Amphipathic Antimicrobial Peptides Illuminate a Reciprocal Relationship between Self-assembly and Cytolytic Activity.

Amphipathic character, encoded within polar sequence patterns of antimicrobial peptides, is a critical structural feature that influences membrane disruptive behavior. Similarly, polar sequence patterns induce self-assembly of amphipathic peptides, which results in the formation of ordered supramolecular structures. The relationship between self-assembly and membrane activity remains an open question of relevance for the development of effective antimicrobial peptides.

Immune suppression sustained allograft acceptance requires PD1 inhibition of CD8+ T cells.

Organ transplant recipients require continual immune-suppressive therapies to sustain allograft acceptance. Although medication nonadherence is a major cause of rejection, the mechanisms responsible for graft loss in this clinically relevant context among individuals with preceding graft acceptance remain uncertain. Here, we demonstrate that skin allograft acceptance in mice maintained with clinically relevant immune-suppressive therapies, tacrolimus and mycophenolate, sensitizes hypofunctional PD1hi graft-specific CD8+ T cells.

EZH2 coordinates memory B-cell programming and recall responses.

Antigen-experienced memory B-cells (MBC) are endowed with enhanced functional properties compared to naïve B cells and play an important role in the humoral response. However, the epigenetic enzymes and programs that govern their rapid differentiation are incompletely understood. Here, the role of the histone H3 lysine 27 methyltransferase EZH2 in the formation of MBC in response to an influenza infection was determined in Mus musculus.

A Retrospective Comparison of Cephalomedullary Nail Fixation of Intertrochanteric Femur Fractures Treated With Locked Versus Backed-off Set Screws.

Introduction: Excessive lag screw sliding after cephalomedullary nail fixation of intertrochanteric fractures can be problematic. Set screws are typically inserted to engage the lag screw and backed off to allow for sliding. The purpose of this study was to determine whether statically locking set screws affected lag screw sliding or cutout.

Reduction of Central Line-Associated Bloodstream Infections on a Transplant Unit.

Background: Central line-associated bloodstream infection (CLABSI) is a preventable complication of central venous catheters (CVC) that can result in prolonged hospitalization, increased cost, and mortality.

Local Problem: CLABSI rates in a solid organ transplant unit were above the National Database of Nursing Quality Indicators target.

Methods: Evidence-based CLABSI prevention interventions were implemented using the Plan-Do-Study-Act process.

Caki-1 Spheroids as a Renal Model for Studying Free Fatty Acid-Induced Lipotoxicity.

Lipotoxicity, resulting from the buildup of excess lipids in non-adipose tissues, is increasingly recognized as a major contributor to the progression of kidney disease, highlighting the need for alternative models to assess its effects on renal cells. The main aim of this study was to investigate the usefulness of Caki-1, a human proximal tubule (PT) and renal cell carcinoma (RCC) representative cell line, as a 3D model system for studying free fatty acid-induced PT lipotoxicity. Caki-1 spheroids were generated and maintained on ultra-low attachment plates and characterized regarding time-dependent morphology changes.

Opportunities to encourage adoption of a biomarker-enabled care pathway for Alzheimer's in primary care.

Unlabelled: Identification of early-stage Alzheimer's disease (AD) remains a challenge due to limited specialist availability, diagnostic access, disease awareness, and cultural factors. Blood-based biomarkers (BBBM) could play a critical role in the identification and referral of patients suspected of AD to specialty care. A multidisciplinary AD Biomarker Task Force was convened to evaluate current biomarker use cases, define an optimal biomarker-enabled AD diagnostic care pathway, and understand factors impacting adoption.

Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside of lymph node (LN) follicles.

Methods: Here, we employed spatial transcriptomics and multiplex imaging to investigate the follicular immune landscaping and the transcriptomic profile in LNs from SLE individuals.

Results: Our spatial transcriptomic analysis revealed robust type I IFN and plasma cell signatures in SLE compared to reactive, control follicles.

Enhancing the diagnostic efficacy of right-to-left shunt using robot-assisted transcranial Doppler: a quality improvement project.

Background: Stroke is the leading cause of adult disability worldwide, with approximately 30% of strokes remaining cryptogenic. One potential important etiology is a patent foramen ovale (PFO), which may contribute to stroke through paradoxical thromboembolism or thromboembolus formation. Recent advancements in robot-assisted transcranial Doppler (raTCD) have shown increased sensitivity in detecting right-to-left shunt (RLS) compared to transthoracic echocardiography (TTE), particularly in detecting the large shunts which are associated with higher stroke risk.

Education Research: Exploring the Impact of Standardized, Condition-Specific Note Templates on Quality Metrics and Efficiency in Multiple Resident Clinics.

Background And Objectives: Electronic health record documentation burden negatively affects physician satisfaction and patient care. Although well-constructed notes are important for care quality and safety, most note templates are created and maintained by individual physicians, leading to inefficiency and variable note quality. This study aimed to assess whether standardized, condition-specific note templates could enhance the efficiency and quality of notes written by neurology residents in the outpatient setting.

A Clinical, Morphologic, and Molecular Comparison of Bonafide Spitz Melanomas and ASTs in the Pediatric Population.

Pediatric Spitz melanoma (SM) with bonafide metastatic disease is rare. In this study, we assembled the largest cohort to date of pediatric SM with a verified Spitz-associated genomic driver and clinical follow-up demonstrating bonafide metastasis. We compared the clinical, morphologic, and molecular features of these SMs to a control cohort of 57 pediatric atypical Spitz tumors (ASTs).

UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor.

TYRO3 plays a critical role in platelet aggregation as a platelet response amplifier. Selective inhibition of TYRO3 may provide therapeutic benefits for treating thrombosis and related diseases without increasing bleeding risk. We employed a structure-based approach and discovered a novel and potent TYRO3 inhibitor UNC9426 () with an excellent Ambit selectivity score ( (1.

Aberrant DNA methylation of genes regulating CD4+ T cell HIV-1 reservoir in women with HIV.

Background: The HIV-1 reservoir in CD4+ T cells (HR) pose a major challenge to curing HIV, with many of its mechanisms still unclear. HIV-1 DNA integration and immune responses may alter the host's epigenetic landscape, potentially silencing HIV-1 replication.

Methods: This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HR.

Whose sleep matters? Untangling the relationships between maternal sleep, child sleep, and maternal depressive symptoms in the first two years of life.

Infants frequently experience sleep problems in early childhood. Poor infant sleep can impact not only infants' cognitive development but also maternal sleep and maternal mental health. Studies have reported associations between infant sleep and maternal sleep and between infant sleep and maternal depression.

Study-phase reinstatement predicts subsequent recall.

Can the brain improve the retrievability of an experience after it has occurred? Systems consolidation theory proposes that item-specific cortical reactivation during post-encoding rest periods facilitates the formation of stable memory representations, a prediction supported by neural evidence in humans and animals. Such reactivation may also occur on shorter timescales, offering a potential account of classic list memory phenomena but lacking in support from neural data. Leveraging the high temporal specificity of intracranial electroencephalography (EEG), we investigate spontaneous reactivation of previously experienced items during brief intervals between individual encoding events.

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging.

Generating New Meniscus Therapies via Recent Breakthroughs in Development, Model Systems, and Clinical Diagnostics.

Over 850,000 surgeries are performed to treat meniscal injuries each year in the United States. Even with repair, patients are likely to develop osteoarthritis (OA) within the next two decades. There is a pressing clinical need to improve meniscal repair procedures to restore tissue function and prevent joint degeneration later in life.

GABA and Glycine Synaptic Release on Axotomized Motoneuron Cell Bodies Promotes Motor Axon Regeneration.

Motor axon regeneration after traumatic nerve injuries is a slow process that adversely influences patient outcomes because muscle reinnervation delays result in irreversible muscle atrophy and suboptimal axon regeneration. This advocates for investigating methods to accelerate motor axon growth. Electrical nerve stimulation and exercise both enhance motor axon regeneration in rodents and patients, but these interventions cannot always be easily implemented.

A Scoping Review of Interventions Designed to Increase Behavioural Health Service Engagement.

Background: A documented underutilization of behavioural health interventions with known efficacy for treating psychological disorders exists. Thus, engagement enhancement approaches (EEAs) exist to help increase individuals' use of behavioural health interventions. EEAs target a range of barriers to treatment; therefore, a wide variety of approaches exist.

Relations of temporoparietal connectivity with neighborhood social fragmentation in youth at clinical high-risk for psychosis.

Temporoparietal brain areas comprise a candidate set of regions for interrogating the brain functional correlates of socioenvironmental factors in people at clinical high-risk for psychosis (CHR-P). Temporal lobe abnormalities have been shown to be common among people with schizophrenia spectrum conditions. Further, temporoparietal brain regions are implicated in tasks relevant to psychosocial outcomes, including coherent autobiographical memory recall and multimodal integration.

Clinical Heterogeneity and Transitions of Obesity in Mexico. A Longitudinal Analysis of Multiple Representative National Surveys.

Background: There is large variation in the individual risk of developing obesity-associated comorbidities. While obesity is highly prevalent in Mexico, data on the extent and heterogeneity of its associated co-morbidities is lacking. Hereby, we estimated the prevalence of different obesity-associated comorbidities, and how they have changed over 15 years.

Changes in Vasectomy Practice Patterns After-Dobbs: A Multi-Institutional Study.

Importance: Following the Dobbs decision overruling Roe vs. Wade, public interest in vasectomies increased. This ruling directly impacted urologic practice patterns, and warrants further investigation.

CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.

Importance: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increase of cellular adenosine triphosphate production.

Objective: To determine the effects of CNM-Au8 on ALS disease progression.

Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial.

Importance: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.

Objective: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.