Tuning mucoadhesion and mucopenetration in self-assembled poly(lactic acid)-block-poly(oligoethylene glycol methacrylate) block copolymer nanoparticles by controlling side-chain lengths.

The capacity to tune the degree of mucoadhesion and mucopenetration of nanoparticles is essential to improving drug bioavailability, transport, and efficacy at mucosal interfaces. Herein, self-assembled nanoparticles (NPs) fabricated from amphiphilic block copolymers of poly(lactic acid) (PLA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA) with various side chain lengths (PLA-POEGMA) are reported to facilitate tunable mucosal interactions. PLA-POEGMA nanoparticles with long PEG side chain lengths ( = 20, or 40) demonstrated mucoadhesive properties based on rheological synergism, calorimetric tracking of mucin-nanoparticle interactions, and the formation of larger NP-mucin hybrid structures; in contrast, NPs fabricated from block copolymers with shorter PEG side chains ( = 2/8-9 or = 8,9) showed poor mucoadhesion but penetrated through the mucin layer with significantly higher permeation rates (>80%).

Terminal complement inhibition and control of hemolysis in patients with paroxysmal nocturnal hemoglobinuria who switched from high-dose eculizumab to ravulizumab: a phase IV, single-arm clinical trial.

Not available.

Decoding the transcriptomic signatures of psychological trauma in human cortex and amygdala.

Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking trauma with psychiatric risk remain incompletely understood. Using RNA-seq data postmortem brain tissue of a cohort of 304 donors (N=136 with trauma exposure), we investigated transcriptional signatures of trauma exposures in two cortical regions (dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex) and two amygdala regions (medial amygdala and basolateral amygdala) associated with stress processing and regulation. We focused on dissecting heterogeneity of traumatic experiences in these transcriptional signatures by investigating exposure to several trauma types (childhood, adulthood, complex, single acute, combat, and interpersonal traumas) and interactions with sex.

Gluconeogenesis and glycogenolysis required in metastatic breast cancer cells.

Introduction: Metabolic adaptability, including glucose metabolism, enables cells to survive multiple stressful environments. Glycogen may serve as a critical storage depot to provide a source of glucose during times of metabolic demand during the metastatic cascade; therefore, understanding glycogen metabolism is critical. Our goal was to determine mechanisms driving glycogen accumulation and its role in metastatic (MCF10CA1a) compared to nonmetastatic (MCF10A-) human breast cancer cells.

Features Associated With the Presence of Specific Bacterial Strains in Pediatric Tracheostomy.

Background: Tracheostomy bypasses physical barriers that decrease microbial access to the lower airway, which can lead to changes to the lung microbiota. Patients often become chronically colonized with potential pathogens. This study described the incidence and prevalence of specific organisms in a 5-y cohort of children with tracheostomy.

Partner and social support in childbearing and rearing in a Gulf Coast Native American community.

Objective: This study sought to understand the roles of partners in pregnancy, childbirth, and childrearing in Indigenous communities. It explores supportive and unsupportive attitudes in the relationships mothers experienced, and how these relationships affected their lives.

Background: Settler colonialism has negatively impacted Indigenous communities.

Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome.

Background: Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

Methods: PTSD was defined among biobank participants ( = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs.

The impact of chronic pain on brain gene expression.

Background: Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression.

Methods: We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors.

Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study.

Background: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).

Methods: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded.

Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.

Purpose: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years.

Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in pediatric paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease of uncontrolled terminal complement activation leading to intravascular hemolysis, thrombotic events and increased morbidity and mortality. This phase 3, open-label, single-arm, multicenter study evaluated ravulizumab treatment in eculizumab-naive or -experienced pediatric patients (aged <18 years) with PNH over a 26-week primary evaluation period (PEP) and 4-year extension period (EP). Patients included in the study received weight-based intravenous ravulizumab dosing.

Enantioselective Total Synthesis of (-)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy.

The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone.

A brief note on substantial sub-daily arsenic variability in pumping drinking-water wells in New Hampshire.

Large variations in redox-related water parameters, like pH and dissolved oxygen (DO), have been documented in New Hampshire (United States) drinking-water wells over the course of a few hours under pumping conditions. These findings suggest that comparable sub-daily variability in dissolved concentrations of redox-reactive and toxic arsenic (As) also may occur, representing a potentially critical public-health data gap and a fundamental challenge for long-term As-trends monitoring. To test this hypothesis, discrete groundwater As samples were collected approximately hourly during one day in May and again in August 2019 from three New Hampshire drinking-water wells (2 public-supply, 1 private) under active pumping conditions.

Factors for which radiology residents choose fellowship.

Purpose: The objective of this study is to assess factors that influence radiology residents' decision to pursue fellowship. Historically a large majority of Diagnostic Radiology (DR) residents have pursued fellowship, but with changes in the job market and the Covid-19 pandemic, this study analyzes the current trends associated with radiology fellowship choice.

Materials And Methods: An anonymous 28-question survey was constructed based on literature review and pilot feedback from university radiology residents.

Clinical Inquiry in Nursing Readiness Fellowship: Increasing Air Force Nurse Corps Evidence-Based Practice Leadership Infrastructure.

Background: Increasing demands to generate, translate, and implement evidence into practice in manpower and budget-constrained environments triggered innovative support for the nursing scientific community. The Clinical Inquiry in Nursing Readiness (CINR) fellowship is a solution to integrate readiness into clinical inquiry priorities and develop future experts in the field.

Methods: This article describes the fellowship program structure, implementation, and contributions to nursing science, readiness, and professional development.

Polymerization of Physisorbed Molecular Monolayers via Overhanging Alkynyl Chains: Characterization of Polymerization Kinetics and Monolayer Durability.

Monolayers self-assembled by triphenyleneethynylene (TPE) compounds bearing two terminal alkynyl chains were polymerized by Glaser-Hay (G-H) alkyne coupling at the acetonitrile-HOPG interface. The alkynyl chains extend into the solution due to the monolayer's dense-packed morphology. Reacting substructures that have no morphology-determining roles is a potential strategy for preserving monolayer morphology throughout polymerization.

Extracellular Vesicles and Bacteriophages: New Directions in Environmental Biocolloid Research.

There is a long-standing appreciation among environmental engineers and scientists regarding the importance of biologically derived colloidal particles and their environmental fate. This interest has been recently renewed in considering bacteriophages and extracellular vesicles, which are each poised to offer engineers unique insights into fundamental aspects of environmental microbiology and novel approaches for engineering applications, including advances in wastewater treatment and sustainable agricultural practices. Challenges persist due to our limited understanding of interactions between these nanoscale particles with unique surface properties and their local environments.

Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome.

Background: Prior epidemiological research has linked PTSD with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records (EHR) provide an opportunity to overcome prior clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

Methods: PTSD was defined among biobank participants (total N=123,365) in a major healthcare system using two ICD code-based definitions: broad (1+ PTSD or acute stress codes versus 0; N=14,899) and narrow (2+ PTSD codes versus 0; N=3,026).

Genetically Regulated Gene Expression in the Brain Associated With Chronic Pain: Relationships With Clinical Traits and Potential for Drug Repurposing.

Background: Chronic pain is a common, poorly understood condition. Genetic studies including genome-wide association studies have identified many relevant variants, which have yet to be translated into full understanding of chronic pain. Transcriptome-wide association studies using transcriptomic imputation methods such as S-PrediXcan can help bridge this genotype-phenotype gap.

Characterizing the Transport and Surface Affinity of Extracellular Vesicles Isolated from Yeast and Bacteria in Well-Characterized Porous Media.

Extracellular vesicles (EVs) are membrane-bounded, nanosized particles, produced and secreted by all biological cell types. EVs are ubiquitous in the environment, operating in various roles including intercellular communication and plant immune modulation. Despite their ubiquity, the role of EV surface chemistry in determining transport has been minimally investigated.

Establishing a pediatric interventional radiology inpatient consult service.

Objective: To delineate pediatric interventional radiology (IR) inpatient consult growth and resulting collections after implementation of a pediatric IR consult service.

Methods: An inpatient IR consult process was created at a single academic children's hospital in October 2019. IR consult note templates were created in Epic (Epic Systems Corporation, Verona, Wisconsin) and utilized by 4 IR physicians.

Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings.

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric syndrome with genetic and environmental influences. In addition to neuroanatomical and circuit-level disturbances, dysregulation of the brain transcriptome is a key phenotypic signature of MDD. Postmortem brain gene expression data are uniquely valuable resources for identifying this signature and key genomic drivers in human depression; however, the scarcity of brain tissue limits our capacity to observe the dynamic transcriptional landscape of MDD.