Principles of gene therapy of the inner ear.

Purpose Of Review: Preclinical auditory research uncovers mechanisms underlying hearing loss and reveals novel therapeutic targets. Inner ear gene therapy offers an attractive alternative to current treatments for deafness. An in-depth understanding of the principles of gene therapy is essential to the design of cochlear gene therapy studies, which must be meticulously selected based on the etiology, pathophysiology, and mechanisms of hearing loss.

AAV-mediated transgene delivery targeting spiral ganglion nonsensory cells.

In-situ neuronal reprogramming in the cochlea through gene therapy offers an avenue to restore hearing loss caused by neuronal damage. One possible source of neuronal conversion is the nonspiral ganglion cells (NSGCs), which include satellite cells, Schwann cells, and otic mesenchyme cells. A major obstacle for this approach is the vector-mediated transgene delivery toward NSGCs.

Targeted spiral ganglion neuron degeneration in parvalbumin-Cre neonatal mice.

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the cochlea; damage to the SGNs leads to irreversible hearing impairment. Mouse models that allow selective SGN degeneration while sparing other cell types in the cochlea are lacking. Here, we investigated a genetic ablation method of the SGN using a Cre-responsive adeno-associated virus (AAV) vector expressing diphtheria toxin subunit-A (DTA).

Mucosal Coverage of Deeply Protruded Implant in the Maxillary Sinus: A Case Report.

Protrusion of the dental implant into the maxillary sinus is known to cause thickening of the sinus mucosa and bacterial sinusitis. However, there are many cases where protruded implants do not cause long-term complications clinically or radiologically. Questions arise about whether the protruding implant was exposed or covered with sinus mucosa.

Evaluation of real-world evidence to assess health outcomes related to deprescribing medications in older adults: an International Society for Pharmacoepidemiology-endorsed systematic review of methodology.

Observational studies using real-world data (RWD) can address gaps in knowledge on deprescribing medications but are subject to methodological issues. Limited data exist on the methods employed to use RWD to measure the effects of deprescribing. To describe methodological approaches used in observational studies of deprescribing medications in older adults, we conducted a systematic review in Medline for observational studies published in English (January 1, 2000, to September 14, 2023) that examined the health effects of medication deprescribing in older adults.

Targeting PLCG2 Suppresses Tumor Progression, Orchestrates the Tumor Immune Microenvironment and Potentiates Immune Checkpoint Blockade Therapy for Colorectal Cancer.

Tumor progression and limited benefits of immune checkpoint blockade (ICB) therapy have been two major challenges in the clinical management of colorectal cancer (CRC). The objective of our research was to explore the role of PLCG2 in CRC progression, tumor microenvironment, and potentiating ICB therapy. Based on bioinformatics analysis and a prospective clinical observational study, the expression, prognostic significance, and clinical relevance of PLCG2 in CRC were unveiled.

Factors Associated With Head and Neck Polytrauma Presentation and Admissions at Emergency Departments of Varying Sizes.

Timely diagnosis of acute head and neck polytrauma presenting to emergency departments (EDs) optimizes outcomes. Since ED capacity influences triage and admission, the authors utilized the National Electronic Injury Surveillance System database to understand how ED size and trauma characteristics affect head and neck polytrauma presentation and admissions. Demographics and injury characteristics from the National Electronic Injury Surveillance System database from 2018 to 2021 were analyzed to delineate factors contributing to polytrauma presence and admission through multivariable logistic regressions.

Deep-learning segmentation to select liver parenchyma for categorizing hepatic steatosis on multinational chest CT.

Unenhanced CT scans exhibit high specificity in detecting moderate-to-severe hepatic steatosis. Even though many CTs are scanned from health screening and various diagnostic contexts, their potential for hepatic steatosis detection has largely remained unexplored. The accuracy of previous methodologies has been limited by the inclusion of non-parenchymal liver regions.

The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach.

Objective: An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis.

Methods: Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life.

Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

Introduction: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings.

Methods: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69).

Laser-Assisted Drug Delivery in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review.

Hypertrophic scars and keloids are the results of an exaggerated healing process and are often associated with significant patient morbidity. Fractional ablative lasers create microchannels in the skin and penetrate into the substance of the scar, inducing a normal healing response in zones of created damage. Focal delivery of scar-modulating agents into the scar through these microchannels-a process termed laser-assisted drug delivery (LADD)-is a promising and developing treatment modality.

Criterion Validation of Tau PET Staging Schemes in Relation to Cognitive Outcomes.

Background: Utilization of NIA-AA Research Framework requires dichotomization of tau pathology. However, due to the novelty of tau-PET imaging, there is no consensus on methods to categorize scans into "positive" or "negative" (T+ or T-). In response, some tau topographical pathologic staging schemes have been developed.

Frailty and uptake of angiotensin receptor neprilysin inhibitor for heart failure with reduced ejection fraction.

Background: Frail older adults may be less likely to receive guideline-directed medical therapy (GDMT)-renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists-for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF.

Methods: Using 2015-2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index.

Neomycin-induced deafness in neonatal mice.

Background: Hearing impairment is a rising public health issue, and current therapeutics fail to restore normal auditory sensation. Animal models are essential to a better understanding of the pathophysiology of deafness and developing therapeutics to restore hearing.

New Methods: Wild-type CBA/CaJ neonatal mice P2-5 were used in this study.

Ingredients of a Natural Oral Nutritional Supplement and Their Role in the Treatment of Osteoarthritis.

Osteoarthritis is a prevalent degenerative disease affecting a large portion of the world's aging population. Currently, nonsteroidal anti-inflammatory drugs and acetaminophen are first-line medications for treating osteoarthritis patients' pain. However, several studies have noted that while these medications control pain they do not halt progressive degeneration and tend to have an unfavorable side-effect profile with prolonged use.

Longitudinal Data Discontinuity in Electronic Health Records and Consequences for Medication Effectiveness Studies.

Electronic health record (EHR) discontinuity (i.e., receiving care outside of the study EHR system), can lead to information bias in EHR-based real-world evidence (RWE) studies.

Diffusion histology imaging differentiates distinct pediatric brain tumor histology.

High-grade pediatric brain tumors exhibit the highest cancer mortality rates in children. While conventional MRI has been widely adopted for examining pediatric high-grade brain tumors clinically, accurate neuroimaging detection and differentiation of tumor histopathology for improved diagnosis, surgical planning, and treatment evaluation, remains an unmet need in their clinical management. We employed a novel Diffusion Histology Imaging (DHI) approach employing diffusion basis spectrum imaging (DBSI) derived metrics as the input classifiers for deep neural network analysis.

Breast cancer treatment-related arm lymphoedema and morbidity: A 6-year experience in an Australian tertiary breast centre.

Aim: Recent surgical de-escalation of the axilla in breast cancer management has led to reduced number of immediate and delayed axillary lymph node dissections (ALND) after sentinel lymph node biopsies (SLNBs). We aim to assess the postoperative impact of SLNB versus immediate and delayed ALND on arm lymphoedema and morbidity.

Methods: A retrospective analysis from a prospectively collected institutional database was performed reviewing the rates of lymphoedema and arm morbidity in terms of shoulder restriction and patient-reported functional deficit in women undergoing axillary surgery for breast cancer between 2013 and 2018.

B3 lesion upgrade rates in a tertiary Australian breast centre: a 8-year experience (2012-2019).

Background: B3 breast lesions identified on core needle biopsy have uncertain malignant potential. Traditional management of these lesions has been surgical excision, but there is growing interest in less invasive and more cost-effective alternatives such as vacuum-assisted excisional biopsy (VAEB). Determining the rate of malignant upgrade for B3 lesions is important as it may identify low-risk lesions where VAEB could be considered.

Diffusion Histology Imaging Combining Diffusion Basis Spectrum Imaging (DBSI) and Machine Learning Improves Detection and Classification of Glioblastoma Pathology.

Purpose: Glioblastoma (GBM) is one of the deadliest cancers with no cure. While conventional MRI has been widely adopted to examine GBM clinically, accurate neuroimaging assessment of tumor histopathology for improved diagnosis, surgical planning, and treatment evaluation remains an unmet need in the clinical management of GBMs.

Experimental Design: We employ a novel diffusion histology imaging (DHI) approach, combining diffusion basis spectrum imaging (DBSI) and machine learning, to detect, differentiate, and quantify areas of high cellularity, tumor necrosis, and tumor infiltration in GBM.

Deep learning with diffusion basis spectrum imaging for classification of multiple sclerosis lesions.

Objective: Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion-defining patterns.

Effectiveness of the GumChucks flossing system compared to string floss for interdental plaque removal in children: a randomized clinical trial.

Flossing, an important oral hygiene skill, is technique-sensitive and challenging for children with developing manual dexterity. GumChucks is a novel flossing device designed to assist children with proper flossing technique. The aim of this study was to assess the efficacy of the GumChucks flossing device compared to string floss (SF).