The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients.Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA.Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing.Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options

Sustainability Agenda for the Pantanal Wetland: Perspectives on a Collaborative Interface for Science, Policy, and Decision-Making.

Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland

Abstract 227: Combined Technique Versus Stent‐Retriever Alone: Angioarchitectural and Technical Analysis

Introduction Combined technique mechanical thrombectomy with contact aspiration with stent‐retriever has been shown to lead to comparable final reperfusion rates compared with stent retriever alone. We aimed to explore if anatomical and technical features could have interaction with the chances of reperfusion by each technique. Methods Retrospective analysis of a prospective mechanical thrombectomy (MT) database. Inclusion criteria: anterior circulation large vessel occlusion(LVO) due to carotid terminus or proximal MCA(M1) occlusion, first‐line stent‐retriever (SR) alone or combined technique (SR plus aspiration), and angiographic run with stent in place. The primary analysis was the interaction between clinical and angiographic characteristics and first‐line MT modality on first‐pass effect (FPE; first‐pass eTICI2c‐3). Secondary analyses aimed to evaluate predictors of FPE. Results A total of 150 patients were included in the analysis (SR alone,n=62 vs. combined technique, n=88). Demographics, vascular risk factors and NIHSS were comparable between groups. The SR group had higher IV‐tPA use (41.9%vs.26.1%,P=0.04), higher rates of FPE(64.5%vs.47.7%,P=0.04) but similar baseline ASPECTS, CTA collateral score, clot burden, as compared to the combined technique. Anatomical and technical variables (reperfusion channel, SR position in dominant MCA division, angle of interaction, diameter of stent proximal to clot, diameter of stent distal to clot, type of extracranial carotid or cavernous carotid tortuosity, clot length were comparable between both groups. None of the anatomical and technical factors were found to have an interaction with the modality (SR alone vs combined technique) on the chances of FPE (Pinteraction >0.05)(Figure). FPE was observed in 54.6% of the entire cohort. Multivariable analysis showed that use of IV‐tPA(OR 156.5,95%CI 4.59‐5334.8,P=0.005), lower angle of interaction (OR 0.94,95%CI 0.89‐0.99,P=0.03), presence of reperfusion channel (OR 145.8,95%CI 1.96‐108277.4),P=0.02), higher clot burden score (OR 8.17,95%CI 1.38 ‐48.21,P=0.02), type‐3 cavernous ICA tortuosity (OR 0.001,95%CI 0‐0.23,P=0.01) were independently associated FPE. Conclusion We could not identify any anatomical or technical features that predisposed to a benefit in adding catheter aspiration to SR thrombectomy. IV r‐TPA, clot burden score, presence of reperfusion channel, type of cavernous carotid tortuosity, and angle of interaction were found independently associated with FPE. Large sample studies are warranted

Abstract 010: Technical Approaches for Intracranial Atherosclerotic Disease Large Vessel Occlusion Strokes

Introduction The optimal management strategy for large vessel occlusion strokes (LVOS) from intracranial atherosclerotic disease (ICAD) remains debated. We aimed to evaluate the efficacy and safety of various acute medical and endovascular management options in patients who underwent mechanical thrombectomy of an ICAD‐related occlusion. Methods Retrospective analysis of ICAD‐related LVOS of a prospective mechanical thrombectomy database at a comprehensive stroke center between November 2010‐May 2023. Endovascular intervention was defined as either angioplasty, stenting, or a combination of both. Acute management was divided into 5 groups: Group#1: proactive antiplatelets (patients who received antiplatelets prior to groin puncture without further endovascular intervention after initial reperfusion); Group#2: reactive antiplatelets (patients who received antiplatelets after groin puncture without further angioplasty and/or stenting after initial reperfusion), Group#3: proactive revascularization (patients treated with angioplasty and/or stenting after initial reperfusion), Group#4: reactive revascularization (patients treated with angioplasty and/or stenting after vessel re‐occlusion after initial reperfusion), and Group #5: rescue revascularization (patients with unsuccessful reperfusion and subsequent angioplasty and/or stenting). Results A total of 200 ICAD‐LVOS MT were identified. Baseline characteristics were comparable between the 5 groups. The rate of TICI2b‐3 final reperfusion was lower in Group 4, while the rate of TICI 2c‐3 final reperfusion was comparable among groups. The rates of in‐hospital re‐occlusion were high even in patients loaded with DAPT before puncture; the rates of re‐occlusion were lower in patients managed with intervention in a proactive manner (Group 3) when compared to those managed in a reactive manner (Group 4) (0% vs 27%, p= 0.005). In ordinal analysis, mRS scores were lowest in Groups 2 and 3.Safety outcomes were comparable with similar rates of symptomatic intracranial hemorrhage (sICH). Conclusion While limited by small subgroup sample size, medical management only was associated with relatively high rates of reocclusion, while proactive angioplasty/stenting with performed best. Symptomatic intracranial hemorrhage was low in medically treated patients. Further studies are warranted

Doped Tin Dioxide (d-SnO₂) and Its Nanostructures: Review of the Theoretical Aspects, Photocatalytic and Biomedical Applications

Nanomaterials based on metal oxides are extensively studied for several applications due to their versatility. Improvements in their performances can be obtained due to specific structural modifications. One possible modification is by doping the crystal structure, which can affect the materials structure and properties, especially in nanosized particles. Electronic features are among the properties that can be modified through the doping process, consequently morphological and optical parameters can also be controlled by this process. In this sense, this review presents some modifications to tin dioxide (SnO2), one the most studied materials, mainly through the doping process and their impact on several properties. The article starts by describing the SnO2 structural features and the computational models used to explain the role of the doping process on these features. Based on those models, some applications of doped SnO2, such as photocatalytic degradation of pollutants, CO2 reduction, and desulfurization of fossil fuels are presented and discussed. Additionally, the review describes many biological applications related to antimicrobial activity for doped SnO2 and its nanostructures. Although most of the examples presented in this article are based on the doped SnO2, it also presents examples related to SnO2 composites with other nanomaterials forming heterojunctions. The metal oxides SnO2, doped-SnO2 and their nanostructures are promising materials, with results reported in many fields presented in this review, such as theoretical and computational chemistry, environmental remediation, nanoparticle morphology control, fossil fuels improvement, and biomedical applications. Although widely explored, there are still fields for innovation and advances with tin dioxide nanostructures, for example, in transparent conducting oxides, in forensics as materials for latent fingerprints visualization, and sensors in medicine for detection of exhaled volatile organic compounds. Therefore, this article aims to be a reference regarding correlating the doping processes and the properties presented by the SnO2 nanostructures

Abstract 223: Pre‐Thrombectomy Diagnosis of Large Vessel Occlusion with Underlying Intracranial Atherosclerotic Disease

Introduction Intracranial atherosclerotic disease (ICAD) is one of the leading causes of ischemic stroke. We sought to identify variables associated with ICAD underlying large vessel occlusion strokes (LVOS) to facilitate pre‐procedural diagnosis. Methods Retrospective analysis of a prospectively collected thrombectomy single comprehensive stroke center database. Inclusion criteria: anterior circulation occlusion involving the intracranial ICA, MCA‐M1/M2/M3 or ACA(A1‐A2‐A3). ICAD cases were matched for age and sex in a 1:1 ratio to non‐ICAD controls. Results A total of 348 patients were included in the analysis. Patients with ICAD more frequently presented with vascular risk factors. ICAD LVOS showed less frequent atrial fibrillation(AF)(4%vs31%,P=0.001), and lower baseline NIHSS(14vs17,P=0.002) compared to the non‐ICAD group. The ICAD group less frequently showed hyperdense vessel sign and territorial cortical infarcts, but presented more frequently borderzone, deep subcortical and bilateral infarcts on CT compared to the non‐ICAD group. ICAD strokes had higher ASPECTS, and more frequently had calcifications at the carotid siphon as well as multifocal intracranial stenosis on CTA. CTA collaterals scores were comparable between groups. The ICAD group had lower median infarct core volume (1vs12 ml;P>0.001), Tmax>4s (249vs276 ml;P>0.003), and Tmax>6s (97vs140 ml;P4:6 s ratio (2vs1;P=0.007) on CTP compared to non‐ICAD group. On multivariable analysis, absence of AF, absence of cortical infarcts, presence calcium at ipsilateral carotid siphon, cerebrovascular stroke risk factors burden (DM‐HTN‐Hyperlipidemia‐smoking), borderzone infarcts either (superficial cortical or Internal deep border zone), and multifocal intracranial stenosis were independent factors associated with ICAD. The model (table 1) by AUC for the whole model had sensitivity of 88% [P=<0.001,95%CI(0.84‐0.91)]. Conclusion In patients with anterior circulation LVO strokes, our study suggests that presence of CVS risk factors burden, calcium at carotid siphon, borderzone infract pattern, absence of territorial cortical infarct pattern, multifocal intracranial stenosis, and absence of AF were predictors for ICAD. Additional validation is warrante

Treatment with cyclic adenosine monophosphate modulators prior to in vitro maturation alters the lipid composition and transcript profile of bovine cumulus–oocyte complexes and blastocysts

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMammalian oocytes resume meiosis spontaneously after removal from the ovarian follicle. We tested the effects of a 2-h prematuration treatment (Pre-IVM) with forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX) in bovine cumulus–oocyte complexes (COCs)301013141328FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2012/50533–22013/05083–12012/23409–92012/10737–8sem informaçã