Seven versus 14 days of antimicrobial therapy for severe multidrug-resistant Gram-negative bacterial infections in intensive care unit patients (OPTIMISE): a randomised, open-label, non-inferiority clinical trial.

Background: Shorter courses of antimicrobial therapy have been shown to be non-inferior to longer durations for the management of several infections. However, data on critically ill patients with severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB) are scarce. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we assessed the non-inferiority of 7-day versus 14-day antimicrobial therapy for patients with intensive care unit (ICU)-acquired severe infections by MDR-GNB.

Research on longevity and associated age data of South American anurans: trends, gaps and recommendations.

Longevity is one of the most important characteristics in the life history of organisms. It is directly associated with growth, reproduction and age of sexual maturity. Despite this, little is known about longevity in South American anuran species, a region considered as a hotspot of world diversity.

Glia-related Acute Effects of Risperidone and Haloperidol in Hippocampal Slices and Astrocyte Cultures from Adult Wistar Rats: A Focus on Inflammatory and Trophic Factor Release.

Antipsychotics are drugs commonly prescribed to treat a variety of psychiatric conditions. They are classified as typical and atypical, depending on their affinity for dopaminergic and serotonergic receptors. Although neurons have been assumed to be the major mediators of the antipsychotic pharmacological effects, glia, particularly astrocytes, have emerged as important cellular targets for these drugs.

Disentangling the veil line for Brazilian biodiversity: An overview from two long-term research programs reveals huge gaps in ecological data reporting.

The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them.

Patient-level cost analysis of intensive care unit acquired infections: A prospective cohort study.

Introduction: Hospital-associated infections (HAIs) are associated with increased mortality and prolonged hospital length-of-stay (LOS). Although some studies have shown that HAIs are associated with increased costs, these studies only used cost estimates, were carried out in a small number of centres, or only in high-income countries.

Methods: We carried out a prospective cohort study in ten Brazilian intensive care units (ICUs) selected from a collaborative platform study (IMPACTO MR).

Managing Children and Adolescents with Type 1 Diabetes and Coexisting Celiac Disease: Real-World Data from a Global Survey.

Introduction: Celiac disease (CD) is among the diseases most commonly associated with type 1 diabetes (T1D). This study aimed to evaluate the worldwide practices and attitudes of physicians involved in pediatric diabetes care regarding diagnosing and managing CD in children with T1D.

Methods: The 30-item survey was conducted between July and December 2023 aimed at targeting pediatricians with special interest in T1D and CD.

Skin Reactions in Children with Type 1 Diabetes Associated with the Use of New Diabetes Technologies-An Observational Study from a Regional Polish Pediatric Diabetes Center.

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records.

Vascular Complications in Children and Young People with Type 1 Diabetes: A Worldwide Assessment of Diabetologists' Adherence to International Recommendations.

Introduction: This global survey evaluated the practices and adherence to international Clinical Practice Consensus Guidelines (CPCG) of physicians involved in pediatric diabetes care regarding screening, prevention and treatment of vascular complications of type 1 diabetes (T1D).

Method: A web-based survey gathering data about respondents' background, practices related to screening, prevention, and treatment of diabetic nephropathy, retinopathy, neuropathy, and macrovascular diseases and a self-assessment of physicians' knowledge based on the ISPAD CPCG 2018 were shared by ISPAD.

Results: We received 175 responses from 62 countries (60% female, median age 42.

A Case Study of a Rare Undifferentiated Spindle Cell Sarcoma of the Penis: Establishment and Characterization of Patient-Derived Models.

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like and .

Assessing the adductor musculature and jaw mechanics of Proterochampsa nodosa (Archosauriformes: Proterochampsidae) through finite element analysis.

Proterochampsids are a group of South American nonarchosaurian archosauromorphs whose general morphology has been historically likened to that of the extant Crocodylia, which purportedly exhibited similar habits by convergence. Taxa from the genus Proterochampsa, for example, show platyrostral skulls with dorsally faced orbits and external nares and elongated snouts that might indicate a feeding habit similar to that of crocodilians. Nonetheless, some aspects of their craniomandibular anatomy are distinct.

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol.

Introduction: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating -secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

First International Survey on Diabetes Providers' Assessment of Skin Reactions in Youth With Type 1 Diabetes Using Technological Devices.

Background: Advances in diabetes technological devices led to optimization of diabetes care; however, long-lasting skin exposure to devices may be accompanied by an increasing occurrence of cutaneous reactions.

Methods: We used an open-link web-based survey to evaluate diabetes-care providers' viewpoint on prevalence, management practices, and knowledge related to skin reactions with the use of diabetes technological devices. A post hoc analysis was applied to investigate differences in the level of awareness on this topic in relation to the experience in diabetes technology.

Inactivated and Immunogenic SARS-CoV-2 for Safe Use in Immunoassays and as an Immunization Control for Non-Clinical Trials.

Successful SARS-CoV-2 inactivation allows its safe use in Biosafety Level 2 facilities, and the use of the whole viral particle helps in the development of analytical methods and a more reliable immune response, contributing to the development and improvement of in vitro and in vivo assays. In order to obtain a functional product, we evaluated several inactivation protocols and observed that 0.03% beta-propiolactone for 24 h was the best condition tested, as it promoted SARS-CoV-2 inactivation above 99.

Sub‑chronic administration of lead alters markers of oxidative stress, acetylcholinesterase and Na+K+‑ATPase activities in rat brain.

This study investigated the effects of sub‑chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA‑RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH‑Px]), acetylcholinesterase (AChE), and Na+K+‑ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed.

Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3β/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.

Homocysteine (Hcy) is a risk factor for neurodegenerative diseases, such as Alzheimer's Disease, and is related to cellular and tissue damage. In the present study, we verified the effect of Hcy on neurochemical parameters (redox homeostasis, neuronal excitability, glucose, and lactate levels) and the Serine/Threonine kinase B (Akt), Glucose synthase kinase-3β (GSK3β) and Glucose transporter 1 (GLUT1) signaling pathway in hippocampal slices, as well as the neuroprotective effects of ibuprofen and rivastigmine alone or in combination in such effects. Male Wistar rats (90 days old) were euthanized and the brains were dissected.

Resistance exercise was safe for the pregnancy and offspring's development and partially protected rats against early life stress-induced effects.

Promising evidence points to gestational physical exercise as the key to preventing various disorders that affect the offspring neurodevelopment, but there are no studies showing the impact of resistance exercise on offspring health. Thus, the aim of this study was to investigate whether resistance exercise during pregnancy is able to prevent or to alleviate the possible deleterious effects on offspring, caused by early life-stress (ELS). Pregnant rats performed resistance exercise throughout the gestational period:they climbed a sloping ladder with a weight attached to their tail, 3 times a week.

Ozone therapy: protocol for treating canine parvovirus infection.

Canine Parvovirus infection is a disease caused by Canine Parvovirus (CPV) that results in hemorrhagic gastroenteritis and secondary infections, mainly in puppies between six weeks and six months old that are not immunized. Since there is no specific treatment for the condition, supportive therapy based on antibiotics, antiemetics, and non-steroidal anti-inflammatory drugs is traditionally used. Ozone therapy is an economical treatment that has bactericidal, fungicidal, and antiviral properties, besides promoting oxygenation and tissue regeneration, as well as anti-inflammatory and analgesic effects, and was used as a complementary therapy in this study.

Twenty years of the International Society for Pediatric and Adolescent Diabetes Science Schools programs: Assessment of their impact on the participants' personal careers and networking development.

Objective: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success.

Methods: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities.

Results: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys.

Customized cationic nanoemulsions loading triamcinolone acetonide for corneal neovascularization secondary to inflammatory processes.

Customized cationic oil-in-water nanoemulsions (NEs) have been produced to improve the bioavailability of poorly water-soluble drugs, such as triamcinolone acetonide (TA). TA is a synthetic glucocorticoid with anti-inflammatory and antiangiogenic therapeutic properties and it is widely used as an effective treatment in ocular disorders. In this work, TA-NEs were characterized using two different custom-made cationic surfactants, showing a high positive surface charge favouring corneal penetration and a particle size below 300 nm.

Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to ≅10 CAR T cells/kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here, we tested CD8α/4-1BB compared to CD28-based anti-CAIX CAR peripheral blood mononuclear cells (PBMCs) releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo.