Mindfulness and Posttraumatic Stress Disorder Symptom Severity in Urban African-American High School Students.

OBJECTIVES: The aim of the current study was to examine the relations among mindfulness, posttraumatic stress disorder (PTSD) symptom severity, and stressful life events (SLEs) in African-American urban adolescents. Another aim was to examine mindfulness as a moderator of the relation between SLEs and PTSD symptom severity in this population. METHOD: Eighty-eight African-American high school students from a low-income urban community completed measures of demographics, PTSD symptom severity, SLEs, and mindfulness. RESULTS: Mindfulness was significantly negatively related to PTSD symptom severity, r(86) = -.70, p < .001, 95% CI [-.58, -79], and SLEs were significantly positively related to PTSD symptom severity, r(86) = .29, p = .003, 95% CI [.09, .47]. Mindfulness was an independent predictor of PTSD symptom severity after accounting for SLEs, B = -1.16, t(84) = -9.06, p < .001, 95% CI [-1.41, -0.90], and SLEs were an independent predictor of PTSD symptom severity after accounting for mindfulness, B = 0.49, t(84) = 2.92, p = .004, 95% CI [0.16, 0.82]. Mindfulness did not moderate the relation between SLEs and PTSD symptom severity, B = -.003, t(84) = -0.15, p = .89, 95% CI [-.04, .03]. IMPLICATIONS: This study has implications for both mindfulness as a potential protective factor against PTSD symptom severity and SLEs as a potential risk factor for increased PTSD symptom severity in African-American urban adolescents.

Paediatric Sudden Sensorineural Hearing Loss: Pooled Analysis and Systematic Review.

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of ≥30 dB in one or both ears, developing within 3 days, affecting ≥3 contiguous frequencies. It is rare in children, but if untreated can cause significant morbidity. During the critical developmental period, it may cause lifelong social, behavioral, and mental sequelae. Currently, little guidance exists on prognosis and management within a pediatric population. A systematic literature review of pediatric SSNHL on PubMed, EMBASE, and the Cochrane CENTRAL database was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. A total of 620 papers met the Medical Subject Headings criteria, of which 14 met analysis criteria-13 were level 4 and 1 was level 2b evidence. A population of 732 individuals was analyzed. Most reported cases of pediatric SSNHL were idiopathic. Other etiologies included viral infection, trauma, ototoxic drugs, and structural abnormalities. Recovery was defined as any improvement in hearing after the initial loss, from "slight" to "complete." Recovery ranged from 20% to 100%, with a pooled rate of 56%. Systemic steroids were the mainstay of treatment, although salvage intratympanic steroid therapy had a role after the failure of systemic steroids. Children with bilateral SSNHL had poorer outcomes than those with unilateral loss, with 29% showing improvement. Two studies reported outcomes with no treatment, for which recovery rate was 7%. This analysis of SSNHL shows that 61% of children with unilateral and 29% of children with bilateral SSNHL demonstrate some recovery, a worse prognosis than adults. Multiple treatment regimens exist, although comparison is challenging owing to inconsistently reported improvement parameters.

Psychometric properties of the Child and Adolescent Mindfulness Measure (CAMM) in racial minority adolescents from low-income environments.

No study has yet assessed the psychometric properties of scores from any mindfulness measure in racial minority adolescents from low-income environments. The present study examined the reliability and validity of Child and Adolescent Mindfulness Measure (CAMM) scores in a nonclinical sample of late adolescents (N = 92) from low-income neighborhoods who predominantly identified as African American. Findings confirmed a one-factor structure for responses to the 10 CAMM items as well as adequate internal consistency (Cronbach's α = .88). In support of validity, CAMM scores demonstrated large significant negative correlations with scores from measures of constructs that should be negatively related to mindfulness, including depressive symptoms, worry, ruminative coping, and involuntary engagement responses to stress. Thus, CAMM scores appear to reliably and validly assess mindfulness in racial minority adolescents from low-income environments. Having a psychometrically sound mindfulness measure for this population will aid in understanding the mechanisms by which mindfulness-based interventions work, which could lead to improved interventions and outcomes for this population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Synthesis and biological evaluation of antiplatelet 2-aminochromones.

The synthesis and biological evaluation of a series of antiplatelet 2-morpholinylchromones has been described. Modification of the C-7 phenylmethoxy group of 8-methyl-7-(phenylmethoxy)-2-(4-morpholinyl)-4H-1-benzopyran-4-one (2) has led to the discovery of a series of 7-[(amino-ethyl)oxy]-8-methyl derivatives which are potent inhibitors of ADP-induced platelet aggregation. Several members of this class proved active in preventing platelet-dependent thrombus formation in the dog, including 8-methyl-7-[2-(4-methyl-1-piperazinyl)ethoxy]-2-(4- morpholinyl)-4H-1-benzopyran-4-one (39) which was devoid of hemodynamic effects at the effective antithrombotic dose.

Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in 3T3-L1 adipocytes by inhibiting a negative control mechanism.

Activation of phosphoinositide 3-kinase (PI 3-kinase) is an early event in insulin signal transduction that is blocked completely in adipocytes from insulin-resistant KKAy mice. Treatment of KKAy mice with pioglitazone, an anti-diabetic thiazolidinedione, partially restores insulin-dependent changes in PI 3-kinase. The mechanism of this effect of pioglitazone was investigated using murine 3T3-L1 cells as an experimental model. Insulin and insulin-like growth factor I (IGF-I) each elicited rapid (within 2 min) and large (2-5-fold) increases in PI 3-kinase activity that could be immunoprecipitated using anti-phosphotyrosine (pY) antibodies. Maximal insulin-induced activity of PI 3-kinase in pY-immunoprecipitates was similar in 3T3-L1 adipocytes and mouse adipocytes, but the kinetics of activation differed. Insulin- and IGF-I-induced changes in PI 3-kinase were each half-maximal at 3-5 nM of hormone and were not additive. Increases in both insulin-induced and IGF-I-induced pY-immunoprecipitable PI 3-kinase activity were observed when 3T3-L1 fibroblasts became confluent and when they adopted the adipocyte phenotype. Pioglitazone (10 microM), administered either acutely or chronically to either 3T3-L1 adipocytes or 3T3-L1 fibroblasts, did not greatly alter the kinetics, magnitude or sensitivity of changes in PI 3-kinase elicited by either insulin or IGF-I. In contrast, the attenuation by isoproterenol of insulin-induced changes in PI 3-kinase was prevented in cells pretreated with pioglitazone. This effect of pioglitazone did not involve inhibition of isoproterenol-elicited accumulation of cyclic AMP. Pioglitazone also prevented attenuation of insulin induced changes in PI 3-kinase by cell penetrating analogs of cyclic AMP. Pioglitazone, therefore, has no direct effect on insulin-stimulated PI 3-kinase activity, but interferes with a cyclic AMP-dependent mechanism that normally antagonizes this action of insulin. These data support the proposition that the facilitation of insulin action by pioglitazone involves, at least in part, an inhibition of a negative control mechanism.

Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in 3T3-L1 adipocytes by inhibiting a negative control mechanism.

Activation of phosphoinositide 3-kinase (PI 3-kinase) is an early event in insulin signal transduction that is blocked completely in adipocytes from insulin-resistant KKAy mice. Treatment of KKAy mice with pioglitazone, an anti-diabetic thiazolidinedione, partially restores insulin-dependent changes in PI 3-kinase. The mechanism of this effect of pioglitazone was investigated, using murine 3T3-L1 cells as an experimental model. Insulin and insulin-like growth factor I (IGF-I) each elicited rapid (within 2 min) and large (2- to 5-fold) increases in PI 3-kinase activity that could be immunoprecipitated using anti-phosphotyrosine (pY) antibodies. Maximal insulin-induced activity of PI 3-kinase in pY-immunoprecipitates was similar in 3T3-L1 adipocytes and mouse adipocytes, but the kinetics of activation differed. Insulin- and IGF-I-induced changes in PI 3-kinase were each half-maximal at 3-5 nM of hormone and were not additive. Increases in both insulin-induced and IGF-I-induced pY-immunoprecipitable PI 3-kinase activity were observed when 3T3-L1 fibroblasts became confluent and when they adopted the adipocyte phenotype. Pioglitazone (10 microM), administered either acutely or chronically to either 3T3-L1 adipocytes or 3T3-L1 fibroblasts, did not alter greatly the kinetics, magnitude or sensitivity of changes in PI 3-kinase elicited by either insulin or IGF-I. In contrast, the attenuation by isoproterenol of insulin-induced changes in PI 3-kinase was prevented in cells pretreated with pioglitazone. This effect of pioglitazone did not involve inhibition of isoproterenol-elicited accumulation of cyclic AMP. Pioglitazone also prevented attenuation of insulin induced changes in PI 3-kinase by cell penetrating analogs of cyclic AMP. Pioglitazone, therefore, has no direct effect on insulin-stimulated PI 3-kinase activity, but interferes with a cyclic AMP-dependent mechanism that normally antagonizes this action of insulin. These data support the proposition that the facilitation of insulin action by pioglitazone involves, at least in part, an inhibition of a negative control mechanism.

A compliance testing program for diagnostic X-ray equipment.

Compliance testing is nominally that part of a quality assurance program dealing with those aspects of X-ray equipment performance that are subject to radiation control legislation. Quality assurance programs for medical X-ray equipment should be an integral part of the quality culture in health care. However while major hospitals and individual medical centers may implement such programs with some diligence, much X-ray equipment can remain unappraised unless there is a comprehensive regulatory inspection program or some form of compulsion on the equipment owner to implement a testing program. Since the late 1950s all X-ray equipment in the State of Western Australia has been inspected by authorized officers acting on behalf of the Radiological Council, the regulatory authority responsible for administration of the State's Radiation Safety Act. However, economic constraints, coupled with increasing X-ray equipment numbers and a geographically large State have significantly affected the inspection rate. Data available from inspections demonstrate that regular compliance and performance checks are essential in order to ensure proper performance and to minimize unnecessary patient and operator dose. To ensure that diagnostic X-ray equipment complies with accepted standards and performance criteria, the regulatory authority introduced a compulsory compliance testing program for all medical, dental and chiropractic diagnostic X-ray equipment effective from 1 January 1997.

Compliance testing of medical diagnostic x-ray equipment: three years' experience at a major teaching hospital in Western Australia.

The impact of a formal compliance testing program has been evaluated three years post-implementation on a major teaching hospital (Sir Charles Gairdner Hospital) with 46 x-ray tubes located throughout 37 rooms. The mandatory program, implemented by the statutory authority in January 1997, called for all medical (including chiropractic and dental) equipment used in human diagnosis to be tested at prescribed frequencies using established protocols. The application of the required test methods demonstrated various non-compliance issues. Notices of non-compliance were received for approximately 60% of the equipment in the hospital following the equipment's first annual test. The reasons for, and the significance of, failure varied according to equipment category, test category, equipment use and equipment age. However, at the end of the third year of testing, approximately 75% of the tested x-ray units satisfied the compliance criteria. The main reasons for non-compliance were found to be design limitations of old technology and the current radiation legislation that makes it difficult for some older equipment to meet the relatively stringent criteria.

The association between status and cohesion in sport teams.

The main objective of this study was to establish the relationship between perceptions of status attributes and cohesion and status ranking and cohesion. A secondary aim was to determine whether age (operationalized by scholastic levels) or culture serves as a moderator in the relationship between either status attributes or status ranking and cohesion. Another secondary aim was to determine if differences are present in the importance attached by athletes to status attributes. Canadian and Indian athletes were tested. Although perceptions of the importance of status attributes and cohesiveness were related, the effect size was small (Green, 1991); perceptions of status ranking and cohesiveness were not related. Neither scholastic level nor culture served as a moderator in the association between either status attributes or status rank and cohesion. The importance that athletes attach to status attributes is similar between scholastic levels and across cultures. The results are discussed in terms of the role of status in sport teams.

Identification of multiple regulatory elements on the human cytochrome P450IA1 gene.

To examine the transcriptional regulation of the human cytochrome P450IA1 gene, a 3574 bp fragment containing 1140 bp of 5' flanking sequences, exon 1 (leader information only), intron 1, and the leader sequences from exon 2, was cloned upstream of the reporter gene, chloramphenicol acetyltransferase, and used to transfect the human hepatoma cell line, HepG2. In transient expression assays, treatment of the transfected cells with 3-methylcholanthrene, benzo[a]pyrene or 2,3,7,8-tetrachlorodibenzofuran was shown to induce the expression of chloramphenicol acetyltransferase 10-fold. Previous studies by other investigators have identified a xenobiotic responsive element at greater than 800 bp 5' to the cap site in the mouse and rat cytochrome P450IA1 gene. In the current report, deletion of sequences from the 5' side of the P450IA1 fragment, as well as internal deletions, were used to identify at least three additional regulatory elements. A second positive, 3-methylcholanthrene responsive element was localized to sequences between -49 and -560 in addition to confirming the location of a similar element between -831 and -1140. These elements flank a potent negative regulatory element that has been conserved between the rat, mouse and human P450IA1 genes and also exhibits significant sequence identity with one of the negative control elements of the human c-Ha-ras1 proto-oncogene. Deletion of the negative control element clearly demonstrated that the fragments containing xenobiotic responsive elements also possess positive, constitutive control activity. A fourth element located within intron 1 was shown to potentiate the activity of 3-methylcholanthrene when the cells were treated simultaneously with the glucocorticoid agonist, dexamethasone.

Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere inhibit protein tyrosine phosphatase 1B and augment insulin action.

Protein tyrosine phosphatase 1B (PTP1B) attenuates insulin signaling by catalyzing dephosphorylation of insulin receptors (IR) and is an attractive target of potential new drugs for treating the insulin resistance that is central to type II diabetes. Several analogues of cholecystokinin(26)(-)(33) (CCK-8) were found to be surprisingly potent inhibitors of PTP1B, and a common N-terminal tripeptide, N-acetyl-Asp-Tyr(SO(3)H)-Nle-, was shown to be necessary and sufficient for inhibition. This tripeptide was modified to reduce size and peptide character, and to replace the metabolically unstable sulfotyrosyl group. This led to the discovery of a novel phosphotyrosine bioisostere, 2-carboxymethoxybenzoic acid, and to analogues that were >100-fold more potent than the CCK-8 analogues and >10-fold selective for PTP1B over two other PTP enzymes (LAR and SHP-2), a dual specificity phosphatase (cdc25b), and a serine/threonine phosphatase (calcineurin). These inhibitors disrupted the binding of PTP1B to activated IR in vitro and prevented the loss of tyrosine kinase (IRTK) activity that accompanied PTP1B-catalyzed dephosphorylation of IR. Introduction of these poorly cell permeant inhibitors into insulin-treated cells by microinjection (oocytes) or by esterification to more lipophilic proinhibitors (3T3-L1 adipocytes and L6 myocytes) resulted in increased potency, but not efficacy, of insulin. In some instances, PTP1B inhibitors were insulin-mimetic, suggesting that in unstimulated cells PTP1B may suppress basal IRTK activity. X-ray crystallography of PTP1B-inhibitor complexes revealed that binding of an inhibitor incorporating phenyl-O-malonic acid as a phosphotyrosine bioisostere occurred with the mobile WPD loop in the open conformation, while a closely related inhibitor with a 2-carboxymethoxybenzoic acid bioisostere bound with the WPD loop closed, perhaps accounting for its superior potency. These CCK-derived peptidomimetic inhibitors of PTP1B represent a novel template for further development of potent, selective inhibitors, and their cell activity further justifies the selection of PTP1B as a therapeutic target.