Executive Functioning, Family Accommodation, and Treatment Response in Youth with OCD and Comorbid ADHD in a Partial Hospital Program.

Few studies have examined differential treatment response, rates of familial accommodation (FA), and executive functioning (EF) in youth with OCD vs. OCD + ADHD, particularly in a partial hospital program (PHP). The current study includes 138 youth diagnosed with OCD only and 102 youth diagnosed with OCD + ADHD in a PHP setting for a total sample of 240 youth (and their families).

Parent-child emotion dynamics in families presenting for behavioral parent training: Is there a link with child behavior, parenting, and treatment outcome?

Objective: Behavioral parent training (BPT) is the standard of care for early onset behavior disorders (BDs), however, not all families benefit. Emotion regulation (ER) is one potential mechanism underlying BPT outcomes, yet there are challenges in capturing intra- and interpersonal aspects of emotion regulation within parent-child interactions that are central to BPT. This study examined how vocally encoded emotional arousal unfolds during parent-child interactions and how parents and children influence each other's arousal (Aim 1), the links between these emotion dynamics, child behavior, and parenting at baseline (Aim 2), and BPT outcome (Aim 3).

Discovery of TRPA1 Antagonist : Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease.

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium ion channel highly expressed in the primary sensory neurons, functioning as a polymodal sensor for exogenous and endogenous stimuli, and has been implicated in neuropathic pain and respiratory disease. Herein, we describe the optimization of potent, selective, and orally bioavailable TRPA1 small molecule antagonists with strong target engagement in rodent models. Several lead molecules in preclinical single- and short-term repeat-dose toxicity studies exhibited profound prolongation of coagulation parameters.

Poverty and the wellbeing of children with sickle cell disease: The mediating role of parenting stress.

Background: Living in poverty in the midst of caring for a child with sickle cell disease (SCD) presents with challenges that may be overwhelming for caregivers. Prior research has shown a relationship between poverty and poor outcomes in children; however, no study has investigated the mediating role of parenting stress on health-related quality of life (HRQOL) for such children.

Procedure: A total of 150 patients, ages 8-17 years and their parents, were enrolled and completed measures of parenting stress (caregivers) and HRQOL (patients).

Parent-identified barriers to accessing exposure therapy: A qualitative study using process mapping.

Background: Youth with anxiety and obsessive-compulsive disorder (OCD) rarely access exposure therapy, an evidence-based treatment. Known barriers include transportation, waitlists, and provider availability. Efforts to improve access to exposure require an understanding of the process that families take to find therapists, yet no prior studies have examined parents' perspectives of the steps involved.

Functional imaging and quantification of multineuronal olfactory responses in .

Many animals perceive odorant molecules by collecting information from ensembles of olfactory neurons, where each neuron uses receptors that are tuned to recognize certain odorant molecules with different binding affinity. Olfactory systems are able, in principle, to detect and discriminate diverse odorants using combinatorial coding strategies. We have combined microfluidics and multineuronal imaging to study the ensemble-level olfactory representations at the sensory periphery of the nematode .

Challenges and opportunities of remote public involvement and community engagement during a pandemic: refining the MapMe childhood healthy weight intervention.

Aims: Including parents and other stakeholders in the development of interventions to address the sensitive public health issues such as childhood obesity, through public involvement is critical. However, the Covid-19 pandemic has created a challenge for public involvement and engagement activities (PICE). The aim of this paper is to describe the process and challenges of setting up, maintaining, evaluating, and recording impact of three public and stakeholder groups via remote methods in the context of the MapMe2 study during the Covid-19 pandemic.

Agreement in the reporting of General Practitioner requested musculoskeletal radiographs: Reporting radiographers and consultant radiologists compared with an index radiologist.

Introduction: This study assessed the inter-observer agreement of reporting radiographers and consultant radiologists compared with an index radiologist when reporting General Practitioner (GP) requested musculoskeletal radiographs. The potential effect of discordant reports on patient management and outcome was also examined.

Methods: Three reporting radiographers, three consultant radiologists and an index radiologist reported on a retrospective randomised sample of 219 GP requested musculoskeletal radiographs, in conditions simulating clinical practice.

Reduction in Virulence over Time in (OsHV-1) Microvariants between 2011 and 2015 in Australia.

Microvariant genotypes of (OsHV-1) are associated with mass mortality events of Pacific oysters in many countries. The OsHV-1 microvariant (µVar) emerged in France 2008 and caused significant economic losses as it became endemic and displaced the previously dominant OsHV-1 reference genotype. Recently, considerable genotypic variation has been described for OsHV-1 microvariants, however, less is known about variation in viral phenotype.

Tpl2 kinase regulates inflammation but not tumorigenesis in mice.

Tumor progression locus 2 (Tpl2, gene name MAP3K8), a mitogen-activated protein kinase, is widely expressed in immune and non-immune cells to integrate tumor necrosis factor (TNF), toll-like receptors (TLRs), and interleukin-1 (IL1) receptor signaling to regulate inflammatory response. Given its central role in inflammatory response, Tpl2 is an attractive small molecule drug target. However, the role of Tpl2 as an oncogene or tumor suppressor gene remains controversial, and its function outside immune cells is not understood.

Preclinical Safety Assessment of a Highly Selective and Potent Dual Small-Molecule Inhibitor of CBP/P300 in Rats and Dogs.

Cyclic adenosine monophosphate-response element (CREB)-binding protein (CBP) and EP300E1A-binding protein (p300) are members of the bromodomain and extraterminal motif (BET) family. These highly homologous proteins have a key role in modulating transcription, including altering the status of chromatin or through interactions with or posttranslational modifications of transcription factors. As CBP and p300 have known roles for stimulating c-Myc oncogenic activity, a small-molecule inhibitor, GNE-781, was developed to selectively and potently inhibit the CBP/p300 bromodomains (BRDs).

Factors associated with willingness to provide biospecimens for genetics research among African American cancer survivors.

This study evaluated factors associated with willingness to provide biospecimens for cancer genetic research among African American cancer survivors. A total of 200 African American adults diagnosed with breast, colon, and/or prostate cancers completed a self-administered survey. Family history information, beliefs about cancer research, cancer genetics and disparities knowledge, willingness to provide a biospecimen, and demographics were obtained.

Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma.

Preclinical and clinical evidence indicates that a subset of asthma is driven by type 2 cytokines such as interleukin-4 (IL-4), IL-5, IL-9, and IL-13. Additional evidence predicts pathogenic roles for IL-6 and type I and type II interferons. Because each of these cytokines depends on Janus kinase 1 (JAK1) for signal transduction, and because many of the asthma-related effects of these cytokines manifest in the lung, we hypothesized that lung-restricted JAK1 inhibition may confer therapeutic benefit.

Improving Access to Care by Admission Process Redesign in a Veterans Affairs Skilled Nursing Facility.

Background: Inefficient and inadequate nursing home screening processes can delay care transitions from hospitals to post-acute care facilities and result in inappropriate and delayed transfers. The increased volume of admission requests and need for efficient and effective transfers between care settings converged to make the Community Living Center (CLC; skilled nursing facility in the Department of Veterans Affairs) admission screening process an organizational priority for improvement. A quality improvement (QI) project was conducted to develop a new process for a 112-bed CLC and improve efficiency and access to care.

Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer.

Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively.

Proof of Concept for an Automated Image Analysis Method to Quantify Rat Bone Marrow Hematopoietic Lineages on H&E Sections.

The bone marrow is an important site for assessment of the hematopoietic toxicity of new drug candidates. Here, we extended our previous work, where we developed a computer algorithm to automatically quantitate overall bone marrow cell density by analyzing digitized images of standard hematoxylin and eosin (H&E) slides of rat bone marrow and further evaluated the capability to quantify myeloid: erythroid + lymphoid (M:EL) ratio and megakaryocyte cell density. We tested the algorithm in a toxicity study, where rats were dosed with two molecules known to affect bone marrow composition, monomethyl auristatin E, and a Bcl-xL inhibitor.

An Automated Image Analysis Method to Quantify Veterinary Bone Marrow Cellularity on H&E Sections.

Bone marrow toxicity is a common finding when assessing safety of drug candidate molecules. Standard hematoxylin and eosin (H&E) marrow tissue sections are typically manually evaluated to provide a semiquantitative assessment of overall cellularity. Here, we developed an automated image analysis method that allows quantitative assessment of changes in bone marrow cell population in sternal bone.

MEK and ERK Kinase Inhibitors Increase Circulating Ceruloplasmin and Cause Green Serum in Rats.

Inhibition of the mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK) pathway is an attractive therapeutic approach for human cancer therapy. In the course of evaluating structurally distinct small molecule inhibitors that target mitogen-activated protein kinase kinase (MEK) and ERK kinases in this pathway, we observed an unusual, dose-related increase in the incidence of green serum in preclinical safety studies in rats. Having ruled out changes in bilirubin metabolism, we demonstrated a 2- to 3-fold increase in serum ceruloplasmin levels, likely accounting for the observed green color.

Assessment of placental transfer and the effect on embryo-fetal development of a humanized monoclonal antibody targeting lymphotoxin-alpha in non-human primates.

An enhanced embryo-fetal development study was conducted in cynomolgus monkeys using pateclizumab, a humanized IgG1 monoclonal antibody (mAb) targeting lymphotoxin-alpha. Pateclizumab administration between gestation days (GD) 20 and 132 did not induce maternal or developmental toxicities. The ratio of fetal-to-maternal serum concentration of pateclizumab was 0.

Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window.

p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window.

PANACEA OR PLACEBO? AN EVALUATION OF THE VALUE OF EMOTIONAL INTELLIGENCE IN HEALTHCARE WORKERS.

The purpose of this study was to empirically investigate the relationship between emotional intelligence and desirable nursing behaviors, measured as organizational citizenship beehavior (OCB). We used Mayer and Salovey's (1997) four-dimensional model of emotional intelligence and Organ's (1988) OCB construct to test the EI-OCB relationships. Using a sample of 137 clinical nurses, and analyzing the data with hierarchical multiple regressions, we obtained results indicating that the EI dimension perceiving emotion was linked to conscientiousness, and facilitating thinking wvas linked to civic virtue.

Beliefs and Preferences for Medical Research Among African-Americans.

Background And Objectives: Numerous factors contribute to underrepresentation of African-Americans in medical research, including beliefs, historical events, structural, and health access obstacles. This study examined beliefs about medical research and the types of study methods preferred among potential African-American research participants.

Methods: A sample of 304 African-American participants from the Washington, DC Metropolitan area, completed a survey evaluating beliefs about medical research and preferred research study methods.

Balancing Efficacy and Safety of an Anti-DLL4 Antibody through Pharmacokinetic Modulation.

Purpose: Although agents targeting Delta-like ligand 4 (DLL4) have shown great promise for angiogenesis-based cancer therapy, findings in recent studies have raised serious safety concerns. To further evaluate the potential for therapeutic targeting of the DLL4 pathway, we pursued a novel strategy to reduce toxicities related to DLL4 inhibition by modulating the pharmacokinetic (PK) properties of an anti-DLL4 antibody.

Experimental Design: The F(ab')2 fragment of anti-DLL4 antibody (anti-DLL4 F(ab')2) was generated and assessed in efficacy and toxicity studies.