Versatile tissue-injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics.

Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA-approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)-based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization.

Mobile Media Content Exposure and Toddlers' Responses to Attention Prompts and Behavioral Requests.

Importance: With personalized touch-screen tablets, young children can choose content and engage in play-like activities. However, tablets may also reduce shared engagement as the action of viewing or touching the screen is often not visible to nearby adults. This may impact communicative gazing and pointing, which is critical to the formation of shared awareness and in turn supports language development.

Noradrenergic tuning of arousal is coupled to coordinated movements.

Matching arousal level to the motor activity of an animal is important for efficiently allocating cognitive resources and metabolic supply in response to behavioral demands, but how the brain coordinates changes in arousal and wakefulness in response to motor activity remains an unclear phenomenon. We hypothesized that the locus coeruleus (LC), as the primary source of cortical norepinephrine (NE) and promoter of cortical and sympathetic arousal, is well-positioned to mediate movement-arousal coupling. Here, using a combination of physiological recordings, fiber photometry, optogenetics, and behavioral tracking, we show that the LC activation is tightly coupled to the return of organized movements during waking from an anesthetized state.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

Objectives: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed.

Design: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science.

Setting: Not applicable.

A call to integrate health equity into learning health system research training.

In 2016, the Agency for Healthcare Research and Quality (AHRQ) recommended seven domains for training and mentoring researchers in learning health systems (LHS) science. Health equity was not included as a competency domain. This commentary from scholars in the Consortium for Applied Training to Advance the Learning health system with Scholars/Trainees (CATALyST) K12 program recommends that competency domains be extended to reflect growing demands for evidence on health inequities and interventions to alleviate them.

microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass.

Background The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells.

ALPACA: A fast and accurate computer vision approach for automated landmarking of three-dimensional biological structures.

Landmark-based geometric morphometrics has emerged as an essential discipline for the quantitative analysis of size and shape in ecology and evolution. With the ever-increasing density of digitized landmarks, the possible development of a fully automated method of landmark placement has attracted considerable attention. Despite the recent progress in image registration techniques, which could provide a pathway to automation, three-dimensional (3D) morphometric data are still mainly gathered by trained experts.

Diagnosis and clinical management of Wiskott-Aldrich syndrome: current and emerging techniques.

Introduction: Wiskott-Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold.

Areas Covered: This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications.

Breaking through barriers: the need for effective research to promote language-concordant communication as a facilitator of equitable emergency care.

Individuals with limited English proficiency (LEP) are at high risk for adverse outcomes in the US health care system. This is particularly true for patients with LEP seeking care in the emergency department (ED). Although professional language interpretation improves the quality of care for these patients, it remains underused.

Pilot evaluation of obesity-specific health-related quality of life following a 12-week non-randomized lifestyle intervention in youth.

Background: Health-related quality of life (HRQOL), a multifaceted construct for understanding health and healthcare outcomes, is comprised of eight domains of well-being and functioning over time and has become an essential factor in assessing outcomes for youth with obesity.

Aims: To evaluate the effect of a community based, lifestyle intervention, on obesity-specific HRQOL using the Sizing Me Up (SMU) in this group of Latino and White youth.

Materials And Methods: For this 12-week family and community-based intervention (ACT; Actively Changing Together), HRQOL was measured before and after the intervention concluded using the obesity-specific HRQOL tool, SMU.

Longitudinal study of early adaptation to the coronavirus disease pandemic among youth with chronic pain and their parents: effects of direct exposures and economic stress.

The novel coronavirus disease (COVID-19) has caused prolonged disruptions in daily life for many communities. Little is known about the impact of the COVID-19 pandemic on the health and well-being of youth with chronic pain and their families. We conducted a longitudinal, mixed-methods study to characterize early adaptation to the COVID-19 pandemic among 250 families of youth (ages 12-21 years) diagnosed with chronic headache (64%) or other chronic pain conditions (36%) and to determine whether direct exposures to COVID-19 and secondary economic stress modified symptom trajectories.

Identification of P218 as a potent inhibitor of DHFR.

is the causative agent of Buruli ulcer, a debilitating chronic disease that mainly affects the skin. Current treatments for Buruli ulcer are efficacious, but rely on the use of antibiotics with severe side effects. The enzyme dihydrofolate reductase (DHFR) plays a critical role in the biosynthesis of folate species and is a validated target for several antimicrobials.

Pediatric Death by Neurologic Criteria: The Ever-Changing Landscape and the Expanding Role of Palliative Care Professionals.

Pediatric palliative care providers are especially suited to support families and medical teams facing a potential diagnosis of brain death, or death by neurologic criteria (DNC), when a child suffers a devastating brain injury. To support pediatric palliative care providers' effectiveness in this role, this article elucidates the clinical determination of DNC and the evolution of the ethical and legal controversies surrounding DNC. Conceptual definitions of death used in the context of DNC have been and continue to be debated amongst academicians, and children's families often have their own concept of death.

Hypoglycaemia avoidance behaviour and exercise levels in active youth with type 1 diabetes.

Aims: The primary goal of this exploratory study was to examine the association between fear of hypoglycaemia (FOH), hypoglycaemia avoidance behaviours and exercise in active youth with type 1 diabetes (T1D).

Methods: 30 youth with T1D who participate in some physical activity (PA), age 15.0 ± 2.

p.P1379S, a benign variant with reduced ATP7B protein level in Wilson Disease.

Background: Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by inherited defects in the gene and results in toxic accumulation of copper in various organs. We previously reported a family with three consecutive generations affected by WD that carries the variant, p.P1379S, which was classified at the time as likely pathogenic.

Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload.

Background The right ventricle exposed to chronic pressure overload exhibits hypertrophy and decompensates when exposed to stress. We hypothesize that impaired ability to increase myocardial oxidative flux through pyruvate dehydrogenase leads to hypertrophied right ventricular (RV) dysfunction when exposed to hemodynamic stress, and pyruvate dehydrogenase stimulation can improve RV function. Methods and Results Infant male Yorkshire piglets (13.

O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.

Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood. In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental. We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.

Mapping genetic variants for cranial vault shape in humans.

The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the genetic basis of normal vault shape in humans.