β-Cell Deletion of Hypoxia-Inducible Factor 1α (HIF-1α) Increases Pancreatic β-Cell Susceptibility to Streptozotocin.

Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic β-cells. Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor which is crucial for cellular responses to low oxygen. Here, we investigate the role of β-cell HIF-1α in β-cell death and diabetes after exposure to multiple low-dose streptozotocin (MLDS).

Variation in Case Exposure During Internal Medicine Residency.

Importance: Variation in residency case exposure affects resident learning and readiness for future practice. Accurate reporting of case exposure for internal medicine (IM) residents is challenging because feasible and reliable methods for linking patient care to residents are lacking.

Objective: To develop an integrated education-clinical database to characterize and measure case exposure variability among IM residents.

The Effect of Ear Covering on Sound Localization and Speech Intelligibility in Operating Room.

Objective: To determine the effect of the surgical bouffant cap on hearing, sound localization, and speech intelligibility in the operating room (OR).

Background: Covering of the ear during surgical procedures has been promoted to prevent surgical site infection (SSI) from ear pathogens. However, the potential impact of ear covering on hearing in the OR has not been studied.

Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma.

Background: The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy.

Methods: We performed a high-throughput, combination chromatin-modifier drug screen against NB cells.

Contrast Enhancement of Cochlea after Direct Microneedle Intracochlear Injection of Gadodiamide through the Round Window Membrane with Minimal Dosage.

Rationale And Objectives: The potential of contrast-enhanced MRI for diagnosing endolymphatic hydrops is limited by long wait times following intravenous (IV) or intratympanic (IT) delivery, high contrast dosages, and inconsistent signal intensity enhancements. This study investigates microneedle-mediated intracochlear (IC) gadodiamide injection for consistent and efficient contrast delivery with minimal contrast dosage.

Materials And Methods: A 100 µm diameter microneedle with 35 µm lumen was used to inject 1 µL of diluted gadodiamide (17.

Hearing Loss and Alzheimer Disease.

Several studies have been done to investigate the role of hearing loss (HL) in cognitive decline. A co-existence of these two conditions has been identified. Recently, thanks to the use of functional MRI and EEG it has been shown that untreated HL can expose patients with cognitive decline to a higher risk of developing Alzheimer Disease (AD).

Navigating a Complex Case of Hypoplastic Right Lung With Bronchiectasis: A Ten-Year Journey.

Unilateral pulmonary hypoplasia (UPH) is a rare congenital disorder that presents rarely in adulthood. Most patients succumb to complications at a young age, and those who survive are rare and susceptible to frequent lifelong pulmonary infections. It has a high infant mortality rate.

Risk of Hearing Loss in Neonates and Toddlers with in Utero Exposure to SARS-CoV-2.

Objective: Given the prevalence of neonatal hearing loss (HL) associated with intrauterine viral exposures, the goal of this study is to provide information on neonatal HL in the context of the COVID-19 pandemic.

Methods: Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. 1007 participants completed the newborn hearing screen as part of routine clinical care (COMBO-EHR cohort) and 555 completed the National Survey of Children's Health (NSCH) at 2 and/or 3 years of age for research purposes (COMBO-RSCH cohort).

Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy.

Hypothesis: Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea.

Background: Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection.

A Case of Atypical Scleroderma Renal Crisis.

Unlabelled: We present the case of a 63-year-old female diagnosed with atypical SSc in the setting of acute SRC. She was undergoing work-up for progressive dyspnoea in the outpatient setting when she was found to have newly diagnosed restrictive lung pathology and worsening renal function, thus prompting acute hospital admission. Given multisystem involvement of the pulmonary and renal systems, the differential diagnosis included autoimmune and connective tissue disorders.

Speech Quality Perception in Unilateral Cochlear Implant Users With Single-Sided Deafness.

Objective: Cochlear implant (CI) users frequently complain about speech quality perception (SQP). In patients undergoing cochlear implantation for single-sided deafness, there is concern that poor SQP from the implanted ear will negatively impact binaural (CI + normal hearing [NH]) SQP. In this study, we investigate if binaural SQP is measurably different than unimplanted NH alone.

Exploring Inner Ear and Brain Connectivity through Perilymph Sampling for Early Detection of Neurological Diseases: A Provocative Proposal.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease.

A Case Report of Primary Derealization Disorder: Diagnostic and Treatment Challenges in a Pakistani Healthcare Setting.

Depersonalization and derealization symptoms are often transient. Recurrent and persistent symptoms can result in a diagnosis of depersonalization/derealization disorder (DDD). Here, we reported a case of a 24-year-old adult male whose presentation was consistent with primary derealization disorder only.

Instrumented insoles for assessment of gait in patients with vestibular schwannoma.

Background: Imbalance and gait disturbances are common in patients with vestibular schwannoma (VS) and can result in significant morbidity. Current methods for quantitative gait analysis are cumbersome and difficult to implement. Here, we use custom-engineered instrumented insoles to evaluate the gait of patients diagnosed with VS.

Mitotic Dysregulation at Tumor Initiation Creates a Therapeutic Vulnerability to Combination Anti-Mitotic and Pro-Apoptotic Agents for MYCN-Driven Neuroblastoma.

amplification occurs in approximately 20-30% of neuroblastoma patients and correlates with poor prognosis. The transgenic mouse model mimics the development of human high-risk neuroblastoma and provides strong evidence for the oncogenic function of MYCN. In this study, we identified mitotic dysregulation as a hallmark of tumor initiation in the pre-cancerous ganglia from mice that persists through tumor progression.

Faecal calprotectin as an inflammatory biomarker to distinguish between bacterial and viral causes of childhood diarrhoea in Indian settings.

Objectives: The purpose of this study was to determine the value of faecal calprotectin (f-CP) in distinguishing between bacterial and viral aetiologies of infective diarrhoea in children attending a tertiary care hospital in Central India.

Methods: Stool samples from children aged 3 months to 10 years who had acute or persistent diarrhoea were processed for microscopy, bacterial culture, and viral antigen detection (Rotavirus and Norovirus). The remaining samples, as well as stool samples from 20 healthy controls, were tested for f-CP using the enzyme linked immunosorbent assay.

Accuracy and Reliability of Different Approaches for the Assessment of Pelvic Floor Muscle Strength: A Systematic Review.

There had been various methods employed for the evaluation of pelvic floor muscle (PFM) strength. The aim of the study was to do a systemic review of these methods for a better understanding of these techniques and to find the best appropriate method. A systemic review of the literature was done using three databases that included: PubMed, Scopus and Web of Science using the keywords "pelvic floor anatomy" and "functional anatomy of pelvic floor muscles" from 1985 to 2022.

Community Health Worker Intervention for Newborns Not Passing Initial Universal Hearing Screening.

Background: Universal newborn hearing screening (UNHS) is effective in identifying newborns with possible hearing loss (HL). Outpatient follow-up for newborns referred after hospital-based screening remains a potential area of improvement. In this study, we evaluate the efficacy of a community health worker (CHW) intervention in promoting adherence to outpatient rescreening for newborns referred after initial UNHS.

The Association of Hearing Loss With Active Music Enjoyment in Hearing Aid Users.

Objective: Hearing aids (HAs) are designed for speech rather than music listening. The impact of HAs on music enjoyment is poorly studied. We examine the effect of HAs on active music enjoyment in individuals with varying levels of hearing loss (HL).

Physiologic Effects of Microneedle-Mediated Intracochlear Dexamethasone Injection in the Guinea Pig.

Objectives: Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM).

Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs.

Hypothesis: Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours.

Background: We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing.

Anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the round window membrane.

Background: We have developed 3D-printed microneedle technology for diagnostic aspiration of perilymph and intracochlear delivery of therapeutic agents. Single microneedle-mediated round window membrane (RWM) perforation does not cause hearing loss, heals within 48-72 h, and yields sufficient perilymph for proteomic analysis. In this study, we investigate the anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the same RWM at different timepoints.