A 3D Model of the Human Lung Airway for Evaluating Permeability of Inhaled Drugs.

Current in vitro cell-based methods, relying on single cell types, have structural and functional limitations in determining lung drug permeability, which is a contributing factor affecting both local and systemic drug levels. To address this issue, we investigated a 3D human lung airway model generated using a cell culture insert, wherein primary human lung epithelial and endothelial cells were cocultured at an air-liquid interface (ALI). To ensure that the cell culture mimics the physiological and functional characteristics of airway tissue, the model was characterized by evaluating several parameters such as cellular confluency, ciliation, tight junctions, mucus-layer formation, transepithelial electrical resistance, and barrier function through assaying fluorescein isothiocyanate-dextran permeability.

Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.

Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.

Detailed Structural Elucidation of Antibody-Drug Conjugate Biotransformation Species Using High Resolution Multiple Reaction Monitoring Mass Spectrometry with Orthogonal Dissociation Methods.

Antibody-drug conjugates (ADCs) are a promising drug modality substantially expanding in both the discovery space and clinical development. Assessing the biotransformation of ADCs and is important in understanding their stability and pharmacokinetic properties. We previously reported biotransformation pathways for the anti-B7H4 topoisomerase I inhibitor ADC, AZD8205, puxitatug samrotecan, that underpin its structural stability using an intact protein liquid chromatography-high resolution mass spectrometry (LC-HRMS) approach.

Cemdomespib Therapy Slows the Progression of Neuromuscular Weakness and Demyelination in the R75W-Connexin 32 Animal Model of Charcot-Marie-Tooth 1X Disease.

Mutations in connexin 32 (Cx32) are a common cause of Charcot-Marie-Tooth 1X (CMT1X) disease, an inherited peripheral neuropathy characterized by progressive neuromuscular weakness and demyelination. There are no approved pharmacologic therapies for CMT1X, and identifying new treatments that slow the onset and severity of neuromuscular decline may aid disease management. Cemdomespib is an orally bioavailable small molecule that improved demyelination and neuromuscular junction (NMJ) morphology in mice lacking Cx32 expression.

Recommended Opioid Receptor Tool Compounds: Comparative for Receptor Selectivity Profiles and for Pharmacological Antinociceptive Profiles.

Opioid agonist ligands bind opioid receptors and stimulate downstream signaling cascades for various biological processes including pain and reward. Historically, before cloning the receptors, muscle contraction assays using isolated organ tissues were used followed by radiolabel ligand binding assays on native tissues. Upon cloning of the opioid G protein-coupled receptors (GPCRs), cell assays using transfected opioid receptor DNA plasmids became the standard practice including S-GTPγS functional and cAMP based assays.

Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases.

Acetyl coenzyme A (acetyl-CoA), a pivotal regulatory metabolite, is a product of numerous catabolic reactions and a substrate for various anabolic responses. Its role extends to crucial physiological processes, such as glucose homeostasis and free fatty acid utilization. Moreover, acetyl-CoA plays a significant part in reshaping the metabolic microenvironment and influencing the progression of several diseases and conditions, including cancer, insulin resistance, diabetes, heart failure, fear, and neuropathic pain.

Pyrazinyl-Substituted Aminoazoles as Covalent Inhibitors of Thrombin: Synthesis, Structure, and Anticoagulant Properties.

This study presents a novel series of -acylated 1,2,4-triazol-5-amines and 1-pyrazol-5-amines, featuring a pyrazin-2-yl moiety, developed as covalent inhibitors of thrombin. These compounds demonstrated potent inhibitory activity, with derivatives and achieving IC values as low as 0.7 and 0.

Cementless fixation in total joint arthroplasty: Factors impacting osseointegration.

•The success of cementless fixation in TJA depends on a multitude of factors including biological, mechanical, implant, surgical, and material properties.•Biologic fixation has become the primary mode of fixation for the majority of primary total hip arthroplasty (THA) surgeries done today in the United States (US) due to its low complication rate and superior longevity compared to cemented fixation.•Cementless fixation has yet to gain wider acceptance in total knee arthroplasty (TKA) and hip hemiarthroplasty due to several factors including host bone quality, implant design, and surgical technique.

Focusing on antimicrobial resistant infections -are we missing the forest for the trees and the patients for pathogens?

Antimicrobial resistance (AMR) is a challenge because it is associated with worse patient outcomes. To solve the problem will take development of interventions and policies which improve patient outcomes by prolonging survival, improving patient symptoms, function and quality of life. Logically, we should look to focusing resources in areas that would have the greatest impact on public health.

The Effect of Antisolvent Treatment on the Growth of 2D/3D Tin Perovskite Films for Solar Cells.

Antisolvent treatment is used in the fabrication of perovskite films to control grain growth during spin coating. We study widely incorporated aromatic hydrocarbons and aprotic ethers, discussing the origin of their performance differences in 2D/3D Sn perovskite (PEAFASnI) solar cells. Among the antisolvents that we screen, diisopropyl ether yields the highest power conversion efficiency in solar cells.

Emerging Trends and Future Opportunities for Battery Recycling.

The global lithium-ion battery recycling capacity needs to increase by a factor of 50 in the next decade to meet the projected adoption of electric vehicles. During this expansion of recycling capacity, it is unclear which technologies are most appropriate to reduce costs and environmental impacts. Here, we describe the current and future recycling capacity situation and summarize methods for quantifying costs and environmental impacts of battery recycling methods with a focus on cathode active materials.

Sulfur Vacancies Limit the Open-Circuit Voltage of SbS Solar Cells.

Antimony sulfide (SbS) is a promising candidate as an absorber layer for single-junction solar cells and the top subcell in tandem solar cells. However, the power conversion efficiency of SbS-based solar cells has remained stagnant over the past decade, largely due to trap-assisted nonradiative recombination. Here we assess the trap-limited conversion efficiency of SbS by investigating nonradiative carrier capture rates for intrinsic point defects using first-principles calculations and Sah-Shockley statistics.

Surface Composition Impacts Selectivity of ZnTe Photocathodes in Photoelectrochemical CO Reduction Reaction.

Light-driven reduction of CO into chemicals using a photoelectrochemical (PEC) approach is considered as a promising way to meet the carbon neutral target. The very top surface of the photoelectrode and semiconductor/electrolyte interface plays a pivotal role in defining the performance for PEC CO reduction. However, such impact remains poorly understood.

Acceptance and commitment therapy group protocol for caregivers of anxious youth: an open trial pilot study.

Introduction: Anxiety disorders are common, distressing, and impairing for children and families. Cognitive-behavioral interventions targeting the role of family interactions in child anxiety treatment may be limited by lack of attention to antecedents to parental control; specifically, internal parent factors such as experiential avoidance and cognitive fusion. This pilot study evaluates the preliminary efficacy of a group-delivered caregiver treatment program, ACT for Parents of Anxious Children (ACT-PAC) that targets parental experiential avoidance, cognitive fusion, and child internalizing symptoms.

Prevalence of co-occurring conditions among youths receiving treatment with primary anxiety, ADHD, or depressive disorder diagnoses.

Introduction: Anxiety disorders, depressive disorders, and attention-deficit/hyperactivity disorder (ADHD) are some of the most common conditions that youths (<18 years old) receive mental health treatment for. These conditions are associated with high-risk substance use or substance use disorders (SUDs). This study sought to identify the proportion of youths (<18 years old) with anxiety disorders, depressive disorders, or ADHD as a primary diagnosis in community mental health centers (CMHCs) having co-occurring high-risk substance use or a SUD.

The Study of Adolescent Resilience (SOAR): a research protocol.

Background: Adolescence is a particularly sensitive period of development for military-connected youth, given the socioemotional and physical changes that occur against the backdrop of the military career of their parent(s). Military-connected adolescents face unique stressors relative to their civilian counterparts, such as military relocations, parental absence due to deployments and trainings, and parental military-related physical and mental injury. These stressors may change family dynamics and disrupt social support networks, which can have lasting implications for adolescent health and well-being.

Demographics, psychiatric comorbidities, and hospital outcomes across eating disorder types in adolescents and youth: insights from US hospitals data.

Objective: The aim of our study was to delineate the differences in demographics, comorbidities, and hospital outcomes by eating disorder types in adolescents and transitional-age youth (15-26 years), and measure the association with psychiatric comorbidities.

Methods: We conducted a cross-sectional study using the nationwide inpatient sample (2018-2019) and included 7,435 inpatients (age 12-24 years) with a primary diagnosis of eating disorders: anorexia nervosa (AN, 71.7%), bulimia nervosa (BN, 4.

Cognitive outcomes of the at-home brain balance program.

Accessibility to developmental interventions for children and adolescents could be increased through virtual, at-home delivery of training programs. Virtual childhood training programs and their effects on cognitive outcomes have not been well studied. To that end, this study examined the effects of the at-home Brain Balance® (BB) program on the cognitive task performance of children and adolescents with baseline developmental and attentional difficulties.

Understanding psychotic-like experiences in children in the context of dimensions of psychological problems.

Introduction: Although psychotic behaviors can be difficult to assess in children, early identification of children at high risk for the emergence of psychotic symptoms may facilitate the prevention of related disorders. Psychotic-like experiences (PLEs), or subthreshold thought and perceptual disturbances, could be early manifestations of psychosis that may predict a future diagnosis of a psychosis-related disorder or nonspecific correlates of a wide range of psychological problems. Additional research is needed regarding how PLEs map onto dimensions of psychopathology in children.

Psychological effects of psychedelics in adolescents.

This study aimed to investigate differences in long-term psychological effects, acute subjective effects, and side effects associated with psychedelic use in adolescents (aged 16-24), compared with adults (aged 25+). Data from two observational online survey cohorts was pooled, involving adolescents (average age 20.4 ± 2.

Resting-state fMRI activation is associated with parent-reported phenotypic features of autism in early adolescence.

Introduction: Autism Spectrum Disorder (ASD) is characterized by deficits in social cognition, self-referential processing, and restricted repetitive behaviors. Despite the established clinical symptoms and neurofunctional alterations in ASD, definitive biomarkers for ASD features during neurodevelopment remain unknown. In this study, we aimed to explore if activation in brain regions of the default mode network (DMN), specifically the medial prefrontal cortex (MPC), posterior cingulate cortex (PCC), superior temporal sulcus (STS), inferior frontal gyrus (IFG), angular gyrus (AG), and the temporoparietal junction (TPJ), during resting-state functional magnetic resonance imaging (rs-fMRI) is associated with possible phenotypic features of autism (PPFA) in a large, diverse youth cohort.

Translation, cross-cultural adaptation and validation of the universal Welch Emotional Connection Screen using primary and bilingual Spanish-speaking coders of videotaped mother-child interactions.

Introduction: Using clear explicit translatable language, we translated the Welch Emotional Connection Screen into a new universal language instrument, the . In this study, we had two aims: Aim 1 was to establish of the uWECS by comparing scores coded by primary Spanish-speaking coders using the Spanish translation of the uWECS to scores coded by bilingual, secondary Spanish-speaking coders using the oWECS. Aim 2 was to establish the in terms of oWECS and uWECS performance in tracking change in autonomic emotional connection (AEC) during the course of an intervention among preschool aged children.

Blueprint for destigmatizing depression and increasing openness to treatment among adolescents using brief social contact-based videos: a qualitative study.

Background: Depression is a major public health concern for adolescents, who exhibit low rates of connection to care despite significant needs. Although barriers to help-seeking such as stigma are well documented, interventions to address stigma and to increase help-seeking behavior are insufficient. Dissemination of short videos in social media offer a promising approach, but designing effective stimuli requires better insight into adolescents' perspectives of their own experiences, barriers, and possible interventions.