Basal Linear Deposit: Normal Physiological Ageing or a Defining Lesion of Age-Related Macular Degeneration?

To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 eyes (age 55-80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 eyes (age 57-88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included.

High Attack Rate of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.1.529 Among 2-Dose Vaccinated Populations in 2 Indoor Entertainment Setting Outbreaks.

We estimated attack rates of severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.

Whole of population-based cohort study of recovery time from COVID-19 in New South Wales Australia.

Background: COVID-19 results in persisting symptoms but there is little systematically collected data estimating recovery time following infection.

Methods: We followed 94% of all COVID-19 cases diagnosed in the Australian state of New South Wales between January and May 2020 using 3-4 weekly telephone interviews and linkage to hospitalisation and death data to determine if they had recovered from COVID-19 based on symptom resolution. Proportional hazards models with competing risks were used to estimate time to recovery adjusted for age and gender.

Effect of selectively knocking down key metabolic genes in Müller glia on photoreceptor health.

The importance of Müller glia for retinal homeostasis suggests that they may have vulnerabilities that lead to retinal disease. Here, we studied the effect of selectively knocking down key metabolic genes in Müller glia on photoreceptor health. Immunostaining indicated that murine Müller glia expressed insulin receptor (IR), hexokinase 2 (HK2) and phosphoglycerate dehydrogenase (PHGDH) but very little pyruvate dehydrogenase E1 alpha 1 (PDH-E1α) and lactate dehydrogenase A (LDH-A).

A Combination Therapy Targeting Endoglin and VEGF-A Prevents Subretinal Fibro-Neovascularization Caused by Induced Müller Cell Disruption.

Purpose: Subretinal fibroneovascularization is one of the most common causes of vision loss in neovascular AMD (nAMD). Anti-VEGF therapy effectively inhibits vascular leak and neovascularization but has little effect on fibrosis. This study aimed to identify a combination therapy to concurrently inhibit subretinal neovascularization and prevent fibrosis.

Identifying positively deviant elderly medical wards using routinely collected NHS Safety Thermometer data: an observational study.

Objective: The positive deviance approach seeks to identify and learn from exceptional performers. Although a framework exists to apply positive deviance within healthcare organisations, there is limited guidance to support its implementation. The approach has also rarely explored exceptional performance on broad outcomes, been implemented at ward level, or applied within the UK.

Small molecule Hedgehog pathway antagonists.

Leveraging our quinolone-1-(2H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: l-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six l-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli mRNA expression.

Dynamin 2 is essential for mammalian spermatogenesis.

The dynamin family of proteins play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal tissues. In the context of reproduction, dynamin 1 (DNM1) and dynamin 2 (DNM2) have recently been shown to act as key mediators of sperm acrosome formation and function. However, little is known about the roles that these proteins play in the developing testicular germ cells.

Quinolone-1-(2H)-ones as hedgehog signalling pathway inhibitors.

A series of quinolone-2-(1H)-ones derived from the Ugi-Knoevenagel three- and four-component reaction were prepared exhibiting low micromolar cytotoxicity against a panel of eight human cancer cell lines known to possess the Hedgehog Signalling Pathway (HSP) components, as well as the seminoma TCAM-2 cell line. A focused SAR study was conducted and revealed core characteristics of the quinolone-2-(1H)-ones required for cytotoxicity. These requirements included a C3-tethered indole moiety, an indole C5-methyl moiety, an aliphatic tail or an ester, as well as an additional aromatic moiety.

When is enough, enough? Understanding and solving your sample size problems in health services research.

Health services researchers face two obstacles to sample size calculation: inaccessible, highly specialised or overly technical literature, and difficulty securing methodologists during the planning stages of research. The purpose of this article is to provide pragmatic sample size calculation guidance for researchers who are designing a health services study. We aimed to create a simplified and generalizable process for sample size calculation, by (1) summarising key factors and considerations in determining a sample size, (2) developing practical steps for researchers-illustrated by a case study and, (3) providing a list of resources to steer researchers to the next stage of their calculations.

Deepening our Understanding of Quality in Australia (DUQuA): a study protocol for a nationwide, multilevel analysis of relationships between hospital quality management systems and patient factors.

Introduction: Despite the growing body of research on quality and safety in healthcare, there is little evidence of the association between the way hospitals are organised for quality and patient factors, limiting our understanding of how to effect large-scale change. The 'Deepening our Understanding of Quality in Australia' (DUQuA) study aims to measure and examine relationships between (1) organisation and department-level quality management systems (QMS), clinician leadership and culture, and (2) clinical treatment processes, clinical outcomes and patient-reported perceptions of care within Australian hospitals.

Methods And Analysis: The DUQuA project is a national, multilevel, cross-sectional study with data collection at organisation (hospital), department, professional and patient levels.

Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis.

Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized.

Developmental expression of Musashi-1 and Musashi-2 RNA-binding proteins during spermatogenesis: analysis of the deleterious effects of dysregulated expression.

Spermatogenesis is a complex developmental process whereby diploid spermatogenic stem cells become haploid and undergo a series of morphological changes to produce physically mature spermatozoa. Crucial to this process are a number of RNA-binding proteins, responsible for the posttranscriptional control of essential mRNAs and particularly pertinent to the two periods of inactive transcription that occur in spermatogenesis. One such group of RNA-binding proteins is the Musashi family, specifically Musashi-1 (MSI1) and Musashi-2 (MSI2), which act as key translational regulators in various stem cell populations and have been linked with the induction of tumorigenesis.

The APC/C activator FZR1 is essential for meiotic prophase I in mice.

Fizzy-related 1 (FZR1) is an activator of the Anaphase promoting complex/cyclosome (APC/C) and an important regulator of the mitotic cell division cycle. Using a germ-cell-specific conditional knockout model we examined its role in entry into meiosis and early meiotic events in both sexes. Loss of APC/C(FZR1) activity in the male germline led to both a mitotic and a meiotic testicular defect resulting in infertility due to the absence of mature spermatozoa.

Barriers and enablers to physical activity among older Australians who want to increase their physical activity levels.

Background: Physical activity interventions targeting older adults are optimized if barriers and enablers are better understood. This study identified barriers and enablers of physical activity and examined whether these were associated with meeting physical activity recommendations.

Methods: 2225 adults aged 65 years and above who perceived themselves to be insufficiently active but would like to be more physically active self-reported their barriers and enablers to physical activity in the 2009 New South Wales Falls Prevention Survey.

Immune regulation of ovarian development: programming by neonatal immune challenge.

Neonatal immune challenge by administration of lipopolysaccharide (LPS) produces enduring alterations in the development and activity of neuroendocrine, immune and other physiological systems. We have recently reported that neonatal exposure to an immune challenge by administration of LPS results in altered reproductive development in the female Wistar rat. Specifically, LPS-treated animals exhibited diminished ovarian reserve and altered reproductive lifespan.

Prevalence and correlates of participation in fall prevention exercise/physical activity by older adults.

Objective: To examine older people's participation in fall prevention exercise/physical activities.

Methods: Participants comprised 5,681 randomly selected older people (≥ 65 years) who took part in the 2009 New South Wales (Australia) Fall Prevention telephone survey (61% response-rate). The instrument consisted of 11 prompted activities including two separate questions on participation in strength and balance training.

Five-year analysis of operative mortality and neonatal outcomes in congenital heart disease.

Background: We sought to compare overall mortality with neonatal outcomes over a five year period to define risk factors for mortality and service development priorities.

Methods: A retrospective cohort study of surgical outcomes following repair or palliation of structural congenital heart defects January 2005-2010. We defined mortality according to contemporary international guidelines and classified surgical procedures using the Risk Adjustment in Congenital Heart Surgery (RACHS-1) score.

Fetal and post-natal diagnosis of major congenital heart disease: implications for medical and psychological care in the current era.

Aim: The fetal or post-natal diagnosis of major congenital cardiac abnormality has important medical and psychological consequences.

Methods: We reviewed infants who underwent cardiac surgery in the first year of life at the Heart Centre for Children, The Children's Hospital at Westmead during 2009. The aims of this study were to: (i) examine the key features of cardiac diagnosis and clinical outcome, and (ii) consider how these data can inform priorities for the delivery of clinical services.

Adding insult to injury: effects of xenobiotic-induced preantral ovotoxicity on ovarian development and oocyte fusibility.

Mammalian females are born with a finite number of nonrenewing primordial follicles, the majority of which remain in a quiescent state for many years. Because of their nonrenewing nature, these "resting" oocytes are particularly vulnerable to xenobiotic insult, resulting in premature ovarian senescence and the formation of dysfunctional oocytes. In this study, we characterized the mechanisms of ovotoxicity for three ovotoxic agents, 4-vinylcyclohexene diepoxide (VCD), methoxychlor (MXC), and menadione (MEN), all of which target immature follicles.