Combinatorial chloride and calcium channelopathy in myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) involves misregulated alternative splicing for specific genes. We used exon or nucleotide deletion to mimic altered splicing of genes central to muscle excitation-contraction coupling processes in mice. Mice with forced-skipping of exon 29 in Ca1.

Synthetic Cell-Based Immunotherapies for Neurologic Diseases.

The therapeutic success and widespread approval of genetically engineered T cells for a variety of hematologic malignancies spurred the development of synthetic cell-based immunotherapies for CNS lymphoma, primary brain tumors, and a growing spectrum of nononcologic disease conditions of the nervous system. Chimeric antigen receptor effector T cells bear the potential to deplete target cells with higher efficacy, better tissue penetration, and greater depth than antibody-based cell depletion therapies. In multiple sclerosis and other autoimmune disorders, engineered T-cell therapies are being designed and currently tested in clinical trials for their safety and efficacy to eliminate pathogenic B-lineage cells.

Incidence, risk factors, and burden of incisional hernia repair after abdominal surgery in France: a nationwide study.

Purpose: Incisional hernias are common after laparotomies. The aims of this study were to assess the rate of incisional hernia repair after abdominal surgery, recurrence rate, hospital costs, and risk factors, in France.

Methods: This national, retrospective, longitudinal, observational study was based on the exhaustive hospital discharge database (PMSI).

Comparing Patient-Reported Outcomes Among Anti-TNF Experienced Patients With Ulcerative Colitis Initiating Vedolizumab Versus Tofacitinib.

Background: Primary and secondary nonresponse to anti-tumor necrosis factor (TNF) therapy is common in patients with ulcerative colitis (UC), yet limited research has compared the effectiveness of subsequent biological therapy.

Objective: We sought to compare the effectiveness of vedolizumab and tofacitinib in anti-TNF experienced patients with UC, focusing on patient-prioritized patient-reported outcomes (PROs).

Methods: We conducted a prospective cohort study nested within the Crohn's & Colitis Foundation's IBD Partners and SPARC IBD initiatives.

Clinical analysis of EV-Fingerprint to predict grade group 3 and above prostate cancer and avoid prostate biopsy.

Background: There is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen-specific risk calculators. We determined the accuracy of the blood-based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies.

Methods: This study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study.

Visceral Adiposity Independently Predicts Time to Flare in Inflammatory Bowel Disease but Body Mass Index Does Not.

Background: Obesity is associated with progression of inflammatory bowel disease (IBD). Visceral adiposity may be a more meaningful measure of obesity compared with traditional measures such as body mass index (BMI). This study compared visceral adiposity vs BMI as predictors of time to IBD flare among patients with Crohn's disease and ulcerative colitis.

The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms.

A minimized version of complement factor H (FH), designated mini-FH, was previously engineered combining the N-terminal regulatory domains (short consensus repeat [SCR]1-4) and C-terminal host-surface recognition domains (SCR19-20) of the parent molecule. Mini-FH conferred enhanced protection, as compared with FH, in an ex vivo model of paroxysmal nocturnal hemoglobinuria driven by alternative pathway dysregulation. In the current study, we tested whether and how mini-FH could block another complement-mediated disease, namely periodontitis.

Suppression of Lung Oxidative Stress, Inflammation, and Fibrosis following Nitrogen Mustard Exposure by the Selective Farnesoid X Receptor Agonist Obeticholic Acid.

Nitrogen mustard (NM) is a cytotoxic vesicant known to cause pulmonary injury that can progress to fibrosis. NM toxicity is associated with an influx of inflammatory macrophages in the lung. Farnesoid X receptor (FXR) is a nuclear receptor involved in bile acid and lipid homeostasis that has anti-inflammatory activity.

[Nausea and vomiting after chemotherapy: an ongoing problem for patients].

Despite advances in the prevention and management of chemotherapy-induced nausea and vomiting (CINV), these side effects remain among the most distressing for patients. We discuss the systematic review and meta-analysis by Patel et al (2022) evaluating effective and safe interventions to prevent acute phase CINV in adult and pediatric patients. With the advent of newer antiemetics during the last few decades, the incidence of CINV has improved especially for patients receiving highly emetogenic chemotherapy.

Development and Validation of Claims-Based Definitions to Identify Incident and Prevalent Inflammatory Bowel Disease in Administrative Healthcare Databases.

Background: To facilitate inflammatory bowel disease (IBD) research in the United States, we developed and validated claims-based definitions to identify incident and prevalent IBD diagnoses using administrative healthcare claims data among multiple payers.

Methods: We used data from Medicare, Medicaid, and the HealthCore Integrated Research Database (Anthem commercial and Medicare Advantage claims). The gold standard for validation was review of medical records.

Autophagy pathways in autoimmune diseases.

Autophagy comprises a growing range of cellular pathways, which occupy central roles in response to energy deprivation, organelle turnover and proteostasis. Over the years, autophagy has been increasingly linked to governing several aspects of immunity, including host defence against various pathogens, unconventional secretion of cytokines and antigen presentation. While canonical autophagy-mediated antigen processing in thymic epithelial cells supports the generation of a self-tolerant CD4 T cell repertoire, mounting evidence suggests that deregulated autophagy pathways contribute to or sustain autoimmune responses.

Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study.

Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h.

Terminal Complement Activation Is Induced by Factors Released from Endplate Tissue of Disc Degeneration Patients and Stimulates Expression of Catabolic Enzymes in Annulus Fibrosus Cells.

Terminal complement complex (TCC) deposition was identified in human degenerated discs. To clarify the role of terminal complement activation in disc degeneration (DD), we investigated respective activating mechanisms and cellular effects in annulus fibrosus (AF) cells. Isolated cells from human AF, nucleus pulposus (NP), and endplate (EP) were stimulated with human serum alone or with zymosan and treated with either the C3 inhibitor Cp40 or the C5 antibody eculizumab.

A Regional Analysis of Low Back Pain Treatments in the Military Health System.

Study Design: Claims-based analysis of cohorts of TRICARE Prime beneficiaries.

Objective: To compare rates of utilization of 5 low back pain (LBP) treatments (physical therapy (PT), manual therapy, behavioral therapies, opioid, and benzodiazepine prescription) across catchment areas and assess their association with the resolution of LBP.

Summary Of Background: Guidelines support focusing on nonpharmacologic management for LBP and reducing opioid use.

Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection.

Bevacizumab-bvzr (Zirabev), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.

Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study.

Background: Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD.

Clustering and prediction of disease progression trajectories in Huntington's disease: An analysis of Enroll-HD data using a machine learning approach.

Introduction: Huntington's disease (HD) is a rare neurodegenerative disease characterized by cognitive, behavioral and motor symptoms that progressively worsen with time. Cognitive and behavioral signs of HD are generally present in the years prior to a diagnosis; however, manifest HD is typically assessed by genetic confirmation and/or the presence of unequivocal motor symptoms. Nevertheless, there is a large variation in symptom severity and rate of progression among individuals with HD.

COVID-19 morbidity in lower versus higher income populations underscores the need to restore lost biodiversity of eukaryotic symbionts.

The avoidance of infectious disease by widespread use of 'systems hygiene', defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this 'biota alteration' leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.

EGFR Pathway Expression Persists in Recurrent Glioblastoma Independent of Amplification Status.

Background: Glioblastoma mortality is driven by tumour progression or recurrence despite administering a therapeutic arsenal consisting of surgical resection, radiation, and alkylating chemotherapy. The genetic changes underlying tumour progression and chemotherapy resistance are poorly understood.

Methods: In this study, we sought to define the relationship between EGFR amplification status, EGFR mRNA expression, and EGFR pathway activity.

Comparison of robotic-assisted minimally invasive esophagectomy versus minimally invasive esophagectomy: A propensity-matched study from a single high-volume institution.

Objective: Robotic-assisted minimally invasive esophagectomy accounts for a growing proportion of esophagectomies, potentially due to improved technical capabilities simplifying the challenging aspects of standard minimally invasive esophagectomy. However, there is limited evidence directly comparing both operations. The objective is to evaluate the short-term and long-term outcomes of robotic-assisted minimally invasive esophagectomy in comparison with the minimally invasive esophagectomy approach for patients with esophageal cancer over a 7-year period at a high-volume center.

Quantitative measurements of intraocular structures and microinjection bleb volumes using intraoperative optical coherence tomography.

Intraoperative optical coherence tomography (OCT) systems provide high-resolution, real-time visualization and/or guidance of microsurgical procedures. While the use of intraoperative OCT in ophthalmology has significantly improved qualitative visualization of surgical procedures inside the eye, new surgical techniques to deliver therapeutics have highlighted the lack of quantitative information available with current-generation intraoperative systems. Indirect viewing systems used for retinal surgeries introduce distortions into the resulting OCT images, making it particularly challenging to make calibrated quantitative measurements.

Education in Focused Lung Ultrasound Using Gamified Immersive Virtual Reality: A Randomized Controlled Study.

Focused lung ultrasound (FLUS) has high diagnostic accuracy in many common conditions seen in a variety of emergency settings. Competencies are essential for diagnostic success and patient safety but can be challenging to acquire in clinical environments. Immersive virtual reality (IVR) offers an interactive risk-free learning environment and is progressing as an educational tool.