Measuring socioeconomic status: Reliability and preliminary validity of different approaches

This study investigated issues related to commonly used socioeconomic status (SES) measures in 140 participants from three cities (Atlanta, Boston, and Toronto) in two countries (United States and Canada). Measures of SES were two from the United States (four-factor Hollingshead scale, Nakao and Treas scale) and one from Canada (Blishen, Carroll, and Moore scale). Reliability was examined both within (interrater agreement) and across (intermeasure agreement) measures. Interrater reliability and classification agreement was high for the total sample (range r = .86 to .91), as were intermeasure correlations and classification agreement (range r = .81 to .88). The weakest agreement across measures was found when families had one wage earner who was female. Validity data for these SES measures with academic and intellectual measures also were obtained. Some support for a simplified approach to measuring SES was found. Implications of these findings for the use of SES in social and behavioral science research are discussed

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews.

OBJECTIVES: Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection. METHODS: PubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers. RESULTS: The performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection. CONCLUSIONS: Although current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach

Sustained attention in children with two etiologies of early hydrocephalus.

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive attention and parent ratings of inattention and hyperactivity and explored the impact of medical variables. Children with SBM did not differ from AS or NC groups on measures of sustained attention, but they committed more errors and responded more slowly. Approximately one-third of the SBM group had attention symptoms, although parent attention ratings were not associated with task performance. Hydrocephalus does not account for the attention profile of children with SBM, which also reflects the distinctive brain dysmorphologies associated with this condition

Relations between the Kaufman Brief Intelligence Test (KBIT) and the Wechsler Intelligence Scale for Children - Third edition (WISC-III) in Children with Reading Disability

Concurrent validity of The Kaufman Brief Intelligence Test (K-BIT) with the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) was evaluated, as well as the K-BIT\u27s accuracy as a predictor of WISC-III scores, in a sample of young children with reading disabilities. The two measures were administered to 65 children from Atlanta, Boston, and Toronto who ranged from 6-5 to 7-11 years of age at testing. Correlations between the verbal, nonverbal, and composite scales of the K-BIT and WISC-III were .60, .48, and .63, respectively. Mean K-BIT scores ranged from 1.2 to 5.0 points higher than the corresponding WISC-III scores. Standard errors of estimation ranged from 10.0 to 12.3 points. In individual cases, K-BIT scores can underestimate or overestimate WISC-III scores by as much as 25 points. Results suggest caution against using the K-BIT exclusively for placement and diagnostic purposes with young children with reading disabilities if IQ scores are required

Protective role of PI3-kinase-Akt-eNOS signalling pathway in intestinal injury associated with splanchnic artery occlusion shock.

Background and purpose: Endothelial NO synthase (eNOS) is a dynamic enzyme tightly controlled by co- and post-translational lipid modifications, phosphorylation and regulated by protein-protein interactions. Here we have pharmacologically modulated the activation of eNOS, at different post-translational levels, to assess the role of eNOS-derived NO and of these regulatory mechanisms in intestinal injury associated with splanchnic artery occlusion (SAO) shock. Experimental approach: SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk for 45 min followed by 30 min of reperfusion. During ischemia, 15 min prior to reperfusion, mice were given geldanamycin, an inhibitor of hsp90 recruitment to eNOS, or LY-294002 an inhibitor of phosphatidylinositol 3-kinase (PI3K), an enzyme that initiates Akt-catalysed phosphorylation of eNOS on Ser 1179. After 30 min of reperfusion, samples of ileum were taken for histological examination or for biochemical studies. Key results: Either LY-294002 or geldanamycin reversed the increased activation of eNOS and Akt observed following SAO shock. These molecular effects were mirrored in vivo by an exacerbation of the intestinal damage. Histological damage also correlated with neutrophil infiltration, assessed as myeloperoxidase activity, and with an increased expression of the adhesion proteins: ICAM-I, VCAM, P-selectin and E-selectin. Conclusions and implications: Overall these results suggest that activation of the Akt pathway in ischemic regions of reperfused ileum is a protective event, triggered in order to protect the intestinal tissue from damage induced by ischaemia/reperfusion through a fine tuning of the endothelial NO pathway. © 2007 Nature Publishing Group All rights reserved

Characterisation of indeterminate focal breast lesions on grey-scale ultrasound: role of ultrasound elastography.

PURPOSE: This study was undertaken to evaluate the role of ultrasound (US) elastography in characterising focal breast lesions classified as indeterminate on B-mode US. MATERIALS AND METHODS: Eighty-four focal breast lesions, 64 benign and 20 malignant (mean diameter, 15.1 mm), detected but not characterised on B-mode US in 72 women, Breast Imaging Reporting and Data System (BI-RADS) US category 3 (n=56) or category 4 (n=28), were studied with US elastography and classified in consensus by two radiologists according to a five-point colour scale. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) of US elastography compared with conventional US were calculated in relation to microhistology (n=67) and cytology (n=17), which were used as the reference standard. RESULTS: A total of 65/84 (77.4%) lesions were correctly classified as benign or malignant using US elastography, whereas the remaining 19/84 (22.6%) were incorrectly assessed. There were no statistically significant differences between US elastography and B-mode US with regard to sensitivity (70% vs. 68.4%), specificity (79.6% vs. 78.5%), PPV (51.8% vs. 48.1%) and NPV 89% vs. 89.5% (p>0.5). By contrast, a statistically significant difference was noted in the evaluation of BI-RADS 3 lesions, in which US elastography had 50% sensitivity, 86% specificity, 30% PPV and 93.5% NPV compared with BI-RADS 4 lesions (78.6%, 57.1%, 64.7% and 72.7%) (p<0.5). CONCLUSIONS: The high NPV of US elastography may help reduce the use of biopsy in BI-RADS 3 lesions, but its low PPV in BI-RADS 4 lesions does not allow avoidance of biopsy on the basis of the US elastographic score alone in this group of lesions

PRODUCTIVE INFECTION OF ISOLATED HUMAN ALVEOLAR MACROPHAGES BY RESPIRATORY SYNCYTIAL VIRUS

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in children and individuals with cell-mediated immunodeficiencies. Airway epithelial cells may be infected with RSV, but it is unknown whether other cells within the lung permit viral replication. We studied whether human alveolar macrophages supported RSV replication in vitro. Alveolar macrophages exposed to RSV demonstrated expression of RSV fusion gene, which increased in a time-dependent manner and correlated with RSV protein expression. RSV-exposed alveolar macrophages produced and released infectious virus into supernatants for at least 25 d after infection. Viral production per alveolar macrophage declined from 0.053 plaque-forming units (pfu)/cell at 24 h after infection to 0.003 pfu/cell by 10 d after infection and then gradually increased. The capability of alveolar macrophages to support prolonged RSV replication may have a role in the pulmonary response to RSV infection

Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed.

Hydrogen sulfide (H(2)S), a novel gaseous transmitter, is considered a physiological regulator of vascular homeostasis. Recent evidence suggests H(2)S as an endothelium-hyperpolarizing factor (EDHF) candidate. To address this issue, we evaluated the vascular effect of sodium hydrogen sulfide (NaHS), an H(2)S donor, on the rat mesenteric arterial bed. NaHS concentration-response curve was performed on preconstricted mesenteric arterial bed. To assess the contribution of EDHF, we performed a pharmacologic dissection using indomethacin, N(G)-nitro-L-arginine methyl ester (L-NAME), or apamin and charybdotoxin as cyclooxygenase, nitric-oxide synthase, and calcium-dependent potassium channel inhibitors, respectively. In another set of experiments, we used 4-(4-octadecylphenyl)-4-oxobutenoic acid, baicalein, or proadifen as phospholipase A(2) (PLA(2)), lipoxygenase, and cytochrome P450 inhibitors, respectively. Finally, an immunofluorescence study was performed to support the involvement of PLA(2) in mesenteric artery challenged by NaHS. NaHS promoted a dual vascular effect (i.e., vasoconstriction and vasodilation). L-NAME or baicalein administration affected neither NaHS-mediated vasodilation nor vasoconstriction, whereas apamin and charybdotoxin significantly inhibited NaHS-induced relaxation. Pretreatment with PLA(2) inhibitor abolished both the contracting and the relaxant effect, whereas P450 cytochrome blocker significantly reduced NaHS-mediated relaxation. The immunofluorescence study showed that NaHS caused a migration of cytosolic PLA(2) close to the nucleus, which implicates activation of this enzyme. Our data indicate that H(2)S could activate PLA(2), which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Because EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H(2)S acts through EHDF release