The Impact of 8 Weeks of Combined Physical Exercise Training on SIRT3 and mTOR in Lymphocytes, and on Lipid Peroxidation.

The sirtuins (SIRT) protein family and the mechanistic/mammalian target of rapamycin (mTOR) are intracellular molecules that have been involved in the regulation of several biological processes, as well as in various aging-related processes. This pilot study, in small scale, aimed to analyze the effects of an 8-week physical exercise program on SIRT3 and mTOR levels in lymphocytes, as well as on lipid peroxidation in middle aged and older men. A total of 9 participants aged between 56 and 73 years were enrolled in an 8-week physical exercise program comprising cardiovascular and high-intensity interval training. The program involved three sessions per week, each lasting 45-60 min, conducted on non-consecutive days. Tests were conducted before and after the experimental period (pre- and post-training). Assessments included a vertical jump, 20 m velocity, ball throwing, and an aerobic capacity test. Lipid peroxidation (MDA) was measured in plasma as an oxidative stress biomarker. Additionally, sirtuin 3 (SIRT3/ß-actin) and mTOR (mTOR/ß-actin) levels were measured in isolated lymphocytes extracted from venous blood. Following the exercise training period, our results demonstrated a significant improvement in aerobic capacity (pre-training: 615.4 ± 45.3 m; post-training: 687.2 ± 34.6 m; t = -2.521; p = 0.012) and 20 m velocity (pre-training: 4.6 ± 0.5 s; post-training: 4.3 ± 0.3 s; t = -2.023; p = 0.04). Concerning blood variables, there was a significant decrease in mTOR levels (pre-training: 0.857 ± 0.593; post-training: 0.214 ± 0.097; t = -2.547; p = 0.011), while no changes were observed in SIRT3 (pre-training: 0.608 ± 0.404; post-training: 0.516 ± 0.390; t = 0.533; p = 0.594) and MDA (pre-training: 8420 ± 4615; post-training: 8800 ± 3163; t = -0.533; p = 0.594). The notable reduction in mTOR levels in lymphocytes following the 8-week physical exercise program suggests a potential role of exercise in modulating immune cell dynamics, particularly in middle-aged and older individuals. Furthermore, the exercise regimen resulted in improvements in physical function, including enhanced aerobic capacity and walking velocity.

A percepção sobre o Programa Saúde na Escola (PSE) em Francisco Morato: desafios para a promoção de saúde / The perception of the School Health Program (PSE) in Francisco Morato: challenges for health promotion

O arcabouço teórico do Programa Saúde na Escola (PSE) é baseado na promoção da saúde (PS), que, ancorada nos determinantes sociais, busca extrapolar o ideário de prevenção de doenças. Nessa perspectiva, este estudo objetivou compreender a aplicação do eixo I (promoção da saúde) e do eixo II (avaliação clínica e psicossocial) no município de Francisco Morato (SP), bem como os sentidos que gestores e profissionais da saúde e da educação e estudantes produzem sobre essas ações. Trata-se de pesquisa qualitativa, na qual a coleta de dados ocorreu por meio de entrevistas em profundidade, com gestoras e profissionais da saúde e da educação, e de uma roda de conversa, com adolescentes de uma escola estadual local. Os discursos registrados por meio dessas duas técnicas constituíram o corpus de análise, em consonância com o referencial da etnometodologia. Para entender os sentidos sobre o PSE em Francisco Morato produzidos pelos entrevistados, este estudo aproximou-se do referencial das práticas discursivas e produção de sentidos no cotidiano, empregando o mapa dialógico para organizar as informações contidas no corpus. Os resultados os achados indicaram uma predominância da visão preventivista nas ações do PSE, direcionadas especialmente à identificação e encaminhamento dos estudantes para a unidade básica de saúde. A falta de alinhamento conceitual e ações fragmentadas, sem adequada articulação entre os setores educação e saúde, limitam a operacionalização do programa. Além disso, percebeu-se que a participação de alunos e familiares no planejamento e controle do programa é inexistente. Os alunos identificam ações pontuais em saúde, mas não a associam ao PSE, que dificulta que se reconheçam como agentes do cuidado em saúde. Diante disso, conclui-se que Francisco Morato necessita investir em processos e ações efetivamente intersetoriais, com foco nos determinantes sociais de saúde.

Sensitivity and Accuracy of Doppler Ultrasound compared to CT Angiography for the Diagnosis of Carotid Webs: Systematic Review.

INTRODUCTION: Carotid webs (CaW) are increasingly recognized as a cause of cryptogenic acute ischemic stroke (AIS). Due to the risk of recurrent ischemic stroke associated with CaW, it is important to identify them. Although several studies report digital subtraction angiography (DSA) and computerized tomography angiography (CTA) to be better at diagnosing CaW than Doppler ultrasound (DUS), it remains to be defined which is the best radiological method to diagnose CaW. Our aim was to evaluate sensitivity and accuracy of DUS compared to CTA for CaW diagnosis. METHODS: We searched PUBMED and EMBASE databases from inception through August 2022. We included studies with patients with CaW diagnosed by DUS and/or CTA, in which both methods were used in each patient. Demographic characteristics, diagnostic reports of each method and histology reports were collected. Descriptive analysis and sensitivity and accuracy estimates were made to evaluate DUS compared to CTA. RESULTS: We included 27 articles in the systematic review (121 patients with CaW). DUS identified 94 patients with CaW and CTA 116 patients. DUS missed diagnosis in 22.3% (27 patients) and CTA did not identified CaW detected by DUS in 4.13% (5 patients). Accuracy rate between DUS and CTA was 73.6% (95% CI 64.8 to 81.2%). Sensitivity of DUS to diagnose CaW compared to CTA was 76.7% (95% CI 68.0 to 84.1%). Most common misdiagnosis with DUS were normal exam (44.4%), atherosclerosis (22.2%) and dissection (22.2%). CONCLUSION: The sensitivity and accuracy of DUS to diagnosis of CaW were moderate. It might detect CaW in some cases in which it was not identified by CTA. Increase recognition of CaW and specific ultrasound protocols may enhance diagnosis of CaW by DUS.

Prevalence of SARS-CoV-2 infection among health care workers in a reference hospital in Brazil.

Health care workers (HCW) are the frontline workforce for COVID-19 patient care and, consequently, are exposed to SARS-CoV-2 infection due to close contact to infected patients. Here, we evaluate the prevalence of SARS-CoV-2 infection among HCW from an infectious disease hospital, reference center for COVID-19 care in the metropolitan area of Sao Paulo city, Brazil. Among 2,204 HCW, 1,417 (64.29%) were subjected to detection of anti-SARS-CoV-2 antibodies by chemiluminescent immunoassay. Out of the total, 271 (19.12%) presented anti-SARS-CoV-2 antibodies. Prevalence varied according to HCW categories. The highest prevalence was observed in workers from outsourced companies, cooks and kitchen assistants, hospital cleaning workers, and maintenance workers. On the other hand, resident physicians and HCW from the institution itself presented lower prevalence (nurses, nursing assistants, physicians, laboratory technicians). Social and environmental factors are important determinants, associated with exposure in the hospital environment, which can determine the greater or lesser risk of infection by pathogens that spread rapidly by air.

Clinical Outcomes of the Deleterious Effects of Aluminum on Neuro-Cognition, Inflammation, and Health: A Review.

Introduction: In the scenario of metal toxicity, aluminum (Al) stands out as a ubiquitous type of metal that can be combined with other elements and form different compounds. Al is widely used daily as an adjuvant in vaccines, antacids, food additives (as components of AI-containing food additives), skin care products, cosmetics, and kitchenware, and can be an element or contaminant present in our daily life. Objective: To present a review of the main deleterious effects of Al on human health. Methods: The search was carried out from September 2022 to February 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2012 to 2023. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusions: A total of 115 files were search returned. Further, 95 articles were evaluated, and 44 were included in this review. Based on the results, measuring Al's relevance to health is essential in medicine. Several studies have demonstrated clinical outcomes and metabolic alterations with Al exposure. The tolerable weekly intake established by the European Food Safety Authority (EFSA) of 1 mg Al/kg body weight can be achieved through dietary exposure alone. Proven neurotoxicity in humans is the critical adverse effect of Al. A carcinogenic effect of Al has not been proven so far. Preventive medicine advocates that exposure to Al should be kept as low as possible. Chelating agents, such as calcium disodium ethylene diamine tetraacetic acid and deferoxamine, are options for acute poisoning, and monomethysilanetriol supplementation may be a long-term strategy with chelation potential. Further studies are needed to assess the impacts of Al on human health.

Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization.

Introduction: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization. Methods: We investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses. Results: We found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells. Discussion: Overall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.

DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients.

OBJECTIVE: Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD. METHODS: After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis. RESULTS: The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD. CONCLUSION: Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p.

Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case Presentation: We report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p- in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p- syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings' samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. Discussion: The sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p- phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p- syndrome, which will allow a better understanding of the genotype-phenotype correlations.

Conventional versus flap-protected free gingival graft: a multicenter randomized clinical trial.

The purpose of this study was to compare the outcomes of a modified gingival graft technique, in which the released flap is positioned and sutured over the graft, with the conventional free gingival graft (FGG) procedure, when both are used for gingival augmentation. A 12-month, multicenter parallel randomized controlled trial was conducted. Subjects with buccal RT2 gingival recessions and keratinized tissue width (KTW) < 2 mm in at least one mandibular incisor were randomized to control group (n = 20; conventional FGG) or test group (n = 20; modified FGG; flap sutured over FGG using sling sutures). The primary outcome (KTW) was measured at baseline and after 3, 6 and 12 months, as was keratinized tissue thickness (KTT). Postoperative pain (POP) and analgesic intake were also recorded. Both techniques promoted a significant increase in KTW and KTT when compared to baseline (p < 0.05) with no significant differences between groups (KTW change of 6.1±1.5 mm and 5.4±1.6 mm, for control and test, respectively; p=0.16). However, test group patients reported less POP after 7 days and used less analgesic medication than control group patients (p < 0.05). We concluded that the modified FGG was comparable to conventional FGG in augmenting keratinized tissue width and thickness at mandibular incisors, but resulted in less patient morbidity.

Prevalence of SARS-CoV-2 infection among health care workers in a reference hospital in Brazil

ABSTRACT Health care workers (HCW) are the frontline workforce for COVID-19 patient care and, consequently, are exposed to SARS-CoV-2 infection due to close contact to infected patients. Here, we evaluate the prevalence of SARS-CoV-2 infection among HCW from an infectious disease hospital, reference center for COVID-19 care in the metropolitan area of Sao Paulo city, Brazil. Among 2,204 HCW, 1,417 (64.29%) were subjected to detection of anti-SARS-CoV-2 antibodies by chemiluminescent immunoassay. Out of the total, 271 (19.12%) presented anti-SARS-CoV-2 antibodies. Prevalence varied according to HCW categories. The highest prevalence was observed in workers from outsourced companies, cooks and kitchen assistants, hospital cleaning workers, and maintenance workers. On the other hand, resident physicians and HCW from the institution itself presented lower prevalence (nurses, nursing assistants, physicians, laboratory technicians). Social and environmental factors are important determinants, associated with exposure in the hospital environment, which can determine the greater or lesser risk of infection by pathogens that spread rapidly by air.

Healthy Lifestyle Deck of cards as a tool for cognitive-behavioral therapy in adults with obesity / Baralho do Estilo de Vida como ferramenta da terapia cognitivo-comportamental de adultos com obesidade

This is a mixed-methodology controlled clinical study that assessed the effect of the Health Lifestyle Deck of cards as a Cognitive-Behavioral Group Therapy tool for obese adults. Method The sample was divided into two groups: Intervention group and Intervention+Deck. The therapy was interdisciplinary handled by psychology, nutrition and physical education professionals, along 12 sessions. The following measures were performed: anthropometric assessment, indicators of binge eating, depression, anxiety and stress, quality of life, self-efficacy for eating habits, and physical activity at the beginning and the end of the intervention. Participants' written and verbal reports' content was analyzed. Results The results were: a reduction in body mass, binge eating, and improvement of self-efficacy to regulate eating habits in both groups. There was an improvement in the psychological domain of quality of life only in the Intervention+Deck group. Conclusion The study concluded that the intervention favored participants' cognitive and behavioral changes.

Este estudo clínico controlado de metodologia mista avaliou o efeito do Baralho do Estilo de Vida como ferramenta da Terapia Cognitivo-comportamental em grupo de adultos com obesidade. Método A amostra foi dividida em dois grupos: grupo Intervenção e grupo Intervenção+Baralho. A terapia foi interdisciplinar com profissionais da psicologia, nutrição e educação física e foram realizadas 12 sessões. As avaliações realizadas foram: avaliação antropométrica, indicadores de compulsão alimentar, depressão, ansiedade e estresse, qualidade de vida, autoeficácia para hábito alimentar e atividade física no início e no fim da intervenção. Foi realizada análise de conteúdo dos relatos verbais e por escrito dos participantes. Resultados Neste sentido, verificou-se redução da massa corporal, da compulsão alimentar e melhora da autoeficácia para regular o hábito alimentar nos dois grupos. Houve melhora no domínio psicológico da qualidade de vida apenas no grupo Intervenção+Baralho. Conclusão O estudo concluiu que a intervenção favoreceu mudanças cognitivas e comportamentais dos participantes.

Conventional versus flap-protected free gingival graft: a multicenter randomized clinical trial

Abstract The purpose of this study was to compare the outcomes of a modified gingival graft technique, in which the released flap is positioned and sutured over the graft, with the conventional free gingival graft (FGG) procedure, when both are used for gingival augmentation. A 12-month, multicenter parallel randomized controlled trial was conducted. Subjects with buccal RT2 gingival recessions and keratinized tissue width (KTW) < 2 mm in at least one mandibular incisor were randomized to control group (n = 20; conventional FGG) or test group (n = 20; modified FGG; flap sutured over FGG using sling sutures). The primary outcome (KTW) was measured at baseline and after 3, 6 and 12 months, as was keratinized tissue thickness (KTT). Postoperative pain (POP) and analgesic intake were also recorded. Both techniques promoted a significant increase in KTW and KTT when compared to baseline (p < 0.05) with no significant differences between groups (KTW change of 6.1±1.5 mm and 5.4±1.6 mm, for control and test, respectively; p=0.16). However, test group patients reported less POP after 7 days and used less analgesic medication than control group patients (p < 0.05). We concluded that the modified FGG was comparable to conventional FGG in augmenting keratinized tissue width and thickness at mandibular incisors, but resulted in less patient morbidity.

Follow-Up by Transcranial Doppler After Rupture of a Giant Intracranial Aneurysm.

Giant intracranial aneurysms (GIA) are rare and manifest primarily through subarachnoid hemorrhage (SAH), cerebral ischemia, or progressive symptoms of mass effect. Transcranial Doppler (TCD) can be used to monitor cerebral vasospasm after treatment of intracranial aneurysm allowing the adjustment of therapeutics and avoiding complications. The authors present a clinical case of a patient with a ruptured intracranial giant aneurysm in which TCD was essential to monitor vasospasm and intracranial hypertension (IH). A 53-year-old male was admitted due to a sudden headache and impaired consciousness, left hemiparesis, and dysarthria. Cerebral CT scan and CT angiography at admission showed a giant aneurysm of the right middle cerebral artery (MCA) with extensive and diffuse intraventricular SAH of Fisher grade IV and Hunt and Hess grade 4. Clipping, placement of an intracranial pressure sensor, and external ventricular drain (EVD) were performed on the same day, with difficulty in preserving the M2 branch and complicated by postoperative extensive right MCA ischemia. On day three of hospitalization, TCD revealed an increased pulsatility index (>1.5) with clinical deterioration leading to re-intervention for a decompressive craniectomy. On day six, a TCD follow-up was performed to monitor blood flow complications, and particularly vasospasm, showing a severe increase in middle blood flow velocity (MBFV) in the right MCA of 205 cm/s and Lindegaard Index > 6. Daily surveillance by TCD was maintained to guide clinical management since the attempt to withdraw the EVD led to clinical deterioration with subsequent worsening of vasospasm. Improvement occurred after surgery as ventriculoperitoneal shunt insertion was performed. TCD had a major role in the clinical orientation of SAH as well as in intracranial pressure management and was decisive to establish long-term treatment.

Lower Energy-Adjusted Nutrient Intakes Occur Among Food Energy Under-Reporters With Poor Mental Health.

Background: Food energy under-reporting is differentially distributed among populations. Currently, little is known about how mental health state may affect energy-adjusted nutrient intakes among food energy under-reporters. Methods: Stratified analysis of energy-adjusted nutrient intake by mental health (poor vs. good) and age/sex was conducted using data from Canadian Community Health Survey (CCHS) respondents (14-70 years; n = 8,233) who were deemed as under-reporters based on Goldberg's cutoffs. Results: Most were experiencing good mental health (95.2%). Among those reporting poor mental health, significantly lower energy-adjusted nutrient intakes tended to be found for fiber, protein, vitamins A, B2, B3, B6, B9, B12, C, and D, and calcium, potassium, and zinc (probability measures (p) < 0.05). For women (51-70 years), all micronutrient intakes, except iron, were significantly lower among those reporting poor mental health (p < 0.05). For men (31-50 years), B vitamin and most mineral intakes, except sodium, were significantly lower among those reporting poor mental health (p < 0.05). Among women (31-50 years) who reported poor mental health, higher energy-adjusted intakes were reported for vitamin B9 and phosphorus (p < 0.05). Conclusions: Among food energy under-reporters, poor mental health tends to lower the report of specific energy-adjusted nutrient intakes that include ones critical for mental health. Future research is needed to discern if these differences may be attributed to deviations in the accurate reports of food intakes, measurement errors, or mental health states.

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients.

In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19.

Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome.

OBJECTIVES: Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. METHODS: The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. RESULTS: The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. CONCLUSIONS: The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases.

Junctional instability in neuroepithelium and network hyperexcitability in a focal cortical dysplasia human model.

Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.

Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome

Abstract Objectives Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. Methods The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. Results The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. Conclusions The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases. HIGHLIGHTS The authors The authors have described three novel rearrangements between chromosomes 5 and 2, 5 and 18, and 5 and Y with chromosomal breakpoints and overlapped phenotypes that were not previously described. One of the main atypical features for 5p- syndrome that the authors report was the presence of seizures that was found in the three patients with rearrangements between different chromosomes and in a patient with a deletion followed by duplication in 5p. The authors suggest physicians conduct further molecular investigation in the presence of atypical clinical features for patients with 5p- syndrome suspicion.

Caminhos da população ribeirinha no acesso à urgência e à emergência: desafios e potencialidades / Caminos de la población ribereña en el acceso a la urgencia y emergencia: desafíos y potencialidades / Paths of the riverside population in the access to urgent and emergency care: challenges and potentialities

O estudo objetivou analisar a produção do acesso da população ribeirinha aos serviços de urgência e emergência em Maués, Amazonas, Brasil, tendo como metodologia a abordagem participativa, uso de mapas falantes e análises das narrativas. Destacou-se a importância do agente comunitário de saúde (ACS) e dos mecanismos de atuação em território ribeirinho, como Unidade Básica de Saúde Fluvial e "ambulanchas". Mas expõe ainda desafios com relação ao transporte sanitário em situações de urgência e emergência e a falta de um profissional de nível superior em território para o atendimento inicial. Além disso, a articulação e a comunicação entre os setores e o processo de referenciamento ainda são deficientes. Assim, é essencial que sejam elaboradas estratégias que integrem os diferentes pontos da Rede, viabilizando essa comunicação e a articulação. E, por meio de encontros com diálogo reflexivo entre a gestão e trabalhadores, sejam pensadas novas estratégias que viabilizem esse acesso.(AU)

El objetivo del estudio fue analizar la producción del acceso de la población ribereña a los servicios de emergencia en Maués, Amazonas, Brasil. Teniendo como metodología el abordaje participativo, el uso de mapas orales y el análisis de las narrativas. Se subrayó la importancia del Agente Comunitario de Salud y de los mecanismos de actuación en territorio ribereño, como UBS Fluvial y "ambulanchas". Pero también expone desafíos con relación al transporte sanitario en situaciones de urgencia y emergencia y la falta de un profesional de nivel superior en el territorio para la atención inicial. Además, la articulación y comunicación entre los sectores y el proceso de referencia todavía es deficiente. Por lo tanto, es esencial la elaboración de estrategias que integren los diferentes puntos de la red, viabilizando esa comunicación y articulación. Y que por medio de encuentros con diálogo reflexivo entre la gestión y los trabajadores se piensen nuevas estrategias que viabilicen ese acceso.(AU)

The study aimed to analyze the riverside population's access to urgent and emergency services in Maués, Amazonas, Brazil, through the methodology of participatory approach and the analysis of talking maps and narratives. The relevance of the Community Health Agent came was highlighted, as well as the importance of mechanisms to deliver care in the riverside territory, such as the Fluvial Primary Care Unit and launches known as ambulanchas. However, challenges also came to light, like transportation in urgent and emergency situations and lack of a professional with a higher education degree to provide initial care in the territory. In addition, articulation and communication between sectors and the referral process are still deficient. Thus, strategies are needed to integrate the different points of the Healthcare Network, enabling communication and articulation. Moreover, new strategies to promote healthcare access must be developed in meetings between management and workers, grounded on reflective dialogue.(AU)

Diet Quality Indices and Physical Activity Levels Associated with Adequacy of Gestational Weight Gain in Pregnant Women with Gestational Diabetes Mellitus.

The aim of this study was to evaluate the Diet Quality Index (DQI) and the Physical Activity (PA) levels associated with adequacy of gestational weight gain in pregnant women with gestational diabetes mellitus (GDM). A total of 172 pregnant women with a single fetus and a diagnosis of GDM participated. Food intake was self-reported on the food frequency questionnaire and DQI was quantified using the index validated and revised for Brazil (DQI-R). To assess PA, the Pregnancy Physical Activity Questionnaire was administered. Gestational weight gain was classified, following the criteria of the Institute of Medicine, into adequate (AWG), insufficient (IWG), or excessive (EWG) weight gain. A multinomial logistic regression analysis was performed, with level of significance <0.05. The participants were divided into 3 groups: AWG (33.1%), IWG (27.3%), and EWG (39.5%). The analysis indicated that if the pregnant women PA fell into tertile 1 or 2, then they had a greater chance of having IWG, whereas those with the lowest scores on the DQI-R, whose PA fell into tertile 2, and pregestational obesity women had the greatest chance of having EWG. This study has shown that low PA levels may contribute towards IWG. On the other hand, a low final DQI-R score, representing inadequate food habits, low PA levels, and pregestational obesity may increase the chance of EWG in patients with GDM.