Irreversible Electroporation and β-Glucan Induced Trained Innate Immunity for the Treatment of Pancreatic Ductal Adenocarcinoma: A Phase II Study.

Introduction: Irreversible electroporation(IRE) has augmented the effects of certain immunotherapies in pancreatic cancer(PDA). Yeast-derived particulate beta-glucan induces trained innate immunity and has successfully reduces murine PC tumor burden. This is a Phase II study to test the hypothesis that IRE may augment beta-glucan induced trained immunity in patients with PDA.

Study protocol for a Prospective Observational study of Safety Threats and Adverse events in Trauma (PrO-STAT): a pilot study at a level-1 trauma centre in Canada.

Introduction: Traumatic injuries are a significant public health concern globally, resulting in substantial mortality, hospitalisation and healthcare burden. Despite the establishment of specialised trauma centres, there remains considerable variability in trauma-care practices and outcomes, particularly in the initial phase of trauma resuscitation in the trauma bay. This stage is prone to preventable errors leading to adverse events (AEs) that can impact patient outcomes.

Enhancing the Immunotherapeutic Effect by IP-001 and Irreversible Electroporation in Mouse Oligometastatic Models of Pancreatic Adenocarcinoma.

Background: This study aimed to evaluate the immunotherapeutic effect of irreversible electroporation (IRE) and IP-001 in pancreatic adenocarcinoma with metastasis.

Methods: Orthotopic models of pancreatic adenocarcinoma with hepatic oligometastasis were established by implantation of tumor tissues (derived from Pan02 or KPC cells) size 2 mm into the pancreas and left liver lobe in C57BL/6J mice. One week after implantation, the tumor-burden mice were subjected to saline control, IRE, IP-001, and IRE+IP-001.

Tracing the transmission of carbapenem-resistant Enterobacterales at the patient: ward environmental nexus.

Introduction: Colonisation and infection with Carbapenem-resistant Enterobacterales (CRE) in healthcare settings poses significant risks, especially for vulnerable patients. Genomic analysis can be used to trace transmission routes, supporting antimicrobial stewardship and informing infection control strategies. Here we used genomic analysis to track the movement and transmission of CREs within clinical and environmental samples.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging underrepresented minority (URM) students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb (LoaL), an orthopaedic research outreach module to teach URM high school students about orthopaedic research.

Compromised macrophages contribute to progression of MASH to hepatocellular carcinoma in FGF21KO mice.

Metabolic dysfunction-associated steatohepatitis is well accepted as a potential precursor of hepatocellular carcinoma. Previously, we reported that fibroblast growth factor 21 (FGF21) revealed a novel anti-inflammatory activity via inhibiting the TLR4-IL-17A signaling, which could be a potential anticarcinogenetic mechanism to prevent to MASH-HCC transition. Here, we set out to determine whether FGF21 has a major impact on Kupffer cells' (KCs) ability during MASH-HCC transition.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research.

Incidents and patterns of among athletes in the USA from 1982 to 2023.

Introduction: is a rare event that occurs following blunt, non-penetrating trauma to the chest, precipitating a ventricular arrhythmia. requires immediate medical attention through cardiopulmonary resuscitation and defibrillation, often resulting in death. is most common condition among young male athletes.

Enhancing patient safety in trauma: Understanding adverse events, assessment tools, and the role of trauma video review.

Objectives: This study aimed to investigate adverse events (AEs) in trauma resuscitation, evaluate contributing factors, and assess methods, such as trauma video review (TVR), to mitigate AEs.

Background: Trauma remains a leading cause of global mortality and morbidity, necessitating effective trauma care. Despite progress, AEs during trauma resuscitation persist, impacting patient outcomes and the healthcare system.

Matrix metalloproteinase-9 deficiency confers resilience in fibrodysplasia ossificans progressiva in a man and mice.

Single case studies of extraordinary disease resilience may provide therapeutic insight into conditions for which no definitive treatments exist. An otherwise healthy 35-year-old man (patient-R) with the canonical pathogenic ACVR1R206H variant and the classic congenital great toe malformation of fibrodysplasia ossificans progressiva (FOP) had extreme paucity of post-natal heterotopic ossification (HO) and nearly normal mobility. We hypothesized that patient-R lacked a sufficient post-natal inflammatory trigger for HO.

Catastrophic injuries and exertional medical events in lacrosse among youth, high school and collegiate athletes: longitudinal surveillance over four decades (1982-2020).

Objective: To determine the incidence rates (IRs) of catastrophic injuries and exertional medical events in lacrosse athletes.

Methods: Catastrophic injuries and exertional medical events in lacrosse in the US among youth or amateur, high school and college athletes were analysed from the National Center for Catastrophic Sport Injury Research (NCCSIR) database from 1982/83 to 2019/20. Frequencies, IRs per 100,000 athlete-seasons (AS) with 95% confidence intervals (CIs), and incidence rate ratios (IRRs) with 95% CIs were calculated.

Strategies to support maternal and early childhood wellness: insight from parent and provider qualitative interviews during the COVID-19 pandemic.

Objectives: The COVID-19 pandemic resulted in rapid changes to the delivery of maternal and newborn care. Our aim was to gain an understanding from parents and healthcare professionals (HCPs) of how the pandemic and associated public health restrictions impacted the peripartum and postpartum experience, as well as longer-term health and well-being of families.

Design: Qualitative study through focus groups.

Polypeptide Substrate Accessibility Hypothesis: Gain-of-Function R206H Mutation Allosterically Affects Activin Receptor-like Protein Kinase Activity.

Although structurally similar to type II counterparts, type I or activin receptor-like kinases (ALKs) are set apart by a metastable helix-loop-helix (HLH) element preceding the protein kinase domain that, according to a longstanding paradigm, serves passive albeit critical roles as an inhibitor-to-substrate-binding switch. A single recurrent mutation in the codon of the penultimate residue, directly adjacent the position of a constitutively activating substitution, causes milder activation of ACVR1/ALK2 leading to sporadic heterotopic bone deposition in patients presenting with fibrodysplasia ossificans progressiva, or FOP. To determine the protein structural-functional basis for the gain of function, R206H mutant, Q207D (aspartate-substituted caALK2) and HLH subdomain-truncated (208 Ntrunc) forms were compared to one another and the wild-type enzyme through in vitro kinase and protein-protein interaction analyses that were complemented by signaling read-out (p-Smad) in primary mouse embryonic fibroblasts and S2 cells.

Reduced GS Domain Serine/Threonine Requirements of Fibrodysplasia Ossificans Progressiva Mutant Type I BMP Receptor ACVR1 in the Zebrafish.

Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic condition characterized by altered skeletal development and extraskeletal bone formation. All cases of FOP are caused by mutations in the type I bone morphogenetic protein (BMP) receptor gene ACVR1 that result in overactivation of the BMP signaling pathway. Activation of the wild-type ACVR1 kinase requires assembly of a tetrameric type I and II BMP receptor complex followed by phosphorylation of the ACVR1 GS domain by type II BMP receptors.

The Relationship Between Stress and Sleep Sufficiency in the Context of Varied Workplace Social Support.

Objective: Sufficient sleep is essential for well-being. We examined the relationship between work-related social support, work stress, and sleep sufficiency, predicting that workers with higher social support would report higher sleep sufficiency across varying levels of work stress.

Methods: The data set analyzed in the present study included 2213 workers from approximately 200 small (<500 employees) businesses in high, medium, and low hazard industries across Colorado.

Multifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein-1 (LMP-1).

A 54-year-old man with a history of unimelic, post-traumatic multifocal heterotopic ossification (HO) and normal genetic analysis of ACVR1 and GNAS had variants of unknown significance (VUS) in PDLIM-7 (PDZ and LIM Domain Protein 7), the gene encoding LMP-1 (LIM Mineralization Protein-1), an intracellular protein involved in the bone morphogenetic protein (BMP) pathway signaling and ossification. In order to determine if the LMP-1 variants were plausibly responsible for the phenotype observed, a series of in vitro experiments were conducted. C2C12 cells were co-transfected with a BMP-responsive reporter as well as the LMP-1 wildtype (wt) construct or the LMP-1 or the LMP-1 constructs (herein designated as LMP-161 or LMP-181) corresponding to the coding variants detected in the patient.

Consensus Statement No. 434: Simulation in Obstetrics and Gynaecology.

Objective: To provide a comprehensive and current overview of the evidence for the value of simulation for education, team training, patient safety, and quality improvement in obstetrics and gynaecology, to familiarize readers with principles to consider in developing a simulation program, and to provide tools and references for simulation advocates.

Target Population: Providers working to improve health care for Canadian women and their families; patients and their families.

Outcomes: Simulation has been validated in the literature as contributing to positive outcomes in achieving learning objectives, maintaining individual and team competence, and enhancing patient safety.

Defining ferritin clinical decision limits to improve diagnosis and treatment of iron deficiency: A modified Delphi study.

Background: Iron deficiency is highly prevalent worldwide and is an issue of health inequity. Despite its high prevalence, uncertainty on the clinical applicability and evidence-base of iron-related lab test cut-offs remains. In particular, current ferritin decision limits for the diagnosis of iron deficiency may not be clinically appropriate nor scientifically grounded.