Testing the Habituation-Based Model of Exposures for Child and Adolescent Anxiety

Exposure has been identified as key to effective treatment of youth anxiety. However, the precise theoretical mechanisms of exposure are a matter of debate. Emotional processing theory emphasizes the need for fear activation during exposure and its habituation both within and across exposures. Despite the popularity of the theory to explain exposure, it has not been tested with anxious youth. To determine whether emotional processing theory parameters predict anxiety severity, coping abilities, and global functioning after cognitive-behavioral treatment. The present study examined 72 youth (M_age = 10.50 years; 45% female; 87.5% non-Hispanic Caucasian) diagnosed with an anxiety disorder and who received family or individual CBT. Three exposure habituation variables—initial fear activation (peak anxiety), within-session habituation, and between-session habituation—were assessed using Subjective Units of Distress and examined as predictors of outcome at posttreatment and at 1-year follow-up. Outcomes were measured using the Coping Questionnaire, Multidimensional Anxiety Scale for Children, Revised Children’s Manifest Anxiety Scale, Children’s Global Assessment Scale, and clinician severity ratings on the Anxiety Disorder Interview Schedule. Emotional processing theory variables did not predict any anxiety outcomes at posttreatment or follow-up with one exception: Initial fear activation predicted less anxiety at follow-up among youth without GAD. In addition, within- and between-session habituation were not associated with one another. Between-session habituation was not associated with initial fear activation. These findings suggest a limited role of habituation within cognitive-behavioral therapy for anxiety in youth. An alternative to emotional processing theory, inhibitory learning theory, is discussed.     

Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only 5 of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extrathyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.     

Effect of patient sex, clinician sex, and sex role on the diagnosis of Antisocial Personality Disorder: models of underpathologizing and overpathologizing biases

This study examined the influence of patient sex and clinician sex and sex role for a case, meeting minimum diagnostic criteria for Antisocial Personality Disorder, in which patient sex was varied. The purpose was to provide an in-depth evaluation of the process by which patient sex and characteristics of clinicians may contribute to bias in personality disorder diagnoses. Psychologists (N = 167) read two cases, including the target case, and provided symptom ratings and diagnoses. A sex-unspecified condition served as a baseline to assess for over- and underpathologizing bias, and diagnoses based on the symptom ratings were compared to assigned diagnoses. Clinician sex role was assessed using the Bem Sex Role Inventory-Short Form. Results revealed that bias occurred when the patient's sex (female) was inconsistent with the gender weighting of the symptoms in the case (masculine), but the direction of the bias was consistent with sex roles (underdiagnosis of sex-role-inconsistent diagnoses, overdiagnosis of sex-role-consistent diagnoses). Path models of over- and underdiagnostic bias were developed using structural equation modeling. Patient sex had a direct effect on diagnostic ratings whereas clinician sex role had an indirect effect through symptom ratings.     

Central melanocortin receptor agonist reduces spontaneous and scheduled meal size but does not augment duodenal preload-induced feeding inhibition

Central melanocortin (MC) receptor agonists inhibit food intake and may be downstream mediators of the effects of central leptin, which (1) reduces food intake by selectively decreasing meal size and (2) augments the feeding-inhibitory effects of gastrointestinal food stimuli. Central administration of the MC-3/4 receptor (MC-3/4R) agonist, MTII, inhibits feeding in rats, but its effects on meal pattern and potential interactions with gastrointestinal controls of food intake remain unclear. We examined meal patterns and intake in male Sprague-Dawley rats following central intracerebroventricular administration of MTII (0.01-1.0 nmol) in two situations: (1) during daytime 60-min scheduled access to liquid glucose (12.5%) in combination with a duodenal preload of 12.5% glucose or physiological saline (4.4 ml/10 min), and (2) during subsequent overnight access to 45 mg of solid chow pellets. Both duodenal glucose preloads and MTII reduced subsequent glucose intake. However, no dose of MTII augmented the reductions in food intake produced by duodenal glucose alone. During overnight access to pelleted chow, the 0.1- and 1.0-nmol doses of MTII reduced food intake, meal size, meal duration, and body weight, and increased the satiety ratio (duration of intermeal interval/preceding meal size) but did not change meal frequency. The present data (1) demonstrate that MTII, like leptin, reduces food intake by a selective reduction in meal size and not meal frequency, and (2) suggest that MTII increases the feeding-inhibitory potency of negative feedback signals critical to the control of meal size during spontaneous chow access, but not scheduled access to palatable liquid nutrient solutions.     

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period,a Single-Center Observational Study

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.     

Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.     

Plasma Free Fatty Acids and Metabolic Effect in Type 2 Diabetes,an Ancillary Study from a Randomized Clinical Trial

Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias. Pentadecanoic acid, heptadecanoic acid and trans-palmitoleic acid are fatty acids that are not synthesized endogenously but are obtained from the diet, particularly dairy, making them reasonable biomarkers of dairy consumption. We investigated the association of dairy fatty acid biomarkers with glycated hemoglobin (HbA1c) and cardiovascular risk factors in type 2 diabetes (T2D). In a clinical trial, 111 participants with T2D (age 58.5 ± 8.9 years, HbA1c 8.09 ± 0.96%) were randomized into three groups: a control group that maintained baseline dairy intake, a low-fat (LF) group that incorporated ≥3 servings/day of LF dairy and a high-fat (HF) group that incorporated ≥3 servings/day of HF dairy. We compared the fatty acids (FA) composition between the three groups at 24 weeks. Pentadecanoic acid and trans-palmitoleic acid increased in the HF group by 14.1% ± 5.4% and 17.5% ± 5.1%, respectively, but not in the control and LF groups (p = 0.0474 and p = 0.0025 for group-by-time interaction, respectively). Those increases were positively associated with changes in total cholesterol, very-low-density lipoprotein cholesterol VLDL-C and triglycerides but were not associated with changes in HbA1c from baseline to 24 weeks. These results suggest that the intervention was successful and that participants were likely compliant, which supports the validity of the main trial.     

A novel approach to delivery of extracorporeal support using a modified continuous flow ventricular assist device in a mid‐volume congenital heart program

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device—based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty‐seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device‐based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.