Confirmatory factor analysis of the BRIEF2 in a sample of youth with Down syndrome.

BACKGROUND: The factor structure of the Behavior Rating Inventory of Executive Function, second edition (BRIEF2) has been widely examined in both typically developing children and specific clinical samples. Despite the frequent use of the BRIEF2 for measuring executive functioning in individuals with Down syndrome, no study has investigated the factorial validity or dimensionality of the BRIEF2 in this population. This study aimed to address this notable gap in the literature. METHODS: Parents of 407 children and youth with Down syndrome aged 6-18 years completed the BRIEF2 as part of different studies led by six sites. Three competing models proposed by previous studies were analysed using Confirmatory Factor Analysis: the theoretical structure of the BRIEF2 where the scales were constrained to load on three factors labelled as Cognitive, Behavioral, and Emotional Regulation, a two-factor correlated model with the merged Behavioral and Emotional regulation, and a single-factor model. RESULTS: The three-factor model provided a better fit than the one- and two-factor models, yet a large correlation was observed between Behavioural and Emotional regulation factors. The results provide meaningful explanatory value for the theoretical structure of the BRIEF2. However, the Behavioral and Emotional regulation factors might be less differentiated and the two-factor structure of the BRIEF2 may also make theoretical and empirical sense. CONCLUSIONS: Although more studies are needed to further examine the factor structure of the BRIEF2 in youth with Down syndrome, this investigation provides preliminary support for the interpretation of the three executive function index scores provided by the BRIEF2: Cognitive, Behavioral, and Emotional Regulation.

Updated profiles of everyday executive function in youth with Down syndrome using the BRIEF-2.

BACKGROUND: Executive function difficulties in youth with Down syndrome (DS) are well recognised using informant-report measures. However, the profile of relative challenges and strengths has not yet been evaluated using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), which includes a new internal factor structure. METHOD: Using the BRIEF-2, profiles of everyday parent-reported executive function (EF) were evaluated in youth with DS (n = 34) and compared with age-based and sex-based norms. EF profiles were also compared across raters (parent vs. teacher, n = 20) and relative to mental age-matched typically developing controls (ns = 19 in each group). RESULTS: Although within-group differences were not revealed on indexes, significant differences were found among BRIEF-2 scales. Across raters, teachers reported significantly more difficulties than parents. Compared with mental age-matched typically developing controls, the DS group was rated more poorly on some but not all BRIEF-2 scales. CONCLUSIONS: At the scale, but not the index level, the BRIEF-2 identifies a variegated EF profile in children with DS. For several of the scales, significant differences were noted relative to both chronological age expectations (using norms) and mental-age expectations (using a developmentally matched comparison group). At the scale level, the BRIEF-2 continues to be a sensitive tool for identifying executive function difficulties as well as profiles of relative strengths and weaknesses in children with DS.

Latent profiles of autism symptoms in children and adolescents with Down syndrome.

BACKGROUND: Down syndrome (DS) is associated with elevated rates of autism spectrum disorder (ASD) and autism symptomatology. To better characterise heterogeneity in ASD symptomatology in DS, profiles of caregiver-reported ASD symptoms were modelled for children and adolescents with DS. METHODS: Participants (n = 125) were recruited through several multi-site research studies on cognition and language in DS. Using the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), two latent profile analyses (LPA) were performed, one on the broad composite scores of social communication and interaction and restricted interests and repetitive behaviour, and a second on the four social dimensions of social communication, social motivation, social awareness, and social cognition. RESULTS: A three-profile model was the best fit for both analyses, with each analysis yielding a low ASD symptom profile, an elevated or mixed ASD symptom profile and a high ASD symptom profile. Associations were observed between profile probability scores and IQ, the number of co-occurring biomedical conditions reported, sex, and SRS-2 form. CONCLUSIONS: Characterising heterogeneity in ASD symptom profiles can inform more personalised supports in this population, and implications for potential therapeutic approaches for individuals with DS are discussed.

Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study.

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay.

BACKGROUND: Hereditary factors are involved in the pathogenesis of atopic dermatitis (AD). However, AD-related gene variations are significantly different across ethnicities. AIM: To identify mutations and single-nucleotide polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients with AD and compare the variations with those observed in nonatopic healthy controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD-related gene variants. METHODS: We carried out REBA to simultaneously detect variations in genes related to barrier or immune function, namely, FLG, SPINK5, KLK7, DEFB1, TNFα, KDR, FCER1A, IL4, IL5,IL5RA, IL9, IL10, IL12, IL12R, IL13 and IL18, from Korean patients with AD, and compared the variation to that in nonatopic healthy controls. RESULTS: The homozygous mutants of KLK7 and SPINK5-2475, and the heterozygous mutants of FLG 3321delA, SPINK5-1156, DEFB1, KDR, IL5RA, IL9 and IL12RB1 were significantly more frequent in AD. It has been predicted that the larger the number of gene variants, the higher the odds ratio of AD prevalence; however, we did not find any significant correlation between the number of gene variants and AD severity. CONCLUSION: Using REBA, we identified more genetic variants that can predict AD occurrence. We also verified that REBA can be used to easily and accurately detect multiple AD-related gene variants simultaneously. In addition, we identified a correlation between KLK7 mutation and AD in Koreans, which is the first such report, to our knowledge.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Applying core principles to the design and evaluation of the 'Take Charge. Take the Test' campaign: what worked and lessons learned.

OBJECTIVES: To describe the application of seven core principles to the design and evaluation of a human immunodeficiency virus (HIV) testing social marketing campaign as a case study example. STUDY DESIGN: The Centers for Disease Control and Prevention (CDC) used a structured social marketing approach, informed by the Ecological Model, the Theory of Planned Behaviour and the Health Belief Model, to develop and evaluate a two-city campaign with print, radio and outdoor advertising; HIV telephone hotlines; an HIV website; community partnerships; and events to promote information seeking and HIV testing. METHODS: The CDC applied seven core principles to design and evaluate the campaign, including formative research, the use of behavioural theories, audience segmentation, message design and pretesting, channel selection, process evaluation and outcome evaluation. RESULTS: Over 200 partners in both cities contributed significantly to campaign efforts. Key informant interviews indicated that, due to increased coordination, city infrastructures for HIV testing improved. More than 9600 individuals attended campaign events in both cities, with 1492 rapid HIV tests administered and 14 newly-identified HIV individuals. Overall, event attendees responded positively to campaign materials and events, and free HIV testing opportunities. The campaign significantly increased information-seeking behaviours in the form of hotline calls and web searches. Audience reaction and receptivity to the final campaign materials was very high. Exposure to campaign messages was associated with increases in key knowledge items, intentions to get tested, and peer-to-peer communication. CONCLUSIONS: The seven core principles, including formative research, behavioural theories and extensive partnerships, acted synergistically to help a campaign reach its target audience with compelling, relevant messages and motivate them to seek information and get an HIV test. Rapid testing removes many barriers by providing a testing process that can be accessed and acted upon quickly in response to media exposure. Findings suggest that modifying the campaign in future implementations to encourage the target audience to attend and participate in rapid testing events, while expanding the number and reach of such events, may have considerable potential to measurably increase testing behaviours.

Molecular cloning of the nahG gene encoding salicylate hydroxylase from Pseudomonas fluorescens.

A gene encoding the salicylate hydroxylase was cloned from the genomic DNA of Pseudomonas fluorescens SME11. The DNA fragment containing the nahG gene for the salicylate hydroxylase was mapped with restriction endonucleases and sequenced. The DNA fragment contained an ORF of 1,305 bp encoding a polypeptide of 434 amino acid residues. The nucleotide and amino acid sequences of the salicylate hydroxylase revealed several conserved regions with those of the enzyme encoded in P. putida PpG7: The homology of the nucleotide sequence is 83% and that of amino acid sequence is 72%. We found large conserved regions of the amino acid sequence at FAD and NADH binding regions. The FAD binding site is located at the amino terminal region and a lysine residue functions as a NADH-binding site.

Properties of clock-controlled and constitutive N-acetyltransferases from chick pineal cells.

The pineal gland synthesizes its hormone melatonin (O-methyl-N-acetylserotonin) from serotonin. Acetyl-CoA: serotonin N-acetyltransferase (SNAT), the enzyme that catalyzes the committed step in this biosynthesis, is largely restricted to the pineal gland and is regulated by adrenergic and circadian mechanisms. Another enzyme, acetyl-CoA: arylamine N-acetyltransferase (ANAT), having an apparently similar activity, is also present in the pineal. This enzyme, however, is not rhythmically regulated. SNAT activity of cultured chick pineal cells was obtained without ANAT after ammonium sulfate precipitation. ANAT activity was retained without SNAT activity after pre-incubation at 37 degrees C. Thus, each enzyme could be examined independently. Overlap in substrate specificity between the two enzymes was minimal. Kinetic analysis of the separated enzyme activities revealed that while SNAT operates via a random or ordered bi bi mechanism, ANAT catalysis occurs through a ping pong bi bi mechanism with substrate inhibition by acetyl-CoA. By size-exclusion chromatography, ANAT was confirmed to be 30-35 kDa, and SNAT was estimated at 15-20 kDa. Taken together, these results indicate that the two enzymes differ in their structure, reactivity, stability, and mechanism of catalysis.

The impact of Hurricane Hugo and the San Francisco earthquake on a sample of people with rheumatoid arthritis.

The health effects of two natural disasters on 32 people with rheumatoid arthritis (RA) were assessed during the second-year wave of interviews in an ongoing 3-year study. Although the severity of Hurricane Hugo exceeded that of the San Francisco earthquake, no significant differences in health impacts were found. Both groups reported significantly increased ratings of RA activity, pain, and depression compared with ratings during the first year. However, comparison with the rest of the sample (n = 767) showed that increases in disease activity and pain were a general phenomenon but that the increase in depression was unique to the disaster subsample. Physician health status assessments also indicated that those who experienced the disaster were more likely to be classified in later stages of the disease subsequent to the disaster and were more likely to experience flares. These results suggest that people with RA may constitute a special high-risk population for adverse health effects after natural disasters.

A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.

Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample.

Replication of LIN28B SNP association with age of menarche in young Filipino women.

BACKGROUND: Age of menarche, or the timing of first menses in girls, is a physiological trait that shows substantial genetic heritability. Earlier age of menarche is associated with increased childhood adiposity and with adult risk of obesity and cardiovascular disease. OBJECTIVES: We sought to further characterize the single nucleotide polymorphism (SNP) rs7759938 from the menarche locus LIN28B in 827 young Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). METHODS: We tested rs7759938 for additive association with age of menarche and also tested whether childhood adiposity, as measured by body mass index (BMI) at age 8, mediated this relationship. RESULTS: We observed nominal association of rs7759938 with age of menarche (ß = -0.118 years, 95% confidence interval = (-0.216, -0.020), P = 0.019) with an effect direction consistent with the previous report. We also observed suggestive evidence that the effect of the SNP on age of menarche was independent of childhood BMI. CONCLUSIONS: These data confirm the strongest gene reported in Europeans (LIN28B) as a contributor to age of menarche in an Asian population.

School-age outcomes of newborns treated for persistent pulmonary hypertension.

OBJECTIVE: The aim of this study was to describe the school-age outcome of a cohort of children treated with intensive care support for persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: From 187 term newborns treated for PPHN as neonates, 109 were seen at school age (73% of 150 survivors and 58.2% of the original cohort). Of these 109 term newborns, 77 were treated with inhaled nitric oxide (iNO); of which 12 received extracorporeal membrane oxygenation (ECMO). The remaining 32 received conventional management with no exposure to iNO. Patients were seen at school age (mean 7.1 years). A medical history and physical exam were completed, growth was measured, and chest X-ray and echocardiogram were performed. Psychometric assessments included the Wechsler Scales (Preschool or Child), Vineland Adaptive Behavior Scales, Kaufman Test of Educational Achievement, Children's Category Test, Wisconsin Card Sorting Test and Achenbach Child Behavior Checklist. RESULT: Medical, neurodevelopmental and social/emotional/behavioral outcome did not differ between children treated with iNO, with or without ECMO, and those managed with no exposure to iNO. Overall, 24% had respiratory problems, 60% had abnormal chest X-rays and 6.4% had some sensorineural hearing loss. The cohort performed at the average level for full scale IQ, adaptive function, academic achievement, higher-order cognition and executive functioning, and social/behavioral/emotional functioning. Overall, 9.2% of the cohort had a full scale IQ less than 70 and 7.4% had an IQ from 70 to 84. CONCLUSION: The outcome for this cohort of children treated as newborns for PPHN, which included a large group of infants exposed to iNO, was comparable to previous reports of children treated with ECMO or conventionally.

TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1.

Lipid rafts have been known to be platforms to initiate cellular signal transduction of insulin-like growth factor (IGF) inducing skeletal muscle differentiation and hypertrophy. Here, tripartite motif 72 (TRIM72), with a really interesting new gene (RING)-finger domain, a B-box, two coiled-coil domains, and a SPRY (SPla and RYanodine receptor) domain, was revealed to be predominantly expressed in the sarcolemma lipid rafts of skeletal and cardiac muscles. Adenoviral TRIM72 overexpression prevented but RNAi-mediated TRIM72 silencing enhanced C2C12 myogenesis by modulating the IGF-induced insulin receptor substrate-1 (IRS-1) activation through the molecular association of TRIM72 with IRS-1. Furthermore, myogenic activity was highly enhanced with increased IGF-induced Akt activation in the satellite cells of TRIM72(-/-) mice, compared to those of TRIM72+/+ mice. Because TRIM72 promoter analysis shows that two proximal E-boxes in TRIM72 promoter were essential for MyoD- and Akt-dependent TRIM72 transcription, we can conclude that TRIM72 is a novel antagonist of IRS-1, and is essential as a negative regulator of IGF-induced muscle differentiation.

Effects of substrates on biofilm formation observed by atomic force microscopy.

Formation of biofilm is known to be strongly dependent on substrates including topography, materials, and chemical treatment. In this study, a variety of substrates are tested for understanding biofilm formation. Sheets of aluminum, steel, rubber, and polypropylene have been used to examine their effects on formation of Pseudomonas aeruginosa biofilm. In particular, the morphological variation, transition, and adhesiveness of biofilm were investigated through local measurement by atomic force microscopy (AFM). Mechanism of removing biofilm from adhering to substrate is also analyzed, thus the understanding of the mechanism can be potentially useful to prevent the biofilm formation. The results reveal that formation of biofilm can remain on rough surface regardless of substrates in hot water, which may easily induce extra-polymeric substances detachment from bacterial surface. By probing using AFM, local force-distance characterization of extra-cellular materials extracted from the bacteria can exhibit the progress of the biofilm formation and functional complexities.

Cloning and sequence analyses of a 2,3-dihydroxybiphenyl 1,2-dioxygenase gene ( bphC) from Comamonas sp. SMN4 for phylogenetic and structural analysis.

A genomic library of biphenyl-degrading Comamonas sp. SMN4 for isolating fragments containing the 2,3-dihydroxybiphenyl 1,2-dioxygenase (23DBDO) gene was constructed. The smallest subclone (pNPX9) encoding 23DBDO activity was sequenced and analyzed. The C-terminal domain of 23DBDO from Comamonas sp. SMN4 had five catalytically essential residues and was more highly conserved than the N-terminal domain. Phylogenetic and structural relationships of 23DBDO from Comamonas sp. SMN4 were analyzed.

Enhancing mammography referral in primary care.

BACKGROUND: This 1-year randomized trial tested the efficacy of behavioral techniques for increasing mammography referrals by primary care physicians in small, community practices. METHODS: Sixty-one practices were randomly assigned to one of three conditions: (1) education-only control, (2) education plus cue enhancement using mammography chart stickers, and (3) education plus cue enhancement plus feedback and token rewards. Quarterly chart audits of a defined sample (N = 11,716) of women patients 50 years of age or older were conducted to document mammography referrals, completions, and compliance. RESULTS: Referral and completion rates increased from baseline to first quarter and gradually declined thereafter. Overall, these rates were higher in the cuing conditions than in the control condition. In contrast, compliance rates in both experimental conditions increased over the year while remaining static in the control condition, demonstrating a strong and continuing effect for cue enhancement. Compliance increases were greatest for physicians who were older, nonwhite, with a second speciality, in solo practice, not members of the AMA, not residency trained, and not board certified. CONCLUSIONS: Chart stickers can significantly increase mammography utilization in small, community practices. These practices are an efficient route to reaching large numbers of older women in need of mammography screening.