Generation of a homozygous (MCRIi031-A-3) WT1 knockout human iPSC line.

The transcription factor WT1 plays a critical role in several embryonic developmental processes such as gonadogenesis, nephrogenesis, and cardiac development. We generated a homozygous (MCRIi031-A-3) WT1 knockout induced pluripotent stem cell (iPSC) line from human fibroblasts using a one-step protocol for CRISPR/Cas9 gene-editing and episomal-based reprogramming. The cells exhibit a normal karyotype and morphology, express pluripotency markers, and have the capacity to differentiate into the three embryonic germ layers. These cell lines will allow us to further explore the role of WT1 in critical developmental processes.

Generation of heterozygous (MCRIi031-A-1) and homozygous (MCRIi031-A-2) SOX9 knockout human iPSC lines.

The transcription factor SOX9 plays a critical role in several embryonic developmental processes such as gonadogenesis, chrondrogenesis, and cardiac development. We generated heterozygous (MCRIi031-A-1) and homozygous (MCRIi031-A-2) SOX9 knockout induced pluripotent stem cell (iPSC) lines from human fibroblasts using a one-step protocol for CRISPR/Cas9 gene-editing and episomal-based reprogramming. Both iPSC lines exhibit a normal karyotype and morphology, express pluripotency markers, and have the capacity to differentiate into the three embryonic germ layers. These cell lines will allow us to further explore the role of SOX9 in critical developmental processes.

Effects of Intravenous Lidocaine on Quality of Recovery After Laparoscopic Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to assess the effects of pre and intraoperative lidocaine infusion on short-term recovery quality after laparoscopic bariatric surgeries. In the search across MEDLINE, Embase, and Cochrane databases, we considered randomized controlled trials comparing intravenous lidocaine vs placebo (saline) for patients with obesity undergoing laparoscopic bariatric surgery. Seven studies (640 patients) were included. The lidocaine group had a significantly higher recovery quality score, a lower morphine consumption, and a notably reduced rate of nausea and vomiting compared with the placebo group. Additionally, Lidocaine infusion was associated with a shorter hospital stay, while no significant difference was observed in the time to bowel function recovery between both groups. In conclusion, lidocaine infusion before and during laparoscopic bariatric surgery contributes to an enhanced quality of recovery.

Performance measurement of Brazilian federal university hospitals: an overview of the public health care services through principal component analysis.

PURPOSE: This paper aimed to contextualize the process of public hospital providing services, based on the measurement of the performance of Federal University Hospitals (HUFs) of Brazil, using the technique of multivariate statistics of principal component analysis. DESIGN/METHODOLOGY/APPROACH: This research presented a descriptive and quantitative character, as well as exploratory purpose and followed the inductive logic, being empirically structured in two stages, that is, the application of principal component analysis (PCA) in four healthcare performance dimensions; subsequently, the full reapplication of principal component analysis in the most highly correlated variables, in module, with the first three main components (PC1, PC2 and PC3). FINDINGS: From the principal component analysis, considering mainly component I, with twice the explanatory power of the second (PC2) and third components (PC3), it was possible to evidence the efficient or inefficient behavior of the HUFs evaluated through the production of medical residency, by specialty area. Finally, it was observed that the formation of two groups composed of seven and eight hospitals, that is, Groups II and IV shows that these groups reflect similarities with respect to the scores and importance of the variables for both hospitals' groups. RESEARCH LIMITATIONS/IMPLICATIONS: Among the main limitations it was observed that there was incomplete data for some HUFs, which made it impossible to search for information to explain and better contextualize certain aspects. More specifically, a limited number of hospitals with complete information were dealt with for 60% of SIMEC/REHUF performance indicators. PRACTICAL IMPLICATIONS: The use of PCA multivariate technique was of great contribution to the contextualization of the performance and productivity of homogeneous and autonomous units represented by the hospitals. It was possible to generate a large quantity of information in order to contribute with assumptions to complement the decision-making processes in these organizations. SOCIAL IMPLICATIONS: Development of public policies with emphasis on hospitals linked to teaching centers represented by university hospitals. This also involved the projection of improvements in the reach of the efficiency of the services of assistance to the public health, from the qualified formation of professionals, both to academy, as to clinical practice. ORIGINALITY/VALUE: The originality of this paper for the scenarios of the Brazilian public health sector and academic area involved the application of a consolidated performance analysis technique, that is, PCA, obtaining a rich work in relation to the extensive exploitation of techniques to support decision-making processes. In addition, the sequence and the way in which the content, formed by object of study and techniques, has been organized, generates a particular scenario for the measurement of performance in hospital organizations.

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

Breast and bowel cancers diagnosed in people 'too young to have cancer': A blueprint for research using family and twin studies.

Young breast and bowel cancers (e.g., those diagnosed before age 40 or 50 years) have far greater morbidity and mortality in terms of years of life lost, and are increasing in incidence, but have been less studied. For breast and bowel cancers, the familial relative risks, and therefore the familial variances in age-specific log(incidence), are much greater at younger ages, but little of these familial variances has been explained. Studies of families and twins can address questions not easily answered by studies of unrelated individuals alone. We describe existing and emerging family and twin data that can provide special opportunities for discovery. We present designs and statistical analyses, including novel ideas such as the VALID (Variance in Age-specific Log Incidence Decomposition) model for causes of variation in risk, the DEPTH (DEPendency of association on the number of Top Hits) and other approaches to analyse genome-wide association study data, and the within-pair, ICE FALCON (Inference about Causation from Examining FAmiliaL CONfounding) and ICE CRISTAL (Inference about Causation from Examining Changes in Regression coefficients and Innovative STatistical AnaLysis) approaches to causation and familial confounding. Example applications to breast and colorectal cancer are presented. Motivated by the availability of the resources of the Breast and Colon Cancer Family Registries, we also present some ideas for future studies that could be applied to, and compared with, cancers diagnosed at older ages and address the challenges posed by young breast and bowel cancers.

Generation of heterozygous (MCRIi030-A-1) and homozygous (MCRIi030-A-2) NR2F2/COUP-TFII knockout human iPSC lines.

The NR2F2 gene encodes the transcription factor COUP-TFII, which is upregulated in embryonic mesoderm. Heterozygous variants in NR2F2 cause a spectrum of congenital anomalies including cardiac and gonadal phenotypes. We generated heterozygous (MCRIi030-A-1) and homozygous (MCRIi030-A-2) NR2F2-knockout induced pluripotent stem cell (iPSC) lines from human fibroblasts using a one-step protocol for CRISPR/Cas9 gene-editing and episomal-based reprogramming. Both iPSC lines exhibited a normal karyotype, typical pluripotent cell morphology, pluripotency marker expression, and the capacity to differentiate into the three embryonic germ layers. These lines will allow us to explore the role of NR2F2 during development and disease.

Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

Mental disorders and discrimination: A prospective cohort study of young twin pairs in Germany.

Background: Mental disorders and perceived discrimination share common risk factors. The association between having a mental disorder and experiencing discrimination is well-known, but the extent to which familial factors, such as genetic and shared environmental factors, might confound this association, including sex differences in familial confounding, remains unexplored. Aims: We investigated potential unmeasured familial confounding in the association between mental disorders and perceived discrimination using a matched twin study design. Method: We examined data from 2044 same-sex twin pairs (n = 4088) aged 16-25 years from the German population-based study 'TwinLife'. We applied random-effects logistic regression to within-individual and within-and-between pair models of the association between mental disorder and perceived discrimination, and used likelihood ratio tests (LRTs) to compare these models. Multivariable models were adjusted for body mass index, educational attainment, and life satisfaction. Results: There were 322 (8.1%) participants with a diagnosed mental disorder, and 15% (n = 604) of the cohort reported having experienced discrimination in the previous 12 months. Mental disorder and discrimination were associated in the adjusted within-individual model (adjusted odds ratio = 2.19, 95% confidence interval: 1.42-3.39, P<0.001). However, the within-and-between pair model showed that this association was explained by the within-pair mean (aOR = 4.24, 95% CI: 2.17-8.29, P<0.001) and not the within-pair difference (aOR = 1.26, 95% CI: 0.70-2.28, P = 0.4) of mental disorder. Therefore, this association was mostly explained by familial confounding, which is also supported by the LRTs for the unadjusted and adjusted models (P<0.001 and P = 0.03, respectively). This familial confounding was more prominent for males than females. Conclusions: Our findings show that the association between mental disorder and discrimination is at least partially explained by unmeasured familial factors. Designing family-based healthcare models and incorporating family members in interventions targeted at ameliorating mental ill-health and experiences of discrimination among adolescents may improve efficacy.

Familial confounding of internalising symptoms and obesity in adolescents and young adults; a co-twin analysis.

BACKGROUND: Obesity and internalising disorders, including depression and anxiety, often co-occur. There is evidence that familial confounding contributes to the co-occurrence of internalising disorders and obesity in adults. However, its impact on this association among young people is unclear. Our study investigated the extent to which familial factors confound the association between internalising disorders and obesity in adolescents and young adults. SUBJECTS/METHODS: We used a matched co-twin design to investigate the impact of confounding by familial factors on associations between internalising symptoms and obesity in a sample of 4018 twins aged 16 to 27 years. RESULTS: High levels of internalising symptoms compared to low levels increased the odds of obesity for the whole cohort (adjusted odds ratio [AOR] = 3.1, 95% confidence interval [CI]: 1.5, 6.8), and in females (AOR = 4.1, 95% CI 1.5, 11.1), but not in males (AOR = 2.8 95% CI 0.8, 10.0). We found evidence that internalising symptoms were associated with an increased between-pair odds of obesity (AOR 6.2, 95% CI 1.7, 22.8), using the paired analysis but not using a within-pair association, which controls for familial confounding. Sex-stratified analyses indicated high internalising symptoms were associated with increased between-pair odds of obesity for females (AOR 12.9, 95% CI 2.2, 76.8), but this attenuated to the null using within-pair analysis. We found no evidence of between or within-pair associations for males and weak evidence that sex modified the association between internalising symptoms and obesity (likelihood ratio test p = 0.051). CONCLUSIONS: Some familial factors shared by twins confound the association between internalising symptoms and obesity in adolescent and young adult females. Internalising symptoms and obesity were not associated for adolescent and young adult males. Therefore, prevention and treatment efforts should especially address familial shared determinants of obesity, particularly targeted at female adolescents and young adults with internalising symptoms and those with a family history of these disorders.

COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors.

BACKGROUND: The absence of expression of the Y-chromosome linked testis-determining gene SRY in early supporting gonadal cells (ESGC) leads bipotential gonads into ovarian development. However, genetic variants in NR2F2, encoding three isoforms of the transcription factor COUP-TFII, represent a novel cause of SRY-negative 46,XX testicular/ovotesticular differences of sex development (T/OT-DSD). Thus, we hypothesized that COUP-TFII is part of the ovarian developmental network. COUP-TFII is known to be expressed in interstitial/mesenchymal cells giving rise to steroidogenic cells in fetal gonads, however its expression and function in ESGCs have yet to be explored. RESULTS: By differentiating induced pluripotent stem cells into bipotential gonad-like cells in vitro and by analyzing single cell RNA-sequencing datasets of human fetal gonads, we identified that NR2F2 expression is highly upregulated during bipotential gonad development along with markers of bipotential state. NR2F2 expression was detected in early cell populations that precede the steroidogenic cell emergence and that retain a multipotent state in the undifferentiated gonad. The ESGCs differentiating into fetal Sertoli cells lost NR2F2 expression, whereas pre-granulosa cells remained NR2F2-positive. When examining the NR2F2 transcript variants individually, we demonstrated that the canonical isoform A, disrupted by frameshift variants previously reported in 46,XX T/OT-DSD patients, is nearly 1000-fold more highly expressed than other isoforms in bipotential gonad-like cells. To investigate the genetic network under COUP-TFII regulation in human gonadal cell context, we generated a NR2F2 knockout (KO) in the human granulosa-like cell line COV434 and studied NR2F2-KO COV434 cell transcriptome. NR2F2 ablation downregulated markers of ESGC and pre-granulosa cells. NR2F2-KO COV434 cells lost the enrichment for female-supporting gonadal progenitor and acquired gene signatures more similar to gonadal interstitial cells. CONCLUSIONS: Our findings suggest that COUP-TFII has a role in maintaining a multipotent state necessary for commitment to the ovarian development. We propose that COUP-TFII regulates cell fate during gonad development and impairment of its function may disrupt the transcriptional plasticity of ESGCs. During early gonad development, disruption of ESGC plasticity may drive them into commitment to the testicular pathway, as observed in 46,XX OT-DSD patients with NR2F2 haploinsufficiency.

Distearoyl phosphatidylglycerol and dioleoyl phosphatidylglycerol increase the retention and reduce the toxicity of amphotericin B-loaded in nanoemulsions.

Aim: To develop nanoemulsions (NEs) loading amphotericin B (AmB) and to evaluate the influence of different excipients on the stability and the supramolecular organization, retention and toxicity of AmB. Materials & methods: The NEs were developed from different oils, surfactants, external media and anionic lipids (disteaoryl phosphatidylglycerol [DSPG] and dioleoyl phosphatidylglycerol [DOPG]). Their impact on the size, pH, zeta potential, AmB encapsulation efficiency, AmB retention and hemolytic potential of the NEs was evaluated. Results & conclusion: The use of soybean oil (lipid matrix), Span 80 (surfactant), phosphate buffer (external phase) and DSPG or DOPG (hydrophobic ion pair) provided better NE stability, higher AmB retention within the NEs and a safer formulation profile in hemolysis tests.

Effects of acute caffeine ingestion on the physical performance of amateur american football athletes / Efeitos da ingestão aguda de cafeína no desempenho de atletas amadores de futebol americano

ABSTRACT The aim of this study was to investigate the effects of acute caffeine ingestion (5 mg.kg-1) on jump, isometric strength and repeated sprint performance in amateur American football athletes. Twelve players (24.6 ± 3.66 years and 115.18 ± 24.35 kg of body weight) ingested a dose of caffeine (5 mg.kg−1) or placebo 60 min prior to a testing session consisting of: 1) countermovement jump (CMJ); 2) isometric mid-tight pull (IMTP); and 3) 3-line drills (200-yd shuttle runs with a 2-minute rest between sprints). Two testing sessions were performed using a double-blind, counterbalanced, crossover design during a pre-season training camp. Results indicated: Caffeine ingestion improved CMJ performance (p = 0.035), but no differences were observed on IMTP strength (p = 0.22) and line drill performance (total time: p = 0.65, and fatigue (%): p = 0.75) when compared to placebo condition. Conclusion: Acute caffeine ingestion improved jump performance, but not isometric strength and repeated sprint with change-of-direction performance in amateur American Football athletes.

RESUMO O objetivo deste estudo foi investigar os efeitos da ingestão aguda de cafeína (5 mg.kg-1) no salto, força isométrica e desempenho de sprints repetidos em atletas amadores de futebol americano. Doze jogadores (24,6 6 ± 3.66 anos e 115,18 ± 24.35 kg de peso corporal) ingeriram uma dose de cafeína (5 mg.kg−1) ou placebo 60 minutos antes de uma sessão de testes que consistia em: 1) Salto contramovimento (CMJ); 2) Meio-agachamento isométrico (IMTP); 3) Corrida de agilidade em L (3-line drill = corrida de agilidade de 200 jardas com 2 minutos de repouso entre os sprints). Duas sessões de teste foram realizadas usando um delineamento cruzado duplo-cego durante o período de pré-temporada de treinamento. Resultados indicaram: A ingestão de cafeína melhorou o desempenho do CMJ (p = 0,035), mas não foram observadas diferenças na força no IMTP (p = 0,22) e no desempenho do exercício de agilidade em L (tempo total: p = 0,65 e fadiga (%): p = 0,75) quando em comparação com a condição placebo. Conclusão: A ingestão aguda de cafeína melhorou o desempenho no salto, mas não na força isométrica e no desempenho de sprints repetidos com mudança de direção em atletas amadores de futebol Americano.

Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment.

Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, - 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization.

Comparison of Different Pneumorrhaphy Methods after Partial Pulmonary Lobectomy in Dogs.

Pulmonary loborraphy can be performed using manual sutures and staples, although other methods, such as tissue adhesives, are also cited in the veterinary literature. Although the surgery is well tolerated in the canine species, failure in pulmonary aerostasis is still a reality since all the methods described so far eventually lead to air leakage after the use of the partial lobectomy technique in the lungs. Within this context, the aim of this research was to compare the effectiveness of different hermetic sealing methods after partial lobectomy of the right caudal lung lobe (RCLL) in dogs. 30 cadavers models were divided in 6 groups: G1-cobbler suture associated with simple continuous; G2-overlapping continuous suture associated with simple continuous suture; G3-Ford interlocking suture; G4-Stapling device; G5-Tissue glue (cyanoacrylate). After performing the sealing techniques, the lungs were submerged in water and inflated with oxygen at positive ventilatory pressures at physiological (up to 14.7 mmHg, which is equivalent to up to 20 cmH2O) and supraphysiological levels (above 14.7 mmHg) to evaluate the performance of the sealing methods. At physiological ventilatory pressure levels, there was no difference between groups. Sealing with surgical glue was superior to interlocking sutures and stapling devices at supraphysiological levels of ventilatory pressure.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

A New Full-Face Mask for Multifunctional Non-Invasive Ventilation.

Background: Noninvasive ventilation (NIV) provides positive pressure through different interfaces. A multifunctional full-face mask prototype was developed to provide NIV from three sources: ICU ventilators, portable ventilators, and high-flow medical gas pipeline systems. This study aimed to evaluate the usability of this prototype mask. Methods: This was a quantitative experimental study, conducted in two phases: the development of a full-face mask prototype NIV interface, and the evaluation of its usability by health professionals (evaluators) using a heuristic approach. The Wolf Mask prototype is a multifunctional full-face mask that makes it possible to deliver positive pressure from three different sources: microprocessor-controlled ICU ventilators, portable ventilators with single-limb circuits, and high-flow medical gas. The evaluation was conducted in three stages: presentation of the prototype to the evaluators; skills testing via simulation in a clinical environment; and a review of skills. Results: The prototype was developed by a multidisciplinary team and patented in Brazil. The evaluators were 10 health professionals specializing in NIV. Seven skills related to handling the prototype were evaluated. Three of the ten evaluators called for (non-urgent) changes to improve recognition of the components of the prototype. Only one evaluator called for (non-urgent) changes to improve recognition of the pieces, assembly, and checking the mask. Conclusions: The newly developed multifunctional full-face mask prototype demonstrated excellent usability for providing noninvasive ventilation from multiple sources. Minor modifications may further improve the design.

Influence of atherosclerosis risk factors on the anatomical distribution of peripheral arterial disease in patients with chronic limb-threatening ischemia: a cross-sectional study.

Background: Atherosclerosis risk factors can have different impacts on cardiovascular diseases and on the anatomical distribution of Peripheral Arterial Disease (PAD). Objectives: To study the influence of atherosclerosis risk factors on the anatomical distribution of PAD in patients with chronic limb-threatening ischemia (CLTI). Methods: We performed an observational, cross-sectional, and analytical study that included 476 hospitalized patients with CLTI due to PAD. We compared the presence of atherosclerosis risk factors (age, gender, diabetes mellitus, smoking, and hypertension) in patients with PAD involving three different anatomic areas (aortoiliac, femoropopliteal, and infrapopliteal). Multivariate analysis was performed to identify associations between atherosclerosis risk factors and PAD distribution. Results: The mean age of the 476 patients was 69 years, 249 (52%) were men, and 273 (57%) had diabetes. Seventy-four percent (353) had minor tissue loss. Multivariate analysis identified three risk factors associated with PAD anatomical distribution (gender, smoking, and DM). Women had a 2.7 (CI: 1.75-4.26) times greater chance of having femoropopliteal disease. Smokers had a 3.6-fold (CI: 1.54-8.30) greater risk of aortoiliac disease. Diabetic patients were 1.8 (CI: 1.04-3.19) times more likely to have isolated infrapopliteal occlusive disease. Conclusions: The study showed that gender, DM, and smoking impact on the anatomical distribution of PAD in patients with CLTI. Diabetic patients were more likely to have only infrapopliteal disease, women had a greater risk of femoropopliteal PAD, and smokers had a greater risk of aortoiliac occlusive disease.