Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. The random-effects model was used to calculate the risk ratios with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3 (RStudio, PBC). RESULTS: Six RCTs comprising 20 574 patients with ACS were included, of whom 10 259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years, and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (risk ratio 0.93; 95% CI 0.90-0.97; P < 0.01) and nonfatal myocardial infarction (risk ratio 0.88; 95% CI 0.81-0.95; P < 0.01). There was no significant difference between groups for revascularization (risk ratio 0.94; 95% CI 0.90-1.00; P = 0.03), all-cause mortality (risk ratio 0.87; 95% CI 0.63-1.21; P = 0.42), or unstable angina (risk ratio 1.05; 95% CI 0.86-1.27; P = 0.64). CONCLUSION: In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and nonfatal myocardial infarction, compared with statin monotherapy.

Decompressive Craniectomy with or Without Dural Closure: Systematic Review and Meta-analysis.

Decompressive craniectomy is used to alleviate intracranial pressure in cases of traumatic brain injury and stroke by removing part of the skull to allow brain expansion. Traditionally, this procedure is followed by a watertight dural suture, although evidence supporting this method is not strong. This meta-analysis examines the feasibility of the open-dura (OD) approach versus the traditional closed-dura (CD) technique with watertight suturing. A systematic review and comparative meta-analysis were conducted on OD and CD dural closure techniques. Medline, Embase, and Cochrane were searched for relevant trials. The primary end point was the rate of complications, with specific analyses for infection and cerebrospinal fluid (CSF) leaks. Mortality, poor neurological outcomes, and operation duration were also assessed. Odds ratios with 95% confidence intervals (CIs) were calculated using a random-effects model. Following a comprehensive search, 930 studies were screened, from which four studies and a total of 368 patients were ultimately selected. The primary outcome analysis showed a reduced likelihood of complications in the OD group when compared with the CD group (368 patients, odds ratio 0.54 [95% CI 0.32-0.90]; I2 = 17%; p < 0.05). Specific analysis of infections and CSF leaks did not show statistically significant results, as well as the evaluation of the mortality rates and poor neurological outcome differences between groups. Assessment of operation duration, however, demonstrated a significant difference between techniques, with a mean reduction of 52.50 min favoring the OD approach (mean difference - 52.50 [95% CI - 92.13 to - 12.87]; I2 = 96%). This study supports the viability of decompressive craniectomy without the conventional time-spending watertight duraplasty closure, exhibiting no differences in the rate of infections or CSF leaks. Furthermore, this approach has been associated with improved rates of complications and faster surgery, which are important aspects of this technique, particularly in its potential to reduce both costs and procedure length.

Brazilian Thoracic Society recommendations for the diagnosis and monitoring of asbestos-exposed individuals.

Asbestos was largely used in Brazil. It is a mineral that induces pleural and pulmonary fibrosis, and it is a potent carcinogen. Our objective was to develop recommendations for the performance of adequate imaging tests for screening asbestos-related diseases. We searched peer-reviewed publications, national and international technical documents, and specialists' opinions on the theme. Based on that, the major recommendations are: Individuals exposed to asbestos at the workplace for ≥ 1 year or those with a history of environmental exposure for at least 5 years, all of those with a latency period > 20 years from the date of initial exposure, should initially undego HRCT of the chest for investigation. Individuals with pleural disease and/or asbestosis should be considered for regular lung cancer monitoring. Risk calculators should be adopted for lung cancer screening, with a risk estimate of 1.5%.

The Effect of Time Pressure on Surgical Skill Retention in Novices: A Randomized Controlled Trial.

BACKGROUND: There are limited opportunities to practice surgical skills and techniques in residency. Therefore, it is important to explore strategies which optimize surgical simulation experiences to enhance learning outcomes and skill retention. METHODS: Novice medical students (n = 29) were recruited to participate in a Fundamentals of Laparoscopic Surgery (FLS) peg transfer task training. Participants were randomly assigned to a control group, practicing the peg transfer task independently, or an experimental group, practicing with time pressure. Participant skill assessments were completed before the training, after the training, and 8-weeks after the training. Subjective and objective stress measurements were taken in the form of self-report surveys and heart rate variability data, respectively. RESULTS: For all the skill assessment measurements, there was no difference between groups in performance on the FLS task. Both groups showed improvement in performance after the training compared to before. The experimental group reported higher stress during and after the training period compared to the control group; however, there was no difference between groups on heart rate variability metrics. CONCLUSION: Time pressure while practicing an FLS task did not significantly impact learning acquisition or retention. However, the experimental group reported higher levels of stress. This preliminary study suggests time pressure does not confer an enhanced surgical skill learning experience for novices.

Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

Region-Specific Decellularization of Porcine Uterine Tube Extracellular Matrix: A New Approach for Reproductive Tissue-Engineering Applications.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection.

Chronic hepatitis B virus (HBV) infection affects 300 million patients worldwide1,2, in whom virus-specific CD8 T cells by still ill-defined mechanisms lose their function and cannot eliminate HBV-infected hepatocytes3-7. Here we demonstrate that a liver immune rheostat renders virus-specific CD8 T cells refractory to activation and leads to their loss of effector functions. In preclinical models of persistent infection with hepatotropic viruses such as HBV, dysfunctional virus-specific CXCR6+ CD8 T cells accumulated in the liver and, as a characteristic hallmark, showed enhanced transcriptional activity of cAMP-responsive element modulator (CREM) distinct from T cell exhaustion. In patients with chronic hepatitis B, circulating and intrahepatic HBV-specific CXCR6+ CD8 T cells with enhanced CREM expression and transcriptional activity were detected at a frequency of 12-22% of HBV-specific CD8 T cells. Knocking out the inhibitory CREM/ICER isoform in T cells, however, failed to rescue T cell immunity. This indicates that CREM activity was a consequence, rather than the cause, of loss in T cell function, further supported by the observation of enhanced phosphorylation of protein kinase A (PKA) which is upstream of CREM. Indeed, we found that enhanced cAMP-PKA-signalling from increased T cell adenylyl cyclase activity augmented CREM activity and curbed T cell activation and effector function in persistent hepatic infection. Mechanistically, CD8 T cells recognizing their antigen on hepatocytes established close and extensive contact with liver sinusoidal endothelial cells, thereby enhancing adenylyl cyclase-cAMP-PKA signalling in T cells. In these hepatic CD8 T cells, which recognize their antigen on hepatocytes, phosphorylation of key signalling kinases of the T cell receptor signalling pathway was impaired, which rendered them refractory to activation. Thus, close contact with liver sinusoidal endothelial cells curbs the activation and effector function of HBV-specific CD8 T cells that target hepatocytes expressing viral antigens by means of the adenylyl cyclase-cAMP-PKA axis in an immune rheostat-like fashion.

Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs.

Background: CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness. Methods: We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%. Findings: 1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases. Interpretation: Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination. Funding: Research supported by Sanofi.

Cardiovascular benefits of GLP-1 receptor agonists in patients living with obesity or overweight: a meta-analysis of randomized controlled trials

BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD - 4.76 mmHg; 95% CI - 6.03, - 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD - 1.41 mmHg; 95% CI - 2.64, - 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). CONCLUSIONS: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis.

Catheter ablation for atrial fibrillation in heart failure with reduced ejection fraction patients: A meta-analysis.

BACKGROUND: The optimal treatment of atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) remains unsettled. OBJECTIVE: The purpose of this study was to assess the efficacy of catheter ablation (CA) and medical therapy compared to medical therapy alone in patients with AF and HFrEF. METHODS: We performed a systematic review of randomized controlled trials (RCTs) comparing CA with guideline-directed medical therapy for AF in patients with HFrEF (left ventricular ejection fraction [LVEF] ≤ 40%). We systematically searched PubMed, Embase, and Cochrane for eligible trials. A random effects model was used to calculate the risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: Six RCTs comprising 1055 patients were included, of whom 530 (50.2%) were randomized to CA. Compared with medical therapy, CA was associated with a significant reduction in heart failure (HF) hospitalization (RR 0.57; 95% CI 0.45-0.72; P < .01), cardiovascular mortality (RR 0.46; 95% CI 0.31-0.70; P < .01), all-cause mortality (RR 0.53; 95% CI 0.36-0.78; P < .01), and AF burden (MD -29.8%; 95% CI -43.73% to -15.90%; P < .01). Also, there was a significant improvement in LVEF (MD 3.8%; 95% CI 1.6%-6.0%; P < .01) and quality of life (Minnesota Living with Heart Failure Questionnaire; MD -4.92 points; 95% CI -8.61 to -1.22 points; P < .01) in the ablation group. CONCLUSION: In this meta-analysis of RCTs of patients with AF and HFrEF, CA was associated with a reduction in HF hospitalization, cardiovascular mortality, and all-cause mortality as well as a significant improvement in LVEF and quality of life.

Cardiovascular Benefits of GLP-1 Receptor Agonists in Patients Living with Obesity or Overweight: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD - 4.76 mmHg; 95% CI - 6.03, - 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD - 1.41 mmHg; 95% CI - 2.64, - 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). CONCLUSIONS: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis. REGISTRATION: PROSPERO identifier number CRD42023475226.

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed. METHODS: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. RESULTS: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). CONCLUSIONS: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells.

Cancer-specific TCF1+ stem-like CD8+ T cells can drive protective anticancer immunity through expansion and effector cell differentiation1-4; however, this response is dysfunctional in tumours. Current cancer immunotherapies2,5-9 can promote anticancer responses through TCF1+ stem-like CD8+ T cells in some but not all patients. This variation points towards currently ill-defined mechanisms that limit TCF1+CD8+ T cell-mediated anticancer immunity. Here we demonstrate that tumour-derived prostaglandin E2 (PGE2) restricts the proliferative expansion and effector differentiation of TCF1+CD8+ T cells within tumours, which promotes cancer immune escape. PGE2 does not affect the priming of TCF1+CD8+ T cells in draining lymph nodes. PGE2 acts through EP2 and EP4 (EP2/EP4) receptor signalling in CD8+ T cells to limit the intratumoural generation of early and late effector T cell populations that originate from TCF1+ tumour-infiltrating CD8+ T lymphocytes (TILs). Ablation of EP2/EP4 signalling in cancer-specific CD8+ T cells rescues their expansion and effector differentiation within tumours and leads to tumour elimination in multiple mouse cancer models. Mechanistically, suppression of the interleukin-2 (IL-2) signalling pathway underlies the PGE2-mediated inhibition of TCF1+ TIL responses. Altogether, we uncover a key mechanism that restricts the IL-2 responsiveness of TCF1+ TILs and prevents anticancer T cell responses that originate from these cells. This study identifies the PGE2-EP2/EP4 axis as a molecular target to restore IL-2 responsiveness in anticancer TILs to achieve cancer immune control.

The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis.

OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

Exposure to urban ambient particles (PM2.5) before pregnancy affects the expression of endometrial receptive markers to embryo implantation in mice: Preliminary results.

Air pollution (AP) is one of the main recent concerns in reproductive healthy due to its potential to promote negative outcomes during pregnancy and male and female fertility. Several studies have demonstrated that AP exposure has been linked to increased embryonic implantation failures, alterations in embryonic, fetal and placental development. For a well-succeeded implantation, both competent blastocyst and receptive endometrium are required. Based on the lack of data about the effect of AP in endometrial receptivity, this study aimed to evaluate he particulate matter (PM) exposure impact on uterine receptive markers in mice and associate the alterations to increased implantation failures due to AP. For this study, ten dams per group were exposed for 39 days to either filter (F) or polluted air (CAP). At fourth gestational day (GD4), females were euthanized. Morphological, ultrastructural, immunohistochemical and molecular analysis of uterine and ovarian samples were performed. CAP-exposed females presented a reduced number of corpus luteum; glands and epithelial cells were increased with pinopodes formation impairment. Immunohistochemistry analysis revealed decreased LIF protein levels. These preliminary data suggests that PM exposure may exert negative effects on endometrial receptivity by affecting crucial parameters to embryonic implantation as uterine morphological differentiation, corpus luteum quantity and LIF expression during implantation window.

Decellularized Bovine Skeletal Muscle Scaffolds: Structural Characterization and Preliminary Cytocompatibility Evaluation.

Skeletal muscle degeneration is responsible for major mobility complications, and this muscle type has little regenerative capacity. Several biomaterials have been proposed to induce muscle regeneration and function restoration. Decellularized scaffolds present biological properties that allow efficient cell culture, providing a suitable microenvironment for artificial construct development and being an alternative for in vitro muscle culture. For translational purposes, biomaterials derived from large animals are an interesting and unexplored source for muscle scaffold production. Therefore, this study aimed to produce and characterize bovine muscle scaffolds to be applied to muscle cell 3D cultures. Bovine muscle fragments were immersed in decellularizing solutions for 7 days. Decellularization efficiency, structure, composition, and three-dimensionality were evaluated. Bovine fetal myoblasts were cultured on the scaffolds for 10 days to attest cytocompatibility. Decellularization was confirmed by DAPI staining and DNA quantification. Histological and immunohistochemical analysis attested to the preservation of main ECM components. SEM analysis demonstrated that the 3D structure was maintained. In addition, after 10 days, fetal myoblasts were able to adhere and proliferate on the scaffolds, attesting to their cytocompatibility. These data, even preliminary, infer that generated bovine muscular scaffolds were well structured, with preserved composition and allowed cell culture. This study demonstrated that biomaterials derived from bovine muscle could be used in tissue engineering.

Effects of blood flow restriction therapy in patients with knee osteoarthritis: protocol for an overview of systematic reviews.

Background: Osteoarthritis (OA) is the most common and prevalent musculoskeletal disease associated with population aging, negatively impacting function and quality of life. A consequence of knee OA is quadriceps muscle weakness. Musculoskeletal rehabilitation using low load exercises, associated with Blood Flow Restriction (BFR) may be a useful alternative to high load exercises when those cannot be tolerated. Several systematic reviews have reported inconclusive results due to discrepancies in study findings, heterogeneity of results, evaluated time points, and research questions explored. Objective: To perform an overview of systematic reviews with meta-analyses, synthesizing the most recent evidence on the effects of muscle strength training with BFR for knee OA. Methodology: Systematic reviews that include primary controlled and randomized clinical trials will be considered for inclusion. Articles will be considered only if they present a clear and reproducible methodological structure, and when they clearly demonstrate that a critical analysis of the evidence was carried out using instrumented analysis. Narrative reviews, other types of review, overviews of systematic reviews, and diagnostic, prognostic and economic evaluation studies will be excluded. Studies must include adults aged 40 years and older with a diagnosis of knee OA. Two authors will perform an electronic search with guidance from an experienced librarian. The following databases will be searched: PubMed via MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), PEDro, Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host, Web of Science, and the gray literature. The search strategy used in the databases will follow the acronym PICOS (population, intervention, comparison, outcome, and study design). Screening (i.e., titles and abstracts) of studies identified by the search strategy will be selected using Rayyan (http://rayyan.qcri.org). The quality assessment will be performed using the "Assessment of Multiple Systematic Reviews" (AMSTAR-2) tool. Systematic Review Registration: PROSPERO, CRD42022367209.

The Corbett Targeted Coin Test: Reliability, criterion related validity, and normative data.

STUDY DESIGN: Clinical measurement. BACKGROUND: Many daily living tasks require in-hand manipulation (IHM). There is a gap in standardized assessment tools for measuring IHM. The Corbett Targeted Coin Test (CTCT) was designed to allow measurement of that fine motor skill. PURPOSE: 1) To evaluate the interrater, test-retest reliability, and validity of the CTCT, and 2) to establish adult norms for the CTCT. METHODS: Reliability and Validity - 30 participants (25 females, age range 21-45) were assessed with the Nine-Hole Peg test and CTCT consecutively by three researchers, then re-evaluated one week later on the CTCT; Reliability was determined using intraclass correlation (ICC2,k) between tests and across testers; Criterion-related validity was determined by comparing scores from nine-hole test and CTCT across testers using ICC2,k. Normative - 190 participants (147 females, age range 20-80) were assessed with the CTCT; mean and standard deviation for participants' scores were calculated by age groups and gender. RESULTS: Test-retest reliability: poor for the right hand (ICCs = -0.29 to 0.45), and poor-moderate for the left hand (ICCs = 0.17-0.56). Inter-rater reliability ranged from moderate to excellent (ICCs = 0.60-0.80). The agreement between CTCT scores and Nine-Hole Peg test was poor for the right (ICC = 0.02; 95% CI: [-0.06, 0.14]) and left hands (ICC = 0.06; 95% CI: [-0.08, 0.28]). CTCT normative data: 41-50 age group demonstrated the highest performance while the 71-80 age group demonstrated the lowest performance. Scores between genders were similar. DISCUSSION: The poor test-retest reliability of CTCT was probably due to practice effect, while interrater reliability indicated that the test can be administered by different testers without compromising the results. The poor validity between tools proves their different constructs. CONCLUSIONS: Use of the CTCT may add another dimension to assessment of dexterity and fine motor skills, specifically, in-hand manipulation, but needs further research on test-retest reliability.

Evaluation of the technique of localization of the epidural space with the aid of a peripheral nerve stimulator and epidurographic, comparing two techniques for determining the infused volume, in rabbits (Oryctolagus Cuniculus).

Veterinary care for rabbits has been growing, and, consequently, the anesthetic and analgesic management of this species must be improved. The aim of the present study was to evaluate the technique of localization of the epidural space with the aid of a peripheral nerve stimulator and epidurographic, comparing two techniques for determining the infused volume in rabbits (Oryctolagus Cuniculus). In a prospective, randomized blinded study, six healthy New Zealand rabbits, adults, and weighing from 2.2 kg to 3.8 kg received two treatments, at 1 week intervals: 0.33 mL/kg (treatment I) or 0.05 mL per centimeter of the spine (treatment II) of ioexol epidurally. In both treatments, a peripheral nerve stimulator (2 Hz, 0.25 mA and 0.1 milliseconds) was used to determine the location of the epidural space. Latero-lateral and ventro-dorsal radiographs were taken after five (T5) and twenty-five minutes (T25) of iohexol administration. The epidural space was correctly accessed in 92% of attempts. Treatment I received a smaller volume of contrast than treatment II, 1.0 ± 0.2 mL versus 2.1 ± 0.1 mL (mean ± standard deviation), respectively (p = 0.007). At T5, the cranial progression of the contrast varied between L4 and L5 in treatment I, and L5 and T10 in treatment II. At T25, no contrast was observed in any rabbit. In conclusion, peripheral nerve stimulator aided in accessing the lumbosacral epidural space, and the administration of 0.05 mL per centimeter of the spine resulted in greater cranial progression of contrast.

Brazilian Thoracic Society recommendations for the diagnosis and monitoring of asbestos-exposed individuals

ABSTRACT Asbestos was largely used in Brazil. It is a mineral that induces pleural and pulmonary fibrosis, and it is a potent carcinogen. Our objective was to develop recommendations for the performance of adequate imaging tests for screening asbestos-related diseases. We searched peer-reviewed publications, national and international technical documents, and specialists' opinions on the theme. Based on that, the major recommendations are: Individuals exposed to asbestos at the workplace for ≥ 1 year or those with a history of environmental exposure for at least 5 years, all of those with a latency period > 20 years from the date of initial exposure, should initially undego HRCT of the chest for investigation. Individuals with pleural disease and/or asbestosis should be considered for regular lung cancer monitoring. Risk calculators should be adopted for lung cancer screening, with a risk estimate of 1.5%.