Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms.

The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity.

The Mouse Metabolic Phenotyping Center (MMPC)Live Program was established in 2023 by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high quality phenotyping services for mouse models of diabetes and obesity. Emerging as the next iteration of the MMPC Program which served the biomedical research community for 20 years (2001-2021), MMPCLive is designed as an outwardly-facing consortium of service cores that collaborate to provide reduced-cost consultation and metabolic, physiologic, and behavioral phenotyping tests on live mice for U.S.

Multiple Options: How to Choose Therapy in Frontline Metastatic Melanoma.

Purpose Of Review: Given the rapid development of multiple targeted and immune therapies for patients with advanced melanoma, it can be challenging to select a therapy based on currently available data. This review aims to provide an overview of frontline options for metastatic melanoma, with practical guidance for selecting a treatment regimen.

Recent Findings: Recently reported data from randomized trials suggests that the majority of patients with unresectable melanoma should receive a PD-1 checkpoint inhibitor as part of their first line therapy, irrespective of BRAF mutation status.

Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis.

Horizontal transmission of gut microbiota attenuates mortality in lung fibrosis.

Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma, resulting in loss of physiological homeostasis, respiratory failure, and death. The immune response in pulmonary fibrosis is dysregulated.

Effects of Isoflurane Anesthesia on C57BL/6J Pups after Cervical Dislocation of Dams.

Inhalant anesthesia is routinely used for cesarian section in many animal species, allowing the safe delivery of neonates and smooth recovery of dams. However, in mice, inhalant anesthesia in cesarean section may be avoided due to fear of negative health effects on retrieved pups. This study compared the effects of isoflurane anesthesia on pups after cervical dislocation of conscious and anesthetized dams.

Unravelling specific diet and gut microbial contributions to inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic condition characterized by periods of spontaneous intestinal inflammation and is increasing in industrialized populations. Combined with host genetic predisposition, diet and gut bacteria are thought to be prominent features contributing to IBD, but little is known about the precise mechanisms involved. Here, we show that low dietary fiber promotes bacterial erosion of protective colonic mucus, leading to lethal colitis in mice lacking the IBD-associated cytokine, interleukin-10.

Characteristics and outcomes of surgical patients admitted to an overnight intensive recovery unit: A retrospective observational study.

Postoperative 'enhanced care' models that sit between critical care and ward-based care may allow for more cost-effective and efficient utilisation of resources for high-risk surgical patients. In this retrospective observational study, we describe an overnight intensive recovery model in a tertiary hospital, termed 'recovery high dependency unit', and the characteristics, treatment, disposition at discharge and in-hospital outcomes of patients admitted to this unit. We included all adult patients (≥18 years) admitted to the recovery high dependency unit for at least one hour between July 2017 and June 2020.

Assessment of the Safety and Efficacy of Pre-emptive Use of Extended-release Buprenorphine for Mouse Laparotomy.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR (bup-ER) is an FDA-indexed extended-release buprenorphine formulation that is an alternative to bup-HCl in mice and rats.

Accelerated fetal growth velocity across the third trimester is associated with increased shoulder dystocia risk among fetuses who are not large-for-gestational-age: A prospective observational cohort study.

Objective: To investigate whether fetuses with accelerated third trimester growth velocity are at increased risk of shoulder dystocia, even when they are not large-for-gestational-age (LGA; estimated fetal weight (EFW) >95th centile).

Methods: Fetal growth velocity and birth outcome data were prospectively collected from 347 nulliparous women. Each had blinded ultrasound biometry performed at 28 and 36 weeks' gestation.

A multicenter characterization of hepatitis associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) predispose patients to immune-related adverse events (irAEs). Although hepatitis is a potentially lethal toxicity, the timing and outcomes have not been well described. In this retrospective study, patients from six international institutions were included if they were treated with ICIs and developed immune-related hepatitis.

Reduced growth velocity from the mid-trimester is associated with placental insufficiency in fetuses born at a normal birthweight.

Background: Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight < 10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ≥ 10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants.

A Review of Immune-Mediated Adverse Events in Melanoma.

The use of checkpoint inhibitor-based immunotherapy has transformed the treatment landscape for melanoma as well as many other cancer types. With the ability to potentiate tumor-specific immune responses, these agents can result in durable tumor control. However, this activation of the immune system can lead to a unique constellation of side effects, distinct from other cancer therapies, collectively termed immune-mediated adverse events (irAEs).

Protons and High-Linear Energy Transfer Radiation Induce Genetically Similar Lymphomas With High Penetrance in a Mouse Model of the Aging Human Hematopoietic System.

Purpose: Humans are exposed to charged particles in different scenarios. The use of protons and high-linear energy transfer (LET) in cancer treatment is steadily growing. In outer space, astronauts will be exposed to a mixed radiation field composed of both protons and heavy ions, in particularly the long-term space missions outside of earth's magnetosphere.

A review of cancer immunotherapy toxicity.

Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action.

Soluble FAS ligand is not required for pancreatic islet inflammation or beta-cell destruction in non-obese diabetic mice.

CD8 T cells play a central role in beta-cell destruction in type 1 diabetes. CD8 T cells use two main effector pathways to kill target cells, perforin plus granzymes and FAS ligand (FASL). We and others have established that in non-obese diabetic (NOD) mice, perforin is the dominant effector molecule by which autoreactive CD8 T cells kill beta cells.

Surgical treatment of spontaneous endometriosis in rhesus macaques (): 11 cases (2007-2011).

To determine long-term outcome for rhesus macaques () with endometriosis that underwent surgical treatment and identify factors potentially associated with long-term outcome. Retrospective case series. 11 female rhesus macaques.

Relative Validity and Reproducibility of a Food Frequency Questionnaire to Assess Nutrients and Food Groups of Relevance to the Gut Microbiota in Young Children.

Dietary fiber is an important nutrient for the gut microbiota, with different fiber fractions having different effects. The aim of this study was to determine the relative validity and reproducibility of a food frequency questionnaire (EAT5 FFQ) for measuring intake of fiber, and low and high fiber foods, in studies examining diet and gut microbiota in young children. One hundred parents of 5-year old children completed the 123-item EAT5 FFQ on two occasions four weeks apart.

Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure.

Cancer-causing genome instability is a major concern during space travel due to exposure of astronauts to potent sources of high-linear energy transfer (LET) ionizing radiation. Hematopoietic stem cells (HSCs) are particularly susceptible to genotoxic stress, and accumulation of damage can lead to HSC dysfunction and oncogenesis. Our group recently demonstrated that aging human HSCs accumulate microsatellite instability coincident with loss of MLH1, a DNA Mismatch Repair (MMR) protein, which could reasonably predispose to radiation-induced HSC malignancies.

Extracorporeal membrane oxygenation retrieval factors and survival to intensive care unit discharge.

Objective: Audit of extracorporeal membrane oxygenation (ECMO) retrieval service operating in Victoria, Australia, regarding retrieval factors and patient survival to intensive care unit (ICU) discharge.

Methods: Retrospective cohort analysis of Adult Retrieval Victoria ECMO retrievals with subsequent ICU admission (n = 88) from January 2014 to December 2017.

Results: Complications occurring during veno-arterial ECMO transfer have significant association with decreased survival to ICU discharge (P = 0.