Schistosoma mansoni: a importância das fases cutânea e pulmonar na imunidade concomitante, no camundongo albino

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.Esquistossômulos com 14 dias de idade, obtidos de camundongos previamente infectados, foram cirurgicamente transferidos para a veia porta de camundongos receptores. Outro grupo de camundongos foi infectado com cercárias por via transcutânea. Noventa dias após, aqueles grupos foram desafiados com 100 cercárias, transcutaneamente, assim como o grupo controle. Duas semanas mais tarde, os animais foram perfundidos e os vermes maduros e imaturos contados separadamente. Diferenças estatisticamente significativas foram observadas na recuperação dos vermes imaturos, quando o grupo controle foi comparado com aqueles grupos infectados duas vezes. Nenhuma diferença estatística foi detectada entre o grupo infectado transcutaneamente e o grupo infectado por inoculação do verme na veia porta. Os resultados demonstraram que a supressão da migração do parasito através da pele e dos pulmões não interfere no desenvolvimento da chamada imunidade concomitante

Tenacidad a la fractura de compuestos cermets 3Al2O3*2SiO2/Ag manufacturados por molienda de alta energía

La fabricación de materiales compuestos de matriz cerámica reforzados con partículas metálicas han propiciado la formación de nuevos materiales conocidos como compuestos CERMETS, materiales que debido a sus elementos precursores poseen propiedades distintas a las de los materiales convencionales. En este trabajo se establece la ruta de fabricación de materiales compuestos cermets base 3Al2O3*2SiO2 reforzados con partículas metálicas de Ag a partir de la formación de la composición química en peso de polvos de 3Al2O3*2SiO2 / 1% Ag en busca de un aumento en la tenacidad a la fractura con respecto al cerámico base. La composición química de polvos es sometida a un proceso de mezcla molienda de alta energía en seco en un molino tipo planetario por 2 horas a 200 rpm. Los polvos posteriormente son conformados en muestras cilíndricas de 20 mm de diámetro y 3 mm de espesor mediante la aplicación de carga uniaxial en frío de 200 MPa. Las muestras son sinterizadas a 1500°C y 1600°C por una y dos horas en un horno de resistencia eléctrica en atmósfera controlada de gas nitrógeno. Los compuestos fabricados son analizados microestructuralmente por microscopia óptica y electrónica de barrido. Se determina la densidad y las propiedades mecánicas de dureza y tenacidad a la fractura, las dos últimas por el método de indentación. Los resultados muestran la viabilidad de fabricación de materiales compuestos cermets así como los cambios en la densidad, la dureza y la tenacidad a la fractura, con respecto al cerámico 3Al2O3*2SiO2 sin refuerzo metálico

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries