Unilateral identification of a rare superficial brachioulnoradial artery contributing to the superficial palmar arch and brachial artery continuing as the interosseous artery: a case report.

The occurrence of variations in human arterial branching of the upper limb has been commonly reported in peer-reviewed literature. However, the variability of upper limb arterial patterns may be underappreciated in medical practice, which can result in clinical and surgical errors. Here we report a case of a rare, unilateral arterial variation of the left upper limb of a 76-year-old Caucasian male cadaver, discovered during a routine educational dissection. Observed characteristics of the variation include a high brachial artery bifurcation into a superficial brachioulnoradial artery and brachial artery continuing as the interosseous artery and then a bifurcation of the superficial brachioulnoradial artery into a superficial radial and a superficial ulnar artery, which eventually contribute to the formation of the superficial palmar arch. The anatomical characteristics, prevalence, embryological origin, and clinical significance of the variation are discussed.

Antibacterial efficacy, mode of action, and safety of a novel nano-antibiotic against antibiotic-resistant Escherichia coli strains.

Globally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to treatment failure with current antibiotics. Enterobacteria, particularly Escherichia coli, cause infections of surgical wound, bloodstream, and urinary tract, including pneumonia and sepsis. Herein, we tested in vitro antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH2-AgNP) against the AR bacteria. Two AR E. coli strains (i.e., ampicillin- and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5α, were tested for susceptibility to NH2-AgNP using Kirby-Bauer disk diffusion and standard growth assays. Dynamic light scattering (DLS) was used to determine cell debris and relative conductance was used as a measure of cell leakage, and results were confirmed with transmission electron microscopy (TEM). Multiple oxidative stress assays were used for in vitro safety evaluation of NH2-AgNP in human lung epithelial cells. Results showed that ampicillin and kanamycin did not inhibit growth in either AR bacterial strain with doses up to 160 µg/mL tested. NH2-AgNP exhibited broad-spectrum bactericidal activity, inhibiting the growth of all three bacterial strains at doses ≥1 µg/mL. DLS and TEM revealed cell debris formation and cell leakage upon NH2-AgNP treatment, suggesting two possible MoAs: electrostatic interactions followed by cell wall damage. Safety evaluation revealed NH2-AgNP as noncytotoxic and antioxidative to human lung epithelial cells. Taken together, these results suggest that NH2-AgNP may serve as an effective and safer bactericidal therapy against AR bacterial infections compared to common antibiotics.

Demographic and clinical characteristics associated with anxiety and depressive symptom outcomes in users of a digital mental health intervention incorporating a relational agent.

BACKGROUND: Digital mental health interventions (DMHIs) may reduce treatment access issues for those experiencing depressive and/or anxiety symptoms. DMHIs that incorporate relational agents may offer unique ways to engage and respond to users and to potentially help reduce provider burden. This study tested Woebot for Mood & Anxiety (W-MA-02), a DMHI that employs Woebot, a relational agent that incorporates elements of several evidence-based psychotherapies, among those with baseline clinical levels of depressive or anxiety symptoms. Changes in self-reported depressive and anxiety symptoms over 8 weeks were measured, along with the association between each of these outcomes and demographic and clinical characteristics. METHODS: This exploratory, single-arm, 8-week study of 256 adults yielded non-mutually exclusive subsamples with either clinical levels of depressive or anxiety symptoms at baseline. Week 8 Patient Health Questionnaire-8 (PHQ-8) changes were measured in the depressive subsample (PHQ-8 ≥ 10). Week 8 Generalized Anxiety Disorder-7 (GAD-7) changes were measured in the anxiety subsample (GAD-7 ≥ 10). Demographic and clinical characteristics were examined in association with symptom changes via bivariate and multiple regression models adjusted for W-MA-02 utilization. Characteristics included age, sex at birth, race/ethnicity, marital status, education, sexual orientation, employment status, health insurance, baseline levels of depressive and anxiety symptoms, and concurrent psychotherapeutic or psychotropic medication treatments during the study. RESULTS: Both the depressive and anxiety subsamples were predominantly female, educated, non-Hispanic white, and averaged 38 and 37 years of age, respectively. The depressive subsample had significant reductions in depressive symptoms at Week 8 (mean change =-7.28, SD = 5.91, Cohen's d = -1.23, p < 0.01); the anxiety subsample had significant reductions in anxiety symptoms at Week 8 (mean change = -7.45, SD = 5.99, Cohen's d = -1.24, p < 0.01). No significant associations were found between sex at birth, age, employment status, educational background and Week 8 symptom changes. Significant associations between depressive and anxiety symptom outcomes and sexual orientation, marital status, concurrent mental health treatment, and baseline symptom severity were found. CONCLUSIONS: The present study suggests early promise for W-MA-02 as an intervention for depression and/or anxiety symptoms. Although exploratory in nature, this study revealed potential user characteristics associated with outcomes that can be investigated in future studies. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov (#NCT05672745) on January 5th, 2023.

User Engagement Clusters of an 8-Week Digital Mental Health Intervention Guided by a Relational Agent (Woebot): Exploratory Study.

BACKGROUND: With the proliferation of digital mental health interventions (DMHIs) guided by relational agents, little is known about the behavioral, cognitive, and affective engagement components associated with symptom improvement over time. Obtaining a better understanding could lend clues about recommended use for particular subgroups of the population, the potency of different intervention components, and the mechanisms underlying the intervention's success. OBJECTIVE: This exploratory study applied clustering techniques to a range of engagement indicators, which were mapped to the intervention's active components and the connect, attend, participate, and enact (CAPE) model, to examine the prevalence and characterization of each identified cluster among users of a relational agent-guided DMHI. METHODS: We invited adults aged 18 years or older who were interested in using digital support to help with mood management or stress reduction through social media to participate in an 8-week DMHI guided by a natural language processing-supported relational agent, Woebot. Users completed assessments of affective and cognitive engagement, working alliance as measured by goal and task working alliance subscale scores, and enactment (ie, application of therapeutic recommendations in real-world settings). The app passively collected data on behavioral engagement (ie, utilization). We applied agglomerative hierarchical clustering analysis to the engagement indicators to identify the number of clusters that provided the best fit to the data collected, characterized the clusters, and then examined associations with baseline demographic and clinical characteristics as well as mental health outcomes at week 8. RESULTS: Exploratory analyses (n=202) supported 3 clusters: (1) "typical utilizers" (n=81, 40%), who had intermediate levels of behavioral engagement; (2) "early utilizers" (n=58, 29%), who had the nominally highest levels of behavioral engagement in week 1; and (3) "efficient engagers" (n=63, 31%), who had significantly higher levels of affective and cognitive engagement but the lowest level of behavioral engagement. With respect to mental health baseline and outcome measures, efficient engagers had significantly higher levels of baseline resilience (P<.001) and greater declines in depressive symptoms (P=.01) and stress (P=.01) from baseline to week 8 compared to typical utilizers. Significant differences across clusters were found by age, gender identity, race and ethnicity, sexual orientation, education, and insurance coverage. The main analytic findings remained robust in sensitivity analyses. CONCLUSIONS: There were 3 distinct engagement clusters found, each with distinct baseline demographic and clinical traits and mental health outcomes. Additional research is needed to inform fine-grained recommendations regarding optimal engagement and to determine the best sequence of particular intervention components with known potency. The findings represent an important first step in disentangling the complex interplay between different affective, cognitive, and behavioral engagement indicators and outcomes associated with use of a DMHI incorporating a natural language processing-supported relational agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT05672745; https://classic.clinicaltrials.gov/ct2/show/NCT05672745.

Changes in stress, burnout, and resilience associated with an 8-week intervention with relational agent "Woebot".

Background: Research investigating the potential for digital mental health interventions with integrated relational agents to improve mental health outcomes is in its infancy. By delivering evidence-based mental health interventions through tailored, empathic conversations, relational agents have the potential to help individuals manage their stress and mood, and increase positive mental health. Aims: The aims of this study were twofold: 1) to assess whether a smartphone app delivering mental health support through a relational agent, Woebot, is associated with changes in stress, burnout, and resilience over 8 weeks, and 2) to identify demographic and clinical factors associated with changes in these outcomes. Method: This exploratory, non-randomized, single-armed, open-labeled trial was conducted from May to July 2022. A total of 256 adults (mean age 39 ± 13.35; 72 % females) recruited through social media advertising enrolled in the study. Participants completed an 8-week intervention period during which they were invited to use a smartphone app called Woebot-LIFE that delivers cognitive behavioral therapy through a relational agent called "Woebot". Participant-reported measures of stress, burnout, and resilience were collected at Baseline, and Week 8. Changes in these outcomes during the study period were assessed. Bivariate and stepwise multiple regression modeling was used to identify sociodemographic and clinical factors associated with observed changes over the 8-week study period. Results: Exposure to Woebot-LIFE was associated with significant reductions in perceived stress and burnout and significantly increased resilience over the 8-week study period. A greater reduction in stress was observed among those with clinically elevated mood symptoms (i.e., Patient Health Questionnaire-8 or Generalized Anxiety Disorder 7-item scores ≥10) at baseline compared to those without; however, the differences in the improvements in resilience scores and burnout between the two groups were not statistically significant. Although a difference in the magnitude of change in stress was observed for participants with and without clinically elevated mood symptoms at baseline, significant improvements in stress, burnout, and resilience over the 8-week study period were observed for both groups. Bivariate analyses showed that race, insurance type, and baseline level of resilience were associated with changes in each of the outcomes, though baseline resilience was the only factor that remained significantly associated with changes in the outcomes in the stepwise multiple regression analyses. Conclusion: Results of this single-arm, exploratory study suggest that conversational agent-guided mental health interventions such as Woebot-LIFE may be associated with reduced stress and burnout and increased resilience in both clinical and non-clinical populations.

Characterizing the innervation of the vulvar vestibule and the immunohistochemical features of neuroproliferative vestibulodynia.

BACKGROUND: Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vulvar vestibule. The finding of increased densities of nerve fibers in the vestibular mucosa of patients with PVD has led to the identification of a neuroproliferative subtype. The etiology of PVD, including neuroproliferative vestibulodynia (NPV), is not fully understood. The gross and microscopic innervation of the vulvar vestibule remains incompletely described, despite the preliminary data supporting the role of peripheral innervation in PVD. AIM: To characterize the gross anatomic and microscopic innervation of the vulvar vestibule through cadaveric dissection and immunohistochemistry. METHODS: The pudendal nerve and inferior hypogastric plexus (IHP) were dissected using 6 cadaveric donors. Histology and immunohistochemistry were used to confirm patterns of innervation identified gross anatomically. Immunohistochemistry was performed on vestibulectomy specimens obtained from 6 patients diagnosed with NPV and compared with cadaveric vestibular tissues. OUTCOMES: Outcomes included (1) dissection of pelvic innervation and (2) immunohistochemical localization of markers for the following: general innervation protein gene product 9.5 (PGP9.5), sensory innervation (calcitonin gene-related peptide), autonomic innervation (vasoactive intestinal polypeptide, tyrosine hydroxylase), neuroproliferation (nerve growth factor [NGF]), and immune activation (C-kit). RESULTS: Perineal (pudendal) nerve branches were traced to the external wall of the vulvar vestibule. Some anatomic heterogeneity was observed in perineal nerve-branching patterns. Fibers from the IHP were identified in close proximity to the vulvar vestibule. Autonomic and sensory nerve fibers were identified in both patient and cadaveric vulvar vestibule samples. Patient samples were characterized by the proliferation of PGP9.5-positive nerve fibers and C-kit-positive mast cells, which were in proximity to neve bundles and showed coexpression with putative NGF-positive cells. NGF expression was localized to a subset of nerves, including those that demonstrated co-expression of sensory and autonomic nerve markers. Increased densities of autonomic fibers positive for vasoactive intestinal polypeptide and tyrosine hydroxylase were observed in 1 patient sample. CLINICAL TRANSLATION: Heterogeneity in gross and microscopic patterns of innervation could explain variability in clinical response to treatment and should be used to inform future therapeutic interventions. STRENGTHS AND LIMITATIONS: This study used a combination of approaches to elucidate the innervation of the vulvar vestibule, including in NPV. The small sample size is a limitation. CONCLUSION: The vulvar vestibule contains both sensory and autonomic innervation, which may originate from the pudendal nerve and IHP. Our results support the existence of a neuroproliferative subtype that is characterized by the proliferation of sensory and autonomic nerve fibers and neuroimmune interactions.

A Relational Agent Intervention for Adolescents Seeking Mental Health Treatment: Protocol for a Randomized Controlled Trial.

BACKGROUND: Unmet pediatric mental health (MH) needs are growing as rates of pediatric depression and anxiety dramatically increase. Access to care is limited by multiple factors, including a shortage of clinicians trained in developmentally specific, evidence-based services. Novel approaches to MH care delivery, including technology-leveraged and readily accessible options, need to be evaluated in service of expanding evidence-based services to youths and their families. Preliminary evidence supports the use of Woebot, a relational agent that digitally delivers guided cognitive behavioral therapy (CBT) through a mobile app, for adults with MH concerns. However, no studies have evaluated the feasibility and acceptability of such app-delivered relational agents specifically for adolescents with depression and/or anxiety within an outpatient MH clinic, nor compared them to other MH support services. OBJECTIVE: This paper describes the protocol for a randomized controlled trial evaluating the feasibility and acceptability of an investigational device, Woebot for Adolescents (W-GenZD), within an outpatient MH clinic for youths presenting with depression and/or anxiety. The study's secondary aim will compare the clinical outcomes of self-reported depressive symptoms with W-GenZD and a telehealth-delivered CBT-based skills group (CBT-group). Tertiary aims will evaluate additional clinical outcomes and therapeutic alliance between adolescents in W-GenZD and the CBT-group. METHODS: Participants include youths aged 13-17 years with depression and/or anxiety seeking care from an outpatient MH clinic at a children's hospital. Eligible youths will have no recent safety concerns or complex comorbid clinical diagnoses; have no concurrent individual therapy; and, if on medications, are on stable doses, based on clinical screening and as well as study-specific criteria. RESULTS: Recruitment began in May 2022. As of December 8, 2022, we have randomized 133 participants. CONCLUSIONS: Establishing the feasibility and acceptability of W-GenZD within an outpatient MH clinical setting will add to the field's current understanding of the utility and implementation considerations of this MH care service modality. The study will also evaluate the noninferiority of W-GenZD against the CBT-group. Findings may also have implications for patients, families, and providers looking for additional MH support options for adolescents seeking help for their depression and/or anxiety. Such options expand the menu of supports for youths with lower-intensity needs as well as possibly reduce waitlists and optimize clinician deployment toward more severe cases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05372913; https://clinicaltrials.gov/ct2/show/NCT05372913. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44940.

Evaluation of the impact of pre-operative stereotactic radiotherapy on the acute changes in histopathologic and immune marker profiles of brain metastases.

The unique acute effects of the large fractional doses that characterize stereotactic radiosurgery (SRS) or radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be empirically demonstrated. The objective of this study is to provide the first in-human evaluation of the acute biological effects of SRS/SRT in resected brain metastasis. Tumor samples from patients who underwent dose-escalated preoperative SRT followed by resection with available non-irradiated primary tumor tissues were retrieved from our institutional biorepository. All primary tumors and irradiated metastases were evaluated for the following parameters: tumor necrosis, T-cells, natural killer cells, vessel density, vascular endothelial growth factor, and apoptotic factors. Twenty-two patients with irradiated and resected brain metastases and paired non-irradiated primary tumor samples met inclusion criteria. Patients underwent a median preoperative SRT dose of 18 Gy (Range: 15-20 Gy) in 1 fraction, with 3 patients receiving 27-30 Gy in 3-5 fractions, followed by resection within median interval of 67.8 h (R: 18.25-160.61 h). The rate of necrosis was significantly higher in irradiated brain metastases than non-irradiated primary tumors (p < 0.001). Decreases in all immunomodulatory cell populations were found in irradiated metastases compared to primary tumors: CD3 + (p = 0.003), CD4 + (p = 0.01), and CD8 + (p = 0.01). Pre-operative SRT is associated with acute effects such as increased tumor necrosis and differences in expression of immunomodulatory factors, an effect that does not appear to be time dependent, within the limited intervals explored within the context of this analysis.

Submandibular gland transfer for the prevention of radiation-induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era.

BACKGROUND: Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans. METHODS: Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans. RESULTS: No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses. CONCLUSIONS: Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

Impact of MRI timing on tumor volume and anatomic displacement for brain metastases undergoing stereotactic radiosurgery.

BACKGROUND: The objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM). METHODS: Consecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning). RESULTS: 101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001). CONCLUSIONS: Changes in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.

Caso de publicación duplicada sobre complicaciones posquirúrgicas en pacientes operados por hernias inguinales / Case of duplicate publication about post-surgical in patients with complications of inguinal hernias

Recientemente leímos con interés el artículo publicado por Saliou y otros, titulado Factores asociados a las complicaciones de la cirugía electiva de las hernias inguinales1 (artículo I) en el cual describen las características asociadas a las complicaciones posquirúrgicas, de pacientes atendidos por hernias inguinales, en el Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora, de una ciudad de Cuba. Sin embargo, este trabajo publicado en la Revista Cubana de Medicina Militar presenta resultados similares a otro publicado previamente en la Revista Cubana de Cirugía, realizado por los mismos autores, cuyo título es "Complicaciones posquirúrgicas de las hernias inguinales"2 (artículo II). Al analizar el contenido de ambos artículos, siguiendo las directrices del Comité Internacional de Directores de Revistas Biomédicas (ICMJE),3 el artículo I sería una publicación duplicada, porque no muestra una clara diferencia entre ambos trabajos, ni cita adecuadamente al artículo II. Además, existe una superposición notoria de los resultados que fueron presentados en ambos trabajos. Esto genera problemas, porque se podría contabilizar inadvertidamente a ambos resultados, lo cual crea un escenario epidemiológico sesgado para posteriores investigaciones. Para que un trabajo sea considerado como una publicación secundaria autorizada, el artículo I debería cumplir las siguientes características: i) la publicación secundaria debería estar dirigido a diferentes lectores, ii) la publicación secundaria debería informar que se basa en un trabajo publicado anteriormente mediante una nota o cita y iii) el título de la publicación secundaria también debería señalar de que se trata de una versión secundaria.3 Esto no se evidencia en el artículo I, a pesar de que el artículo II ya estaba publicado (fecha de aprobación: octubre del 2019 vs fecha de publicación: abril - junio del 2019, respectivamente). En el caso de tratarse de manuscritos basados en la misma base de datos, que también contempla el ICMJE,3 el método analítico y las conclusiones deberían ser marcadamente diferentes, sin embargo, esto no queda claro entre ambos manuscritos. Si bien el artículo I efectúa una asociación entre las complicaciones posquirúrgicas, y algunas características de los pacientes operados por hernias inguinales, y el artículo II solo describe las características de las complicaciones posquirúrgicas de estos pacientes, se observa una aparente omisión intencional de datos en el artículo II, para poder dar estas ligeras diferencias entre ambos artículos. En este artículo no se presentan datos iniciales tales como edad, sexo y antecedentes clínicos necesarios para una mejor comprensión de los resultados. Todas estas características de los pacientes, solo aparecen para el análisis del...(AU)

CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.

OBJECTIVE: Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). METHODS: Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. RESULTS: Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C1917 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C1917 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C1917 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C1917 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). CONCLUSIONS: Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

CT measurements of central pulmonary vasculature as predictors of severe exacerbation in COPD.

To identify a predictive value for the exacerbation status of chronic obstructive pulmonary disease (COPD) subjects, we evaluated the relationship between pulmonary vascular measurements on chest CT and severe COPD exacerbation.Six hundred three subjects enrolled in the COPDGene population were included and divided into nonexacerbator (n = 313) and severe exacerbator (n = 290) groups, based on whether they had an emergency room visit and/or hospitalization for COPD exacerbation. We measured the diameter of the main pulmonary artery (MPA) and ascending aorta (AA) at 2 different sites of the MPA (the tubular midportion and bifurcation) on both axial images and multiplanar reconstructions. Using multiple logistic regression analyses, we evaluated the relationship between each CT-measured pulmonary vasculature and exacerbation status.Axial and multiplanar MPA to AA diameter ratios (PA:AA ratios) at the tubular midportion and the axial PA:AA ratios at the bifurcation indicated significant association with severe exacerbation. The strongest association was found with the axial PA:mean AA ratio at the bifurcation (adjusted odds ratio [OR] = 12.53, 95% confidence interval [CI] = 2.35-66.74, P = .003) and the axial PA:major AA ratio at the tubular midportion (adjusted OR = 10.72, 95% CI = 1.99-57.86, P = .006). No differences were observed in the MPA diameter. Receiver operating characteristic analysis of these variables indicates that they may serve as a good predictive value for severe exacerbation (area under the curve, 0.77-0.78). The range of cut-off value for PA:AA ratio was 0.8 to 0.87.CT-measured PA:AA ratios at either the bifurcation or the tubular site, measured either on axial or multiplanar images, are useful for identification of the risk of severe exacerbation, and consequently can be helpful in guiding the management of COPD. Although CT measurement was used at the level of pulmonary bifurcation in previous studies, we suggest that future studies should monitor the tubular site of the MPA for maximum diagnostic value of CT in pulmonary hypertension or severe COPD exacerbation, as the tubular site of the MPA remains relatively constant on CT images.

Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux.

Esophageal pH monitoring remains a primary diagnostic tool for detecting gastroesophageal reflux disease (GERD). GERD that is refractory to proton pump inhibitor (PPI) medications may be related to CYP2C19 variants. Current PPI dosing practices in children do not take into account CYP2C19 allelic variants, which may lead to underdosing and subsequently to a misperception of PPI therapy failure. We hypothesized that pH probe acid exposure outcomes associate with CYP2C19*17 alleles among children with clinical concern for GERD. We identified a retrospective cohort of 74 children (age range 0.71-17.1 years, mean 8.5, SD 4.6) with stored endoscopic tissue samples and who had also undergone esophageal pH testing while on PPI therapy. These individuals were genotyped for common CYP2C19 alleles and were dichotomized to either CYP2C19*17 allelic carriers without corresponding loss of function alleles as cases vs controls. Associations between pH probe acid exposure outcomes and CYP2C19*17 alleles were investigated. Compared to controls, children who carry CYP2C19*17 alleles without corresponding loss-of-function alleles demonstrated statistically significant longer times with pH < 4 (76.46 vs 33.47 minutes, P = .03); and higher percent of time with pH < 4.0 (5.71 vs 2.67 minutes, P = .04). These findings remained statistically significant using multiple-regression modeling with test duration, PPI dose, and race as confounding variables. PPI therapy in children with *17 alleles may be better optimized with CYP2C19 genotype-guided dosing prior to pH probe testing.

Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment.

When pediatric gastroesophageal reflux disease (GERD) that is refractory to proton pump inhibitor (PPI) medication treatment is identified in clinical practice and anti-reflux surgery (ARS) is being considered, genetic factors related to PPI metabolism by the CYP2C19 enzyme are currently not part of the clinical decision-making process. Our objective was to test the hypothesis that the distribution of the extensive metabolizer (EM) phenotypes among children undergoing ARS after failing PPI therapy would differ compared to controls (children with no history of ARS). We conducted a case-control study between children across the Nemours Health System from 2000 to 2014 who received ARS after failing PPI therapy and a control group comprised of healthy children. Our results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and 41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a multiple-regression model to account for race as a potential confounding variable and the EM group was significantly associated with ARS compared to controls (OR 9.78, CI 1.25-76.55, p < 0.03). CONCLUSION: Among children with medically refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding to the EM phenotype was associated with ARS. Prospective comparative personalized medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided dosing improves response to PPI therapy without a corresponding increase in adverse effects in children. What is known: • Anti-reflux surgery (ARS) is one of the most common surgical procedures performed in children for the indication of refractory gastroesophageal reflux disease (GERD). What is new: • Individualizing PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment failures and reduce the need for anti-reflux surgery (ARS).

Society of Pediatric Psychology Workforce Survey: Factors Related to Compensation of Pediatric Psychologists.

Objective: To summarize compensation results from the 2015 Society of Pediatric Psychology (SPP) Workforce Survey and identify factors related to compensation of pediatric psychologists. Methods: All full members of SPP ( n = 1,314) received the online Workforce Survey; 404 (32%) were returned with usable data. The survey assessed salary, benefits, and other income sources. The relationship between demographic and employment-related factors and overall compensation was explored. Results: Academic rank, level of administrative responsibility, and cost of living index of employment location were associated with compensation. Compensation did not vary by gender; however, women were disproportionately represented at the assistant and associate professor level. Conclusions: Compensation of pediatric psychologists is related to multiple factors. Longitudinal administration of the Workforce Survey is needed to determine changes in compensation and career advancement for this profession over time. Strategies to increase the response rate of future Workforce Surveys are discussed.

The Brief Early Childhood Screening Assessment: Preliminary Validity in Pediatric Primary Care.

OBJECTIVE: Brief, well-validated instruments are needed to facilitate screening for early childhood behavioral and emotional problems (BEPs). The objectives of this study were to empirically reduce the length of the Early Childhood Screening Assessment (ECSA) and to assess the validity and reliability of this shorter tool. METHODS: Using caregiver ECSA responses for 2467 children aged 36 to 60 months seen in primary care, individual ECSA items were ranked on a scale ranging from "absolutely retain" to "absolutely delete." Items were deleted sequentially beginning with "absolutely delete" and going up the item prioritization list, resulting in 35 shorter versions of the ECSA. A separate primary care sample (n = 69) of mothers of children aged 18 to 60 months was used to determine the sensitivity and specificity of each shorter ECSA version using psychiatric diagnosis on the Diagnostic Infant and Preschool Assessment as the gold standard. The version with the optimal balance of sensitivity, specificity, and length was selected as the Brief ECSA. Associations between Brief ECSA scores and other pertinent measures were evaluated to estimate reliability and validity. RESULTS: A 22-item measure reflected the best combination of brevity, sensitivity and specificity. A cutoff score of 9 or higher on the 22-item Brief ECSA demonstrated acceptable sensitivity (89%) and specificity (85%) for predicting a psychiatric diagnosis. Brief ECSA scores correlated significantly and in expected directions with scores on pertinent measures and with demographic variables. CONCLUSION: The results indicate that the Brief ECSA has sound psychometric properties for identifying young children with BEPs in primary care.

Pediatric Psychologists' Career Satisfaction: 2015 Society of Pediatric Psychology Workforce Survey Results.

Little is known about the career satisfaction of pediatric psychologists, who specialize in psychological research, teaching, and clinical service in the context of pediatric healthcare. As part of the larger Society of Pediatric Psychology Workforce Survey and in collaboration with the American Psychological Association Center for Workforce Studies, this study aimed to: (1) describe the career domains which pediatric psychologists perceive to be important and their satisfaction in each domain, and (2) compare satisfaction of pediatric psychologists across work settings, number of positions, appointment duration, professional roles, career stage, academic rank, and gender. Responses from 336 pediatric psychologists demonstrated high career satisfaction. Domains of career satisfaction that received mean scores indicating high importance include balance of work and personal lives, peer/collegial support, and flexibility and choice in the workplace, but on average respondents reported being only somewhat satisfied in these domains. Total satisfaction scores were significantly higher among pediatric psychologists in 9-10 month appointments, primarily research careers, and at higher academic ranks, but scores were similar across employment settings and genders. To enhance career satisfaction and retention, pediatric psychologists may seek additional mentorship or explore new employment roles, and administrators and managers may consider adopting workplace policies or making environmental changes that could address specific areas of need. PUBLIC SIGNIFICANCE STATEMENT: This study suggests that overall, pediatric psychologists are highly satisfied with their employment. However, there may be some important aspects of their work that could be more satisfying. The findings have implications for identifying professional development strategies that can maintain or enhance satisfaction.

The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye.

A critical aspect of vertebrate eye development is closure of the choroid fissure (CF). Defects in CF closure result in colobomas, which are a significant cause of childhood blindness worldwide. Despite the growing number of mutated loci associated with colobomas, we have a limited understanding of the cell biological underpinnings of CF closure. Here, we utilize the zebrafish embryo to identify key phases of CF closure and regulators of the process. Utilizing Laminin-111 as a marker for the basement membrane (BM) lining the CF, we determine the spatial and temporal patterns of BM breakdown in the CF, a prerequisite for CF closure. Similarly, utilizing a combination of in vivo time-lapse imaging, ß-catenin immunohistochemistry and F-actin staining, we determine that tissue fusion, which serves to close the fissure, follows BM breakdown closely. Periocular mesenchyme (POM)-derived endothelial cells, which migrate through the CF to give rise to the hyaloid vasculature, possess distinct actin foci that correlate with regions of BM breakdown. Disruption of talin1, which encodes a regulator of the actin cytoskeleton, results in colobomas and these correlate with structural defects in the hyaloid vasculature and defects in BM breakdown. cloche mutants, which entirely lack a hyaloid vasculature, also possess defects in BM breakdown in the CF. Taken together, these data support a model in which the hyaloid vasculature and/or the POM-derived endothelial cells that give rise to the hyaloid vasculature contribute to BM breakdown during CF closure.