Adolescent seizure impacts oligodendrocyte maturation, neuronal-glial circuit Formation, and myelination in the mammalian forebrain.

Oligodendrocyte progenitor cells differentiate into oligodendrocytes, which myelinate axons during development and following demyelinating injury. However, the mechanisms that drive the timing and specificity of developmental myelination are not well understood. We hypothesized that oligodendrocyte progenitor cell proliferation and differentiation would be affected by pathological neuronal activity during adolescent development when developmental myelination is occurring and that this would also impact neuron-to-oligodendrocyte progenitor cell connectivity and myelination.

High ionic strength vector formulations enhance gene transfer to airway epithelia.

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelia to achieve therapeutic correction. Hypertonic saline (HTS) is frequently administered to people with CF to enhance mucus clearance. HTS transiently disrupts epithelial cell tight junctions, but its ability to improve gene transfer has not been investigated.

High ionic strength vector formulations enhance gene transfer to airway epithelia.

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelia to achieve therapeutic correction. Hypertonic saline (HTS) is frequently administered to people with CF to enhance mucus clearance. HTS transiently disrupts epithelial cell tight junctions, but its ability to improve gene transfer has not been investigated.

Lipid vesicle-based molecular robots.

A molecular robot, which is a system comprised of one or more molecular machines and computers, can execute sophisticated tasks in many fields that span from nanomedicine to green nanotechnology. The core parts of molecular robots are fairly consistent from system to system and always include (i) a body to encapsulate molecular machines, (ii) sensors to capture signals, (iii) computers to make decisions, and (iv) actuators to perform tasks. This review aims to provide an overview of approaches and considerations to develop molecular robots.

Reciprocal mutations of lung-tropic AAV capsids lead to improved transduction properties.

Considerable effort has been devoted to developing adeno-associated virus (AAV)-based vectors for gene therapy in cystic fibrosis (CF). As a result of directed evolution and capsid shuffling technology, AAV capsids are available with widespread tropism for airway epithelial cells. For example, AAV2.

Empirical analysis of a plan-of-the-day strategy to approximate daily online reoptimization for prostate CBCT-guided adaptive radiotherapy.

Purpose: Adaptive radiotherapy (ART) can improve the dose delivered to the patient in the presence of anatomic variations. However, the required time, effort, and clinical resources are intensive. This work analyzed a plan-of-the-day (POD) approach on clinical patients treated with online ART to explore implementations that balance dosimetric benefit and clinical resource cost.

Examining the Relationship Between HIV-Related Stigma and the Health and Wellbeing of Children and Adolescents Living with HIV: A Systematic Review.

Human immunodeficiency virus (HIV) affects millions of people globally. The associated stigma remains a challenge for individuals living with HIV and children and adolescents face the additional challenge of withstanding the peer, pubertal and identity challenges associated with growing up. The current systematic review aimed to define and explore the major stigma-related challenges of children and adolescents from their own perspectives.

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry and Correlation with Toxicity.

Purpose: Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation.

Development and implementation of a novel peer mentoring program for undergraduate nursing students.

Objectives: Given the dynamic and high-stress environment of nursing education today, the need arose for the development and implementation of a novel peer mentoring program to support undergraduate nursing students. Peer mentoring refers to a network of support in which a more skilled or experienced person serves as a role model for a less skilled person for professional development and personal growth. Peer mentoring provides a support system that encourages self-confidence and increases self-worth for both the mentee and the mentor.

Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.

Purpose: Combining external beam radiation therapy (EBRT) and prostate seed implant (PSI) is efficacious in treating intermediate- and high-risk prostate cancer at the cost of increased genitourinary toxicity. Accurate combined dosimetry remains elusive due to lack of registration between treatment plans and different biological effect. The current work proposes a method to convert physical dose to biological effective dose (BED) and spatially register the dose distributions for more accurate combined dosimetry.

Challenges of conducting kidney health checks among patients at risk of chronic kidney disease and attending an urban Aboriginal and Torres Strait Islander primary healthcare service.

Background: The increasing incidence of chronic kidney disease (CKD) globally highlights the importance of early targeted screening of at-risk persons in primary healthcare settings. This study investigated the early detection of CKD among Aboriginal and Torres Strait Islander patients attending an urban primary healthcare service.

Methods: Routine data extracted for all patients with an active electronic medical record on 7 December 2017 were used to identify patients who were eligible to have a kidney health check (KHC), comprising estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR) tests.

WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia.

In cystic fibrosis (CF), reduced HCO secretion acidifies the airway surface liquid (ASL), and the acidic pH disrupts host defenses. Thus, understanding the control of ASL pH (pH) in CF may help identify novel targets and facilitate therapeutic development. In diverse epithelia, the WNK (with-no-lysine [K]) kinases coordinate HCO and Cl transport, but their functions in airway epithelia are poorly understood.

Experiences and wellbeing of Samaritans crisis line volunteers in Ireland during the COVID-19 pandemic: A qualitative study.

Background: The literature demonstrates that working in a crisis line volunteer role, despite being rewarding, poses a risk of adverse effects on health and additional pressure exists with the COVID-19 pandemic. Despite this, there is limited research on the experiences of such volunteers.

Aims: This study aimed to explore the experiences of Samaritans volunteers in Ireland during the COVID-19 pandemic, thereby contributing to the overall knowledge of crisis line volunteering, and gaining an understanding of how this role is impacted by the pandemic.

Gene Therapy Potential for Genetic Disorders of Surfactant Dysfunction.

Pulmonary surfactant is critically important to prevent atelectasis by lowering the surface tension of the alveolar lining liquid. While respiratory distress syndrome (RDS) is common in premature infants, severe RDS in term and late preterm infants suggests an underlying genetic etiology. Pathogenic variants in the genes encoding key components of pulmonary surfactant including surfactant protein B (SP-B, gene), surfactant protein C (SP-C, gene), and the ATP-Binding Cassette transporter A3 (ABCA3, gene) result in severe neonatal RDS or childhood interstitial lung disease (chILD).

Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization.

Introduction: Fate determination of germline stem cells remains poorly understood at the chromatin structure level.

Objectives: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors.

Methods: The offspring production from oocytes transdifferentiated from mouse SSCs with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs.

Functional correction of CFTR mutations in human airway epithelial cells using adenine base editors.

Mutations in the CFTR gene that lead to premature stop codons or splicing defects cause cystic fibrosis (CF) and are not amenable to treatment by small-molecule modulators. Here, we investigate the use of adenine base editor (ABE) ribonucleoproteins (RNPs) that convert A•T to G•C base pairs as a therapeutic strategy for three CF-causing mutations. Using ABE RNPs, we corrected in human airway epithelial cells premature stop codon mutations (R553X and W1282X) and a splice-site mutation (3849 + 10 kb C > T).

Chronic Eosinophilic Leukaemia Associated with JAK2 Exon 13 Insertion/Deletion Mutations.

Chronic eosinophilic leukaemia, not otherwise specified (CEL, NOS), is a diagnosis of exclusion made in cases in which there is clonal eosinophilia but an absence of genetic aberrations that define other disease subtypes. There is a need for further characterization of these cases in order to inform risk stratification and management. The importance of JAK2 mutations in myeloproliferative neoplasms (MPN) as a whole is well established, although their role specifically in eosinophilic disorders is less clear, with only a minority of cases demonstrating JAK2 abnormalities.

Lentiviral vectors transduce lung stem cells without disrupting plasticity.

Life-long expression of a gene therapy agent likely requires targeting stem cells. Here we ask the question: does viral vector transduction or ectopic expression of a therapeutic transgene preclude airway stem cell function? We used a lentiviral vector containing a GFP or cystic fibrosis transmembrane conductance regulator () transgene to transduce primary airway basal cells from human cystic fibrosis (CF) or non-CF lung donors and monitored expression and function after differentiation. Ussing chamber measurements confirmed CFTR-dependent chloride channel activity in CF donor cells.

Measles virus exits human airway epithelia within dislodged metabolically active infectious centers.

Measles virus (MeV) is the most contagious human virus. Unlike most respiratory viruses, MeV does not directly infect epithelial cells upon entry in a new host. MeV traverses the epithelium within immune cells that carry it to lymphatic organs where amplification occurs.

A Naturally Occurring Polymorphism in the Base of Sudan Virus Glycoprotein Decreases Glycoprotein Stability in a Species-Dependent Manner.

Sudan virus (SUDV) is one of five filoviruses that compose the genus that has been responsible for episodic outbreaks in Central Africa. While the SUDV glycoprotein (GP) structure has been solved, GP residues that affect SUDV entry have not been extensively examined; many of the entry characteristics of SUDV GP are inferred from studies with the Zaire Ebola virus (EBOV) GP. Here, we investigate the effect on virus entry of a naturally occurring polymorphism in SUDV GP.

Increased CFTR expression and function from an optimized lentiviral vector for cystic fibrosis gene therapy.

Despite significant advances in cystic fibrosis (CF) treatments, a one-time treatment for this life-shortening disease remains elusive. Stable complementation of the disease-causing mutation with a normal copy of the CF transmembrane conductance regulator () gene fulfills that goal. Integrating lentiviral vectors are well suited for this purpose, but widespread airway transduction in humans is limited by achievable titers and delivery barriers.

Assessing the benefits and usefulness of Schwartz Centre rounds in second-year medical students using clinical educator-facilitated group work session: not just "a facilitated moan"!

Background: An experiential curriculum exposing medical students to the clinic early has many benefits but comes with the emotional stress this environment engenders. Schwartz rounds (SR) are an effective means to combat emotional stress and increasingly used in UK and USA hospitals. Recent studies show that the SR format may also provide benefits for medical students.