Characterization of cement mortars with regional organic and inorganic additives.

The present investigation establishes the basis for future studies in the southeast of México for the improvement of building materials by combining regional organic and inorganic nanoparticles in admixtures to formulate cement mortars with durability potential in structures of concrete. The characterization of the organic extract of Albzia tomentosa by nuclear magnetic resonance (NMR) revealed the presence of epicatechin (tannin related) and sucrose. Calcium zinc hydroxide dihydrate nanoparticles (CZ NPs) showed the highest surface area of 60.7 m2 g-1. The electrical resistivity, propagation of ultrasound velocity and water absorption by capillarity properties were individually evaluated for the organic extract, the inorganic nanoparticles and their admixtures in cement mortars, at a curing time of 7, 28 and 96 days with and optimal concentration of 5 mg mL-1 of the added additives. The best results were obtained at 96 days showing slightly but clear improvement of the electrical resistivity (23.40 ± 0.022 kΩ cm, 22.40 ± 0.004 kΩ cm and 22.29 ± 0.013 kΩ cm), propagation of ultrasound velocity (1370 ± 10 m s-1, 1345 m s-1 ± 6, 1310 ± 9 m s-1) and capillary coefficient (0.0044 kg m-2s-1/2, 0.0045 kg m-2s-1/2 and 0.0049 kg m-2s-1/2) properties of the cement mortars with CZ NPs, extraction Albizia solution (EAS) and CZ NPs + EAS respectively when compared to the mortar control (19.91 ± 0.036 kΩ cm, 1266 ± 15 m s-1 and 0.0082 kg m-2s-1/2).

Efficacy and safety of microvascular decompression with or without partial sensory rhizotomy: a comprehensive meta-analysis and systematic review in treating trigeminal neuralgia.

Classical trigeminal neuralgia (TN), caused by vascular compression of the nerve root, is a severe cause of pain with a considerable impact on a patient's quality of life. While microvascular decompression (MVD) has lower recurrence rates when compared with partial sensory rhizotomy (PSR) alone, refractoriness can still be as high as 47%. We aimed to assess the efficacy and safety profile of MVD + PSR when compared to standalone MVD for TN. We searched Medline, Embase, and Web of Science following PRISMA guidelines. Eligible studies included those with ≥ 4 patients, in English, published between January 1980 and December 2023, comparing MVD vs. MVD + PSR for TN. Endpoints were pain cure, immediate post-operative pain improvement, long-term effectiveness, long-term recurrence, and complications (facial numbness, hearing loss, and intracranial bleeding). We pooled odds ratios (OR) with 95% confidence intervals with a random-effects model. I2 was used to assess heterogeneity, and sensitivity and Baujat analysis were conducted to address high heterogeneity. Eight studies were included, comprising a total of 1,338 patients, of whom 1,011 were treated with MVD and 327 with MVD + PSR. Pain cure analysis revealed a lower likelihood of pain cure in patients treated with MVD when compared to patients treated with MVD + PSR (OR = 0.30, 95% CI: 0.13 to 0.72). Immediate postoperative pain improvement assessment revealed a lower likelihood of improvement in the MVD group when compared with the MVD + PSR group (OR = 0.31, 95% CI: 0.10 to 0.95). Facial numbness assessment revealed a lower likelihood of occurrence in MVD alone when compared to MVD + PSR (OR = 0.08, 95% CI: 0.04 to 0.15). Long-term effectiveness, long-term recurrence, hearing loss, and intracranial bleeding analyses revealed no difference between both approaches. Our meta-analysis identified that MVD + PSR was superior to MVD for pain cure and immediate postoperative pain improvement for treating TN. However, MVD + PSR demonstrated a higher likelihood of facial numbness complications. Furthermore, identified that hearing loss and intracranial bleeding complications appear comparable between the two treatments, and no difference between long-term effectiveness and recurrence.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Kink bands promote exceptional fracture resistance in a NbTaTiHf refractory medium-entropy alloy.

Single-phase body-centered cubic (bcc) refractory medium- or high-entropy alloys can retain compressive strength at elevated temperatures but suffer from extremely low tensile ductility and fracture toughness. We examined the strength and fracture toughness of a bcc refractory alloy, NbTaTiHf, from 77 to 1473 kelvin. This alloy's behavior differed from that of comparable systems by having fracture toughness over 253 MPa·m1/2, which we attribute to a dynamic competition between screw and edge dislocations in controlling the plasticity at a crack tip. Whereas the glide and intersection of screw and mixed dislocations promotes strain hardening controlling uniform deformation, the coordinated slip of <111> edge dislocations with {110} and {112} glide planes prolongs nonuniform strain through formation of kink bands. These bands suppress strain hardening by reorienting microscale bands of the crystal along directions of higher resolved shear stress and continually nucleate to accommodate localized strain and distribute damage away from a crack tip.

Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Recent Advances on Targeting Proteases for Antiviral Development.

Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible for causing diseases in humans, like the West Nile virus (WNV) and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the mechanisms behind blocking viral protease's function is pivotal for the development of new antiviral drugs and therapeutical strategies. Apart from directly inhibiting the target protease, usually by targeting its active site, several new pathways have been explored to impair its activity, such as inducing protein aggregation, targeting allosteric sites or by inducing protein degradation by cellular proteasomes, which can be extremely valuable when considering the emerging drug-resistant strains. In this review, we aim to discuss the recent advances on a broad range of viral proteases inhibitors, therapies and molecular approaches for protein inactivation or degradation, giving an insight on different possible strategies against this important class of antiviral target.

Ultrasound-Guided Resection of High-Grade Gliomas: A Single-Arm Meta-Analysis.

BACKGROUND: High-grade gliomas (HGGs) present a challenge in neuro-oncology, often necessitating surgical resection for optimal management. Ultrasound holds promise in achieving better gross total resection (GTR) and improving outcomes. This meta-analysis systematically evaluates literature providing robust evidence on the use of intraoperative ultrasonography (iUSG) in HGG resection. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines a comprehensive search was made across PubMed, Embase, Cochrane, and Web of Science utilized terms related to iUSG for HGG resection. The meta-analysis examined randomized trials and observational cohort studies on iUSG-guided HGG resection. GTR, subtotal resection, and postresection complications were assessed. Statistical analysis, employing R software for a single proportion analysis with confidence intervals of 95%, I2 statistics for heterogeneity, and the instrumental variables method with restricted maximum likelihood for a random effects model. RESULTS: A total of 178 patients were included in our study. The GTR overall rate in patients with iUSG-guided resection was found to be 64% (95% confidence interval: 46%-81%). Two-dimensional ultrasound remains dominant at 80% against other options of ultrasound. Complications were reported at a 15% rate (95% confidence interval: 7%-23%). CONCLUSIONS: Our study provided robust data on the utilization of iUSG-guided resection regarding the attainment of GTR and the complications related to resection. However, challenges such as outcome heterogeneity and limited complication reporting highlight the need for further research to optimize iUSG in HGG treatment. Long-term follow-up studies on patient survival and postsurgery quality of life will complement existing literature, guiding clinical practices in managing HGG.

Acquisition-invariant brain MRI segmentation with informative uncertainties.

Combining multi-site data can strengthen and uncover trends, but is a task that is marred by the influence of site-specific covariates that can bias the data and, therefore, any downstream analyses. Post-hoc multi-site correction methods exist but have strong assumptions that often do not hold in real-world scenarios. Algorithms should be designed in a way that can account for site-specific effects, such as those that arise from sequence parameter choices, and in instances where generalisation fails, should be able to identify such a failure by means of explicit uncertainty modelling. This body of work showcases such an algorithm that can become robust to the physics of acquisition in the context of segmentation tasks while simultaneously modelling uncertainty. We demonstrate that our method not only generalises to complete holdout datasets, preserving segmentation quality but does so while also accounting for site-specific sequence choices, which also allows it to perform as a harmonisation tool.

Follow-up de dispositivos cardíacos implantáveis suscetíveis a recall através de monitoramento remoto: resultados de um serviço de referência

INTRODUÇÃO: Em março de 2021 a Biotronik emitiu um comunicado sobre uma possível depleção prematura da bateria de cardiodesfibriladores implantáveis (CDI) e ressincronizadores cardíacos com desfibrilador (TRC-D). A empresa não orientou troca imediata das baterias e sugeriu o acompanhamento através de monitoramento remoto desses pacientes com dispositivos implantados em nosso serviço. Relatamos neste trabalho a taxa de recall. MÉTODOS: Estudo retrospectivo observacional com pacientes com CDI e TRC-D Biotronik suscetíveis a recall implantados no Instituto Dante Pazzanese de Cardiologia entre os anos de 2015 a 2021. Em consulta médica, os pacientes foram convidados a participar do monitoramento remoto com o uso do monitor CardioMessenger Smart, orientados quanto ao comunicado da empresa e sobre como manusear o aparelho. RESULTADOS: Foram identificados 76 pacientes com dispositivos passíveis de disfunção. Através de contato telefônico, observou-se que 34 pacientes já haviam falecido. Uma paciente foi submetida à troca do gerador previamente ao comunicado por desgaste da bateria. Dos 41 restantes, realizouse o monitoramento remoto de 73% (30), sendo 2 TRC-D e 28 CDI. Não ocorreu a monitorização de 10 pacientes devido à não disponibilização dos aparelhos pela empresa. Não foi possível contato com um paciente. Durante o follow-up de 2 anos, 6,6% dos casos (2) apresentaram depleção prematura da bateria, sendo submetidos à troca do gerador. CONCLUSÃO: A percentagem de recall encontrada neste estudo foi relevante e o monitoramento remoto foi fundamental para a detecção precoce e prevenção de uma situação potencialmente fatal.

Postoperative Seizure Prophylaxis in Meningioma Resection: A Systematic Review and Meta-Analysis.

BACKGROUND: Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023. RESULTS: Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I2 = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity between the studies (I2 = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses. CONCLUSIONS: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

Enhancing meningioma resection: a comprehensive study on the safety and effectiveness of Onyx™ presurgical embolization.

Presurgical embolization (PE) has emerged as an interesting strategy to help turn brain tumor resection more amenable. This study aims to systematically review the safety and effectiveness of Onyx™ PE in meningioma resection. We followed Cochrane Collaboration and PRISMA for systematic review and meta-analysis, querying PUBMED, Cochrane Library, Web of Science, and Embase databases. Major complications were defined as other artery occlusion, visual deficits due to PE, or non temporary nerve damage, while minor included transitory conditions and others without clinical implications. A total of 186 patients were included, in which 120 were WHO grade I (80%), II (16%), and III (4%). Patient baseline characteristics and complications were distributed in groups without or with individual patient data analysis. Individual Patient Data Meta-Analysis (IPDMA) was performed on the last category, comprising 51 meningiomas that underwent Onyx™ PE. Among available data, 70%, 17%, and 13% were WHO grade I, II, and III, respectively. Considering all studies, tumor characteristics regarding grade underscored a certain homogeneity. Complications occurred at a rate of 9% (95% CI, 4 to 14%; I2 = 35%), with the rate of major complications significantly lower at only 1% (95% CI, 0 to 3%; I2 = 32%), whereas of minor complications was 7% (95% CI, 3 to 10%; I2 = 0%). Mean surgery blood loss was 668.7 (95% CI, 534.9 to 835.8; I2 = 0%) in IPDMA. Onyx™ PE is promising for safer surgical meningioma resection, despite limitations. Further studies are required to validate efficacy, enhance patient selection, and refine techniques.

CO2-plasma surface treatment of graphite sheet electrodes for detection of chloramphenicol, ciprofloxacin and sulphanilamide.

Graphite sheet (GS) electrodes are flexible and versatile substrates for sensing electrochemical; however, their use has been limited to incorporate (bio)chemical modifiers. Herein, we demonstrated that a cold (low temperature) CO2 plasma treatment of GS electrodes provides a substantial improvement of the electrochemical activity of these electrodes due to the increased structural defects on the GS surface as revealed by Raman spectroscopy (ID/IG ratio), and scanning electron microscopy images. XPS analyses confirmed the formation of oxygenated functional groups at the GS surface after the plasma treatment that are intrinsically related to the substantial increase in the electron transfer coefficient (K0 values increased from 1.46 × 10-6 to 2.09 × 10-3 cm s-1) and with reduction of the resistance to charge transfer (from 129.8 to 0.251 kΩ). The improved electrochemical activity of CO2-GS electrodes was checked for the detection of emerging contaminant species, such as chloramphenicol (CHL), ciprofloxacin (CIP) and sulphanilamide (SUL) antibiotics, at around + 0.15, + 1.10 and + 0.85 V (versus Ag/AgCl), respectively, by square wave voltammetry. Limit of detection values in the submicromolar range were achieved for CHL (0.08 µmol L-1), CIP (0.01 µmol L-1) and SFL (0.11 µmol L-1), which enabled the sensor to be successfully applied to natural waters and urine samples (recovery values from 85 to 119%). The CO2-GS electrode is highly stable and inexpensive ($0.09 each sensor) and can be easily inserted in portable 3D printed cells for environmental on-site analyses.

Assessing informative tract segmentation and nTMS for pre-operative planning.

BACKGROUND: Deep learning-based (DL) methods are the best-performing methods for white matter tract segmentation in anatomically healthy subjects. However, tract annotations are variable or absent in clinical data and manual annotations are especially difficult in patients with tumors where normal anatomy may be distorted. Direct cortical and subcortical stimulation is the gold standard ground truth to determine the cortical and sub-cortical lo- cation of motor-eloquent areas intra-operatively. Nonetheless, this technique is invasive, prolongs the surgical procedure, and may cause patient fatigue. Navigated Transcranial Magnetic Stimulation (nTMS) has a well-established correlation to direct cortical stimulation for motor mapping and the added advantage of being able to be acquired pre-operatively. NEW METHOD: In this work, we evaluate the feasibility of using nTMS motor responses as a method to assess corticospinal tract (CST) binary masks and estimated uncertainty generated by a DL-based tract segmentation in patients with diffuse gliomas. RESULTS: Our results show CST binary masks have a high overlap coefficient (OC) with nTMS response masks. A strong negative correlation is found between estimated uncertainty and nTMS response mask distance to the CST binary mask. COMPARISON WITH EXISTING METHODS: We compare our approach (UncSeg) with the state-of-the-art TractSeg in terms of OC between the CST binary masks and nTMS response masks. CONCLUSIONS: In this study, we demonstrate that estimated uncertainty from UncSeg is a good measure of the agreement between the CST binary masks and nTMS response masks distance to the CST binary mask boundary.

Factors affecting the transferability of bioindicators based on stream fish assemblages.

The development of multimetric indices (MMIs) to measure the biotic condition of aquatic habitats is based on metrics derived from biological assemblages. Considering fish assemblages, the inconsistencies in metrics responses outside of the places where they were developed limit MMI transferability and applicability to other locations, requiring local calibration. The factors behind the low transferability of these MMIs are still poorly understood. We investigated how environmental dissimilarity and spatial distance influence the transferability of metrics generated from local stream fish assemblages to other regions. We also tested whether functional and taxonomic metrics respond differently to the spatial distance. We used data from 239 fish assemblages from streams distributed across a Brazilian, the upper Parana basin and characterized each site according to the level of anthropogenic disturbance at the landscape scale using an Anthropogenic Pressure Index (API). We divided the upper Parana basin into sub-basins and used two of them to create template response models of the metrics in relation to the API. We used these response models to predict the responses outside the template sub-basins. Our response variable representing a metric of transferability was the absolute difference between metric's predicted and observed value for each site (prediction error). We thus modeled the prediction error in relation to the predictor variables that were i) the environmental dissimilarity between each site with the average of the sites from template sub-basins (climatic, topographic and soil type variables) and ii) the spatial distance (overland and watercourse distance) between each site and the center of the template sub-basin. We found that errors in metric predictions were associated with both environmental dissimilarity and spatial distance. Furthermore, functional and taxonomic metrics responded equally to spatial distance. These results indicate the need for local calibration of metrics when developing MMIs, especially if the protocols already available come from distant and environmentally dissimilar places.

AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity In Vitro.

SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp's, making it essential for viral replication and has been successfully targeted for the development of antivirals. The first oral Mpro inhibitor, nirmatrelvir, was approved for treatment of COVID-19 in late December 2021 in combination with ritonavir as Paxlovid. Increasing the arsenal of antivirals and development of protease inhibitors and other antivirals with a varied mode of action remains a priority to reduce the likelihood for resistance emerging. Here, we report results from an artificial intelligence-driven approach followed by in vitro validation, allowing the identification of five fragment-like Mpro inhibitors with IC50 values ranging from 1.5 to 241 µM. The three most potent molecules (compounds 818, 737, and 183) were tested against SARS-CoV-2 by in vitro replication in Vero E6 and Calu-3 cells. Compound 818 was active in both cell models with an EC50 value comparable to its measured IC50 value. On the other hand, compounds 737 and 183 were only active in Calu-3, a preclinical model of respiratory cells, showing selective indexes twice as high as those for compound 818. We also show that our in silico methodology was successful in identifying both reversible and covalent inhibitors. For instance, compound 818 is a reversible chloromethylamide analogue of 8-methyl-γ-carboline, while compound 737 is an N-pyridyl-isatin that covalently inhibits Mpro. Given the small molecular weights of these fragments, their high binding efficiency in vitro and efficacy in blocking viral replication, these compounds represent good starting points for the development of potent lead molecules targeting the Mpro of SARS-CoV-2.

Intestinal intussusception of Meckel's diverticulum, a case report and literature review of the last five years.

Meckel's diverticulum is the most common gastrointestinal tract anomaly. It arises from the incomplete closure of the omphalomesenteric conduit, which is a true diverticulum at the antimesenteric border of the ileum. Although the majority of patients are asymptomatic, they can present with inflammation, hemorrhage, intussusception, intestinal obstruction, and perforation, among others; this constitutes an important differential diagnosis for acute abdomen. A 19-year-old female sought medical attention because of intermittent diffuse abdominal pain for two months, nausea, and diarrhea. In the requested imaging tests, tomography, and enterotomography, a diagnosis of Meckel's diverticulum with some degree of intussusception was suggested. The patient underwent elective surgical treatment without complications and was discharged on the second postoperative day with clinical improvement. In this section, we review publications on similar cases published in the last five years.

Intestinal intussusception of Meckel's diverticulum, a case report and literature review of the last five years

ABSTRACT Meckel's diverticulum is the most common gastrointestinal tract anomaly. It arises from the incomplete closure of the omphalomesenteric conduit, which is a true diverticulum at the antimesenteric border of the ileum. Although the majority of patients are asymptomatic, they can present with inflammation, hemorrhage, intussusception, intestinal obstruction, and perforation, among others; this constitutes an important differential diagnosis for acute abdomen. A 19-year-old female sought medical attention because of intermittent diffuse abdominal pain for two months, nausea, and diarrhea. In the requested imaging tests, tomography, and enterotomography, a diagnosis of Meckel's diverticulum with some degree of intussusception was suggested. The patient underwent elective surgical treatment without complications and was discharged on the second postoperative day with clinical improvement. In this section, we review publications on similar cases published in the last five years.

Qualidade de vida e aspectos funcionais de pacientes pós-Covid-19 submetidos à reabilitação pulmonar / Quality of life and functional aspects of post-Covid-19 patients submitted to pulmonary rehabilitation

INTRODUÇÃO: pacientes que tiveram Covid-19, independente do espectro clínico da doença, podem apresentar sintomas persistentes após a alta hospitalar por até 14 meses. Estes pacientes apresentam comprometimentos funcionais e de qualidade de vida sendo, portanto, indicada a reabilitação pulmonar. Este estudo avaliou os aspectos funcionais e a qualidade de vida de pacientes pós-Covid-19 atendidos em um programa de reabilitação pulmonar. MÉTODOS: trata-se de um estudo prospectivo do tipo coorte clínica. Os pacientes pós-Covid-19 que integraram um programa de reabilitação pulmonar por seis semanas consecutivas foram avaliados em relação às variáveis funcionalidade pelo Índice de Barthel e pela escala PCFS, e a qualidade de vida pelo SF-36 na admissão (T0) e após seis semanas de reabilitação (T1). RESULTADOS: Onze pacientes que participaram do estudo apresentaram melhora da funcionalidade tanto pelo Índice de Barthel (p<0,01) como pela escala PCFS (p<0,01) e, também, melhora da qualidade de vida nos domínios capacidade funcional (p< 0,01), limitação por aspectos físicos (p<0,05) e aspectos sociais (p<0,01) no T1 em relação ao T0. CONCLUSÃO: pacientes pós-Covid-19 apresentaram melhora da funcionalidade e da qualidade de vida após um programa de reabilitação pulmonar (AU),

INTRODUCTION: patients who have Covid-19, regardless of the clinical spectrum of the disease, may present, after hospital discharge, persistent symptoms for up to 14 months. These patients have functional and quality of life impairments and, therefore, pulmonary rehabilitation for six consecutive weeks is indicated. This article evaluated the functional aspects and quality of life of post-Covid-19 patients treated in a pulmonary rehabilitation program. METHODS: this is a prospective clinical cohort study. Post-Covid-19 patients who joined a pulmonary rehabilitation program were evaluated concerning the variables functionality by the Barthel Index and the PCFS scale, and quality of life by the SF-36 at admission (T0) and after six weeks of rehabilitation treatment (T1). RESULTS: Eleven patients who participated in the study showed improved functionality both by the Barthel Index (p<0.01) and the PCFS scale (p<0.01) and also improved quality of life in the functional capacity domains (p < 0.01), limitation due to physical aspects (p<0.05) and social aspects (p<0.01) at T1 compared to T0. CONCLUSION: post-Covid-19 patients showed improved functionality and quality of life after a pulmonary rehabilitation program (AU).

Taquicardia ventricular catecolaminérgica com mutação do GENE RYR2 - troca do nucleotídeo C. 7433T>C em família com histórico de síncope e morte súbita / Catecholaminergic ventricular tachycardia with GENE RYR2 mutation - C.7433T>C nucleotide exchange in a family with a history of syncope and sudden death

INTRODUÇÃO: Eventos súbitos na adolescência são sempre dramáticos e causam impacto na família e na sociedade. Histórias recorrentes são subdiagnosticadas e tragédias familiares ficam sem explicação devido à falta de compreensão do generalista sobre as causas de morte súbita sem cardiopatia estrutural. O diagnóstico de canalopatias muitas vezes depende da análise do ECG em suas diversas modalidades e na maioria dos casos medidas clínicas podem ser o suficiente para salvar vidas. OBJETIVO: Descrever 2 casos de taquicardia ventricular catecolaminérgica (TVPC) em adolescentes primos em primeiro grau com vasto histórico de morte súbita familiar. DESCRIÇÃO DOS CASOS: Caso 1 - Paciente, 14 anos, sexo feminino, coração estruturalmente normal com síncope durante dança. Histórico familiar de morte súbita antes dos 40 anos (irmã, avô e 3 primos de primeiro grau). Todos os eventos relacionados a estresse físico/emocional. Apresentava Holter e ECG de repouso normais. Teste ergométrico com episódios de taquicardia ventricular não sustentada polimórfica, no pico do esforço. Submetida a estudo genético, com mutação no gene RYR2. Introduzido nadolol, mantendo-se sem novos episódios de síncope e com TE sem taquicardia ventricular. Segue assintomática em acompanhamento regular (hoje com 22 anos) e suspensa das atividades esportivas. Caso 2 - Paciente 18 anos, sexo feminino com síncope após estresse emocional. Possui história familiar de morte súbita (avó aos 30 anos, primo aos 14 anos e outro primo aos 17 anos). Possui prima com diagnóstico de TVPC com teste genético positivo para mutação no gene RYR2 com troca do nucleotídeo c.7433T>C. Teste ergométrico com EV frequentes polimórficas ao esforço. Recebe nadolol e evolui estável sem novos episódios de síncope. Teste ergométrico de controle não evidencia taquicardia ventricular. CONCLUSÃO: 1) O diagnóstico de TVPC depende da anamnese, histórico familiar e da avaliação do ECG de esforço; 2) O uso de Nadolol ou Propranolol permite uma redução significativa do número de eventos quando associado à suspensão da atividade física; 3) Apesar da síncope ser um evento de prenúncio de morte sua não repetição após o tratamento promove maior segurança para terapia farmacológica isolada.