Resistance Training with Instability Does Not Hamper Total Training Volume and Muscle Strength Gains in Older Adults: a Secondary Analysis from REI Study.

Background: Resistance training with instability (REI) emerged as a promising training modality for older adults aiming to counteract age-related changes. Objectives: We compared the effects of 12 weeks of REI and traditional resistance exercise (RE) on muscle strength in older adults with cognitive impairment. We further explored if total training volume (TTV) significantly differs among training groups. Methods: This is a secondary analysis of the REI study. Participants were randomly assigned to REI (n=22) or RE (n=23). RE protocol involved moderate-intensity, free-weight, and machines-based resistance exercises (3 sets, 10-15 repetitions). REI received a similar training protocol, in which exercises were simultaneously performed with instability/unstable devices (e.g., squat exercise under a foam pad or Bosu® ball). Maximal isometric strength and isokinetic parameters were assessed at baseline and after completion of a 12-week intervention through a hydraulic handgrip and isokinetic dynamometer, respectively. TTV (sets × repetitions × load) was computed based on external training load over the 12 weeks. Results: No differences were observed between groups (p=.35) after the intervention. Over 12 weeks, REI and RE improved isometric handgrip strength (p<.001) and isokinetic performance (p=.04). We also did not find differences in the TTV between training groups (p=.28). Conclusion: We demonstrated that both REI and RE training induced similar gains in muscle strength. Combining unstable surfaces/instability devices did not hamper TTV, which may have clinical applications in the context of exercise for older adults.

In silico approaches for drug repurposing in oncology: a scoping review.

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

Evaluation of BH3 mimetics as a combination therapy with irradiation in head and neck squamous cell carcinoma.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is a common cancer with a five-year survival rate around 60%, indicating a need for new treatments. BH3 mimetics are small molecules that inhibit anti-apoptotic Bcl-2 family proteins, resulting in apoptosis induction. METHODS: We performed a high-throughput screen using a Myogel matrix to identify the synergy between irradiation and the novel BH3 mimetics A-1155463, A-1331852, and navitoclax in 12 HNSCC cell lines, normal (NOF) and cancer-associated fibroblasts (CAF), and dysplastic keratinocytes (ODA). Next, we examined synergy in an apoptosis assay, followed by a clonogenic assay and a Myogel spheroid on selected HNSCC cell lines. Finally, we applied zebrafish larvae xenograft to validate the effects of navitoclax and A-1331852. RESULTS: All three BH3 mimetics exhibited a strong synergy with irradiation in eight HNSCC cell lines and ODAs, but not in NOFs and CAFs. A-1155463 and A-1331852 induced apoptosis and reduced proliferation, and together with irradiation, significantly increased apoptosis and arrested proliferation. A-1331852 and navitoclax significantly decreased the clonogenicity compared with the control, and combination treatment led to a decreased clonogenicity compared with monotherapy or irradiation. However, unlike navitoclax or A-1155463, only A-1331852 significantly reduced cancer cell invasion. Furthermore, in spheroid and zebrafish, irradiation appeared ineffective and failed to significantly increase the drug effect. In the zebrafish, A-1331852 and navitoclax significantly reduced the tumor area and metastasis. CONCLUSIONS: Our findings encourage the further preclinical investigation of BH3 mimetics, particularly A-1331852, as a single agent or combined with irradiation as a treatment for HNSCC.

Effects of 12-Weeks of Home-Based Exercise Training on Physical and Cognitive Function of Older Adults: Randomized Trial Comparing Virtual Versus Minimal Supervision in the Context of the Covid-19 Pandemic in Brazil.

Background: We investigated the effects of a 12-week home-based exercise program delivered with virtual or minimal supervision on the physical and cognitive function of community-dwelling older adults in the context of the COVID-19 pandemic in Brazil. Methods: The study was registered on the Brazilian Registry of Clinical Trials platform (code: RBR-8qby2wt). Thirty-eight older adults (81% female and 68±7 years old), non-disabled, and without cognitive impairment or dementia, were randomly assigned to a 12-week home-based exercise program: 1) virtual supervision (classes remotely delivered through video conference by trained staff), or 2) minimal supervision (once-weekly contact to touch base through standardized text messages). The participants initially performed two sets of 10 repetitions three times a week, with a 60-second interval. The volume and complexity of the exercises were progressively increased. (e.g., the number of sets increased to 3 and later to 4). At baseline and follow-up, we collected remote measurements of physical function (muscle strength and power, functional muscular fitness) and cognition (processing speed, inhibitory control, verbal fluency). Results: Participants in the minimal supervision home-based exercise group significantly improved the Stroop test (-1.6 sec, 95% CI = -3.20; -0.09). No significant between-group differences were observed for physical and cognitive outcomes. Conclusion: A home-based exercise program delivered with virtual or minimal supervision can produce similar effects, and may help to maintain physical and cognitive capabilities among healthy, high-functioning older adults who experienced mobility restrictions due to the COVID-19 pandemic in Brazil.

Long-term consequences of COVID-19 on mental health and the impact of a physically active lifestyle: a narrative review.

BACKGROUND: Coronavirus-19 disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory viruses damage not only the upper respiratory tract in humans, but also several different organs such as the brain. Some of the neurological consequences of COVID-19 reported are anosmia, headache, stroke, declined cognitive function, and impaired mental health, among others. People who had COVID-19 have a higher risk of sequelae in the central nervous system (CNS). However, it is not known which are all possible sequelae and how long will last the long-term effects of the COVID-19 pandemic on behavioral patterns and quality of life. AIM: We intend to address the long-term impacts of COVID-19 on mental health and the relevance of physical exercise during the pandemic. METHODS: We conducted a literature search using PubMed to find the articles that were related to these themes. RESULTS: We found 23,489 papers initially, and then we applied the inclusion/exclusion criteria to narrow down our search to 3617 articles and selected 1380 eligible articles after a thorough reading of titles and abstracts. The findings indicated that COVID-19 impacted general mental health and led many not only hospitalized patients to develop cognitive decline, memory impairment, anxiety, sleep alterations, and depressive-like behavior. Furthermore, the fear of vaccines and their effects had negatively affected mental health and directly impacted mortality rates in unvaccinated COVID-19 patients. CONCLUSIONS: Preventive measures must be undertaken, such as the vaccination of the entire population, vaccination hesitancy discouragement by creating awareness among individuals, and people's engagement in a physically active lifestyle, since being physically active is a low-cost and effective measure to restore or inhibit the negative outcomes from COVID-19 on mental health.

Treinamento de força com e sem instabilidade não melhora os níveis gerais de capacidade intrínseca em idosos com queixas cognitivas / Resistance training with and without instability does not improve overall levels of intrinsic capacity in older adults with cognitive complaints

INTRODUÇÃO: Capacidade intrínseca (CI) é um construto que engloba capacidades físicas e mentais para o autocuidado e envelhecimento saudável. A compreensão do papel potencial do treinamento resistido, com e sem instabilidade, para promover o CI precisa ser esclarecida. OBJETIVO: Avaliar o impacto do treinamento de força sobre os níveis de capacidade intrínseca em idosos com queixas cognitivas. MÉTODOS: Idosos com queixas cognitivas (n=67) foram aleatoriamente designados para 12 semanas de TF tradicional (n=23), TF com dispositivos de instabilidade (TFI) (n=22) ou controle (n=22). Ambos os grupos de treinamento realizaram três séries de 10- 15 repetições. O grupo TFI realizou exercícios utilizando dispositivos de instabilidade. O grupo controle recebeu aulas semanais de educação em saúde. Os domínios da CI foram de mobilidade e velocidade da marcha (locomotora), função global e executiva (cognitivo), força de preensão e teste de caminhada de seis minutos (vitalidade), e sintomas depressivos e autoeficácia (psicológicos) por meio de escores-z compostos. Calculamos os níveis globais de CI pela soma de cada pontuação composta. RESULTADOS: Diferença significativa intragrupo nos níveis gerais de CI (∆TFI = +1.69, ∆TF = +1.30) e seus respectivos domínios (Locomoção: ∆TFI = +2.32, ∆TF = +3.21; Cognição: ∆TFI = +2.31; Vitalidade: ∆TFI = +1.23, ∆TF = +1.42; e Psicológico: ∆TFI = -0.65, ∆TF = -0.62). Contudo, não houve diferenças entre os grupos. Análise de sensibilidade mesclando os grupos de treinamento revelou diferença significativa para o domínio locomotor após 12 semanas (+1.97, p=0.045). CONCLUSÃO: Treinamento de força com e sem dispositivos de instabilidade não melhorou os níveis de CI em idosos com queixas cognitivas.

INTRODUCTION: Intrinsic capacity (IC) is a construct that encompasses physical and mental capacities important for self-care and healthy aging. Understanding the potential role of resistance training with and without instability to promote IC needs to be clarified. OBJECTIVE: To assess the impact of resistance training on intrinsic capacity levels in older adults with cognitive complaints. METHODS: Older adults with cognitive complaints (n=67) were randomly assigned to either 12 weeks of traditional RE (n=23), RE with instability devices (REI) (n=22), or control (n=22). Both training groups performed three sets of 10-15 repetitions. REI group performed each exercise using instability devices. The control group received weekly health education classes. IC domains were analyzed using mobility and gait velocity (locomotor), global and executive functioning (cognitive), grip strength and six-minute walking test (vitality), and depressive symptoms and self-efficacy (psychological) through z-composite scores. We computed global levels of IC by the sum of each composite score. RESULTS: A significant within-group difference (improvement) in overall levels of IC (∆REI = +1.69, ∆RE = +1.30) and all their domains (Locomotion: ∆REI = +2.32, ∆RE = +3.21; Cognition: ∆REI = +2.31; Vitality: ∆REI = +1.23, ∆RE = +1.42; and Psychological: ∆REI = -0.65, ∆RE = -0.62). However, no between-group differences were observed at the completion of the trial. Sensitivity analysis merging training groups revealed a between-group difference for the locomotor domain (+1.97, p=0.045). CONCLUSION: Resistance training with and without instability devices did not improve IC levels among older adults with cognitive complaints.

Videoconference assessment of functional and cognitive measures in Brazilian older adults: a reliability and feasibility study / Uso de videoconferência para a avaliação de medidas funcionais e cognitivas de idosos brasileiros: um estudo de confiabilidade e viabilidade

OBJECTIVE: We aimed to determine the feasibility and reliability of videoconference assessment of functional and cognitive status among older adults in the context of the COVID-19 pandemic. METHODS: Thirty community-dwelling older adults (86.70% women) with a mean age of 69.77 (SD = 6.60) years who were physically independent and had no signs of cognitive impairment were included in the sample. An independent and experienced researcher assessed functional (chair rise test, chair stand test, sitting and rising test) and cognitive (Montreal Cognitive Assessment, parts A and B of the Trail Making Test, the Stroop test, the verbal fluency test) performance in real-time on the Google Meet platform on 2 non-consecutive days. The reliability of the measures was analyzed using the intraclass correlation coefficient (ICC), a paired t-test, or Wilcoxon and Bland-Altman analysis. The feasibility of the assessment was investigated using a standardized 14-item questionnaire. RESULTS: All functional performance measures showed excellent intra-rater reliability, with ICCs from 0.90 (95%CI 0.78 ­ 0.95) for the sitting and rising test to 0.98 (95%CI 0.96 ­ 0.99) for the chair rise test. Our analysis also showed mixed levels of reliability across measures, including good ICC (ranging from 0.79 ­ 0.91) for the Montreal Cognitive Assessment, part B of the Trail Making Test, and the congruent and neutral trials in the Stroop test, but poor-to-moderate ICC (ranging from 0.42 ­ 0.58) for the other cognitive assessments. In general, the participants reported good feasibility for the assessment format. CONCLUSION: In healthy and highly educated older adults, videoconferencing is a feasible method of determining functional and cognitive performance. Functional measures showed excellent reliability indexes, whereas cognitive data should be interpreted carefully, since the reliability varied from poor to moderate. (AU)

OBJETIVO: Nosso objetivo foi determinar a viabilidade e confiabilidade de medidas funcionais e cognitivas por meio de uma videoconferência baseada na web entre idosos no contexto da pandemia de COVID-19. METODOLOGIA: Trinta idosos [idade = 69,77 (desvio padrão ­ DP = 6,60) anos; 86,70% mulheres], que vivem de forma independente na comunidade (independente fisicamente e sem sinais de comprometimento cognitivo) participaram do estudo. Um avaliador independente e experiente entregou, em tempo real, avaliações funcionais (Chair Rise Test ­ CRT, Chair Stand Test, Sitting and Rising Test ­ SRT) e cognitivas (MoCA, Teste de Trilhas A e B, Stroop Test e Fluência Verbal) por meio da Plataforma Google Meet em dois dias não consecutivos. A confiabilidade das medidas foi analisada pelo Coeficiente de Correlação Intraclasse (CCI), teste t pareado ou análise de Wilcoxon e Bland-Altman. A viabilidade da avaliação foi examinada com o uso de um questionário padronizado de 14 itens. RESULTADOS: Todas as medidas de desempenho funcional demonstraram excelente confiabilidade intra-avaliador [CCI variando de 0,90 (intervalo de confiança ­ IC95% 0,78 ­ 0,95) para SRT e 0,98 (IC95% 0,96 ­ 0,99) para CRT]. Além disso, nossa análise mostrou níveis mistos de confiabilidade entre as medidas, enquanto o MoCA, Teste de Trilhas B e as fases Interferência e Leitura do Stroop Test tiveram excelente CCI (variando de 0,79 a 0,91) e as outras avaliações cognitivas com CCI ruim a moderado (variando de 0,42 a 0,58). Em geral, os participantes demonstraram boa viabilidade com o formato das avaliações. CONCLUSÃO: Em idosos saudáveis e com alta escolaridade, a videoconferência baseada na web é uma alternativa viável para determinar o desempenho funcional e medidas cognitivas. As medidas funcionais apresentaram excelentes índices de confiabilidade, enquanto os dados cognitivos devem ser interpretados com cautela, visto que atingiram índices de confiabilidade de ruim a moderado. (AU)

Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling.

Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.

Changes in Physical Functioning and Fall-Related Factors in Older Adults Due to COVID-19 Social Isolation.

Background: Social isolation has been one of the main measures for the prevention of COVID-19. It's possible that, in addition to the natural aging-related deficits, social isolation has accelerated the decline of the different components of physical and mental capacity in older adults. This study aimed to compare the functional capacity and concern about falling in older adults before and during COVID-19 social isolation. Method: This observational longitudinal study was carried out with 45 community dwelling older adults (mean age 65.6 ± 4.6 years, 88.8% women). Functional capacity and concerns about falling assessments were carried out before the COVID-19 pandemic, and between the 16th and 18th week of social isolation. All testes were face-to-face, except the second FES-I assessment, which took place via telephone call in order to minimize a prolonged person-to-person contact. Muscle strength, muscle power, functional mobility, functional muscle fitness, upper and lower body flexibility, dynamic balance, and Efficacy Scale were assessments. Results: Regarding functional capacity, there was 14% decline in muscle strength (p<.001), 7% in power (p=.001), 11% in functional mobility (p=.001), 20% in functional muscle fitness (p=.001), and 60% in upper body flexibility (p=.001) and 33% lower body flexibility (p=.003). The dynamic balance and the concern about falling showed no statistically significant differences. Conclusion: Thus, it can be concluded that there was a decline in older adults' functional capacity during COVID-19 social isolation.

In silico approaches for drug repurposing in oncology: Protocol for a scoping review of existing evidence.

Drug repurposing has been applied in the biomedical field to optimize the use of existing drugs, leading to a more efficient allocation of research resources. In oncology, this approach is particularly interesting, considering the high cost related to the discovery of new drugs with therapeutic potential. Computational methods have been applied to predict associations between drugs and their targets. However, drug repurposing has not always been promising and its efficiency has yet to be proven. Therefore, the present scoping review protocol was developed to screen the literature on how in silico strategies can be implemented in drug repurposing in oncology. The scoping review will be conducted according to the Arksey and O'Malley framework (2005) and the Joanna Briggs Institute recommendations. We will search the PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We will include peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between January 1, 2003, and December 31, 2021. Data will be charted and findings described according to review questions. We will report the scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR).

The Epigenetic Role of MiRNAs in Endocrine Crosstalk Between the Cardiovascular System and Adipose Tissue: A Bidirectional View.

Overweight and obesity (OBT) is a serious health condition worldwide, and one of the major risk factors for cardiovascular disease (CVD), the main reason for morbidity and mortality worldwide. OBT is the proportional increase of Adipose Tissue (AT) compared with other tissue and fluids, associated with pathological changes in metabolism, hemodynamic overload, cytokine secretion, systemic inflammatory profile, and cardiac metabolism. In turn, AT is heterogeneous in location, and displays secretory capacity, lipolytic activation, insulin sensitivity, and metabolic status, performing anatomic, metabolic, and endocrine functions. Evidence has emerged on the bidirectional crosstalk exerted by miRNAs as regulators between the heart and AT on metabolism and health conditions. Here, we discuss the bidirectional endocrine role of miRNAs between heart and AT, rescuing extracellular vesicles' (EVs) role in cell-to-cell communication, and the most recent results that show the potential of common therapeutic targets through the elucidation of parallel and /or common epigenetic mechanisms.

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

Forces and Specific Energy of Polyamide Grinding.

This work investigated the grinding process of reinforced and nonreinforced polyamide materials using an Al2O3 grinding wheel. Samples were ground using a custom-made setup of sensors to evaluate in-line temperature, forces, and power. The surface roughness and images were acquired to assess the quality of the final products. The novelty of the work is to correlate the energy evaluation with the process efficiency during processing. Grinding at high cutting depths achieves good surface quality indicators, such as Ra < 5 µm and Rz < 5 µm. Results also reveal that special attention should be given to the infeed speed when cutting unfilled materials to produce good results. With high values of energy partition, the specific grinding energy stabilizes around 60 J/mm³. Strains must be applied quickly because, to ensure the unfilled materials respond better at this cutting depth, the reinforced materials suffer a slight degradation of quality.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Hygromechanical Performance of Polyamide Specimens Made with Fused Filament Fabrication.

The material performance of polyamide (PA) samples made with fused filament fabrication (FFF) was analyzed. The authors implemented a well-structured framework to identify the filaments main properties before processing them and characterizing the printed samples. Unfilled and glass-fiber reinforced PA were investigated, focusing on moisture absorption and its effects on dimensional stability and mechanical performance. The properties were collected using differential scanning calorimetry and Fourier-transform infrared spectroscopy, whereas the specimens were characterized by employing compression tests. This framework allowed for the moisture determination, as well as the influence of the moisture absorption. A significant impact was detected for the glass-fiber reinforced PA, with a decrease in the dimensional and mechanical performance. The novelty of this study was to define a well-structured framework for testing the moisture influence of FFF components.

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs.

Physical exercise consequences on memory in obesity: A systematic review.

Obesity is associated with changes in memory. Thus, the aim of this systematic review was to investigate the physical exercise consequences on memory in obesity. A search was carried out in the PubMed, Lilacs, and Scielo databases with the following descriptors: "physical exercise," "memory," and "obesity." A total of 16 studies were analyzed in this review. Low, moderate, and high intensity exercise training showed positive effects on memory in patients with obesity (100%). The animal models of obesity used in their physical exercise protocols: treadmill (72.7%) or wheel running (27.3%). Most of the animal studies (81.8%) revealed positive effects of the physical exercise protocol on memory in obesity. Mouse was the most commonly used animal (54.5%), and a 60% high-fat diet (HFD) was the most commonly method used to induce obesity (82%). We did not identify any knockout model of obesity that was used to evaluate memory and used physical exercise as the main intervention. Thus, exercise training, independently if it is resistance or endurance training, seems to be an excellent intervention to prevent and inhibit cognitive impairment and memory loss on obese patients and animal models of obesity.

Exercise-linked consequences on epilepsy.

OBJECTIVE: Epilepsy is a brain disorder that leads to seizures and neurobiological, cognitive, psychological, and social consequences. Physical inactivity can contribute to worse epilepsy pathophysiology. Here, we review how physical exercise affects epilepsy physiopathology. METHODS: An extensive literature search was performed and the mechanisms of physical exercise on epilepsy were discussed. The search was conducted in Scopus and PubMed. Articles with relevant information were included. Only studies written in English were considered. RESULTS: The regular practice of physical exercise can be beneficial for individuals with neurodegenerative diseases, such as epilepsy by decreasing the production of pro-inflammatory and stress biomarkers, increasing socialization, and reducing the incidence of epileptic seizures. Physical exercise is also capable of reducing the symptoms of depression and anxiety in epilepsy. Physical exercise can also improve cognitive function in epilepsy. The regular practice of physical exercise enhances the levels of brain-derived neuro factor (BDNF) in the hippocampi, induces neurogenesis, inhibits oxidative stress and reactive gliosis, avoids cognitive impairment, and stimulates the production of dopamine in the epileptic brain. CONCLUSION: Physical exercise is an excellent non-pharmacological tool that can be used in the treatment of epilepsy.

Additional Functional Performance Gains After 24-Week Unstable Strength Training With Cognitive Training in Community-Dwelling Healthy Older Adults: A Randomized Trial.

The authors investigated the effects of unstable strength training (UST) without or with cognitive training (C+UST) on functional performance in community-dwelling older adults. A total of 50 participants were randomly assigned (1:1) to either 24 weeks of thrice-weekly UST (n = 25) or C+UST (n = 25). All participants performed moderate-intensity strength exercises using unstable surfaces, and C+UST participants simultaneously received cognitive training in addition to UST. Primary outcomes included measures of functional performance: single- and dual-task timed up and go tests. Secondary outcomes included dynamic balance, mobility, handgrip strength, flexibility, quality of life, and concern about falling. The authors observed similar improvements on functional performance through the interventions. The C+UST group experienced additional gains at completion (single-task timed up and go: -0.90 s, 95% confidence interval [-2.38, -0.03]; dual-task timed up and go: -4.80 s, 95% confidence interval [-8.65, -0.95]) compared with the UST group. Moreover, significant differences were observed in mobility (sitting-rising test: -1.34, 95% confidence interval [-2.00, -0.20]) at 24 weeks. Both exercise modes improved single-task functional performance, while adding cognitive-training-optimized dual-task functional performance gains.

Associação entre preocupação com quedas e sintomas depressivos em idosos com comprometimento cognitivo: um estudo transversal / Association between concern about falling and depression symptoms in cognitively impaired older adults: a cross-sectional study

Preocupações com quedas e sintomatologia depressiva são fatores de risco de queda bem conhecidos em idosos. No entanto, se ambos os fatores estão inter-relacionados, não está totalmente elucidado entre os indivíduos com problemas cognitivos. Para iluminar este campo, analisamos a associação entre a preocupação com quedas e sintomas depressivos em idosos com déficits cognitivos. Este estudo transversal foi composto por 67 idosos da comunidade, com deficiência cognitiva (idade: 71 ± 5 anos; sexo: 78% feminino). Avaliamos suas preocupações sobre quedas (independentes) e sintomas de depressão (desfecho) usando a Falls Efficacy Scale - International (FESI) e a versão curta da Geriatric Depression Scale (GDS-15), respectivamente. As covariáveis incluíram idade, sexo, escolaridade, histórico de quedas, função física (Short-Physical Performance Battery) e função cognitiva (versão brasileira do Montreal Cognitive Assessment). Modelos de regressão linear foram realizados para examinar a relação independente entre os escores FESI e GDS. Todas as análises foram calculadas usando o STATA e a significância foi estabelecida em P <0,05. Os participantes com sintomas depressivos mais elevados (GDS ≥ 5 pontos) apresentaram uma pontuação significativamente menor no FESI (diferença média: -5,3 pontos; IC 95% = -9,9 a -0,7; p = 0,02). O modelo de regressão mostrou associação entre FESI e GDS-15 após ajuste para fatores de confusão (ß = 0,08; IC 95% = 0,02; 0,14), sugerindo que maiores preocupações com quedas estão associadas a maiores sintomas depressivos. A preocupação com quedas está associada a sintomas depressivos entre idosos com comprometimento cognitivo, independentemente da função física geral, cognição global e histórico de quedas.

Concerns about falling and depressive symptomatology are well-known fall-risk factors in older people. However, whether both factors are inter-related it is not fully elucidated among individuals with cognitive issues. To shed light in this field, we analyzed the association between the concerns about falling and depressive symptoms in older adults with cognitive impairments. This cross-sectional study was composed of 67 community-dwelling cognitively impaired older adults(age: 71±5 years; sex: 78% female). We assessed their concerns about falling (independent) and depression symptoms (outcome) using the Falls Efficacy Scale - International (FESI) and the short-version of Geriatric Depression Scale (GDS-15), respectively. Covariates included age, sex, education, fall history, physical (Short-Physical Performance Battery), and cognitive function (Brazilian version of Montreal Cognitive Assessment). Linear regression models were performed in order to examine the independent relationship between FESI and GDS scores. All analyses were computed using STATA and significance was set at P<0.05. Participants with higher depressive symptoms (GDS ≥ 5 points) showed a significantly poor score on FESI (Mean difference: -5.3 points; 95%CI = -9.9 to -0.7; p=0.02). The regression model showed an association between the FESI and GDS-15 after adjustment for confounders (ß=0.08; 95% CI= 0.02; 0.14), suggesting that higher concerns about falling are associated with higher depressive symptoms. Concerns about falling are associated with depressive symptoms among cognitively impaired older adults independently of overall physical function, global cognition, and fall history.