Cell-specific delivery of GJB2 restores auditory function in mouse models of DFNB1 deafness and mediates appropriate expression in NHP cochlea.

Mutations in the gene cause the most common form of human hereditary hearing loss, known as DFNB1. is expressed in two cell groups of the cochlea-epithelial cells of the organ of Corti and fibrocytes of the inner sulcus and lateral wall-but not by sensory hair cells or neurons. Attempts to treat mouse models of DFNB1 with AAV vectors mediating nonspecific expression have not substantially restored function, perhaps because inappropriate expression in hair cells and neurons could compromise their electrical activity.

The auditory midbrain mediates tactile vibration sensing.

Vibrations are ubiquitous in nature, shaping behavior across the animal kingdom. For mammals, mechanical vibrations acting on the body are detected by mechanoreceptors of the skin and deep tissues and processed by the somatosensory system, while sound waves traveling through air are captured by the cochlea and encoded in the auditory system. Here, we report that mechanical vibrations detected by the body's Pacinian corpuscle neurons, which are distinguished by their ability to entrain to high-frequency (40-1,000 Hz) environmental vibrations, are prominently encoded by neurons in the lateral cortex of the inferior colliculus (LCIC) of the midbrain.

Evaluating the effectiveness of mailout smoking cessation support: A systematic review and meta-analysis.

Objective: One of the main barriers to smoking cessation support is accessibility. Mailout supports can potentially mitigate access barriers, but their effectiveness has not been explored. The aim of this review is to evaluate the effectiveness of mailout smoking cessation support.

ARSA Variant Associated With Late Infantile Metachromatic Leukodystrophy and Carrier Rate in Individuals of Ashkenazi Jewish Ancestry.

Metachromatic leukodystrophy (MLD) is a rare neurodegenerative lysosomal storage disease resulting from bi-allelic pathogenic variants in the ARSA gene. MLD is distinguished clinically based on the age of onset into late-infantile, juvenile, and adult. The late-infantile type is the most severe phenotype presenting with hypotonia, weakness, gait abnormalities, which progresses to mental and physical decline leading to early death.

Impact of routine pre-operative risk assessment on patients undergoing emergency major abdominal surgery in a regional Victorian hospital.

Background: Routine preoperative risk assessment (RPRA) using objective risk prediction tools may improve the perioperative outcomes of emergency major abdominal surgery (EMAS). This project aims to identify whether the introduction of RPRA with the 'National Emergency Laparotomy Audit (NELA) Calculator' as standard-of-care for EMAS at a regional Victorian hospital has improved postoperative outcomes, reduced unplanned postoperative critical care unit (CCU) admission rates, and impacted the 'no-lap' rate.

Methods: An audit was performed including all adult general surgery patients who required EMAS at Bendigo Health between September 2017 and August 2022, including those palliated up-front.

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.

A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non-Syndromic Hearing Loss.

Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next-generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants.

Aboriginal and Torres Strait Islander people who smoke and want to quit - a cohort profile from the Koori Quit Pack study.

Introduction: Reducing the prevalence of smoking is a national priority, however there is limited evidence on what smoking cessation supports are utilised, accessible, and effective among Aboriginal and Torres Strait Islander people. This paper describes a cohort profile of Aboriginal and Torres Strait Islander people who smoke and want to quit to inform tailored smoking cessation interventions.

Method: Aboriginal and Torres Strait Islander people residing in New South Wales (NSW), Australian Capital Territory (ACT), and Victoria, who were smokers wanting to quit, were recruited through health services and online advertisements from May to October 2022.

Parental Patterns of Alcohol Consumption During the COVID-19 Pandemic: Scoping Review.

Background: The declaration of the COVID-19 pandemic led to public health restrictions that impacted the lives of people across the globe. Parents were particularly burdened with balancing multiple responsibilities, such as working from home while caring for and educating their children. Alcohol use among parents is an area that warrants further exploration.

The effectiveness of internet-based group behavioural interventions on lifestyle modifications: A systematic review.

Objectives: To examine the effectiveness of internet-based group interventions incorporating social support elements in addressing behaviours related to smoking, nutrition, alcohol consumption, physical activity, and obesity.

Methods: A literature search was undertaken in six databases from inception to April 2024. Articles were eligible if they reported on group-based online interventions targeting smoking, nutrition, alcohol consumption, physical activity, and obesity, and included interactive features aimed at promoting social engagement and support.

ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.

Context.—: Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1).

Objective.

Koori Quit Pack: A feasibility study of a multi-component mailout smoking cessation support for Aboriginal and Torres Strait Islander people: "I would recommend it to anybody. It's just so much easier".

Introduction: Smoking is the leading cause of preventable death among Aboriginal and Torres Strait Islander people. The Koori1 Quit Pack study aimed to assess the feasibility of a multi-component mailout smoking cessation intervention to reduce smoking among Aboriginal and Torres Strait Islander people.

Methods: A non-randomised, single-group feasibility study conducted among Aboriginal and Torres Strait Islander people who reported current smoking.

"It's changed my life. I'm not smoking anymore. I don't want to smoke anymore": exploring the acceptability of mailout smoking cessation support for and by Aboriginal and Torres Strait Islander people.

Introduction: Aboriginal and Torres Strait Islander people want to quit smoking. There is global evidence of combination Nicotine Replacement Therapy (c-NRT) alongside behavioural support as best practice approach to smoking cessation care. However, there is limited adherence and acceptability research regarding NRT and behavioural supports for Aboriginal and Torres Strait Islander people.

The auditory midbrain mediates tactile vibration sensing.

Vibrations are ubiquitous in nature, shaping behavior across the animal kingdom. For mammals, mechanical vibrations acting on the body are detected by mechanoreceptors of the skin and deep tissues and processed by the somatosensory system, while sound waves traveling through air are captured by the cochlea and encoded in the auditory system. Here, we report that mechanical vibrations detected by the body's Pacinian corpuscle neurons, which are unique in their ability to entrain to high frequency (40-1000 Hz) environmental vibrations, are prominently encoded by neurons in the lateral cortex of the inferior colliculus (LCIC) of the midbrain.

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.

Acute aortic dissection (AAD) - a lethal disease: the epidemiology, pathophysiology and natural history.

Aortic dissection is a life-threatening condition that is often under-recognised. In the first in a series of articles about the condition, the epidemiology, pathology, classification and clinical presentation of aortic dissection are discussed.

Biochemical and molecular confirmation of alkaptonuria in a Sumatran orangutan (Pongo abelii).

A 6-yr-old female orangutan presented with a history of dark urine that turned brown upon standing since birth. Repeated routine urinalysis and urine culture were unremarkable. Urine organic acid analysis showed elevation in homogentisic acid consistent with alkaptonuria.

Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial.

Background: Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population.

Methods: The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1).

Biallelic Loss-of-Function Variants in Are Associated with Peripheral Neuropathy and Hearing Loss.

Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control.

Reducing Opioid Use for Chronic Pain With a Group-Based Intervention: A Randomized Clinical Trial.

Importance: Opioid use for chronic nonmalignant pain can be harmful.

Objective: To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care.

Design, Setting, And Participants: Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain.