A multiplexed, single-cell sequencing screen identifies compounds that increase neurogenic reprogramming of murine Muller glia.

Retinal degeneration in mammals causes permanent loss of vision, due to an inability to regenerate naturally. Some non-mammalian vertebrates show robust regeneration, via Muller glia (MG). We have recently made significant progress in stimulating adult mouse MG to regenerate functional neurons by transgenic expression of the proneural transcription factor Ascl1.

Development and use of two Xenopus laevis spleen stromal cell lines to study the role of splenic stromal cells in anuran immune processes.

The spleen is an important immune organ in adult Xenopus laevis, supporting the differentiation of B cells and acting as the main peripheral lymphoid organ. Key to these processes are the supporting non-hematopoietic cells, or stromal cells, within the spleen tissue. Despite the importance of the spleen to frog immunity, few frog cell lines originating from spleen tissue have been reported.

Regulating the formation of Müller glia-derived progenitor cells in the retina.

We summarize recent findings in different animal models regarding the different cell-signaling pathways and gene networks that influence the reprogramming of Müller glia into proliferating, neurogenic progenitor cells in the retina. Not surprisingly, most of the cell-signaling pathways that guide the proliferation and differentiation of embryonic retinal progenitors also influence the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). Further, the neuronal differentiation of MGPC progeny is potently inhibited by networks of neurogenesis-suppressing genes in chick and mouse models but occurs freely in zebrafish.

Four-tract tractography: multiparametric direct targeting of the dentatorubrothalamic tract.

This video article presents a case study of a 70-year-old male with medically refractory essential tremor treated with magnetic resonance-guided focused ultrasound (MRgFUS). Following an initial successful ablation of the right thalamus, the patient underwent left-sided thalamotomy. After two tractography-guided sonications, the authors observed a significant reduction in his right-hand tremor with no immediate side effects.

Two conjectures on 3D Voronoi structures: a toolkit with biomedical case studies.

3D Voronoi scaffolds are widely applied in the field of additive manufacturing as they are known for their light weight structural resilience and share many topological similarities to various natural (bone, tumours, lymph node) and synthetic environments (foam, functionally gradient porous materials). Unfortunately, the structural design features that promote these topological similarities (such as the number of vertices) are often unpredictable and require the trial and error of varying design features to achieve the desired 3D Voronoi structure. This article provides a toolkit, consisting of equations, based on over 12 000 3D Voronoi structures.

Vertebral Artery Variation and Imposed Risks Associated with Anterior Cervical Discectomy and Fusion Procedures - A Case Study with Surgeons' Perspectives.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a common cervical procedure with more than 137,000 cases in the United States (U.S.) each year.

Differential effects of digital mindfulness-based interventions on creative potential and responsibility among middle school students.

Background: Creativity and responsibility are enhanced by meditation among adults, but such effects have not been studied in adolescents. Moreover, the determinants of the ethical effect (such as responsibility) of meditation are unclear.

Aims: To address this gap by investigating the impact of digital in-class meditation programmes in middle school, focusing on intentions (self-centred vs.

Simulation in Nurse Anesthesia Educational Programs: A Report by the AANA Simulation Subcommittee.

Simulation is an integral part of the healthcare educational landscape and a key element in the future of graduate professional education. For the past three decades, simulation-based educational methodology has been gaining popularity in nurse anesthesia educational programs (NAEP). There is currently limited objective evidence documenting modalities used or educational outcomes addressed through simulation in NAEPs.

Poverty proofing healthcare: A qualitative study of barriers to accessing healthcare for low-income families with children in northern England.

Poverty impacts negatively on children's health and future life chances. Access to the UK's National Health Service (NHS) is based on clinical need rather than the ability to pay but horizontal inequities in access exist. Children North East, a charity supporting children experiencing poverty, are working with partners to reduce the impacts of poverty on NHS access.

Adaptive foraging behaviours in the Horn of Africa during Toba supereruption.

Although modern humans left Africa multiple times over 100,000 years ago, those broadly ancestral to non-Africans dispersed less than 100,000 years ago. Most models hold that these events occurred through green corridors created during humid periods because arid intervals constrained population movements. Here we report an archaeological site-Shinfa-Metema 1, in the lowlands of northwest Ethiopia, with Youngest Toba Tuff cryptotephra dated to around 74,000 years ago-that provides early and rare evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

Oncoplastic Breast Reconstruction in Morbidly Obese Patients: An Acceptable Practice.

Background: Breast cancer is the most common noncutaneous malignancy amongst women. Lumpectomy with adjuvant radiation is a mainstay of surgical treatment. Oncoplastic breast reconstruction reduces the resultant breast deformity.

Comparative effectiveness of digital mental healthcare models for adults with epilepsy: A study protocol of a randomized controlled trial.

Objective: Mental health complaints are prevalent among people with epilepsy, yet there are major barriers that prevent access to psychological care, including high out-of-pocket costs and a lack of accessible specialized services. The purpose of the current study is to examine the comparative efficacy, acceptability, cost-effectiveness, and long-term outcomes of a digital psychological intervention when delivered under two models of care (i.e.

Presentation and outcomes of paediatric craniopharyngioma in the west of Scotland: a 25 year experience.

Purpose: Craniopharyngiomas can be aggressive leading to significant complications and morbidity. It is not clear whether there are any predictive factors for incidence or outcomes. Our aim was therefore to record the incidence, presentation, characteristics and progression of paediatric craniopharyngiomas in the West of Scotland.

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells.

Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors.

Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering.

Ongoing cell therapy trials have demonstrated the need for precision control of donor cell behavior within the recipient tissue. We present a methodology to guide stem cell-derived and endogenously regenerated neurons by engineering the microenvironment. Being an "approachable part of the brain," the eye provides a unique opportunity to study neuron fate and function within the central nervous system.

A multiplexed, single-cell sequencing screen identifies compounds that increase neurogenic reprogramming of murine Muller glia.

Retinal degeneration in mammals causes permanent loss of vision, due to an inability to regenerate naturally. Some non-mammalian vertebrates show robust regeneration, via Muller glia (MG). We have recently made significant progress in stimulating adult mouse MG to regenerate functional neurons by transgenic expression of the proneural transcription factor Ascl1.

Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors.

The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, here we treat established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAP CAFs results in loss of the structural integrity of desmoplastic matrix.

Inducing Neural Regeneration from Glia Using Proneural bHLH Transcription Factors.

Endogenous regeneration strategies to replace lost neurons hold great promise for treating neurodegenerative disorders. In the majority of cases, neural regeneration is induced by converting resident glial cells into neurogenic precursors. This review will outline how proneural bHLH transcription factors can be used to reprogram glia in the brain and retina into a source for new neurons.

Longitudinal Olfactory Patterns in Multiple Sclerosis: A Scoping Review and Implication for Use in Management of Disease.

Background: Although studies regarding multiple sclerosis (MS) and olfactory dysfunction (OD) have been previously described and summarized, there is not a sole review of longitudinal studies regarding the matter. This review examines the existing literature investigating MS and its effect on olfaction. In addition, the role of OD in the diagnosis and prognosis of MS is explored.

Understanding implementation completion of tailored motivational interviewing in multidisciplinary adolescent HIV clinics.

Background: Understanding the barriers and facilitators of implementation completion is critical to determining why some implementation efforts fail and some succeed. Such studies provide the foundation for developing further strategies to support implementation completion when scaling up evidence-based practices (EBPs) such as Motivational Interviewing.

Method: This mixed-methods study utilized the Exploration, Preparation, Implementation, and Sustainment framework in an iterative analytic design to compare adolescent HIV clinics that demonstrated either high or low implementation completion in the context of a hybrid Type III trial of tailored motivational interviewing.

Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors.

The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, we treat established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAPCAFs results in loss of the structural integrity of desmoplastic matrix.

Restricting access to antibiotics: The effectiveness of a 'no repeats' government policy intervention.

Background: Australia has a high rate of antibiotic use. Government policy interventions are one strategy to optimise the use of antibiotics. On 1 April 2020, the Australian Government Department of Health introduced a policy intervention to increase the quality use of four antibiotics.

The amphibian invitrome: Past, present, and future contributions to our understanding of amphibian immunity.

Many amphibian populations are declining worldwide, and infectious diseases are a leading cause. Given the eminent threat infectious diseases pose to amphibian populations, there is a need to understand the host-pathogen-environment interactions that govern amphibian susceptibility to disease and mortality events. However, using animals in research raises an ethical dilemma, which is magnified by the alarming rates at which many amphibian populations are declining.

Relations between provider adherence to a tailored motivational intervention protocol and competence in motivational interviewing.

Objectives: To evaluate the association between provider adherence to Tailored Motivational Interviewing implementation strategy and motivational interviewing (MI) competence.

Methods: 156 youth-focused HIV providers enrolled in a parent implementation science trial completed: a) quarterly standardized patient assessments (SPI) during Baseline; b) a workshop, individual coaching sessions, and quarterly SPI plus feedback during Implementation; and c) quarterly SPI during Sustainment. Competence was measured using the MI-CRS and tracking data was used to assess adherence.