RNA sequencing was performed on a NovaSeq6000 system (Illumina). Taxonomic analysis was performed using the Kraken2 bacterial database. Then, sequences with a taxonomic classification were annotated against the Universal Protein Knowledgebase for functional annotation and the Comprehensive Antibiotic Resistance Database for AR-like gene identification. RESULTS: Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria represented the dominant phyla, whereas Fusobacteria, Spirochetes, and Synergistetes were among the nondominant phyla. The top ten species were mainly represented by obligate (or quasiobligate) anaerobes, including Gram-negative (eg, Capnocytophaga sp. oral taxon 323, Fusobacterium nucleatum, Prevotella intermedia, Prevotella oris, Tannerella forsythia, and Tannerella sp. oral taxon HOT-286) and Gram-positive species (eg, Olsenella uli and Parvimonas micra). Transcripts encoding moonlighting proteins (eg, glycolytic proteins, translational elongation factors, chaperonin, and heat shock proteins) were highly expressed, potentially affecting bacterial adhesion, biofilm formation, host defense evasion, and inflammation induction. Endodontic bacteria expressed genes conferring resistance to antibiotic classes commonly used in dentistry, with a high prevalence and expression of tetracycline and lincosamide resistance genes. Antibiotic efflux and antibiotic target alteration/protection were the main resistance mechanisms. CONCLUSIONS: Metatranscriptomics revealed the activity of potential endodontic pathogens, which expressed putative virulence factors and a wide diversity of genes potentially involved in AR.