Alcohol drinking is associated with greater calcium activity in mouse central amygdala dynorphin-expressing neurons.

Unlabelled: Alcohol use disorder (AUD) is a chronic disease that poses significant economic burden and health risks. It is pivotal to better understand brain mechanisms engaged by alcohol that promote misuse. The central amygdala (CeA) has emerged as a key mediator of excessive preclinical alcohol consumption.

Measuring differences in the ERG in myopia using the RETeval device with skin electrodes.

Introduction: Previous research suggests that the electroretinogram (ERG) is reduced and delayed in non-pathological myopia. However, the invasive nature of the electrode and cumbersome equipment required has prevented the widescale uptake of ERG measures. This study investigated whether previously reported changes to the ERG response in myopia are also observable when measured using non-invasive skin electrodes and a hand-held ERG device.

K2 channel positive modulation reduces alcohol drinking in female C57BL/6J mice.

Although men have historically exhibited higher levels of alcohol use disorder (AUD) diagnosis, the gap between men and women has been diminishing quickly. Preclinical screening for pharmacological treatments for AUD has typically focused solely on males, ignoring the possibility that males and females may differ mechanistically for the same behavioral phenotype. To ensure the efficacy of treatment targets across the sexes, it is crucial to study the pharmacological effects of AUD treatments in males and females.

Bilateral deep brain stimulation (DBS) of globus pallidus internus (GPi) for the treatment of benign hereditary chorea and other childhood onset choreas: a single-center experience.

Purpose: Chorea is a clinical sign characterized by involuntary, rapid, unpredictable, and irregular muscle movements that can affect various parts of the body. It can be seen in various medical conditions, both neurological and systemic, of genetic and acquired etiology. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been used to treat various types of chorea.

Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species.

Alcohol use disorder (AUD) is the most prevalent substance use disorder but there is incomplete knowledge of the underlying molecular etiology. Here, we examined the cytosolic proteome from the nucleus accumbens core (NAcC) of ethanol drinking rhesus macaques to identify ethanol-sensitive signaling proteins. The targets were subsequently investigated using bioinformatics, genetic, and pharmacological manipulations in mouse models of ethanol drinking.

Transgenic expression of human cytochrome P450 2E1 in C. elegans and rat PC-12 cells sensitizes to ethanol-induced locomotor and mitochondrial effects.

Chronic alcohol (ethanol) use is increasing in the United States and has been linked to numerous health issues in multiple organ systems including neurological dysfunction and diseases. Ethanol toxicity is mainly driven by the metabolite acetaldehyde, which is generated through three pathways: alcohol dehydrogenase (ADH2), catalase (CAT), and cytochrome P450 2E1 (CYP2E1). ADH2, while the main ethanol clearance pathway in the liver, is not expressed in the mammalian brain, resulting in CAT and CYP2E1 driving local metabolism of ethanol in the central nervous system.

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.

Objectives: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy.

Methods: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme.

Therapeutic Targeting of Glioblastoma and the Interactions with Its Microenvironment.

Glioblastoma (GBM) is the most common primary malignant brain tumour, and it confers a dismal prognosis despite intensive multimodal treatments. Whilst historically, research has focussed on the evolution of GBM tumour cells themselves, there is growing recognition of the importance of studying the tumour microenvironment (TME). Improved characterisation of the interaction between GBM cells and the TME has led to a better understanding of therapeutic resistance and the identification of potential targets to block these escape mechanisms.

An evaluation of optometric advanced skills within a UK tertiary based setting.

Introduction: Hospital-based optometrists are undertaking extended roles across ophthalmology that may require them to perform advanced skills (AS). Moorfields Eye Hospital (MEH) is the largest UK employer of hospital-based optometrists, it was sought to investigate which AS are being performed at this centre and how they align to the four pillars of advanced clinical practice (ACP).

Methods: An online survey was sent to MEH optometrists in May 2022 that asked about professional status, sub-specialties worked, qualifications, acquisition and validation of AS, research and leadership.

Investigating the Spatiotemporal Summation of Perimetric Stimuli in Dry Age-Related Macular Degeneration.

Purpose: To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry.

Methods: Twenty participants with dry AMD (mean age, 74.6 years) and 20 healthy controls (mean age, 67.

Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability and excessive alcohol intake are poorly understood. Small-conductance Ca-activated K (K2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a key contributor to alcohol-induced functional neuroadaptations in alcohol-drinking monkeys and alcohol-dependent mice. Here, this cross-species analysis focused on KCNN3 DNA methylation, gene expression, and single nucleotide polymorphisms, including alternative promoters in KCNN3, that could influence surface trafficking and function of K2 channels.

Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage.

Purpose: The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco's area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity.

Methods: One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans.

Enhanced Transport at High Plasma Pressure and Subthreshold Kinetic Ballooning Modes in Wendelstein 7-X.

High-performance fusion plasmas, requiring high pressure β, are not well understood in stellarator-type experiments. Here, the effect of β on ion-temperature-gradient-driven (ITG) turbulence is studied in Wendelstein 7-X (W7-X), showing that subdominant kinetic ballooning modes (KBMs) are unstable well below the ideal MHD threshold and get strongly excited in the turbulence. By zonal-flow erosion, these subthreshold KBMs (stKBMs) affect ITG saturation and enable higher heat fluxes.

Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability and excessive alcohol intake are poorly understood. Small-conductance Ca-activated K (K2 or SK) channels encoded by the family of genes have emerged from preclinical studies as a key contributor to alcohol-induced functional neuroadaptations in alcohol-drinking monkeys and alcohol dependent mice. Here, this cross-species analysis focused on DNA methylation, gene expression, and single nucleotide polymorphisms including alternative promoters in that could influence surface trafficking and function of K2 channels.

Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder.

Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences. The inability of individuals with AUD to regulate drinking may involve functional deficits in cortical areas that normally balance actions that have aspects of both reward and risk. Among these, the orbitofrontal cortex (OFC) is critically involved in goal-directed behavior and is thought to maintain a representation of reward value that guides decision making.

Health-related quality-of-life results from the randomised phase II TAVAREC trial on temozolomide with or without bevacizumab in 1p/19q intact first-recurrence World Health Organization grade 2 and 3 glioma (European Organization for Research and Treatment of Cancer 26091).

Background: In an international randomised controlled phase II study of temozolomide (TMZ) versus TMZ in combination with bevacizumab (BEV) in locally diagnosed non-1p/19q co-deleted World Health Organization grade 2 or 3 gliomas with a first and contrast-enhancing recurrence after initial radiotherapy, and overall survival at 12 months was not significantly different (61% in the TMZ arm and 55% in the TMZ + BEV arm).

Objectives: Health-related quality of life (HRQoL) was a key secondary end-point in this trial, and the main objective of this study was to determine the impact of the addition of BEV to TMZ on HRQoL.

Methods: HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (version 3) and QLQ-BN20 at baseline, and then every 12 weeks until disease progression.

Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder.

Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences. The inability of individuals with AUD to regulate drinking may involve functional deficits in cortical areas that normally balance actions that have aspects of both reward and risk. Among these, the orbitofrontal cortex (OFC) is critically involved in goal-directed behavior and is thought to maintain a representation of reward value that guides decision making.

Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field.

Purpose: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established.

Spatiotemporal summation of perimetric stimuli in healthy observers.

Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size.

Temporal summation in myopia and its implications for the investigation of glaucoma.

Purpose: We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non-pathological axial myopia compared to non-myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density.

Methods: Achromatic contrast thresholds were measured for a GIII-equivalent stimulus (0.

Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging.

Purpose: To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2).

Methods: Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations.