A carnitine transporter at the blood-brain barrier modulates sleep via glial lipid metabolism in .

To regulate brain function, peripheral compounds must traverse the blood-brain barrier (BBB), an interface between the brain and the circulatory system. To determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen for genes affecting sleep in . We observed reduced sleep with knockdown of solute carrier , a carnitine transporter, as determined by isotope flux.

A Prognostic Model to Predict Hearing Recovery in Patients With Idiopathic Sudden Onset Sensorineural Hearing Loss.

Importance: The prognosis of idiopathic sudden onset sensorineural hearing loss (iSSNHL) is uncertain, which creates challenges in clinical decision-making for ear, nose, and throat (ENT) physicians and adds to the burden of the condition experienced by patients.

Objective: To develop and internally validate a prognostic model for hearing recovery among patients with iSSNHL to support ENT surgeons in making informed and individualized treatment decisions.

Design, Settings, And Participants: This prognostic study and model used cohort data from the Sudden Onset Sensorineural Hearing Loss study, which included 812 patients (age ≥16 years) diagnosed with iSSNHL at 76 National Health Service ENT departments in the UK from December 2019 to May 2022.

Manometric findings in children with eosinophilic esophagitis and persistent post-remission dysphagia.

Objectives: Dysphagia is a frequent symptom of active eosinophilic esophagitis (EoE), but at times it persists despite attaining histologic healing and lack of fibro-stenotic changes. We aimed to describe the manometric findings in this subset of patients.

Methods: A retrospective review of charts between 2013 and 2023 at a tertiary pediatric gastroenterology center, treating roughly 1500 EoE patients per year.

Chronic hyperglycemia aggravates lung function in a -Tg murine model.

Cystic fibrosis-related diabetes (CFRD), the most common comorbidity in cystic fibrosis (CF), leads to increased mortality by accelerating the decline in lung function. Tg transgenic mice overexpressing the epithelial sodium channel β subunit exhibit spontaneous CF-like lung disease, including airway mucus obstruction and chronic inflammation. Here, we established a chronic CFRD-like model using Tg mice made diabetic by injection of streptozotocin (STZ).

Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: In eosinophilic gastrointestinal diseases, the role of eosinophils in disease pathogenesis and the effect of eosinophil depletion on patient outcomes are unclear. Benralizumab, an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α, might eliminate gastric tissue eosinophils and improve outcomes in eosinophilic gastritis. We aimed to assess the efficacy and safety of benralizumab in patients with eosinophilic gastritis.

The α-dystrobrevins play a key role in maintaining the structure and function of the extracellular matrix-significance for protein elimination failure arteriopathies.

The extracellular matrix (ECM) of the cerebral vasculature provides a pathway for the flow of interstitial fluid (ISF) and solutes out of the brain by intramural periarterial drainage (IPAD). Failure of IPAD leads to protein elimination failure arteriopathies such as cerebral amyloid angiopathy (CAA). The ECM consists of a complex network of glycoproteins and proteoglycans that form distinct basement membranes (BM) around different vascular cell types.

Castaneroxy A From the Leaves of Inhibits Virulence in .

Methicillin-resistant (MRSA) represents one of the most serious infectious disease concerns worldwide, with the CDC labeling it a "serious threat" in 2019. The current arsenal of antibiotics works by targeting bacterial growth and survival, which exerts great selective pressure for the development of resistance. The development of novel anti-infectives that inhibit quorum sensing and thus virulence in MRSA has been recurrently proposed as a promising therapeutic approach.

Cruciferous vegetables () confer cytoprotective effects in intestines.

Varieties and cultivars of the cruciferous vegetable are widely presumed to elicit positive influences on mammalian health and disease, particularly related to their indole and sulforaphane content. However, there is a considerable gap in knowledge regarding the mechanisms whereby these plant-derived molecules elicit their beneficial effects on the host. In this study, we examined the chemical variation between varieties and evaluated their capacity to both activate Nrf2 in the intestine and elicit cytoprotection.

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective.

Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s' golden age of discovery.

Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants.

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation.

Objective: We hypothesized that very early onset EoE (V-EoE) would be enriched for early-life and genetic factors and have worse presentation and prognosis than later-onset pediatric EoE (L-EoE).

Methods: We conducted a single-site, retrospective review comparing patients diagnosed at age 12 months or less (V-EoE, n = 57) and age 14 to 18 years (L-EoE, n = 70).

The student-centered classroom: the new gut feeling.

A student-centered, interactive course-based undergraduate research experience (CURE) was implemented in a microbiology course in order to provide an authentic research experience and to stimulate student interest and improve understanding of fermentation, probiotics, the human microbiome and related topics. Students were immersed in the scientific process as they used fundamental techniques to investigate the probiotic composition of a fermented milk beverage, kefir-an unknown question with no predetermined outcomes. In order to assess the benefits and effect of this learning experience on the students, pre- and post-study surveys were administered using Qualtrics.

Fermentation revival in the classroom: investigating ancient human practices as CUREs for modern diseases.

A course-based undergraduate research experience (CURE) was designed to integrate key microbiological principles and techniques into an authentic research experience in a classroom setting and was implemented in an undergraduate microbiology laboratory course. Students conducted a 6-week study in order to determine the identity and quantity of unique probiotic species from various types of kefir. This course module followed an inquiry-based pedagogical approach in which students use the scientific process to investigate an unknown question with no predetermined outcome.

Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery.

The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated.

Neurologic Complications due to Severe Micronutrient Deficiencies in an American Adolescent.

Micronutrient deficiencies are a major global health problem but are less common in developed nations. If left unidentified and untreated, micronutrient deficiencies can lead to serious, sometimes irreversible, sequelae such as with vitamin A deficiency and vision loss. Providers should recognize these issues not only in chronically ill and hospitalized patients but in those with non-illness-related malnutrition due to parent/child-selected restricted diets.

Targeting ESKAPE pathogens with anti-infective medicinal plants from the Greater Mpigi region in Uganda.

Antibiotic resistance poses one of the greatest threats to global health today; conventional drug therapies are becoming increasingly inefficacious and limited. We identified 16 medicinal plant species used by traditional healers for the treatment of infectious and inflammatory diseases in the Greater Mpigi region of Uganda. Extracts were evaluated for their ability to inhibit growth of clinical isolates of multidrug-resistant ESKAPE pathogens.

Effect of a Practice-wide Anti-TNF Proactive Therapeutic Drug Monitoring Program on Outcomes in Pediatric Patients with Inflammatory Bowel Disease.

Background: Reports on the feasibility and effectiveness of translating proactive, antitumor necrosis factor (TNF) therapeutic drug monitoring (TDM) for inflammatory bowel disease into practice-wide quality improvement (QI) are lacking. We aimed to determine whether a TDM QI program improved outcomes at a large academic pediatric gastroenterology practice.

Methods: We instituted local anti-TNF TDM practice guidelines to proactively monitor and optimize drug levels (goal >5 μg/mL).

Triterpenoid acids isolated from Schinus terebinthifolia fruits reduce Staphylococcus aureus virulence and abate dermonecrosis.

Staphylococcus aureus relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of "430D-F5", a refined extract derived from the fruits of Schinus terebinthifolia, a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid (1), 3-oxotirucalla-7,24Z-dien-26-oic acid (2) and 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid (3).

Genomic analysis of variability in Delta-toxin levels between strains.

Background: The delta-toxin (δ-toxin) of is the only hemolysin shown to cause mast cell degranulation and is linked to atopic dermatitis, a chronic inflammatory skin disease. We sought to characterize variation in δ-toxin production across strains and identify genetic loci potentially associated with differences between strains.

Methods: A set of 124 strains was genome-sequenced and δ-toxin levels in stationary phase supernatants determined by high performance liquid chromatography (HPLC).