The role of dystrophin isoforms and interactors in the brain.

Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.

Retainer Bias: Ethical and Practical Considerations for the Forensic Neuropsychologist.

How is it that practicing forensic neuropsychologists occasionally see substandard work from other colleagues, or more fundamentally, have such disparate opinions on the same case? One answer might be that in every profession, competence varies. Another possibility has little to do with competence, but professional conduct. In this paper we discuss the process by which retainer bias may occur.

Validating and updating the OHTS-EGPS model predicting 5-year glaucoma risk among ocular hypertension patients using electronic records.

Objective: To validate and update the OHTS-EGPS model predicting risk of conversion from OHT to glaucoma using electronic medical records (EMR).

Design: Evaluation and update of a risk prediction algorithm using EMRs and linked visual field (VF) tests.

Participants: Newly diagnosed OHT patients attending hospital glaucoma services in England.

Retinal Ganglion Cell Subtypes and Their Vulnerability in Glaucoma.

The detection of selective retinal ganglion cell damage in glaucoma has been a long sought-after goal, not just for the development of clinical tests for the early detection of glaucoma but for the elucidation of potential mechanisms underlying retinal ganglion cell loss. Early reports of the selective vulnerability of larger retinal ganglion cells (RGCs) in human studies did not translate simply to the loss of a particular class of RGC but more likely reflected shrinkage and degeneration across all RGC classes. Subsequent studies of nonhuman primate (NHP) models of glaucoma indicated some selectivity with great damage to the magnocellular vs parvocellular pathways.

Plasma and serum volume remain unchanged following a 12-h fast from food and drink despite changes in blood and urinary hydration markers.

Background/objectives: The effect of mild dehydration on plasma and serum volume has not been well established. Furthermore, the ability of urinary and blood biomarkers to monitor small hydration changes have not been solidified. There were two objectives of this research: 1.

Patient preferences for ocular hypertension monitoring: a discrete choice experiment.

Background/aims: To elicit the preferences and calculate the willingness to pay (WTP) of patients with ocular hypertension (OHT) for eye monitoring services in the UK.

Methods: Patients with OHT aged at least 18 years recruited from four NHS ophthalmology departments were included in the study. Patients' preferences and WTP for an OHT monitoring service in the National Health Service were elicited using a discrete choice experiment (DCE) within a postal survey based on six attributes: (1) how OHT monitoring is organised, (2) monitoring frequency, (3) travel time from home, (4) use of a risk calculator for conversion to glaucoma, (5) risk of developing glaucoma in the next 10 years and (6) cost of monitoring.

Oral nicotinamide provides robust, dose-dependent structural and metabolic neuroprotection of retinal ganglion cells in experimental glaucoma.

A compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss.

ARID1A in Gynecologic Precancers and Cancers.

The highest frequency of genetic alterations in the tumor suppressor ARID1A occurs in malignancies of the female reproductive tract. The prevalence of ARID1A alterations in gynecologic precancers and cancers is summarized from the literature, and the putative mechanisms of tumor suppressive action examined both in benign/precursor lesions including endometriosis and atypical hyperplasia and in malignancies of the ovary, uterus, cervix and vagina. ARID1A alterations in gynecologic cancers are usually loss-of-function mutations, resulting in diminished or absent protein expression.

'It's not meant to be for life, but it carries on': a qualitative investigation into the psychosocial needs of young retinoblastoma survivors.

Objective And Design: Retinoblastoma (Rb) is a rare childhood eye cancer, with 45% of individuals impacted by heritable disease and the remainder impacted non-heritably. The condition can leave survivors with life-long psychological and social challenges. This qualitative study examined the psychosocial needs of teenagers and young adults living beyond Rb.

Guideline for the management of infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs.

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection.

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs.

A systematic review of combined surgery and brachytherapy approaches for children and young people with relapsed and refractory rhabdomyosarcoma (Local-REFoRMS).

Approximately one third of children with rhabdomyosarcoma relapse or have refractory disease. Treatment approaches include a combination of systemic therapies and local therapies, directed at tumour site(s). This review was conducted to evaluate the effectiveness and safety of the combination of surgery and brachytherapy as local therapy for treating children and young people with relapsed/refractory rhabdomyosarcoma.

Networking to Optimize exon 53 Skipping in the Brain of Mouse Model.

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene that disrupt the open reading frame and thus prevent production of functional dystrophin proteins. Recent advances in DMD treatment, notably exon skipping and AAV gene therapy, have achieved some success aimed at alleviating the symptoms related to progressive muscle damage. However, they do not address the brain comorbidities associated with DMD, which remains a critical aspect of the disease.

What matters to you? Engaging with children in the James Lind Alliance Children's Cancer Priority Setting Partnership.

Background: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children's Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises.

Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs.

Gene Gun DiOlistic Labelling of Retinal Ganglion Cells.

Gene gun DiOlistic labelling enables the detailed visualization of retinal ganglion cells (RGCs) dendritic structure. Since the level of labelling is independent of cellular health, it is useful for the characterization of neuronal structure in degenerating neurons where expressed reporters may be inadequate. The method uses compressed helium gas to fire tungsten or gold microparticles coated in carbocyanine dyes (DiD, DiI, DiO) into flat mounted retinas.

Central Retinal Artery Occlusion with Concomitant Intracranial Hemorrhage Secondary to Endocarditis.

Purpose: To report a case of central retinal artery occlusion (CRAO) associated with subacute endocarditis secondary to a dental infection. . A 27-year-old male presented with acute monocular vision loss in the setting of a stroke and seizure.

Brain-derived neurotrophic factor measurements in mouse serum and plasma using a sensitive and specific enzyme-linked immunosorbent assay.

This study is about the quantification and validation of BDNF levels in mouse serum and plasma using a sensitive immunoassay. While BDNF levels are readily detectable in human serum, the functional implications of these measurements are unclear as BDNF released from human blood platelets is the main contributor to the serum levels of BDNF. As mouse platelets do not contain BDNF, this confounding factor is absent in the mouse.

Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models.

Nucleic acid-based therapies have demonstrated great potential for the treatment of monogenetic diseases, including neurologic disorders. To date, regulatory approval has been received for a dozen antisense oligonucleotides (ASOs); however, these chemistries cannot readily cross the blood-brain barrier when administered systemically. Therefore, an investigation of their potential effects within the central nervous system (CNS) requires local delivery.

Brain-derived neurotrophic factor released from blood platelets prevents dendritic atrophy of lesioned adult central nervous system neurons.

In humans and other primates, blood platelets contain high concentrations of brain-derived neurotrophic factor due to the expression of the gene in megakaryocytes. By contrast, mice, typically used to investigate the impact of CNS lesions, have no demonstrable levels of brain-derived neurotrophic factor in platelets, and their megakaryocytes do not transcribe significant levels of the gene. Here, we explore potential contributions of platelet brain-derived neurotrophic factor with two well-established CNS lesion models, using 'humanized' mice engineered to express the gene under the control of a megakaryocyte-specific promoter.

Assessment of Lab4P Probiotic Effects on Cognition in 3xTg-AD Alzheimer's Disease Model Mice and the SH-SY5Y Neuronal Cell Line.

Aging and metabolic syndrome are associated with neurodegenerative pathologies including Alzheimer's disease (AD) and there is growing interest in the prophylactic potential of probiotic bacteria in this area. In this study, we assessed the neuroprotective potential of the Lab4P probiotic consortium in both age and metabolically challenged 3xTg-AD mice and in human SH-SY5Y cell culture models of neurodegeneration. In mice, supplementation prevented disease-associated deteriorations in novel object recognition, hippocampal neurone spine density (particularly thin spines) and mRNA expression in hippocampal tissue implying an anti-inflammatory impact of the probiotic, more notably in the metabolically challenged setting.