In vitro evaluation of the selective cytotoxicity and genotoxicity of three synthetic ortho-nitrobenzyl derivatives in human cancer cell lines, with and without metabolic activation.

Although the presence of nitro groups in chemicals can be recognized as structural alerts for mutagenicity and carcinogenicity, nitroaromatic compounds have attracted considerable interest as a class of agents that can serve as source of potential new anticancer agents. In the present study, the in vitro cytotoxicity, genotoxicity, and mutagenicity of three synthetic ortho-nitrobenzyl derivatives (named ON-1, ON-2 and ON-3) were evaluated by employing human breast and ovarian cancer cell lines. A series of biological assays was carried out with and without metabolic activation. Complementarily, computational predictions of the pharmacokinetic properties and druglikeness of the compounds were performed in the Swiss ADME platform. The MTT assay showed that the compounds selectively affected selectively the cell viability of cancer cells in comparison with a nontumoral cell line. Additionally, the metabolic activation enhanced cytotoxicity, and the compounds affected cell survival, as demonstrated by the clonogenic assay. The comet assay, the cytokinesis-block micronucleus assay, and the immunofluorescence of the γ-H2AX foci formation assay have that the compounds caused chromosomal damage to the cancer cells, with and without metabolic activation. The results obtained in the present study showed that the compounds assessed were genotoxic and mutagenic, inducing double-strand breaks in the DNA structure. The high selectivity indices observed for the compounds ON-2 and ON-3, especially after metabolic activation with the S9 fraction, must be highlighted. These experimental biological results, as well as the theoretical properties predicted for the compounds have shown that they are promising anticancer candidates to be exploited in additional studies.

Effects of Essential Oils on Biological Characteristics and Potential Molecular Targets in Spodoptera frugiperda.

Spodoptera frugiperda control methods have proved to be inefficient, which justifies the search for new control measures. In this search for botanical insecticides for controlling S. frugiperda, the following were evaluated: (i) the toxicity of essential oils (EOs) from Cinnamodendron dinisii, Eugenia uniflora, and Melaleuca armillaris; (ii) the effect of EOs on life table parameters against S. frugiperda; (iii) the chemical characterization of EOs; and (iv) the in silico interaction of the chemical constituents present in the three EOs with the molecular targets of S. frugiperda. The EO from E. uniflora had the lowest LD50 (1.19 µg of EO/caterpillar). The major compounds bicyclogermacrene (18.64%) in C. dinisii and terpinolene (57.75%) in M. armillaris are highly predicted to interact with the octopamine receptor (OctpR). The compound 1,8-cineole (21.81%) in M. armillaris interacts mainly with a tolerant methoprene receptor (MET) and curzerene (41.22%) in E. uniflora, which acts on the OctpR receptor. Minor compounds, such as nerolidol in C. dinisii and ß-elemene in E. uniflora, are highly ranked for multiple targets: AChE, MET, OctpR, and 5-HT1. It was concluded that the EO from E. uniflora negatively affects several biological parameters of S. frugiperda development and is promising as an active ingredient in formulations for controlling this insect pest.

Override rate of drug-drug interaction alerts in clinical decision support systems: A brief systematic review and meta-analysis.

Primary studies have demonstrated that despite being useful, most of the drug-drug interaction (DDI) alerts generated by clinical decision support systems are overridden by prescribers. To provide more information about this issue, we conducted a systematic review and meta-analysis on the prevalence of DDI alerts generated by CDSS and alert overrides by physicians. The search strategy was implemented by applying the terms and MeSH headings and conducted in the MEDLINE/PubMed, EMBASE, Web of Science, Scopus, LILACS, and Google Scholar databases. Blinded reviewers screened 1873 records and 86 full studies, and 16 articles were included for analysis. The overall prevalence of alert generated by CDSS was 13% (CI95% 5-24%, p-value <0.0001, I^2 = 100%), and the overall prevalence of alert override by physicians was 90% (CI95% 85-95%, p-value <0.0001, I^2 = 100%). This systematic review and meta-analysis presents a high rate of alert overrides, even after CDSS adjustments that significantly reduced the number of alerts. After analyzing the articles included in this review, it was clear that the CDSS alerts physicians about potential DDI should be developed with a focus on the user experience, thus increasing their confidence and satisfaction, which may increase patient clinical safety.

Successful Pregnancy in Isolated 17,20-lyase Deficiency Without Glucocorticoid Use or Assisted Reproduction Techniques.

Isolated 17,20-lyase deficiency (ILD) is a partial form of 17α-hydroxylase/17,20-lyase deficiency that typically presents with infertility and lack of pubertal development. Successful live births have been achieved using assisted reproductive techniques. We present a case of spontaneous pregnancy in an 18-year-old female with ILD without reproduction treatments or glucocorticoid use. She presented to our clinic with absence of pubarche and oligomenorrhea and had typical external genitalia and complete breast development. Follicular phase progesterone and estradiol were within reference values, and androgen levels were undetectable. Corticosterone was increased, and cortisol responded partially to the ACTH-stimulation test. This profile raised a suspicion for ILD, which was confirmed by the finding of the homozygous p.R347H variant in the CYP17A1 gene. Sex steroid replacement and glucocorticoid use during stress were prescribed. She returned 2 years later 20 weeks pregnant. Her gestation was uneventful, and a full-term healthy male was born. This phenomenon could be partially explained by sufficient estrogen synthesis via residual 17,20-lyase enzymatic activity. Intermittent estradiol use may have favored uterine development and fine-tuned the pituitary-gonadal axis rhythm. Normal progesterone levels may have permitted an adequate endometrial "implantation window" without glucocorticoid use. Finally, elevated corticosterone may have compensated for the partial cortisol deficiency.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

CONTEXT: Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. OBJECTIVE: This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". DATA EXTRACTION: Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS: The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. CONCLUSIONS: Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021284006.

Clear aligner's adverse effects: A systematic review protocol.

With the growing popularity of clear aligners, more patients have chosen to use them instead of traditional orthodontic braces to correct their malocclusions. Clear aligners offer distinct advantages over conventional fixed braces, such as limited aesthetic impact, the convenience of easily removing them for meals, improved accessibility for brushing and flossing, and a treatment approach that avoids the use of metal, minimizing potential irritation to the cheeks and gums. Manufacturers point out a disadvantage that can be administered in this type of treatment. Still, to our knowledge, a comprehensive review of the published literature assessing the adverse/negative effects of clear aligners has not yet been conducted. A systematic review, with or without meta-analysis, will be performed. The inclusion criteria will be studies involving individuals using clear aligners and reporting potential adverse/negative effects during or after treatment. No restrictions about time or language will be applied. The studies screening will be conducted in two stages. Two independent reviewers will initially evaluate the title and abstract under the eligibility criteria. Subsequently, the same two reviewers will examine the articles' full text in-depth. The results will be synthesized in the form of a narrative description and incorporate a meta-analysis if justified. Furthermore, we will present details regarding the sample characteristics, intervention, study objectives, methodologies employed, and primary findings. This study aims to investigate the potential adverse effects and their frequency among orthodontic patients wearing clear aligners. Moreover, the outcomes of this review have the potential to illuminate specific inherent limitations of aligner therapy as a comprehensive orthodontic approach.

Tuning the Chemical and Electrochemical Properties of Paper-Based Carbon Electrodes by Pyrolysis of Polydopamine.

Electrochemical paper-based analytical devices represent an important platform for portable, low-cost, affordable, and decentralized diagnostics. For this kind of application, chemical functionalization plays a pivotal role to ensure high clinical performance by tuning surface properties and the area of electrodes. However, controlling different surface properties of electrodes by using a single functionalization route is still challenging. In this work, we attempted to tune the wettability, chemical composition, and electroactive area of carbon-paper-based devices by thermally treating polydopamine (PDA) at different temperatures. PDA films were deposited onto pyrolyzed paper (PP) electrodes and thermally treated in the range of 300-1000 °C. After deposition of PDA, the surface is rich in nitrogen and oxygen, it is superhydrophilic, and it has a high electroactive area. As the temperature increases, the surface becomes hydrophobic, and the electroactive area decreases. The surface modifications were followed by Raman, X-ray photoelectron microscopy (XPS), laser scanning confocal microscopy (LSCM), contact angle, scanning electron microscopy (SEM-EDS), electrical measurements, transmission electron microscopy (TEM), and electrochemical experiments. In addition, the chemical composition of nitrogen species can be tuned on the surface. As a proof of concept, we employed PDA-treated surfaces to anchor [AuCl4]- ions. After electrochemical reduction, we observed that it is possible to control the size of the nanoparticles on the surface. Our route opens a new avenue to add versatility to electrochemical interfaces in the field of paper-based electrochemical biosensors.

Green banana biomass anti-obesogenic, anti-hyperlipidemic, antidiabetic, and intestinal function potential effects: a systematic review.

CONTEXT: Apparently, the consumption of resistant-starch food sources, such as green banana biomass, stimulates the proliferation of short-chain fatty acid intestinal bacteria producers, which can contribute to intestinal health and reduce the risk of chronic diseases. However, the available scientific evidence is scarce and no study has systematically evaluated such evidence. OBJECTIVE: The aim of this study was to analyze the potential effects of green banana biomass on anthropometry, body composition, and biochemical and intestinal variables in humans and animals. DATA SOURCES: The Cochrane Library, Embase, Medline/PubMed, Scopus, and Web of Science electronic databases were searched in January 2024 for eligible articles. Studies that tested the effects of cooked peeled or unpeeled green banana on anthropometric, biochemical, and/or intestinal variables were included. DATA EXTRACTION: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The classification and assessment of the quality of studies were based on the relevant criteria related to the design of these studies and the quality criteria checklist of the Academy of Nutrition and Dietetics manual. Twelve studies published between 2001 and 2021 were included in the review. DATA ANALYSIS: The results of human studies indicate that the ingestion of green banana biomass controlled intestinal dysfunction (50-300 g/day for 5-14 days or 30 g/day for 8 wk) in children, and showed potential anti-obesogenic, anti-hyperlipidemic, and antidiabetic (40 g/day for 24 wk) effects in adults. In rats, biomass consumption led to potential anti-obesogenic (25 g/day for 8 wk), anti-hyperlipidemic, and antidiabetic (∼8-30 g/day for 12 wk) effects. CONCLUSION: Consumption of green banana biomass seems to exert beneficial effects on intestinal function and potential effects on obesity, dyslipidemia, and diabetes. These effects may be related to increased fecal short-chain fatty acid concentrations as a result of type 3 resistant starch present in biomass. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/TKCWV).

BENEFITS OF A CLINICAL PATHWAY IN TOTAL KNEE ARTHROPLASTY.

Objective: Demonstrate whether a multiprofessional Clinical Pathway Program in Total Knee Arthroplasty (CPPA) contributesto optimizing hospital care. Method: Retrospective study of medical data of care indicators in 310 patients divided into two groups: A- who underwent arthroplasty in the last biennium before the introduction of the CPPA (n=144) and group B- who underwent TKA in the biennium after the introduction of the CPPA (n=166). Results: Postoperative showed a significant difference in favor of group B over group A for hospitalization time in days 4.33 ± 2.79 and 5.4 ± 1.67 (p<0.001), time of prophylactic antibiotic in hours 28.13 ± 33.77 and 81.49 ± 40.91 (p<0.001), referral to the intensive care unit 40.9% and 73.4% (p<0.001), initiation of thromboprophylaxis within 24 hours 97.9% and 82.5% (p<0.001), use of elastic stockings and/or intermittent compression prescribed for thromboprophylaxis 89.5% and 31.2% (p<0.001), initiation of rehabilitation within 24 hours 90.1% and 66.1% (p<0.001), readmissions within 30 days 4.1% and 3% (p = 0.76), readmissions 90 days 2.7% and 6.6% (p = 0.183), transfusions 5.5% and 15.2% (p = 0.033). Conclusion: The implementation of a multiprofessional CPPA contributed to the implementation of care protocols, favoring greater patient safety. Level of Evidence III; Retrospective Comparative Study.

Objetivo: Demonstrar se um Programa de Cuidados Clínicos multiprofissional em Artroplastia Total de Joelho (PCCA) contribui para a otimização assistencial hospitalar. Método: Estudo retrospectivo em prontuários de indicadores assistenciais em 310 pacientes divididos em dois grupos: A- submetidos a artroplastia no último biênio antecessor a introdução do PCCA (n=144) e grupo B- submetidos a ATJ no biênio após a introdução do PCCA (n=166). Resultados: Indicadores pós-operatórios mostraram diferença significativa a favor do grupo B sobre o grupo A para tempo de hospitalização em dias 4,33 ± 2,79 e 5,4 ± 1,67 (p<0,001), tempo de antibiótico profilático em horas 28,13 ± 33,77 e 81,49 ± 40,91 (p<0,001), encaminhamento para unidade de terapia intensiva 40,9% e 73,4% (p<0,001), início da tromboprofilaxia dentro de 24h 97,9% e 82,5% (p<0,001), uso de meias elásticas e/ou compressão intermitente prescritos para tromboprofilaxia 89,5% e 31,2% (p<0,001), tempo para iniciação da reabilitação em 24h 90,1% e 66,1% (p<0,001), readmissões em 30 dias 4,1% e 3% (p = 0,76), readmissões 90 dias 2,7% e 6,6% (p = 0,183), transfusões 5,5% e 15,2% (p = 0,033). Conclusão: A implementação de um PCCA multiprofissional contribuiu para o cumprimento dos protocolos assistenciais favorecendo maior segurança para os pacientes. Nível de Evidência III; Estudo Retrospectivo Comparativo.

Randomized trial of effect of bariatric surgery on blood pressure after 5 years

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

BioProtIS: Streamlining protein-ligand interaction pipeline for analysis in genomic and transcriptomic exploration.

The identification of protein-ligand interactions plays a pivotal role in elucidating biological processes and discovering potential bioproducts. Harnessing the capabilities of computational methods in drug discovery, we introduce an innovative Inverted Virtual Screening (IVS) pipeline. This pipeline Integrated molecular dynamics and docking analyses to ensure that protein structures are not only energetically favorable but also representative of stable conformations. The primary objective of this pipeline is to automate and streamline the analysis of protein-ligand interactions at both genomic and transcriptomic scales. In the contemporary post-genomic era, high-throughput computational screening for bioproducts, biological systems, and therapeutic drugs has become a cornerstone practice. This approach offers the promise of cost-effectiveness, time efficiency, and optimization of laboratory work. Nevertheless, a notable deficiency persists in the availability of efficient pipelines capable of automating the virtual screening process, seamlessly integrating input and output, and leveraging the full potential of open-source tools. To bridge this critical gap, we have developed a versatile pipeline known as BioProtIS. This tool seamlessly integrates a suite of state-of-the-art tools, including Modeller, AlphaFold, Gromacs, FPOCKET, and AutoDock Vina, thus facilitating the streamlined docking of ligands with an expansive repertoire of proteins sourced from genomes and transcriptomes, and substrates. To assess the pipeline's performance, we employed the transcriptomes of Cereus jamacaru (a cactus species) and Aspisoma lineatum (firefly), along with the genome of Homo sapiens. This integration not only improves the accuracy of ligand-protein interactions by minimizing replicability deviations but also optimizes the discovery process by enabling the simultaneous evaluation of multiple substrates. Furthermore, our pipeline accommodates distinct testing scenarios, such as blind docking or site-specific targeting, which are invaluable in applications ranging from drug repositioning to the exploration of new allosteric binding sites and toxicity assessments. BioProtIS has been designed with modularity at its core. This inherent flexibility empowers users to make custom modifications directly within the source code, tailoring the pipeline to their specific research needs. Moreover, it lays the foundation for seamless integration of diverse docking algorithms in future iterations, promising ongoing advancements in the field of computational biology. This pipeline is available for free distribution and can be download at: https://github.com/BBMDO/BioProtIS.

Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Main Pathogens Causing Infections and Antibiotic Resistance Profile in Major Burns in Brazil Comparing Two Periods: 2015/2016 and 2019/2020.

Sepsis is the main cause of death in major burns. In this retrospective study conducted in a reference hospital in Brazil, the main agents causing infection and the resistance profile to antibiotics were identified. In addition, the epidemiological profile, length of hospital stay, type of burn, and total body surface area (TBSA) in major burns were collected from medical records, comparing the years 2015/2016 and 2019/2020. In both time periods, there was a predominance of males with a mean age of 43 years. Burns with less than 30% of TBSA predominated. There was a significant increase in positive cultures (P = .00026), from 58.7% to 80%, and an increase in skin punch culture collection from 25.6% to 43.9% in the years 2019/2020. The predominant etiological agent was Pseudomonas aeruginosa, followed by Acinetobacter baumannii resistant to carbapenems, and Staphylococcus aureus in both evaluated periods. The percentage of deaths was higher in 2019/2020 (26.2% vs. 14.6%; P = .026). The length of hospital stay was shorter in the latter period (P = .0081). Sepsis was the cause of death in 81.2% of cases in 2015/2020 and 78.3% in 2019/2020. Among the deaths, P. aeruginosa was the main agent identified. There was no change in the main pathogens and bacterial antibiotic resistance between the 2 time periods.

Association of vitamin D and cognition in people with type 2 diabetes: a systematic review.

CONTEXT: There is a high prevalence of vitamin D deficiency and impaired cognitive function in people with type 2 diabetes mellitus (T2DM). OBJECTIVE: To critically and systematically review the literature on the association between vitamin D status and cognitive performance in people with type 2 diabetes. DATA SOURCES: This review was conducted according to PRISMA recommendations. MEDLINE, SCOPUS, the Cochrane Library, and Web of Science databases were searched using the terms "Diabetes Mellitus, Type 2", "Cognitive Function", and "Vitamin D". DATA EXTRACTION: Eight observational and 1 randomized study were included, containing data of 14 648 adult and elderly individuals (19-74 y). All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS: There is no strong evidence that lower serum concentrations of vitamin D and vitamin D-binding protein are associated with worsening cognitive function in individuals with T2DM. Vitamin D supplementation (12 wk) improved the scores of some executive functioning tests, although there was no difference between low doses (5000 IU/wk) and high doses (50 000 IU/wk). CONCLUSIONS: There is no high-quality evidence demonstrating an association between vitamin D status and cognitive function, or clinical benefits on cognition from vitamin D supplementation in individuals with T2DM. Future studies are needed. Systematic Review Registration: PROSPERO registration no. CRD42021261520.

Prediction of acute fish toxicity (AFT) and fish embryo toxicity (FET) tests by cytotoxicity assays using liver and embryo zebrafish cell lines (ZFL and ZEM2S).

Fish cell-based assays represent potential alternative methods to vertebrates' use in ecotoxicology. In this study, we evaluated the cytotoxicity of thirteen chemicals, chosen from OECD guidelines 236 and 249, in two zebrafish cell lines (ZEM2S and ZFL). We aimed to investigate whether the IC50 values obtained by viability assays (alamar blue, MTT, CFDA-AM, and neutral red) can predict the LC50 values of Acute Fish Toxicity (AFT) test and Fish Embryo Toxicity (FET) test. There was no significant difference between the values obtained by the different viability assays. ZFL strongly correlated with AFT and FET tests (R2AFT = 0.73-0.90; R2FET48h = 0.79-0.90; R2FET96h = 0.76-0.87), while ZEM2S correlated better with the FET test (48h) (R2 = 0.70-0.86) and weakly with AFT and FET tests (96h) (R2AFT = 0.68-0.74 and R2FET96h = 0.62-0.64). The predicted LC50 values allowed the correct categorization of the chemicals in 76.9% (AFT test) - 90.9% (FET test) using ZFL and in 30.7% (AFT test) - 63.6% (FET test) using ZEM2S considering the US EPA criterion for classifying acute aquatic toxicity. ZFL is a promising cell line to be used in alternative methods to adult fish and fish embryos in ecotoxicity assessments, and the method performed in 96-well plates is advantageous in promoting high-throughput cytotoxicity assessment.

Benefits of a clinical pathway in total knee arthroplasty / Beneficios de um programa de cuidados clínicos em artroplastia total de joelho

ABSTRACT Objective: Demonstrate whether a multiprofessional Clinical Pathway Program in Total Knee Arthroplasty (CPPA) contributesto optimizing hospital care. Method: Retrospective study of medical data of care indicators in 310 patients divided into two groups: A- who underwent arthroplasty in the last biennium before the introduction of the CPPA (n=144) and group B- who underwent TKA in the biennium after the introduction of the CPPA (n=166). Results: Postoperative showed a significant difference in favor of group B over group A for hospitalization time in days 4.33 ± 2.79 and 5.4 ± 1.67 (p<0.001), time of prophylactic antibiotic in hours 28.13 ± 33.77 and 81.49 ± 40.91 (p<0.001), referral to the intensive care unit 40.9% and 73.4% (p<0.001), initiation of thromboprophylaxis within 24 hours 97.9% and 82.5% (p<0.001), use of elastic stockings and/or intermittent compression prescribed for thromboprophylaxis 89.5% and 31.2% (p<0.001), initiation of rehabilitation within 24 hours 90.1% and 66.1% (p<0.001), readmissions within 30 days 4.1% and 3% (p = 0.76), readmissions 90 days 2.7% and 6.6% (p = 0.183), transfusions 5.5% and 15.2% (p = 0.033). Conclusion: The implementation of a multiprofessional CPPA contributed to the implementation of care protocols, favoring greater patient safety. Level of Evidence III; Retrospective Comparative Study.

RESUMO Objetivo: Demonstrar se um Programa de Cuidados Clínicos multiprofissional em Artroplastia Total de Joelho (PCCA) contribui para a otimização assistencial hospitalar. Método: Estudo retrospectivo em prontuários de indicadores assistenciais em 310 pacientes divididos em dois grupos: A- submetidos a artroplastia no último biênio antecessor a introdução do PCCA (n=144) e grupo B- submetidos a ATJ no biênio após a introdução do PCCA (n=166). Resultados: Indicadores pós-operatórios mostraram diferença significativa a favor do grupo B sobre o grupo A para tempo de hospitalização em dias 4,33 ± 2,79 e 5,4 ± 1,67 (p<0,001), tempo de antibiótico profilático em horas 28,13 ± 33,77 e 81,49 ± 40,91 (p<0,001), encaminhamento para unidade de terapia intensiva 40,9% e 73,4% (p<0,001), início da tromboprofilaxia dentro de 24h 97,9% e 82,5% (p<0,001), uso de meias elásticas e/ou compressão intermitente prescritos para tromboprofilaxia 89,5% e 31,2% (p<0,001), tempo para iniciação da reabilitação em 24h 90,1% e 66,1% (p<0,001), readmissões em 30 dias 4,1% e 3% (p = 0,76), readmissões 90 dias 2,7% e 6,6% (p = 0,183), transfusões 5,5% e 15,2% (p = 0,033). Conclusão: A implementação de um PCCA multiprofissional contribuiu para o cumprimento dos protocolos assistenciais favorecendo maior segurança para os pacientes. Nível de Evidência III; Estudo Retrospectivo Comparativo.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

Processos formativos para o enfrentamento das violências contra as mulheres no setor saúde: uma revisão integrativa / Educational processes to combat violence against women in the health sector: an integrative review

Resumo O setor saúde compõe a rede de enfrentamento das violências contra as mulheres, sendo necessário que os seus serviços ofertem atenção qualificada, o que se depara com o desafio de uma exígua formação de seus profissionais sobre a temática, mesmo que esteja prevista na Política Nacional de Enfrentamento à Violência Contra as Mulheres. Este estudo busca analisar como profissionais da saúde têm se qualificado para atuar no enfrentamento da violência contra as mulheres no Brasil. A partir de uma revisão integrativa da literatura, 16 artigos foram analisados, abordando tanto trajetórias formativas quanto experiências de formação no contexto acadêmico e em serviço. A formação sobre violências contra as mulheres se mostrou insuficiente, o que pode ocasionar oportunidades perdidas de detecção, atendimento e encaminhamento dos casos no setor de saúde ou para outros serviços da rede de atendimento. Foram identificados processos formativos ocorridos em graduações e em serviço, todos no âmbito da atenção primária à saúde, que podem impulsionar futuras formações, necessidade reafirmada em todos os artigos. Sugerem-se parcerias entre universidades e Sistema Único de Saúde, bem como processos formativos reflexivos e participativos que considerem a complexidade social das violências contra as mulheres.

Abstract The health sector can contribute to the combat of violence against women, if its services offer qualified care, but there are challenges such as the lack of health professional qualification, even though it is provided in the National Policy to Combat Violence Against Women. This study aims to analyze how health workers have been qualified to act in the prevention and confrontation of violence against women in Brazil. An integrative literature review was made and sixteen articles were analyzed, addressing training trajectories and experience reports, both in the academic and the health service context. The training on this theme proved to be insufficient, which could lead to missed opportunities for detection, care and referral of these cases to the health sector or others related to the care network. Reports on educational experiences were identified in degree courses and in Primary Health Care services, which could boost future educational processes, a need reaffirmed in all the articles. The university, in collaboration with the Unified Health System (SUS), can contribute with reflective, participatory educational processes that consider the social complexity of violence against women.

How the Adequate Choice of Plant Species Favors the Restoration Process in Areas Susceptible to Extreme Frost Events.

This work aimed to evaluate the impacts caused by extreme frost events in an ecological restoration area. We grouped the species in three ways: (1) type of trichome coverage; (2) shape of the seedling crown; and (3) functional groups according to the degree of damage caused by frost. The variables of the restored area and species characteristics were selected to be subjected to linear generalization analysis models (GLMs). A total of 104 individuals from seven species were sampled. The most affected species were Guazuma ulmifolia Lam. (98% of leaves affected), followed by Cecropia pachystachia Trécul and Hymenea courbaril L. (both 97%), Inga vera Willd. (84%), and Senegalia polyphylla (DC.) Britton & Rose with 75%. Tapirira guianensis Aubl. was considered an intermediate species, with 62% of the crown affected. Only Solanum granulosoleprosum Dunal was classified as slightly affected, with only 1.5% of leaves affected. With the GLM analysis, it was verified that the interaction between the variables of leaf thickness (Χ² = 37.1, df = 1, p < 0.001), trichome coverage (Χ² = 650.5, df = 2, p < 0.001), and leaf structure culture (Χ² = 54.0, df = 2, p < 0.001) resulted in a model with high predictive power (AIC = 927,244, BIC = 940,735, Χ² = 6947, R² = 0.74, p < 0.001). Frost-affected crown cover was best explained by the interaction between the three functional attributes (74%). We found that there is a tendency for thicker leaves completely covered in trichomes to be less affected by the impact of frost and that the coverage of the affected crown was greatly influenced by the coverage of trichomes. Seedlings with leaves completely covered in trichomes, thicker leaves, and a funneled or more open crown structure are those that are most likely to resist frost events. The success of ecological restoration in areas susceptible to extreme events such as frost can be predicted based on the functional attributes of the chosen species. This can contribute to a better selection of species to be used to restore degraded areas.