Identification of a short, single site matriglycan that maintains neuromuscular function in the mouse.

Matriglycan (-1,3-β-glucuronic acid-1,3-α-xylose-) is a polysaccharide that is synthesized on α-dystroglycan, where it functions as a high-affinity glycan receptor for extracellular proteins, such as laminin, perlecan and agrin, thus anchoring the plasma membrane to the extracellular matrix. This biological activity is closely associated with the size of matriglycan. Using high-resolution mass spectrometry and site-specific mutant mice, we show for the first time that matriglycan on the T317/T319 and T379 sites of α-dystroglycan are not identical.

Opioidergic signaling contributes to food-mediated suppression of AgRP neurons.

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR).

A pilot study on our non-traditional, varied writing accountability group for historically excluded and underrepresented persons in STEMM.

Underrepresented faculty have higher burnout rates and lower grant attainment rates when compared with their non-minority counterparts. Many in science, technology, engineering, mathematics, and medicine (STEMM) disciplines, including underrepresented individuals, often have difficulty dedicating time to the writing process, with trainees often being relegated to laboratory tasks in their training years, resulting in a lack of practice in academic writing. Notably, past studies have shown that grant attainment rates of underrepresented individuals are lower than their majority counterparts.

Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.

After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFP cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFP cells.

The Iowa Health Data Resource (IHDR): an innovative framework for transforming the clinical health data ecosystem.

Importance: This manuscript will be of interest to most Clinical and Translational Science Awards (CTSA) as they retool for the increasing emphasis on translational science from translational research. This effort is an extension of the EDW4R work that most CTSAs have done to deploy infrastructure and tools for researchers to access clinical data.

Objectives: The Iowa Health Data Resource (IHDR) is a strategic investment made by the University of Iowa to improve access to real-world health data.

How Many Patients Qualify for Extended Oral Antibiotic Prophylaxis Infection Following Primary and Revision Hip and Knee Arthroplasties?

Extended oral antibiotic prophylaxis (EOAP) has been suggested to reduce rates of periprosthetic joint infection (PJI) postoperatively after total joint arthroplasty (TJA). The purpose of this multicenter study is to define how many TJA patients are considered high risk for developing PJI based on published EOAP criteria and determine whether this status is associated with socioeconomic or demographic factors. All primary and aseptic revision TJAs performed in 2019 at three academic medical centers were reviewed.

Active Gα Mutants Accelerate Breast Tumor Metastasis via the c-Src Pathway.

Constitutively active mutations in the Gα and Gα subunits of heterotrimeric G proteins have been found in various human cancers, including breast cancer, but their precise roles in tumor formation, progression, and metastasis remain poorly understood. This study focused on GαR243H and GαR179C mutants in breast cancer. These mutants alone were insufficient to initiate mammary tumor formation in mice.

Suture Selection to Minimize Postoperative Postinflammatory Hyperpigmentation in Patients With Skin of Color During Mohs Micrographic Surgery.

The effects of suture selection on postinflammatory hyperpigmentation (PIH) in patients with skin of color who have had Mohs micrographic surgery (MMS) are limited. During the COVID-19 pandemic, fast-absorbing gut sutures reduced the need for in-person follow-up visits without increasing the frequency of postoperative complications. Although absorbable gut sutures are popular, they are highly reactive and can induce inflammation in patients with skin of color.

Injectable long-acting ivacaftor-loaded poly (lactide-co-glycolide) microparticle formulations for the treatment of cystic fibrosis: In vitro characterization and in vivo pharmacokinetics in mice.

Optimizing a sustained-release drug delivery system for the treatment of cystic fibrosis (CF) is crucial for decreasing the dosing frequency and improving patients' compliance with the treatment regimen. In the current work, we developed an injectable poly(D,L-lactide-co-glycolide) (PLGA) microparticle formulation loaded with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that increases the open probability of the CFTR anion channel, using a single emulsion solvent evaporation technique. We aimed to study the effect of different parameters on the characteristics of the prepared formulations to select an optimized microparticle formulation to be used in an in vivo pharmacokinetic study in mice.

Accuracy of patient-reported spell duration: A comparative study.

Clinicians rely heavily on patient histories to make medical diagnoses, most of which are inherently subjective and prone to inaccuracies. The aim of this study is to compare the subjective versus objective duration of spells through a retrospective chart review of patients admitted to the epilepsy monitoring unit at our tertiary care medical center. One hundred patients were analyzed.

Tobacco smoke exposure recruits inflammatory airspace monocytes that establish permissive lung niches for .

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to () growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current and never smokers by performing single-cell RNA sequencing (scRNA-seq), flow cytometry, and functional assays.

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension.

Introduction: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable.

Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank.

Background: In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGS ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGS would be negatively associated with remission.

Antibiotic stewardship in Indian palliative care: a single-center retrospective study.

Objective: Characterize antibiotic prescribing behaviors at an Indian palliative care center after the initiation of the Antibiotic Order Form (AOF): an antibiotic stewardship program involving a paper form to track antibiotic use and to provide prescription guidelines.

Design: Retrospective chart review.

Setting: Trivandrum Institute of Palliative Sciences (TIPS) is a palliative care organization in Kerala, India.

Pituitary Crooke Cell Adenoma: Two Cases of an Aggressive Pituitary Adenoma.

Crooke cell adenoma (CCA) is a rare and aggressive subtype of a corticotroph adenoma, which requires lifetime surveillance. There have been 106 cases of CCAs reported in the English literature. We describe 2 cases of CCA, a 48-year-old man and an 84-year-old woman who both presented with binocular diplopia and temple pain.

Awareness with paralysis and symptoms of post-traumatic stress disorder among mechanically ventilated emergency department survivors (ED-AWARENESS-2 Trial): study protocol for a pragmatic, multicenter, stepped wedge cluster randomized trial.

Background: Awareness with paralysis (AWP) is memory recall during neuromuscular blockade (NMB) and can cause significant psychological harm. Decades of effort and rigorous trials have been conducted to prevent AWP in the operating room, where prevalence is 0.1-0.

Implementing a 3 year, longitudinal point of care ultrasound curriculum in an internal medicine residency program.

Purpose: Point-of-care ultrasound (POCUS) is highly utilized in the critical care setting. There is also growing evidence supporting use of POCUS by internal medicine (IM) physicians as an extension of traditional physical diagnostic skills. As part of the newly formed curriculum at our residency program, we performed pre and post curriculum assessment of the residents' ability to acquire focused cardiac, lung, pleural, abdominal and vascular images.

Re-visiting the call for translation of cancer survivorship research: collaborative multidisciplinary approaches to improve translation and dissemination.

Background: The number of cancer survivors in the US is dramatically increasing and survivors are living longer, making the ongoing care and quality of life in this growing population an important public health issue. Although there has been significant progress in cancer survivorship research, gaps in translating this research to real-world settings to benefit survivors remain.

Methods: The number and type of cancer survivorship research activities in past and current projects were gathered in reports and work plans from the Cancer Prevention and Control Research Network (CPCRN).

AgRP neurons encode circadian feeding time.

Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic state and elicit feeding, but the regulation of these neurons across daily timescales is poorly understood. Using a combination of neuron dynamics measurements and timed optogenetic activation in mice, we show that daily AgRP-neuron activity was not fully consistent with existing models of homeostatic regulation.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals.