Challenges of Engaging Primary Care Providers in Specialized Telementoring Education About Sickle Cell Disease for Sickle Cell Specialists: Results from the Sickle Cell Disease Training and Mentoring Program for Primary Care Providers (STAMP) Project ECHO.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 100,000 individuals in the U.S. A lack of knowledgeable providers, particularly for adult patients, has led to a significant number of adults without access to high-quality care.

PBAE-PEG based lipid nanoparticles for lung cell-specific gene delivery.

Exemplified by successful use in COVID-19 vaccination, delivery of modified mRNA encapsulated in lipid nanoparticles provides a framework for treating various genetic and acquired disorders. However, lipid nanoparticles that can deliver mRNA into specific lung cell types have not yet been established. Here, we sought whether poly(®-amino ester)s (PBAE) or PEGylated PBAE (PBAE-PEG) in combination with 4A3-SC8/DOPE/cholesterol/DOTAP lipid nanoparticles (LNP) could deliver mRNA into different types of lung cells in vivo.

T1 signal intensity ratio variability based on sampling strategies in the pancreas of children and young adults.

Purpose: T1-weighted signal intensity ratios (SIR) comparing pancreas to spleen (SIRps) or muscle (SIRpm) can semiquantitatively assess T1 signal change associated with pancreatitis. However, there is no standardized methodology for generating these ratios. We set out to determine the impact of MRI sequence as well as region of interest (ROI) location, shape, and size on T1 SIR.

Practice Advisory for Postoperative Pain Management of Thoracic Surgical Patients: Executive Summary: A Report by Society of Cardiovascular Anesthesiologists.

Patients after thoracic surgery experience significant pain that can disrupt normal respiratory mechanics, increase the risk of respiratory complications, and impair recovery. Poorly controlled postoperative pain can develop into persistent postoperative pain. In addition, using opioids for pain control in the thoracic surgical population makes them more susceptible to opioid-related side effects due to their pre-existing comorbidities.

A novel POT1-TPD presentation: A germline pathogenic POT1 variant discovered in a patient with newly diagnosed posterior fossa ependymoma.

Introduction: POT1 tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently reported malignancies [1]. Protection of telomeres protein 1 (POT1) is part of the shelterin protein complex to maintain/protect telomeres [2].

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Ultra high density imaging arrays in diffuse optical tomography for human brain mapping improve image quality and decoding performance.

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13-40 mm) afforded by the HD-DOT grid.

MicroRNA Expression Profile in Acute Ischemic Stroke.

Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels.

Using a Hand-Held Icterometer to Screen for Neonatal Jaundice: Validation, Feasibility, and Acceptability of the Bili-Ruler in Kumasi, Ghana.

Background: Neonatal jaundice (NNJ) remains a leading cause of newborn mortality in much of sub-Saharan Africa. We sought to examine the validity of using a hand-held icterometer as a screening tool to determine which newborns need further assessment. Additionally, we sought to assess the feasibility of its use among mothers.

Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles.

Many micro-particles including pathogens strongly adhere to hosts. It remains elusive how macrophages detach these surface-bound particles during phagocytosis. We show that, rather than binding directly to these particles, macrophages form unique β integrin-mediated adhesion structures at the cell-substrate interfaces, specifically encircling the surface-bound particles.

Practice Advisory for Postoperative Pain Management of Cardiac Surgical Patients: A Report by Society of Cardiovascular Anesthesiologists.

Moderate to severe pain after cardiac surgery is relatively common, which increases the risk of postoperative cardiopulmonary complications and delays hospital discharge. Opioids have been useful agents for postoperative pain control after cardiac surgery, but are associated with serious adverse effects. As a result, multimodal analgesia has been adopted widely to decrease reliance on opioids for treating postoperative pain, reduce opioid-related adverse effects, and promote early recovery.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Notch dimerization provides robustness against environmental insults and is required for vascular integrity.

The Notch intracellular domain (NICD) regulates gene expression during development and homeostasis in a transcription factor complex that binds DNA either as monomer, or cooperatively as dimers. Mice expressing Notch dimerization-deficient (NDD) alleles of Notch1 and Notch2 have defects in multiple tissues that are sensitized to environmental insults. Here, we report that cardiac phenotypes and DSS (Dextran Sodium Sulfate) sensitivity in NDD mice can be ameliorated by housing mice under hypo-allergenic conditions (food/bedding).

Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.

Dietary high salt intake is increasingly recognized as a risk factor for cognitive decline and dementia, including Alzheimer's disease (AD). Recent studies have identified a population of disease-associated astrocytes (DAA)-like astrocytes closely linked to amyloid deposition and tau pathology in an AD mouse model. However, the presence and role of these astrocytes in high-salt diet (HSD) models remain unexplored.

Circulating and Magnetic Resonance Imaging Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease.

Background: We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn's disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content.

Methods: Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers.

A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and as a Combination Vaccine Candidate.

Background: Noroviruses, which cause epidemic acute gastroenteritis, and parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P NP).

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy.

Background: Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry.

Is temperament associated with academic school readiness in children born very preterm?

Research Findings: Temperament, which can be assessed as early as three months, is associated with school readiness and later academic achievement in children born full term. Although children born preterm demonstrate a dysregulated temperament and are at significant risk for lower school readiness, we found no studies investigating whether early temperament is associated with school readiness in this at-risk population. Investigating whether temperament is a precursor of academic risk in preterm children can facilitate early identification and possible intervention efforts.

October 2024 ACIP Meeting Update: Influenza, COVID-19, RSV and Other Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 23-24, 2024, to discuss influenza vaccines, chikungunya vaccines, coronavirus disease (COVID-19) vaccines, RSV immunizations, meningococcal vaccines, human papillomavirus (HPV) vaccines, pneumococcal vaccines, and adult and child/adolescent immunization schedule revisions. This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population.

Alkaline urine is associated with increased risk of calcium phosphate nephrolithiasis in medically complex children receiving enteral nutrition.

Introduction: Calcium phosphate stones are commonly found in medically complex children (MCC) receiving enteral feeds. The objective of this study is to investigate the etiology for calcium phosphate stones in this patient population.

Study Design: This is a retrospective cohort study of gastrostomy fed, MCC who presented to a high-volume Pediatric Stone Center from 2015 to 2019.

Does exercise demonstrate a dose-dependent benefit with cognition in Parkinson's disease?

Background: Exercise confers motor benefits in Parkinson's disease (PD) and may even have disease modifying effects. While the impact of exercise on motor symptoms and quality of life is well-studied in PD, its relationship with cognitive performance warrants further attention.

Methods: In people with PD, self-reported exercise information was quantified using the Rapid Assessment of Physical Activity (RAPA).