The pulsatile brain, pulse pressure, cognition, and antihypertensive treatments in older adults: a functional NIRS study.

Age-related arterial stiffness increases pulsatility that reaches the cerebral microcirculation, compromises cerebrovascular health and lead to cognitive decline. The presence of cardiovascular risk factors (CVRFs) such as high blood pressure can exacerbate this effect. Despite extensive research on the impact of antihypertensive treatments on reducing arterial stiffness, little is known about the impact of antihypertensive treatments on pulsatility in cerebral microcirculation.

Assessment of viable Enterobacteriaceae and Enterococcus spp. across the agro-ecosystem of an antibiotic-free swine farm.

Agricultural practices, specifically the use of antibiotics and other biocides, have repercussions on human, animal and plant health. The aim of this study was to evaluate the levels of Enterobacteriaceae and Enterococcus, as antibiotic resistant marker bacteria, in various matrices across the agro-ecosystem of an antibiotic-free swine farm in Quebec (Canada), namely pig feed, feces, manure, agricultural soil, water and sediment from a crossing stream, and soil from nearby forests. Samples were collected in fall 2022, spring and fall 2023 and spring 2024.

Measurement of Λ_{b}^{0}, Λ_{c}^{+}, and Λ Decay Parameters Using Λ_{b}^{0}→Λ_{c}^{+}h^{-} Decays.

A comprehensive study of the angular distributions in the bottom-baryon decays Λ_{b}^{0}→Λ_{c}^{+}h^{-}(h=π,K), followed by Λ_{c}^{+}→Λh^{+} with Λ→pπ^{-} or Λ_{c}^{+}→pK_{S}^{0} decays, is performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of 9  fb^{-1} collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The decay parameters and the associated charge-parity (CP) asymmetries are measured, with no significant CP violation observed. For the first time, the Λ_{b}^{0}→Λ_{c}^{+}h^{-} decay parameters are measured.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial.

Importance: Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial.

Objective: To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium.

Perilymph sampling in Mongolian gerbil, technical note and procedure evaluation.

Objective: The aim of this study is to detail and evaluate the surgical procedure for perilymph sampling from the cochlear apex in the Mongolian gerbil.

Design: Perilymph sampling from the cochlear apex was performed one to three time in 12 male gerbils aged 8 to 12 months via the submandibular route. 11 of them were previously implanted with intracochlear implants loaded with dexamethasone and placed in the scala tympani, the 12th was used to collect control samples.

An amygdala-cortical circuit for encoding generalized fear memories.

Generalized learning is a fundamental process observed across species, contexts, and sensory modalities that enables animals to use past experiences to adapt to changing conditions. Evidence suggests that the prefrontal cortex (PFC) extracts general features of an experience that can be used across multiple situations. The anterior cingulate cortex (ACC), a region of the PFC, is implicated in generalized fear responses to novel contexts.

Early achievement of hemostasis defined by transfusion velocity: A possible mechanism for whole blood survival benefit.

Introduction: Whole blood resuscitation is associated with survival benefits in observational cohort studies. The mechanisms responsible for outcome benefits have not been adequately determined. We sought to characterize the achievement of hemostasis across patients receiving early whole blood versus component resuscitation.

Whole cranberry fruit powder supplement reduces the incidence of culture-confirmed urinary tract infections in females with a history of recurrent urinary tract infection: A 6-month multicenter, randomized, double-blind, placebo-controlled trial.

Background: High prevalence of urinary tract infections (UTI), including cystitis, and concern for antimicrobial resistance justify safe and effective non-antibiotic therapies for prevention of recurrent UTI (rUTI). This study investigated the effect of a whole cranberry fruit powder supplement on incidence of culture-confirmed UTI (primary outcome) in females with rUTI history.

Methods: This multicenter, 6-month, randomized, placebo-controlled, double-blind study enrolled 150 healthy females (18-65 years, body mass index (BMI) >17.

A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold.

A straightforward synthetic route towards DAB-1 scaffolded dimeric iminosugars is described here, starting from readily available bis-glycosylamines. The method allows the integration of a variety of linkages (aryl, alkyl, polyethyleneglycol chains) between both iminosugars through the choice of the bis-amine used in the first step. Moreover, an additional substituent (allyl, ethynyl) may be inserted into the structure via nucleophilic addition of an organometallic reagent to the starting bis-glycosylamine.

Can robotic arm-assisted total knee arthroplasty be applied to valgus deformity.

Introduction: Total knee arthroplasty (TKA) in valgus knees is challenging. Optimal ligament balance, implant neutral or moderate valgus alignment are crucial but conventional instrumentations usually lead to outliers. Robotic arm assisted TKA (RATKA) advantages could answer this challenge.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial.

In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD.

Early Cold Stored Platelet Transfusion Following Traumatic Brain Injury: A Randomized Clinical Trial.

Objective: To determine the feasibility, efficacy, and safety of cold stored compared to room temperature platelet transfusion in patients with traumatic brain injury.

Summary Background Data: Data demonstrating the safety and efficacy of cold stored platelet transfusion are lacking following traumatic brain injury.

Methods: A phase 2, randomized, open label, clinical trial was performed at a single U.

Covert variations of a musician's loudness during collective improvisation capture other musicians' attention and impact their interactions.

While research on auditory attention in complex acoustical environment is a thriving field, experimental studies thus far have typically treated participants as passive listeners. The present study-which combined real-time covert loudness manipulations and online probe detection-investigates for the first time to our knowledge, the effects of acoustic salience on auditory attention during live interactions, using musical improvisation as an experimental paradigm. We found that musicians were more likely to pay attention to a given co-performer when this performer was made sounding louder or softer; that such salient effect was not owing to the local variations introduced by our manipulations but rather likely to be driven by the more long-term context; and that improvisers tended to be more strongly and more stably coupled when a musician was made more salient.

Viral niche-partitioning: comparative genomics of giant viruses across environmental gradients in a high Arctic freshwater-saltwater lake.

Giant viruses (GVs; ) impact the biology and ecology of a wide range of eukaryotic hosts, with implications for global biogeochemical cycles. Here, we investigated GV niche separation in highly stratified Lake A at the northern coast of Ellesmere Island, Nunavut, Canada. This lake is composed of a layer of ice-covered freshwater that overlies saltwater derived from the ancient Arctic Ocean, and it therefore provides a broad gradient of environmental conditions and ecological habitats, each with a distinct protist community and rich assemblages of associated GVs.

End-of-life issues in the ITU - 10 important points to remember.

End-of-life (EOL) issues have become increasingly common in intensive therapy units (ITUs), largely due to advances in critical care that enable patients to be kept alive for extended periods. Death in the ITU now generally follows an EOL decision, which can pose ethical, emotional, and practical challenges. Our approach to such issues should be based on adherence to the four bioethical principles -autonomy, beneficence, nonmaleficence, and distributive justice- as well as the concept of proportionate care, and requires careful and effective communication with the whole ITU team, including the patient and their family.

Insights into the effects of subretinal voretigene neparvovec-rzyl in RPE65-associated Leber congenital amaurosis: an 18-Month report.

Objective: Assess safety and effectiveness of subretinal gene replacement therapy at 18 months post treatment.

Design: Retrospective, longitudinal study conducted at the Hospital for Sick Children in Toronto, Canada.

Participants: Patients with bi-allelic RPE65 variants, early onset retinal degeneration, and residual viable retina who underwent voretigene neparvovec r-zyl gene replacement therapy.

The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery.

A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipidation. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex.

Decision support guided fluid challenges and stroke volume response during high-risk surgery: a post hoc analysis of a randomized controlled trial.

Intravenous fluid is administered during high-risk surgery to optimize stroke volume (SV). To assess ongoing need for fluids, the hemodynamic response to a fluid bolus is evaluated using a fluid challenge technique. The Acumen Assisted Fluid Management (AFM) system is a decision support tool designed to ease the application of fluid challenges and thus improve fluid administration during high-risk surgery.

Quantifying tear exchange during rigid contact lens wear using corneoscleral profilometry: A proof of concept study.

Introduction: Tear exchange during contact lens wear is essential for ocular surface integrity, facilitating debris removal, and maintaining corneal metabolism. Fluorophotometry and fluorogram methods are typically used to measure tear exchange, which require hardware modifications to a slit lamp biomicroscope. This manuscript introduces an alternative method using a corneoscleral profilometer, the Eye Surface Profiler (ESP), to quantify tear exchange during corneal and scleral rigid lens wear by assessing fluorescence intensity changes over time.

Prevalence of and risk factors for osteoporosis and fragility fracture in adults with cerebral palsy: A systematic review.

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors.

Safety and efficacy of trifluridine/tipiracil +/- bevacizumab plus XB2001 (anti-IL-1α antibody): a single-center phase 1 trial.

In the tumour microenvironment, IL-1α promotes neoangiogenesis, matrix remodelling, tumour proliferation, chemoresistance, and metastases. Highly expressed in human colorectal cancers, IL-1α is associated with poor prognosis. XB2001, a fully human monoclonal antibody neutralizing IL-1α, was evaluated for safety and preliminary efficacy with trifluridine/tipiracil (FTD/TPI) and bevacizumab in metastatic colorectal cancer patients previously treated with oxaliplatin- and irinotecan-based chemotherapies.