PCDH15 dual-AAV gene therapy for deafness and blindness in Usher syndrome type 1F models.

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore an approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual-adeno-associated virus (dual-AAV) strategy to deliver the full-length PCDH15 coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION).

Objective: To investigate whether there is an association between semaglutide and risk of NAION.

Design, Setting, And Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.

Insights into the diversity and survival strategies of soil bacterial isolates from the Atacama Desert.

The Atacama Desert, the driest, with the highest radiation, and one of the most ancient deserts in the world, is a hostile environment for life. We have a collection of 74 unique bacterial isolates after cultivation and confirmation by 16S rRNA gene sequencing. Pigmentation, biofilm formation, antimicrobial production against MG1655 and HG003, and antibiotic resistance were assessed on these isolates.

PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.

Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a stereocilia protein required for normal hearing in mice, and for the formation of the transient stereocilia surface coat, expressed during early postnatal development. While the function of the stereocilia coat remains unclear, growing evidence supports PKHD1L1 as a human deafness gene.

The possible clinical utility of the alcohol biomarker phosphatidylethanol for managing suspected alcohol withdrawal in hospitalized patients: A case report.

Background And Objectives: The decision to initiate pharmacotherapy for alcohol withdrawal is typically based on examining self-reported use of alcohol and symptoms of withdrawal. Phosphatidylethanol (PEth) is a biomarker that could aim in clinical decision-making in withdrawal management.

Methods: This report describes three cases highlighting the potential clinical utility of PEth in caring for individuals at risk for alcohol withdrawal.

PCDH15 Dual-AAV Gene Therapy for Deafness and Blindness in Usher Syndrome Type 1F.

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore a novel approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual adeno-associated virus (AAV) strategy to deliver the full-length PCDH15 coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice.

The Incidence and Disparities in Use of Stigmatizing Language in Clinical Notes for Patients With Substance Use Disorder.

Objective: The language used to describe people with substance use disorder impacts stigma and influences clinical decision making. This study evaluates the presence of stigmatizing language (SL) in clinical notes and detects patient- and provider-level differences.

Methods: All free-text notes generated in a large health system for patients with substance-related diagnoses between December 2020 and November 2021 were included.

"But I didn't drink!": What to do with discordant phosphatidylethanol results.

Liver transplantation (LT) teams must be adept at detecting, evaluating, and treating patients' alcohol use, given its prominence among psychological and behavioral phenomena which cause and contribute to liver diseases. Phosphatidylethanol (PEth) is a highly useful alcohol biomarker increasingly recommended for routine use in hepatology and LT. PEth is unique among alcohol biomarkers because of its wide detection window, high sensitivity and specificity, and the correlation of its numerical value with different patterns of alcohol use.

Teachers' online preparedness in times of crises: trends from Norway and US.

The closing of schools world-wide in March 2020 due to the COVID-19 pandemic resulted in a rapid and unexpected shift from predominantly in-person teaching to online teaching practices. As teacher educators in the field of educational technology, we wondered about the preparedness of teachers for making the transition to fully online environments. Through an internationally distributed survey consisting of predominantly open-ended questions, we captured teachers' perceptions of this transition.

Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F.

Usher syndrome type 1 F (USH1F), caused by mutations in the protocadherin-15 gene (PCDH15), is characterized by congenital deafness, lack of balance, and progressive blindness. In hair cells, the receptor cells of the inner ear, PCDH15 is a component of tip links, fine filaments which pull open mechanosensory transduction channels. A simple gene addition therapy for USH1F is challenging because the PCDH15 coding sequence is too large for adeno-associated virus (AAV) vectors.

Patients' experiences with continuation or discontinuation of buprenorphine before painful procedures: A brief report.

Background And Objectives: Patients with opioid use disorder may be asked by their clinicians to discontinue maintenance buprenorphine treatment before surgical operations due to concerns that buprenorphine will interfere with acute pain management. However, discontinuation of buprenorphine may not be well tolerated or safe for all patients. We, therefore, administered a survey to better understand the experiences of patients on buprenorphine treatment who had previously undergone painful procedures and had their buprenorphine maintenance treatment either continued or discontinued before the procedure.

Correlation of Superlattice Cross-Plane Thermal Conductivity with Emission Wavelength in InAlAs/InGaAs Quantum Cascade Lasers.

The low cross-plane thermal conductivity of quantum cascade lasers (QCLs) is a significant limitation in their Continuous-Wave (CW) performance. Structural parameters such as individual layer thicknesses and interface density vary for QCLs with different target emission wavelengths, and these design parameters are expected to influence the cross-plane thermal conductivity. Though previous works have used theoretical models and experimental data to quantify thermal conductivity, the correlation between target wavelength and thermal conductivity has yet to be reported for QCLs.

Cost-Effectiveness Analysis: Personal Systems Approach in Improving Medication Adherence in Adult Kidney Transplant Patients.

Interventions to improve medication nonadherence in transplantation have recently moved from a focus on motivation and intention, to a focus on person-level quality improvement strategies. These strategies link adherence to established daily routines, environmental cues, and supportive people. The objective of this evaluation was to estimate the cost of implementation and the cost-effectiveness of a person-level intervention shown to increase medication adherence.

Disseminated Mycobacterial Infection as a Sequelae of Bladder Biopsy.

Disseminated infections have been commonly documented in the immunocompromised and patients who undergo treatment for non-muscle invasive bladder cancer with the Bacillus Calmette-Guerin vaccine; however, it was unique to our patient's case that she had no record of receiving vaccination in her native country, was immunocompetent, and had exposure to bovine livestock before immigrating to the United States. A 57-year-old woman with no significant medical history presented with complaints of abdominal pains and yellowing of her skin. Laboratory workup was consistent with cholestatic hepatitis.

Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis.

Background: The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients.

Multidimensional mechanisms of metformin in cancer treatment.

Metformin has been in clinical use for more than half a century, yet its molecular mechanism of action is not entirely understood. Metformin has been shown to have antiproliferative and synergistic effects on various types of cancers. The anticancer effects of metformin are potentially applicable to both diabetic and nondiabetic patients.

Teaching Spiritual and Religious Competencies to Psychiatry Residents: A Scoping and Systematic Review.

Purpose: For many persons worldwide, mental health is inseparably linked with spirituality and religion (S&R), yet psychiatrists have repeatedly expressed doubts regarding their preparedness to address patients' spirituality or religion appropriately. In recent decades, medical educators have developed and implemented curricula for teaching S&R-related competencies to psychiatry residents. The authors reviewed the literature to understand the scope and effectiveness of these educational initiatives.

AAV-S: A versatile capsid variant for transduction of mouse and primate inner ear.

Gene therapy strategies using adeno-associated virus (AAV) vectors to treat hereditary deafnesses have shown remarkable efficacy in some mouse models of hearing loss. Even so, there are few AAV capsids that transduce both inner and outer hair cells-the cells that express most deafness genes-and fewer still shown to transduce hair cells efficiently in primates. AAV capsids with robust transduction of inner and outer hair cells in primate cochlea will be needed for most clinical trials.

Omega 3 Fatty Acids and COVID-19: A Comprehensive Review.

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020.

A Pilot Randomized Controlled Trial Using SystemCHANGE™ Approach to Increase Physical Activity in Older Kidney Transplant Recipients.

Background: Cardiovascular disease is the leading cause of death in kidney transplant recipients. Physical activity after transplant is the most modifiable nonpharmacological factor for improving cardiovascular outcomes. Few studies have tested walking interventions to enhance daily steps and health outcomes in older kidney recipients.

Recruitment of Older Kidney Transplant Recipients to a Longitudinal Study.

Background: Currently, limited information is available regarding selection of the most successful strategies for recruitment of older adult kidney transplant recipients as research participants.

Objective: The aim of this study was to explore multiple modes of recruitment strategies to enroll older kidney transplant recipients in a 1-year longitudinal study.

Methods: We used a feasibility design to explore the following recruitment methods: face-to-face contact in the transplant clinic, paper flyers placed in the transplant clinic, Facebook, an online transplant newsletter, and a university website listing of research studies.

Improving medication adherence and outcomes in adult kidney transplant patients using a personal systems approach: SystemCHANGE™ results of the MAGIC randomized clinical trial.

This study determined if a SystemCHANGE™ intervention was more efficacious than attention control in increasing immunosuppressive medication adherence and improving outcomes in adult kidney transplant recipients during a 6-month intervention phase and subsequent 6-month (no intervention) maintenance phase. The SystemCHANGE™ intervention taught patients to use person-level quality improvement strategies to link adherence to established daily routines, environmental cues, and supportive people. Eighty-nine patients (average age 51.