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Sample records for genotype affects outcome

  1. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

    PubMed Central

    Mills, Philippa B.; Camuzeaux, Stephane S.M.; Footitt, Emma J.; Mills, Kevin A.; Gissen, Paul; Fisher, Laura; Das, Krishna B.; Varadkar, Sophia M.; Zuberi, Sameer; McWilliam, Robert; Stödberg, Tommy; Plecko, Barbara; Baumgartner, Matthias R.; Maier, Oliver; Calvert, Sophie; Riney, Kate; Wolf, Nicole I.; Livingston, John H.; Bala, Pronab; Morel, Chantal F.; Feillet, François; Raimondi, Francesco; Del Giudice, Ennio; Chong, W. Kling; Pitt, Matthew

    2014-01-01

    The first described patients with pyridox(am)ine 5’-phosphate oxidase deficiency all had neonatal onset seizures that did not respond to treatment with pyridoxine but responded to treatment with pyridoxal 5’-phosphate. Our data suggest, however, that the clinical spectrum of pyridox(am)ine 5’-phosphate oxidase deficiency is much broader than has been reported in the literature. Sequencing of the PNPO gene was undertaken for a cohort of 82 individuals who had shown a reduction in frequency and severity of seizures in response to pyridoxine or pyridoxal 5’-phosphate. Novel sequence changes were studied using a new cell-free expression system and a mass spectrometry-based assay for pyridoxamine phosphate oxidase. Three groups of patients with PNPO mutations that had reduced enzyme activity were identified: (i) patients with neonatal onset seizures responding to pyridoxal 5’-phosphate (n = 6); (ii) a patient with infantile spasms (onset 5 months) responsive to pyridoxal 5’-phosphate (n = 1); and (iii) patients with seizures starting under 3 months of age responding to pyridoxine (n = 8). Data suggest that certain genotypes (R225H/C and D33V) are more likely to result in seizures that to respond to treatment with pyridoxine. Other mutations seem to be associated with infertility, miscarriage and prematurity. However, the situation is clearly complex with the same combination of mutations being seen in patients who responded and did not respond to pyridoxine. It is possible that pyridoxine responsiveness in PNPO deficiency is affected by prematurity and age at the time of the therapeutic trial. Other additional factors that are likely to influence treatment response and outcome include riboflavin status and how well the foetus has been supplied with vitamin B6 by the mother. For some patients there was a worsening of symptoms on changing from pyridoxine to pyridoxal 5’-phosphate. Many of the mutations in PNPO affected residues involved in binding flavin

  2. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome.

    PubMed

    Mills, Philippa B; Camuzeaux, Stephane S M; Footitt, Emma J; Mills, Kevin A; Gissen, Paul; Fisher, Laura; Das, Krishna B; Varadkar, Sophia M; Zuberi, Sameer; McWilliam, Robert; Stödberg, Tommy; Plecko, Barbara; Baumgartner, Matthias R; Maier, Oliver; Calvert, Sophie; Riney, Kate; Wolf, Nicole I; Livingston, John H; Bala, Pronab; Morel, Chantal F; Feillet, François; Raimondi, Francesco; Del Giudice, Ennio; Chong, W Kling; Pitt, Matthew; Clayton, Peter T

    2014-05-01

    The first described patients with pyridox(am)ine 5'-phosphate oxidase deficiency all had neonatal onset seizures that did not respond to treatment with pyridoxine but responded to treatment with pyridoxal 5'-phosphate. Our data suggest, however, that the clinical spectrum of pyridox(am)ine 5'-phosphate oxidase deficiency is much broader than has been reported in the literature. Sequencing of the PNPO gene was undertaken for a cohort of 82 individuals who had shown a reduction in frequency and severity of seizures in response to pyridoxine or pyridoxal 5'-phosphate. Novel sequence changes were studied using a new cell-free expression system and a mass spectrometry-based assay for pyridoxamine phosphate oxidase. Three groups of patients with PNPO mutations that had reduced enzyme activity were identified: (i) patients with neonatal onset seizures responding to pyridoxal 5'-phosphate (n = 6); (ii) a patient with infantile spasms (onset 5 months) responsive to pyridoxal 5'-phosphate (n = 1); and (iii) patients with seizures starting under 3 months of age responding to pyridoxine (n = 8). Data suggest that certain genotypes (R225H/C and D33V) are more likely to result in seizures that to respond to treatment with pyridoxine. Other mutations seem to be associated with infertility, miscarriage and prematurity. However, the situation is clearly complex with the same combination of mutations being seen in patients who responded and did not respond to pyridoxine. It is possible that pyridoxine responsiveness in PNPO deficiency is affected by prematurity and age at the time of the therapeutic trial. Other additional factors that are likely to influence treatment response and outcome include riboflavin status and how well the foetus has been supplied with vitamin B6 by the mother. For some patients there was a worsening of symptoms on changing from pyridoxine to pyridoxal 5'-phosphate. Many of the mutations in PNPO affected residues involved in binding flavin mononucleotide or

  3. Association of FMR1 Genotypes with In Vitro Fertilization (IVF) Outcomes Based on Ethnicity/Race

    PubMed Central

    Gleicher, Norbert; Weghofer, Andrea; Lee, Irene H.; Barad, David H.

    2011-01-01

    The FMR1 gene, mapping to an area of the X chromosome closely associated with autoimmunity also affects ovarian reserve, with specific genotypes associated with distinct ovarian aging patterns. They, therefore, could also be associated with differences of in vitro fertilization (IVF) outcomes, reported between races/ethnicities. We analyzed 339 consecutive IVF patients, 232 Caucasian, 59 African and 48 Asian, for FMR1 genotypes, and tested by multiple logistic regressions for associations between race/ethnicity, FMR1 genotype, autoimmunity and pregnancy chances with IVF. FMR1 genotypes were predictive of pregnancy (P = 0.046), het-norm/low most significantly and with decreasing chance in comparison to norm genotypes (OR 0.44; 95% CI 0.23–0.85; P = 0.014). Race/ethnicity was, overall, independently associated (P = 0.03), African demonstrating decreased odds in comparison to Caucasian (OR 0.33. 95%CI 0.13–0.79; P = 0.014). Autoimmunity did not differ but interaction of autoimmunity with FMR1 genotype almost reached significance (P = 0.07). Logistic regression with race/ethnicity and interaction between FMR1 genotype and autoimmunity in the model, demonstrated 2.5-times the odds of being associated with autoimmune positivity (OR 2.5, 1.34–4.55; P = 0.004). FMR1 genotypes offer a possible explanation for differences in IVF outcomes between races/ethnicities. PMID:21526209

  4. Factors affecting outcomes in colonoscopy.

    PubMed

    Selehi, Seema; Leung, Edmund; Wong, Ling

    2008-01-01

    There are many factors that influence successful outcomes in colonoscopy. The aims of this study were to evaluate these factors and determine ways to improve outcomes. All participants (N=229) who underwent planned colonoscopy between July and September 2004 were retrospectively included. Participants included 118 men and 111 women with a mean age of 59 years. Completion rate was 92%. Reasons of failure included poor bowel preparation (2.2%, p< .025), bowel looping (2.2%, p< .025), participant discomfort (1.3%), and obstructing lesion (1.3%). Mean midazolam dose was 3.8 mg. Three participants (1.3%) had midazolam alone, and all had complete colonoscopy. One hundred thirty-three participants (60.7%) had additional meperidine, with a completion rate of 94%. Eighty three participants (37.9%) had additional meperidine and Buscopan, with a completion rate reduced to 89.2%. There was no correlation between sedatives used and completion rate. Completion rate of colonoscopy in our unit was acceptable at 92%. A combination of midazolam and meperidine gave the best completion rates (94%). The two main reasons for incompletion were poor bowel preparation and excessive bowel looping. PMID:18300826

  5. Intracranial ependymoma: factors affecting outcome.

    PubMed

    Massimino, Maura; Buttarelli, Francesca R; Antonelli, Manila; Gandola, Lorenza; Modena, Piergiorgio; Giangaspero, Felice

    2009-03-01

    Ependymomas account for 2-9% of all neuroepithelial tumors, amounting to 6-12% of all intracranial tumors in children and up to 30% of those in children younger than 3 years. Recent findings provide evidence that intracranial and spinal ependymomas share similar molecular profiles with the radial glia of their corresponding locations. The management of intracranial ependymoma is still not optimal. The 5-year progression-free survival for children with ependymoma ranges between 30 and 50% with a worse prognosis for patients with residual disease after surgery. The prognostic relevance of most factors are still being debated. Recent studies, in which the current WHO classification criteria were applied, reported the relationship between histological grade and outcome. Biomolecular studies have identified that gain of 1q25 and EGFR overexpression correlate to poor prognosis, whereas low expression of nucleolin correlated with a favorable outcome. Ependymomas have been considered a 'surgical disease', where completeness of excision can be reached in approximately half of the cases. At present the standard treatment is radiation therapy for all patients after gross-total or near-total resection. For high-risk patients, with residual tumor, an interesting, although experimental, approach could be chemotherapy followed by secondary surgery and postoperative conformal irradiation. PMID:19284379

  6. APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals.

    PubMed

    Dumanis, Sonya B; DiBattista, Amanda M; Miessau, Matthew; Moussa, Charbel E H; Rebeck, G William

    2013-01-01

    Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer's disease and other conditions of brain damage. Using APOE knock-in mice, we have previously shown that APOE-ε4 Targeted Replacement (TR) mice have fewer dendritic spines and reduced branching in cortical neurons. As dendritic spines are post-synaptic sites of excitatory neurotransmission, we used APOE TR mice to examine whether APOE genotype affected the various elements of the glutamate-glutamine cycle. We found that levels of glutamine synthetase and glutamate uptake transporters were unchanged among the APOE genotypes. However, compared with APOE-ε3 TR mice, APOE-ε4 TR mice had decreased glutaminase levels (18%, p < 0.05), suggesting decreased conversion of glutamine to glutamate. APOE-ε4 TR mice also had increased levels of the vesicular glutamate transporter 1 (20%, p < 0.05), suggesting that APOE genotype affects pre-synaptic terminal composition. To address whether these changes affected normal neurotransmission, we examined the production and metabolism of glutamate and glutamine at 4-5 months and 1 year. Using high-frequency (13)C/(1)H nuclear magnetic resonance spectroscopy, we found that APOE-ε4 TR mice have decreased production of glutamate and increased levels of glutamine. These factors may contribute to the increased risk of neurodegeneration associated with APOE-ε4, and also act as surrogate markers for Alzheimer's disease risk. PMID:22862561

  7. Do School Facilities Affect Academic Outcomes?

    ERIC Educational Resources Information Center

    Schneider, Mark

    This review explores which facility attributes affect academic outcomes the most and in what manner and degree. The research is examined in six categories: indoor air quality, ventilation, and thermal comfort; lighting; acoustics; building age and quality; school size; and class size. The review concludes that school facilities affect learning.…

  8. Early Adolescent Affect Predicts Later Life Outcomes

    PubMed Central

    Kansky, Jessica; Allen, Joseph P.; Diener, Ed

    2016-01-01

    Background Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. Methods To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as a predictor of relationship, adjustment, self worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilized multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Results Early adolescent positive affect predicted less relationship problems (less self-reported and partner-reported conflict, greater friendship attachment as rated by close peers), healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. Conclusions The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. PMID:27075545

  9. Motivated behavioral outcomes affect ratings of attractiveness.

    PubMed

    Bernard, Larry C; Hardy, David J

    2014-12-01

    A relatively new theory of motivation posits that purposeful human behavior may be partly explained by multidimensional individual differences "traits of action" (motives). Its 15 motives can be characterized according to their purpose: individual integrity, competitiveness, and cooperativeness. Existing evidence supports the model on which the motives are based and the reliability and validity of strategies to assess them. This experiment tested whether the hypothetical results of consistent, motivated cooperative and competitive behavior could affect ratings of attractiveness. Male and female participants (N = 98; M age = 18.8, SD = 1.4) were shown 24 opposite-sex facial photos ranging in attractiveness. The photos were paired with one of three conditions representing theoretical outcomes that would result from low, control, and high levels of cooperative and competitive motives. As predicted, outcome descriptions representing high motive strength of six motives statistically significantly affected ratings of attractiveness. This result was independent of sex of participant and consistent with the theory. PMID:25457092

  10. Host genotype and tumor phenotype of chemokine decoy receptors integrally affect breast cancer relapse

    PubMed Central

    Shao, Zhi-Ming

    2015-01-01

    Purpose Chemokines may play vital roles in breast cancer progression and metastasis. The primary members of chemokine decoy receptors (CDR), DARC and D6, are expressed in breast tumors and lymphatic/hematogenous vessels. CDRs sequestrate the pro-malignant chemokines. We hypothesized that breast cancer patients carrying different levels of CDR expression in tumor and/or in host might have differing clinical outcomes. Methods This prospective observational study measured both expression and germline genotype of DARC and D6 in 463 primary breast cancer patients enrolled between 2004 and 2006. The endpoint was breast cancer relapse-free survival (RFS). Results There was a significant association between the co-expression of CDR (immunohistochemical expression of both DARC and D6) with RFS (hazard ratio [HR] of 0.32, 95% confidence interval [CI] 0.19 to 0.54). Furthermore, the co-genotype of two non-synonymous polymorphisms (with two major alleles of DARC-rs12075 and D6-rs2228468 versus the others) significantly related to relapse. Mechanistically, the variant-alleles of these two polymorphisms significantly decreased by 20–30% of CCL2/CCL5 (CDR ligands) levels relative to their major counterparts. Multivariate analysis highlighted that the co-expression and co-genotype of CDR were independent predictors of RFS, with HR of 0.46 (95% CI 0.27 to 0.80) and 0.56 (95% CI 0.37 to 0.85), respectively. The addition of host CDR genetic information to tumor-based factors (including co-expression of CDR) improved the relapse prediction ability (P = 0.02 of AUC comparison). Conclusion The host genotype and tumor phenotype of CDR integrally affect breast cancer relapse. Host-related factors should be considered for individualized prediction of prognosis. PMID:26314842

  11. PEPA-1* genotype affects return rate for hatchery steelhead

    USGS Publications Warehouse

    Reisenbichler, R.R.; Hayes, M.C.; Rubin, S.P.; Wetzel, L.A.; Baker, B.M.

    2006-01-01

    Allozymes continue to be useful as genetic markers in a variety of studies; however, their utility often hinges on the selective neutrality of the allelic variation. Our study tested for neutrality between the two most common alleles (*100 and *110) at the cytosol nonspecific dipeptidase locus (PEPA-1*) in steelhead Oncorhynchus mykiss from Dworshak National Fish Hatchery in Idaho. We tested for differential growth and survival among fish with the * 100/100, *100/ 110, and *110/110 genotypes rearing in a hatchery or a natural stream. We repeated the study for two year-classes, using heterozygous (*100/110) adults to make the experimental crosses. This design avoided differences in family contribution among genotypes because each cross produced all three genotypes. We divided the progeny from each family into two groups. One group was reared in a hatchery for 1 year and then released for migration to the sea and subsequent return to the hatchery as adults. The other group was released into a natural stream and monitored for 3 years. We found no significant differences in size or survival among PEPA-1* genotypes for either the naturally reared fish or the hatchery-reared fish immediately prior to release as smolts. For females, survival to returning adult also was similar among genotypes; however, hatchery-reared males with the *110/110 genotype returned at a higher rate than did males with the *100/ 100 genotype; heterozygous males were intermediate. These results indicate that selection occurs at the PEPA-1* locus or at one or more loci tightly linked to it. The finding of nearly equal frequencies for these two alleles in the source population suggests that selection differentials among genotypes reverse or vary from year to year; otherwise, steady directional selection would drive the *100 allele to low frequencies or extinction. Locus PEPA-1* seems inappropriate for genetic marks in studies of steelhead that span the full life cycle and probably should be avoided

  12. The relative importance of trait vs. genetic differentiation for the outcome of interactions among plant genotypes.

    PubMed

    Abbott, Jessica M; Stachowicz, John J

    2016-01-01

    Functional trait differences and genetic distance are increasingly used as metrics to predict the. outcome of species interactions and the maintenance of diversity. We apply these ideas to intraspecific diversity for the seagrass Zostera marina (eelgrass), by explicitly testing the influence of trait distance and genetic relatedness on the outcome of pairwise interactions among eelgrass genotypes. Increasing trait distance (but not relatedness) between eelgrass genotypes decreased the likelihood that both would persist over a year-long field experiment, contrary to our expectations based on niche partitioning. In plots in which one genotype excluded another, the biomass and growth of the remaining genotype increased with the trait distance and genetic relatedness of the initial pair, presumably due to a legacy of past interactions. Together these results suggest that sustained competition among functionally similar genotypes did not produce a clear winner, but rapid exclusion occurred among genotypes with distinct trait combinations. Borrowing from coexistence theory, we argue that fitness differences between genotypes with distinct traits overwhelmed any stabilizing effects of niche differentiation. Previously observed effects of eelgrass genetic diversity on performance may rely on nonadditive interactions among multiple genotypes or sufficient environmental heterogeneity to increase stabilizing forces and/or interactions. PMID:27008778

  13. Cropping history affects nodulation and symbiotic efficiency of distinct hairy vetch genotypes with resident soil rhizobia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Presence of compatible rhizobia strains is essential for nodulation and BNF of hairy vetch (Vicia villosa, HV). We evaluated how past HV cultivation affects nodulation and nitrogen fixation across host genotypes. Five groups of HV genotypes were inoculated with soil dilutions from six paired fields,...

  14. Southeast Asian patients with chronic hepatitis C: the impact of novel genotypes and race on treatment outcome.

    PubMed

    Dev, Anouk T; McCaw, Rhonda; Sundararajan, Vijaya; Bowden, Scott; Sievert, William

    2002-11-01

    Hepatitis C virus (HCV) genotype and other host and viral factors influence treatment outcome in chronic HCV infection. We evaluated the effect of race and genotype on interferon and ribavirin treatment outcome in 70 Southeast Asian (SEA) and 50 white patients. Genotype was based on the 5' untranslated region (5'UTR) with a commonly used line probe assay (INNO-LiPA HCV II) that may mistype genotype 7, 8, or 9 as 1b. HCV core region sequencing resulted in reclassification of 8 genotype 1 and 25 genotype 1b SEA subjects as genotype 7, 8, or 9. Twenty-six SEA genotype 7, 8, and 9 (79%) and 10 SEA true genotype 1b (59%) patients achieved a sustained virologic response (SVR) compared with 15 (34%) white genotype 1b patients. Logistic regression analysis showed that SEA patients with genotype 7, 8, or 9 were more likely to achieve a SVR than white genotype 1b patients (OR 16.56; 95%CI 4.16, 65.91) as were SEA true genotype 1b patients compared with white genotype 1b patients (OR 4.63; 95%CI 1.19, 18.04). In conclusion, a proportion of SEA patients classified by INNO-LiPA as genotype 1b were in reality genotype 7, 8, or 9. In comparison with white genotype 1b patients, both SEA genotype 1b and SEA genotype 7, 8, and 9 patients showed a significantly greater SVR. HCV core sequencing was necessary to determine genotype accurately in persons potentially exposed to HCV genotypes 7, 8, or 9. This study also supports the concept that race and ethnicity are important determinants of treatment outcome in HCV infected patients. PMID:12395338

  15. Clinical Features and Outcomes of Patients With Genotype 3 Hepatitis C Virus Infection in Korea

    PubMed Central

    Cha, Ra Ri; Lee, Sang Soo; Lee, Chang Min; Ji, Sung Bok; Jung, Hee Cheul; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae-Hyo; Jung, Woon Tae; Lee, Ok-Jae

    2016-01-01

    Abstract Hepatitis C virus (HCV) genotype 3 infection is very rare in high-income Asia Pacific. The aim of our retrospective observational study was to evaluate the incidence, clinical features, and treatment outcomes of patients with a genotype 3 HCV infection in the Gyeongnam Province of Korea. Ninety-eight consecutive patients diagnosed with a genotype 3 HCV infection at Gyeongsang National University Hospital, between January 2005 and December 2014, were enrolled into the study. Relevant characteristics of the study group included: 80.6% men, mean age of 41.8 years, and including 69 patients with chronic hepatitis, 25 with liver cirrhosis, and 4 with hepatocellular carcinoma (HCC). Risk factors for HCV infection, sustained virologic response rate, development of HCC, and mortality in patients with genotype 3 were retrospectively analyzed. Among all patients diagnosed with a HCV infection during the study period, the prevalence of genotype 3 was 7.3%. The incidence of genotype 3 was higher in young patients with a risk factor of IVDU (54.0%) and tattooing (62.3%). Among 45 treatment-naive genotype 3 patients, sustained virologic response was achieved with a combination of pegylated-interferon alpha and ribavirin in 75.6%. The cumulative 5-year incidence of HCC was 13.6%, and 8.9% for overall mortality. Liver cirrhosis at enrollment was an independent risk factor for HCC development. This is the first study to elucidate the clinical features and outcomes among the patients with HCV genotype 3 infection in Korea. Further prospective studies are needed to investigate transmission routes and outcomes for HCV genotype 3 infections. PMID:26871824

  16. Association between susceptible genotypes to periodontitis and clinical outcomes of periodontal regenerative therapy: A systematic review

    PubMed Central

    Koidou, Vasiliki-Petros

    2016-01-01

    Background The aim of this review is to systematically investigate the effect of a susceptible genotype to periodontitis with the clinical outcomes of periodontal regeneration. Material and Methods Based on a focused question, an electronic search identified 155 unique citations. Three journals (Journal of Periodontology, Journal of Clinical Periodontology and Journal of Periodontal Research), references of relevant studies and review articles were hand-searched. Two independent reviewers implementing eligibility inclusion criteria selected the studies. Results Of the 155, four studies fulfilled the inclusion criteria. All studies were published between 2000 and 2004 and the samples’ size was 40 to 86 patients. Polymorphisms of Interleukin-1 (IL-1) gene were included in all. Three out of four studies failed to identify an association between susceptible genotypes to periodontitis and clinical outcomes of periodontal regeneration, while one found an association. The heterogeneity and small number of studies included prevented the conduct of a meta-analysis. No studies were identified evaluating the effect of other genotypes and as a result only IL-1 genotype studies were included. Conclusions Within the limits of the present review, no direct conclusion for the effect of a susceptible IL-1 genotype status to the clinical outcome after periodontal regeneration could be drawn. The need of more qualitative studies to explore a possible association emerges. Key words:Periodontitis, genotype, periodontal therapy, regeneration, susceptibility, systematic review. PMID:26946210

  17. Conception of Learning Outcomes in the Bloom's Taxonomy Affective Domain

    ERIC Educational Resources Information Center

    Savickiene, Izabela

    2010-01-01

    The article raises a problematic issue regarding an insufficient base of the conception of learning outcomes in the Bloom's taxonomy affective domain. The search for solutions introduces the conception of teaching and learning in the affective domain as well as presents validity criteria of learning outcomes in the affective domain. The…

  18. Serotonin Transporter Genotype Linked to Adolescent Substance Use Treatment Outcome through Externalizing Behavior.

    PubMed

    Chung, Tammy; Cornelius, Jack R; Martin, Christopher S; Ferrell, Robert; Maisto, Stephen A; Clark, Duncan B

    2014-01-01

    Meta-analyses suggest that the serotonin transporter linked polymorphic region (5-HTTLPR) short (S) allele, relative to the long (L) allele, is associated with risk for alcohol dependence, particularly among individuals with early onset antisocial alcoholism. Youth in substance use treatment tend to show antisocial or externalizing behaviors, such as conduct problems, which predict worse treatment outcome. This study examined a pathway in which 5-HTTLPR genotype is associated with externalizing behavior, and the intermediate phenotype of externalizing behavior serves as a link between 5-HTTLPR genotype and substance use treatment outcome in youth. Adolescents (n = 142) who were recruited from addictions treatment were genotyped for 5-HTTLPR polymorphisms (S and LG carriers vs. LALA), assessed for externalizing and internalizing behaviors shortly after starting treatment, and followed over 6-months. 5-HTTLPR genotype was not associated with internalizing behaviors, and was not directly associated with 6-month substance use outcomes. However, 5-HTTLPR genotype was associated with externalizing behaviors (S and LG > LALA), and externalizing behaviors predicted alcohol and marijuana problem severity at 6-month follow-up. Results indicated an indirect (p < 0.05) and non-specific (i.e., both alcohol and marijuana severity) effect of 5-HTTLPR genotype on youth substance use treatment outcomes, with externalizing behaviors as an important linking factor. Adolescents in substance use treatment with low expressing (S and LG) 5-HTTLPR alleles and externalizing behavior might benefit from intervention that addresses serotonergic functioning, externalizing behaviors, and substance use to improve outcomes. PMID:25072039

  19. GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

    PubMed Central

    Lin, Wey-Ran; Chiang, Jy-Ming; Liang, Kung-Hao; Lim, Siew-Na; Lai, Ming-Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau-Ting

    2016-01-01

    Abstract Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC. A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis. Of these patients, 18% patients had GALNT14-rs9679162 “TT” and 82% had the “GT” + “GG” genotypes. The analysis showed that the “TT” genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the “TT” genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the “TT” genotype was the only independent predictor for OS. Finally, the “TT” genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the “TT” genotype was the only independent predictor for unfavorable RFS (P = 0.007). GALNT14 “TT” genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy. PMID:27124048

  20. Genotypic variation in tomatoes affecting processing and antioxidant attributes.

    PubMed

    Siddiqui, Mohammed Wasim; Ayala-Zavala, J F; Dhua, R S

    2015-01-01

    Tomatoes are widely consumed either raw or after processing and can provide a significant proportion of the total antioxidants in the diet associated with beneficial health properties. Over the last two or three decades an increasing interest for processing and antioxidant attributes in tomatoes has arisen. The screening of processing attributes of tomatoes is subject of a large number of articles; however, special interest has been addressed to the biochemical composition. The postharvest and industrial processing of tomato in tomato-based products includes several steps. Processing and antioxidant characteristics of the raw fruit are important considering the processing steps and final product. To respond to consumer and industrial complaints, breeders should know the range of genetic variability available in tomato resources, including local genotypes, for improving the mentioned attributes. Characterization and conservation of traditional and modern varieties is a major goal for their preservation and utilization. The bioactive contents have an impact on the processed destines so their stability must be contemplated while selecting the tomato fruits for processing. The endeavor of this review was to examine comprehensively the variation in processing and antioxidant attributes among tomatoes. Role of tomato peel in terms of bioactive contents and information on high pigment (hp) tomato mutants are also touched to some extent. Probably, patterns of variation identified/discussed in this paper would give impetus for planning breeding strategies to develop and improve the new processing cultivars with good antioxidant status. PMID:24279355

  1. Demotivation: Affective States and Learning Outcomes

    ERIC Educational Resources Information Center

    Falout, Joseph; Elwood, James; Hood, Michael

    2009-01-01

    Demotivation can negatively influence the learner's attitudes and behaviors, degrade classroom group dynamics and teacher's motivation, and result in long-term and widespread negative learning outcomes. 900 university EFL learners were surveyed to investigate the demotivating factors in learning English as a foreign language (EFL) in Japan, and…

  2. AB128. Neonatal diabetes mellitus: genotype, phenotype and outcome

    PubMed Central

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc; Flanagan, Sarah; Ellard, Sian; Craig, Maria; Nguyen, Dat Phu; Nguyen, Hoan Thi

    2015-01-01

    Background and objective Neonatal diabetes mellitus (NDM) is a rare (1:300,000-400,000 newborns) but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. Two main groups have been recognized on clinical grounds, transient NDM (TNDM) and permanent NDM (PNDM). This article aims to describe clinical features and laboratory manifestations of patient with NDM and evaluate outcome of management. Methods and materials Clinical features, biochemical finding, mutation analysis and management outcome of 24 cases 24 unrelated families were study. All exon of KCNJ11, ABCC8 and INS genes were amplified from genomic DNA and directly sequenced. If the mutation of KCNJ11, ABCC8 and INS has failed to detect, methylation—specific PCR will be done to detect the loss of methylated region on chromosome 6q24. Results Twenty-four cases (11 girls and 13 boys) onset at 67.3±44 days of age with gestation age of 38.79±2.2 weeks and birth weight of 2,720.8±571.7 g. 9/24 cases admitted with the feature of polydipsia, polyuria and 17 cases with diabetes keton acidosis with pH of 7.13±0.18, blood glucose of 34.8±10.0 mmoL/L, HbA1C of 7.9%±2.9%. Mutation analysis showed six patients with heterozygous for a KCNJ11 missense mutation, seven patients with ABCC8 mutations, four patients with abnormal of chromosom 6, six patients with INS mutation, one patient with EIF2AK3 mutation. The patients have been followed up during 54.4±46.6 months (4 months to 14 years). Five patients with TNDM stop insulin at 8.25±5.8 months of diagnosis: four cases have abnormal of 6q24, one case has ABCC8 mutation. Now all cases have normoglycemic (blood glucose: 5.0 and 5.9 mmoL/L), one patient has mild development delay and four patients has normal development. Nineteen patients with PNDM: 13 cases successfully transferred onto sulfonylureas and did not need insulin injections, six cases require insulin. In there, two cases with DEND syndrome have

  3. Affective Outcomes of a World Geography Course

    ERIC Educational Resources Information Center

    Forsyth, Alfred S., Jr.; Maier, Joan N.

    2006-01-01

    Affective goals and objectives, rarely stated in geographic education standards, textbooks or course syllabi, include improving students' attitudes toward other people. World geography courses expose students to other parts of the world and to people different from themselves. Although affective goals may not be stated for such courses, could it…

  4. Trait Affect and Job Search Outcomes

    ERIC Educational Resources Information Center

    Cote, Stephane; Saks, Alan M.; Zikic, Jelena

    2006-01-01

    The present study examines the role of trait affect in job search. One hundred and twenty-three university students completed measures of positive and negative affectivity, conscientiousness, job search self-efficacy, job search clarity, and job search intensity during their last year of school while on the job market. At the end of the school…

  5. Monoamine Oxidase A (MAOA) Genotype Predicts Greater Aggression Through Impulsive Reactivity to Negative Affect

    PubMed Central

    Chester, David S.; DeWall, C. Nathan; Derefinko, Karen J.; Estus, Steven; Peters, Jessica R.; Lynam, Donald R.; Jiang, Yang

    2015-01-01

    Low functioning MAOA genotypes have been reliably linked to increased reactive aggression, yet the psychological mechanisms of this effect remain largely unknown. The low functioning MAOA genotype’s established link to diminished inhibition and greater reactivity to conditions of negative affect suggest that negative urgency, the tendency to act impulsively in the context of negative affect, may fill this mediating role. Such MAOA carriers may have higher negative urgency, which may in turn predict greater aggressive responses to provocation. To test these hypotheses, 277 female and male participants were genotyped for an MAOA SNP yet to be linked to aggression (rs1465108), and then reported their negative urgency and past aggressive behavior. We replicated the effect of the low functioning MAOA genotype on heightened aggression, which was mediated by greater negative urgency. These results suggest that disrupted serotonergic systems predispose individuals towards aggressive behavior by increasing impulsive reactivity to negative affect. PMID:25637908

  6. Implicit emotion regulation affects outcome evaluation.

    PubMed

    Yang, Qiwei; Tang, Ping; Gu, Ruolei; Luo, Wenbo; Luo, Yue-jia

    2015-06-01

    Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes. PMID:25332404

  7. Rockford, Ill.: Cognitive and Affective Outcomes.

    ERIC Educational Resources Information Center

    Baldwin, Thomas F.; And Others

    1978-01-01

    Describes the operational tests of the two-way interactive cable television system using a firefighter training series administered to the Rockford (Illinois) fire department. Cognitive and affective measurement instruments described indicate a significant difference favoring two-way systems of in-service training programs. (JMF)

  8. Do gravidity and age affect pregnancy outcome?

    PubMed

    Santow, G; Bracher, M

    1989-01-01

    Fetal loss has generally been found to vary with gravidity, previous experience of fetal loss, and maternal age, but the literature is divided on the reasons for these associations. In this paper we examine pregnancy histories obtained retrospectively from a nationally representative one-in-one-thousand sample of women in Australia aged 20 to 59 years. The relations of fetal loss ratios with both gravidity and previous outcome are consistent with heterogeneity of risk over the study population and a stopping rule, whereby high-risk women undertake more pregnancies than low-risk women to achieve the same number of live births. Evidence is presented that elevated loss ratios in the teens indicate not higher risk but a selection for short gestation intervals, while loss ratios beyond the mid-thirties do not point unequivocally to a substantial increase in risk at the older reproductive ages. PMID:2814570

  9. Surgical technique affects outcomes in acromioclavicular reconstruction.

    PubMed

    Grassbaugh, Jason A; Cole, Chad; Wohlrab, Kurt; Eichinger, Josef

    2013-01-01

    Optimal treatment for acromioclavicular (AC) dislocation is unknown. Numerous surgical procedures for AC injuries have been described with little comparison. This study sought to compare the clinical and radiographic results of various surgical techniques in order to identify the optimal surgical technique. Ninety patients met inclusion criteria of AC reconstruction at this institution. A retrospective review of outcomes was performed using the electronic records system. Radiographs were measured for pre- and postoperative grade and percent elevation versus the contralateral side. Overall revision rate was 9%. Suture button fixation had a revision rate of 0% compared to 14% (p = .01). Reconstruction procedures performed with distal clavicle excision showed a higher revision rate, 17% compared to 0% (p = .003). There were no statistically significant clinical differences. AC reconstructions performed with suture button construct were superior to other surgical techniques. Procedures performed with distal clavicle excision were inferior to those without. PMID:23449059

  10. The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice

    PubMed Central

    Yokoyama, Yoshinobu; Miyagi, Takuya; Hikita, Hayato; Yoshioka, Teppei; Mukai, Kaori; Nawa, Takatoshi; Sakamori, Ryotaro; Ohkawa, Kazuyoshi; Hiramatsu, Naoki; Takahashi, Takeshi; Suemizu, Hiroshi; Ryo, Akihide; Tatsumi, Tomohide; Takehara, Tetsuo

    2015-01-01

    Background & Aims At least eight genotypes of Hepatitis B virus (HBV) have been identified. HBV genotype C is the most common genotype in Japan, although the incidence of HBV genotype A is increasing. The reason underlying the differences in viral multiplication of the HBV genotypes is unclear, especially in vivo. The purpose of this study was to elucidate the differences in HBV load and the persistence of viremia in vivo between genotypes A and C. Methods Immunodeficient NOG mice were transfected by hydrodynamic injection with the HBV expression plasmids pHBA1.2 or pHBC1.2, which contain overlength (1.2-mer) copies of the genomes of HBV genotype A or C, respectively. Results One day after transfection, the number of HBcAg-positive hepatocytes and serum HBV DNA levels were similar between mice transfected with pHBA1.2 and pHBC1.2. Serum levels of HBV DNA, HBsAg and HBeAg in mice transfected with pHBA1.2 were maintained over 5 months. In contrast, those in mice with pHBC1.2 gradually decreased over time and reached undetectable levels within 3 months after transfection. HBcAg-stained hepatocytes were detected in mice transfected with pHBA1.2, but not pHBC1.2, 5 months post-transfection. Double-staining immunohistochemistry revealed that the number of cleaved caspase3-stained, HBcAg-positive hepatocytes in the pHBC1.2-transfected mice was higher than in the pHBA1.2-transfected mice 3 days post-transfection. Moreover, the plasmid DNA and covalently closed circular DNA levels were decreased in the livers of pHBC1.2-transfected mice. These results suggested that hepatocytes expressing HBV genotype C were eliminated by apoptosis in the absence of immune cells more often than in hepatocytes expressing HBV genotype A. Conclusions Immunodeficient mice transfected with HBV genotype A develop persistent viremia, whereas those transfected with HBV genotype C exhibit transient viremia accompanied by apoptosis of HBV-expressing hepatocytes. This differences may affect the

  11. The Neural Basis of Risky Choice with Affective Outcomes

    PubMed Central

    Suter, Renata S.; Pachur, Thorsten; Hertwig, Ralph; Endestad, Tor; Biele, Guido

    2015-01-01

    Both normative and many descriptive theories of decision making under risk are based on the notion that outcomes are weighted by their probability, with subsequent maximization of the (subjective) expected outcome. Numerous investigations from psychology, economics, and neuroscience have produced evidence consistent with this notion. However, this research has typically investigated choices involving relatively affect-poor, monetary outcomes. We compared choice in relatively affect-poor, monetary lottery problems with choice in relatively affect-rich medical decision problems. Computational modeling of behavioral data and model-based neuroimaging analyses provide converging evidence for substantial differences in the respective decision mechanisms. Relative to affect-poor choices, affect-rich choices yielded a more strongly curved probability weighting function of cumulative prospect theory, thus signaling that the psychological impact of probabilities is strongly diminished for affect-rich outcomes. Examining task-dependent brain activation, we identified a region-by-condition interaction indicating qualitative differences of activation between affect-rich and affect-poor choices. Moreover, brain activation in regions that were more active during affect-poor choices (e.g., the supramarginal gyrus) correlated with individual trial-by-trial decision weights, indicating that these regions reflect processing of probabilities. Formal reverse inference Neurosynth meta-analyses suggested that whereas affect-poor choices seem to be based on brain mechanisms for calculative processes, affect-rich choices are driven by the representation of outcomes’ emotional value and autobiographical memories associated with them. These results provide evidence that the traditional notion of expectation maximization may not apply in the context of outcomes laden with affective responses, and that understanding the brain mechanisms of decision making requires the domain of the decision

  12. Sublineages of Mycobacterium tuberculosis Beijing genotype strains and unfavorable outcomes of anti-tuberculosis treatment.

    PubMed

    Hang, Nguyen T L; Maeda, Shinji; Keicho, Naoto; Thuong, Pham H; Endo, Hiroyoshi

    2015-05-01

    The influence of Mycobacterium tuberculosis (MTB) lineages/sublineages on unfavorable tuberculosis (TB) treatment outcomes is poorly understood. We investigated the effects of Beijing genotype sublineages and other factors contributing to treatment outcome. Patients newly diagnosed with sputum smear-positive and culture-positive TB in Hanoi, Vietnam, participated in the study. After receiving anti-TB treatment, they were intensively followed up for the next 16 months. MTB isolates collected before treatment were subjected to drug susceptibility testing, and further analyzed to determine MTB (sub) lineages and their clonal similarities. Of 430 patients, 17 had treatment failure and 30 had TB recurrence. Rifampicin resistance was associated with treatment failure {adjusted odds ratio = 6.64 [95% confidence interval (CI), 1.48-29.73]}. The modern Beijing genotype was significantly associated with recurrent TB within 16 months [adjusted hazard ratio = 3.29 (95% CI, 1.17-9.27)], particularly after adjustment for the relevant antibiotic resistance. Human immunodeficiency virus coinfection and severity on chest radiographs were not significantly associated with unfavorable outcomes. Our findings provide further understanding of the influence of MTB strains on unfavorable treatment outcomes. Multiple risk factors should be considered for the optimal management of TB. PMID:25732626

  13. Hepatitis B virus genotypes in southwest Iran: Molecular, serological and clinical outcomes

    PubMed Central

    Mojiri, Anahita; Behzad-Behbahani, Abbas; Saberifirozi, Mehdei; Ardabili, Maryam; Beheshti, Mahmood; Rahsaz, Marjan; Banihashemi, Mehrdad; Azarpira, Negar; Geramizadeh, Bita; Khadang, Baharak; Moaddeb, Afsaneh; Ghaedi, Mojgan; Heidari, Tahereh; Torab, Ardeshir; Salah, Alireza; Amirzadeh, Saeid; Jowkar, Zahra; Mehrabani, Davood; Amini-Bavil-Olyaee, Samad; Dehyadegari, Mohammad Ali

    2008-01-01

    AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV found in different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV-infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease. PMID:18330939

  14. Interaction between host genotype and environmental conditions affects bacterial density in Wolbachia symbiosis.

    PubMed

    Mouton, Laurence; Henri, Hélène; Charif, Delphine; Boulétreau, Michel; Vavre, Fabrice

    2007-04-22

    Regulation of microbial population density is a necessity in stable symbiotic interactions. In Wolbachia symbiosis, both bacterial and host genotypes are involved in density regulation, but environmental factors may also affect bacterial population density. Here, we studied the interaction between three strains of Wolbachia in two divergent homozygous lines of the wasp Leptopilina heterotoma at two different temperatures. Wolbachia density varied between the two host genotypes at only one temperature. Moreover, at this temperature, reciprocal-cross F1 insects displayed identical Wolbachia densities, which were intermediate between the densities in the two parental lines. While these findings confirm that the host genotype plays an important role in Wolbachia density, they also highlight its interaction with environmental conditions, making possible the evolution of local adaptations for the regulation of Wolbachia density. PMID:17251124

  15. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

    PubMed

    Giampieri, Riccardo; Salvatore, Lisa; Del Prete, Michela; Prochilo, Tiziana; D'Anzeo, Marco; Loretelli, Cristian; Loupakis, Fotios; Aprile, Giuseppe; Maccaroni, Elena; Andrikou, Kalliopi; Bianconi, Maristella; Bittoni, Alessandro; Faloppi, Luca; Demurtas, Laura; Montironi, Rodolfo; Scarpelli, Marina; Falcone, Alfredo; Zaniboni, Alberto; Scartozzi, Mario; Cascinu, Stefano

    2016-01-01

    Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy. PMID:27117754

  16. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients

    PubMed Central

    Giampieri, Riccardo; Salvatore, Lisa; Del Prete, Michela; Prochilo, Tiziana; D’Anzeo, Marco; Loretelli, Cristian; Loupakis, Fotios; Aprile, Giuseppe; Maccaroni, Elena; Andrikou, Kalliopi; Bianconi, Maristella; Bittoni, Alessandro; Faloppi, Luca; Demurtas, Laura; Montironi, Rodolfo; Scarpelli, Marina; Falcone, Alfredo; Zaniboni, Alberto; Scartozzi, Mario; Cascinu, Stefano

    2016-01-01

    Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients’ progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy. PMID:27117754

  17. Defining and Assessing Affective Outcomes in Undergraduate Pediatric Dentistry.

    ERIC Educational Resources Information Center

    Cullen, Claire L.

    1990-01-01

    The affective aspect of the curriculum is defined as the development of appropriate and measurable values such as ethical behavior, honesty, tolerance, and becoming a life-long learner. In outcome assessment of the affective category, the goal is to evaluate the transition of the student to a professional. (MLW)

  18. Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa

    PubMed Central

    Beale, Mathew A.; Sabiiti, Wilber; Robertson, Emma J.; Fuentes-Cabrejo, Karen M.; O’Hanlon, Simon J.; Jarvis, Joseph N.; Loyse, Angela; Meintjes, Graeme; Harrison, Thomas S.; May, Robin C.; Fisher, Matthew C.; Bicanic, Tihana

    2015-01-01

    Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients’ cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is

  19. Institutional Factors Affecting Biophysical Outcomes in Forest Management

    ERIC Educational Resources Information Center

    Coleman, Eric A.

    2009-01-01

    Although there is considerable interest in the impact of diverse policies affecting the biophysical outcomes in forests, gaining a substantial sample over time of forests under different institutional arrangements has been difficult. This article analyzes data from 46 forests located in six countries over time. In forests where policies have been…

  20. Factors Affecting the Outcomes of School Bond Elections in Iowa.

    ERIC Educational Resources Information Center

    Lode, Marlin D.

    In spite of a nationwide concern for the crumbling infrastructure of school buildings, the prospects of passing bond issues to repair or replace buildings are elusive. This study examined positive and negative factors that affected the outcomes of school bond elections in four purposefully-selected school districts in Iowa. Variables that…

  1. Affective Neural Responses Modulated by Serotonin Transporter Genotype in Clinical Anxiety and Depression

    PubMed Central

    Oathes, Desmond J.; Hilt, Lori M.; Nitschke, Jack B.

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/LG carriers showed less activity than their LA/LA counterparts in both regions and less activity than S/LG healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  2. The Scion/Rootstock Genotypes and Habitats Affect Arbuscular Mycorrhizal Fungal Community in Citrus

    PubMed Central

    Song, Fang; Pan, Zhiyong; Bai, Fuxi; An, Jianyong; Liu, Jihong; Guo, Wenwu; Bisseling, Ton; Deng, Xiuxin; Xiao, Shunyuan

    2015-01-01

    Citrus roots have rare root hairs and thus heavily depend on arbuscular mycorrhizal fungi (AMF) for mineral nutrient uptake. However, the AMF community structure of citrus is largely unknown. By using 454-pyrosequencing of 18S rRNA gene fragment, we investigated the genetic diversity of AMF colonizing citrus roots, and evaluated the impact of habitats and rootstock and scion genotypes on the AMF community structure. Over 7,40,000 effective sequences were obtained from 77 citrus root samples. These sequences were assigned to 75 AMF virtual taxa, of which 66 belong to Glomus, highlighting an absolute dominance of this AMF genus in symbiosis with citrus roots. The citrus AMF community structure is significantly affected by habitats and host genotypes. Interestingly, our data suggests that the genotype of the scion exerts a greater impact on the AMF community structure than that of the rootstock where the physical root-AMF association occurs. This study not only provides a comprehensive assessment for the community composition of the AMF in citrus roots under different conditions, but also sheds novel insights into how the AMF community might be indirectly influenced by the spatially separated yet metabolically connected partner—the scion—of the grafted citrus tree. PMID:26648932

  3. Genotype-phenotype correlation and pregnancy outcomes of partial trisomy 14q: A systematic review.

    PubMed

    Bregand-White, Julia; Saller, Devereux N; Clemens, Michele; Surti, Urvashi; Yatsenko, Svetlana A; Rajkovic, Aleksandar

    2016-09-01

    Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc. PMID:27286879

  4. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

    PubMed

    Madlensky, L; Natarajan, L; Tchu, S; Pu, M; Mortimer, J; Flatt, S W; Nikoloff, D M; Hillman, G; Fontecha, M R; Lawrence, H J; Parker, B A; Wu, A H B; Pierce, J P

    2011-05-01

    We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold. PMID:21430657

  5. Tamoxifen Metabolite Concentrations, CYP2D6 Genotype and Breast Cancer Outcomes

    PubMed Central

    Madlensky, Lisa; Natarajan, Loki; Tchu, Simone; Pu, Minya; Mortimer, Joanne; Flatt, Shirley W.; Nikoloff, D. Michele; Hillman, Grantland; Fontecha, Marcel R.; Lawrence, H. Jeffrey; Parker, Barbara A.; Wu, Alan H.B.; Pierce, John P.

    2011-01-01

    We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen, and to examine potential correlates of endoxifen concentrations including CYP2D6 metabolizer phenotype and body mass index (BMI). Tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen concentrations were measured from 1370 estrogen receptor positive breast cancer patients participating in the Women’s Healthy Eating and Living (WHEL) Study, and tested for associations with breast cancer outcomes. Breast cancer outcomes were not associated with tamoxifen, 4-hydroxytamoxifen or N-desmethyltamoxifen concentrations. For endoxifen, a threshold was identified suggesting that women in the upper four quintiles of endoxifen had a 26% lower recurrence rate than women in the bottom quintile. (HR=0.74; 95% CI, [0.55, 1.00]). Predictors of membership in this higher risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and low tamoxifen concentrations. This study suggests a minimal threshold at which endoxifen is effective against breast cancer recurrence, which 80% of tamoxifen-takers achieve. PMID:21430657

  6. Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder

    PubMed Central

    Furmark, Tomas; Henningsson, Susanne; Appel, Lieuwe; Åhs, Fredrik; Linnman, Clas; Pissiota, Anna; Faria, Vanda; Oreland, Lars; Bani, Massimo; Pich, Emilio Merlo; Eriksson, Elias; Fredrikson, Mats

    2009-01-01

    Background Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)–related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls. Methods We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms. Results Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles. Limitations Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrolment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli. Conclusion Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT–related genes into account. PMID:19125211

  7. Psychosocial predictors of treatment outcome for trauma-affected refugees

    PubMed Central

    Sonne, Charlotte; Carlsson, Jessica; Bech, Per; Vindbjerg, Erik; Mortensen, Erik Lykke; Elklit, Ask

    2016-01-01

    Background The effects of treatment in trials with trauma-affected refugees vary considerably not only between studies but also between patients within a single study. However, we know little about why some patients benefit more from treatment, as few studies have analysed predictors of treatment outcome. Objective The objective of the study was to examine possible psychosocial predictors of treatment outcome for trauma-affected refugees. Method The participants were 195 adult refugees with posttraumatic stress disorder (PTSD) who were enrolled in a 6- to 7-month treatment programme at the Competence Centre for Transcultural Psychiatry (CTP), Denmark. The CTP Predictor Index used in the study included 15 different possible outcome predictors concerning the patients’ past, chronicity of mental health problems, pain, treatment motivation, prerequisites for engaging in psychotherapy, and social situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ). Other outcome measures included the Hopkins Symptom Check List-25, the WHO-5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms Checklist-90, Global Assessment of Functioning scales, and pain rated on visual analogue scales. The relations between treatment outcomes and the total score as well as subscores of the CTP Predictor Index were analysed. Results Overall, the total score of the CTP Predictor Index was significantly correlated to pre- to post treatment score changes on the majority of the ratings mentioned above. While employment status was the only single item significantly correlated to HTQ-score changes, a number of single items from the CTP Predictor Index correlated significantly with changes in depression and anxiety symptoms, but the size of the correlation coefficients were modest. Conclusions The total score of the CTP Predictor Index correlated significantly with outcomes on most

  8. Birth order, family environments, academic and affective outcomes.

    PubMed

    Marjoribanks, Kevin

    2003-06-01

    Relations were examined among birth order, family social status, family learning environments, and a set of affective and academic outcomes. Data were collected as part of an Australian longitudinal study (4,171 females and 3,718 males). Analysis suggested that birth order continued to have small but significant associations with adolescents' self-concept and educational aspirations and with young adults' educational attainment, after taking into account differences in family social status and family learning environments. PMID:12931949

  9. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.

    PubMed

    Schmid, Christoph; Labopin, Myriam; Socié, Gerard; Daguindau, Etienne; Volin, Liisa; Huynh, Anne; Bourhis, Jean Henri; Milpied, Noel; Cornelissen, Jan; Chevallier, Patrice; Maertens, Johan; Jindra, Pavel; Blaise, Didier; Lenhoff, Stig; Ifrah, Norbert; Baron, Frédéric; Ciceri, Fabio; Gorin, Claude; Savani, Bipin; Giebel, Sebastian; Polge, Emmanuelle; Esteve, Jordi; Nagler, Arnon; Mohty, Mohamad

    2015-10-22

    To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 ± 5% in NPM1(mut)/FLT3(wt), 75 ± 3% in NPM1(wt)/FLT3(wt), 66 ± 3% in NPM1(mut)/FLT3-ITD, and 54 ± 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) and with a triple negative genotype (2-year OS: 100%/77 ± 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). PMID:26351297

  10. Vitamin D-related gene polymorphisms do not influence the outcome and serum vitamin D level in pegylated interferon/ribavirin therapy combined with protease inhibitor for patients with genotype 1b chronic hepatitis C.

    PubMed

    Arai, Taeang; Atsukawa, Masanori; Tsubota, Akihito; Kondo, Chisa; Shimada, Noritomo; Abe, Hiroshi; Itokawa, Norio; Nakagawa, Ai; Okubo, Tomomi; Aizawa, Yoshio; Iwakiri, Katsuhiko

    2015-11-01

    Although several vitamin D-related gene polymorphisms were reported to affect the outcome of pegylated interferon/ribavirin (PR) therapy in chronic hepatitis C patients, there are no reports on the impact of the vitamin D-related gene polymorphisms in PR therapy combined with protease inhibitor (PI). Vitamin D-related gene polymorphisms were determined in 177 genotype 1b-infected chronic hepatitis C patients who received 12 weeks of PR therapy with telaprevir, a first-generation PI, followed by 12 weeks of PR therapy. The sustained virologic response (SVR) rate was 83.1% (147 of 177 patients). The frequencies of vitamin D-related gene polymorphisms were: 83 non-TT and 94 TT genotypes for GC, 97 non-AA and 80 AA genotypes for DHCR7, 151 non-AA and 26 AA genotypes for CYP2R1, 162 non-GG and 15 GG genotypes for CYP27B1, and 105 non-GG and 72 GG genotypes for VDR gene. Multivariate analysis extracted IL28B TT genotype (P = 2.05 × 10(-6)) and serum 25(OH) D3 level (P = 0.024) as independent factors contributing to the achieving of SVR. The SVR rate in IL28B TT genotype patients with serum 25(OH) D3 level of < 25 ng/ml was significantly low compared to other patients. None of the vitamin D-related gene polymorphisms affected the treatment outcome and serum 25(OH) D3 level. In conclusions, the IL28B polymorphism and serum 25(OH) D3 level contributed significantly and independently to SVR in PR combined with PI for genotype 1b-infected chronic hepatitis C patients. However, none of vitamin D-related gene polymorphisms had an impact on the treatment outcome and serum 25(OH) D3 level. PMID:25964133

  11. Affective neural responses modulated by serotonin transporter genotype in clinical anxiety and depression.

    PubMed

    Oathes, Desmond J; Hilt, Lori M; Nitschke, Jack B

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L(G) carriers showed less activity than their L(A)/L(A) counterparts in both regions and less activity than S/L(G) healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  12. Vestibular rehabilitation strategies and factors that affect the outcome.

    PubMed

    Eleftheriadou, Anna; Skalidi, Nikoleta; Velegrakis, Georgios A

    2012-11-01

    Ever since the introduction of Cawthorne-Cooksey exercises, vestibular rehabilitation (VR) has been gaining popularity in the treatment of the dizzy patient. Numerous studies support the effectiveness of VR in improving balance/walking skills, eye-head coordination and the quality of life of the patient. Different rehabilitation protocols have been used to treat patients with peripheral and central vestibular disorders. Assessment of the patients' progress is based on the patients' selfperception of dizziness and their functional skills. Factors such as age, medication, time of onset of vertigo and home based VR have been evaluated on their effect on the rehabilitation's outcome. The aim of this review is to evaluate rehabilitation strategies and discuss the factors that affect the outcome. PMID:22526580

  13. Felt affect in good- and poor-outcome schizophrenia

    PubMed Central

    Sovani, Anuradha; Thatte, Shubha; Deshpande, C.G.

    2005-01-01

    Background: Family members and caregivers may misinterpret blunted affect as a true lack of emotion in patients with schizophrenia. Aim: To assess felt affect or experienced emotion among low- and high-functioning schizophrenics. Methods: Two hundred people with schizophrenia were assessed using the Global Assessment of Functioning scale of DSM-IV and the Positive and Negative Affect Schedule (PANAS). Results: The findings reveal that people with good- and poor-outcome schizophrenia show no significant differences in the emotions experienced, implying that felt affect is comparable regardless of the severity of symptoms in chronic schizophrenia. In fact, low-functioning patients scored a mean (SD) of 46.07 (13.13) on the PANAS, in contrast to a slightly lower scored by high-functioning patients (44.33 [12.03]). Conclusion: Although patients may show flat affect, and therefore be mistakenly considered withdrawn and apathetic by the observer, they do, in fact, experience as much, or perhaps even more emotion than their higher-functioning counterparts.

  14. Do waiting times affect health outcomes? Evidence from coronary bypass.

    PubMed

    Moscelli, Giuseppe; Siciliani, Luigi; Tonei, Valentina

    2016-07-01

    Long waiting times for non-emergency services are a feature of several publicly-funded health systems. A key policy concern is that long waiting times may worsen health outcomes: when patients receive treatment, their health condition may have deteriorated and health gains reduced. This study investigates whether patients in need of coronary bypass with longer waiting times are associated with poorer health outcomes in the English National Health Service over 2000-2010. Exploiting information from the Hospital Episode Statistics (HES), we measure health outcomes with in-hospital mortality and 28-day emergency readmission following discharge. Our results, obtained combining hospital fixed effects and instrumental variable methods, find no evidence of waiting times being associated with higher in-hospital mortality and weak association between waiting times and emergency readmission following a surgery. The results inform the debate on the relative merits of different types of rationing in healthcare systems. They are to some extent supportive of waiting times as an acceptable rationing mechanism, although further research is required to explore whether long waiting times affect other aspects of individuals' life. PMID:27299977

  15. Genotypic and Phenotypic Diversity Does Not Affect Productivity and Drought Response in Competitive Stands of Trifolium repens

    PubMed Central

    Huber, Heidrun; During, Heinjo J.; Bruine de Bruin, Fabienne; Vermeulen, Peter J.; Anten, Niels P. R.

    2016-01-01

    Clonal plants can form dense canopies in which plants of different genetic origin are competing for the uptake of essential resources. The competitive relationships among these clones are likely to be affected by extreme environmental conditions, such as prolonged drought spells, which are predicted to occur more frequently due to global climate change. This, in turn, may alter characteristics of the ecological system and its associated functioning. We hypothesized that the relative success of individual clones will depend on the size of the ramets as ramets with larger leaves and longer petioles (large ramets) were predicted to have a competitive advantage in terms of increased light interception over smaller-sized ramets. Under drier conditions the relative performances of genotypes were expected to change leading to a change in genotype ranking. We also hypothesized that increased genotypic and phenotypic diversity will increase stand performance and resistance to drought. These hypotheses and the mechanisms responsible for shifts in competitive relationships were investigated by subjecting genotypes of the important pasture legume Trifolium repens to competition with either genetically identical clones, genetically different but similarly sized clones, or genetically as well as morphologically different clones under well-watered and dry conditions. Competitive relationships were affected by ramet size with large genotypes outperforming small genotypes in diverse stands in terms of biomass production. However, large genotypes also produced relatively fewer ramets than small genotypes and could not benefit in terms of clonal reproduction from competing with smaller genotypes, indicating that evolutionary shifts in genotype composition will depend on whether ramet size or ramet number is under selection. In contrast to our hypotheses, diversity did not increase stand performance under different selection regimes and genotype ranking was hardly affected by soil

  16. Genotypic and Phenotypic Diversity Does Not Affect Productivity and Drought Response in Competitive Stands of Trifolium repens.

    PubMed

    Huber, Heidrun; During, Heinjo J; Bruine de Bruin, Fabienne; Vermeulen, Peter J; Anten, Niels P R

    2016-01-01

    Clonal plants can form dense canopies in which plants of different genetic origin are competing for the uptake of essential resources. The competitive relationships among these clones are likely to be affected by extreme environmental conditions, such as prolonged drought spells, which are predicted to occur more frequently due to global climate change. This, in turn, may alter characteristics of the ecological system and its associated functioning. We hypothesized that the relative success of individual clones will depend on the size of the ramets as ramets with larger leaves and longer petioles (large ramets) were predicted to have a competitive advantage in terms of increased light interception over smaller-sized ramets. Under drier conditions the relative performances of genotypes were expected to change leading to a change in genotype ranking. We also hypothesized that increased genotypic and phenotypic diversity will increase stand performance and resistance to drought. These hypotheses and the mechanisms responsible for shifts in competitive relationships were investigated by subjecting genotypes of the important pasture legume Trifolium repens to competition with either genetically identical clones, genetically different but similarly sized clones, or genetically as well as morphologically different clones under well-watered and dry conditions. Competitive relationships were affected by ramet size with large genotypes outperforming small genotypes in diverse stands in terms of biomass production. However, large genotypes also produced relatively fewer ramets than small genotypes and could not benefit in terms of clonal reproduction from competing with smaller genotypes, indicating that evolutionary shifts in genotype composition will depend on whether ramet size or ramet number is under selection. In contrast to our hypotheses, diversity did not increase stand performance under different selection regimes and genotype ranking was hardly affected by soil

  17. Course and cognitive outcome in major affective disorder.

    PubMed

    Kessing, Lars Vedel

    2015-11-01

    Knowledge of the course and outcome of major affective illness has clinical as well as theoretical implications. In understanding the pathophysiology of the major affective disorders, an essential question in the interplay between biological, psychological and social factors is whether the individual is changed biologically by experiencing an affective episode or not. A biological change may be reflected in a changed risk of experiencing new episodes and changed chances of recovery from these episodes for the individual, and may possibly also be reflected in persisting altered cognitive function as an expression of brain function affected during a longer period. Previous studies of the course of affective episodes are flawed by a number of drawbacks such as various definitions of recovery and recurrence, various kinds of bias and confounders, low statistical power, and statistical analyses conducted without survival models and without paying attention to diagnostic instability or the individual heterogeneity of the course of episodes. Totally, these drawbacks and pitfalls affect the results of previous studies in unpredictable ways and make it hazardous to draw conclusions about the effect of prior affective episodes on the subsequent course of unipolar and bipolar disorder. The present thesis avoided most of these pitfalls or adjusted for them in analyses of hospital data from the Danish Psychiatric Central Register, collected nationwide from 1971 to 1993. Hospitalisation was used as an expression of an affective episode. On average, a progressive course with increasing risk of recurrence with every new episode was found for unipolar and bipolar affective disorders. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the risk of recurrence was the same for the two disorders. However, analyses with frailty models revealed that for unipolar men, this progressive course was due to a subgroup of patients

  18. Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation.

    PubMed

    Sekine, Takuya; Marin, David; Cao, Kai; Li, Li; Mehta, Pramod; Shaim, Hila; Sobieski, Catherine; Jones, Roy; Oran, Betul; Hosing, Chitra; Rondon, Gabriela; Alsuliman, Abdullah; Paust, Silke; Andersson, Borje; Popat, Uday; Kebriaei, Partow; Muftuoglu, Muharrem; Basar, Rafet; Kondo, Kayo; Nieto, Yago; Shah, Nina; Olson, Amanda; Alousi, Amin; Liu, Enli; Sarvaria, Anushruti; Parmar, Simrit; Armstrong-James, Darius; Imahashi, Nobuhiko; Molldrem, Jeffrey; Champlin, Richard; Shpall, Elizabeth J; Rezvani, Katayoun

    2016-07-14

    The ability of cord blood transplantation (CBT) to prevent relapse depends partly on donor natural killer (NK) cell alloreactivity. NK effector function depends on specific killer-cell immunoglobulin-like receptors (KIR) and HLA interactions. Thus, it is important to identify optimal combinations of KIR-HLA genotypes in donors and recipients that could improve CBT outcome. We studied clinical data, KIR and HLA genotypes, and NK-cell reconstitution in CBT patients (n = 110). Results were validated in an independent cohort (n = 94). HLA-KIR genotyping of recipient germline and transplanted cord blood (CB) grafts predicted for large differences in outcome. Patients homozygous for HLA-C2 group alleles had higher 1-year relapse rate and worse survival after CBT than did HLA-C1/C1 or HLA-C1/C2 (HLA-C1/x) patients: 67.8% vs 26.0% and 15.0% vs 52.9%, respectively. This inferior outcome was associated with delayed posttransplant recovery of NK cells expressing the HLA-C2-specific KIR2DL1/S1 receptors. HLA-C1/x patients receiving a CB graft with the combined HLA-C1-KIR2DL2/L3/S2 genotype had lower 1-year relapse rate (6.7% vs 40.1%) and superior survival (74.2% vs 41.3%) compared with recipients of grafts lacking KIR2DS2 or HLA-C1 HLA-C2/C2 patients had lower relapse rate (44.7% vs 93.4%) and better survival (30.1% vs 0%) if they received a graft with the combined HLA-C2-KIR2DL1/S1 genotype. Relapsed/refractory disease at CBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, we propose the inclusion of KIR genotyping in graft selection criteria for CBT. HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/S2 CB graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft. PMID:27247137

  19. Evaluation of Factors Affecting the Surgical Outcome in Tympanoplasty

    PubMed Central

    Naderpour, Masoud; Jabbari Moghadam, Yalda; Ghanbarpour, Ensieh; Shahidi, Nikzad

    2016-01-01

    Introduction: Tympanoplasty is a standard procedure to repair tympanic membrane perforation. The aim of this study is to evaluate the results of tympanoplasty (hearing improvement and tympanic membrane closure rate) in patients suffering from chronic perforation of the tympanic membrane by considering the prognostic factors. Materials and Methods: In a prospective study, based on the results of tympanoplasty with temporal graft fascia in 60 patients in the ENT department of the Medical Science University of Tabriz, we evaluated prognostic factors, such as age, sex, smoking, size, and site of perforation, for the outcome of this surgery. Results: The rate of surgical success- integration of the graft- was 93.3%. Improvement of hearing, as demonstrated through audiometry, occurred in 93% of cases. We did not find any factors to be statistically significant to affect surgical outcome. Conclusion: Even by considering the influence of different factors on the results of a tympanoplasty operation, according to the statistical results of this study, there is not a significant difference in the results of the operation, neither in the health of the tympanic membrane after surgery nor in hearing development. PMID:27280095

  20. Recurrence of hepatitis C virus genotype-4 infection following orthotopic liver transplantation: Natural history and predictors of outcome

    PubMed Central

    Mudawi, Hatim; Helmy, Ahmed; Kamel, Yasser; Al Saghier, Mohammed; Al Sofayan, Mohammed; Al Sebayel, Mohammed; Khalaf, Hatem; Al Bahili, Hamad; Al Shiek, Yasser; Alawi, Khalil; AlJedai, Ahmed; Mohamed, Hazem; Al Hamoudi, Waleed; Abdo, Ayman

    2009-01-01

    BACKGROUND AND OBJECTIVES: There are few reports on hepatitis C virus genotype 4 (HCV-4) recurrences after orthotopic liver transplantation (OLT). Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes. PATIENTS AND METHODS: All patients who underwent OLT (locally or abroad) for HCV related hepatic cirrhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed. RESULTS: Of 116 patients who underwent OLT for hepatitis C, 46 (39.7%) patients satisfied the criteria of recurrent hepatitis C. Twenty-nine (63%) patients were infected with HCV genotype 4. Mean (SD) for age was 54.9 (10.9) years. Nineteen of the HCV genotype 4 patients (65.5%) were males, 21 (72.4%) received deceased donor grafts, and 7 (24.1%) developed ≥1 acute rejection episodes. Pathologically, 7 (24.1%) and 4 (13.8%) patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 (31%) HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease. CONCLUSION: This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes. PMID:19318754

  1. Type of Speech Material Affects Acceptable Noise Level Test Outcome.

    PubMed

    Koch, Xaver; Dingemanse, Gertjan; Goedegebure, André; Janse, Esther

    2016-01-01

    The acceptable noise level (ANL) test, in which individuals indicate what level of noise they are willing to put up with while following speech, has been used to guide hearing aid fitting decisions and has been found to relate to prospective hearing aid use. Unlike objective measures of speech perception ability, ANL outcome is not related to individual hearing loss or age, but rather reflects an individual's inherent acceptance of competing noise while listening to speech. As such, the measure may predict aspects of hearing aid success. Crucially, however, recent studies have questioned its repeatability (test-retest reliability). The first question for this study was whether the inconsistent results regarding the repeatability of the ANL test may be due to differences in speech material types used in previous studies. Second, it is unclear whether meaningfulness and semantic coherence of the speech modify ANL outcome. To investigate these questions, we compared ANLs obtained with three types of materials: the International Speech Test Signal (ISTS), which is non-meaningful and semantically non-coherent by definition, passages consisting of concatenated meaningful standard audiology sentences, and longer fragments taken from conversational speech. We included conversational speech as this type of speech material is most representative of everyday listening. Additionally, we investigated whether ANL outcomes, obtained with these three different speech materials, were associated with self-reported limitations due to hearing problems and listening effort in everyday life, as assessed by a questionnaire. ANL data were collected for 57 relatively good-hearing adult participants with an age range representative for hearing aid users. Results showed that meaningfulness, but not semantic coherence of the speech material affected ANL. Less noise was accepted for the non-meaningful ISTS signal than for the meaningful speech materials. ANL repeatability was comparable across

  2. Type of Speech Material Affects Acceptable Noise Level Test Outcome

    PubMed Central

    Koch, Xaver; Dingemanse, Gertjan; Goedegebure, André; Janse, Esther

    2016-01-01

    The acceptable noise level (ANL) test, in which individuals indicate what level of noise they are willing to put up with while following speech, has been used to guide hearing aid fitting decisions and has been found to relate to prospective hearing aid use. Unlike objective measures of speech perception ability, ANL outcome is not related to individual hearing loss or age, but rather reflects an individual’s inherent acceptance of competing noise while listening to speech. As such, the measure may predict aspects of hearing aid success. Crucially, however, recent studies have questioned its repeatability (test–retest reliability). The first question for this study was whether the inconsistent results regarding the repeatability of the ANL test may be due to differences in speech material types used in previous studies. Second, it is unclear whether meaningfulness and semantic coherence of the speech modify ANL outcome. To investigate these questions, we compared ANLs obtained with three types of materials: the International Speech Test Signal (ISTS), which is non-meaningful and semantically non-coherent by definition, passages consisting of concatenated meaningful standard audiology sentences, and longer fragments taken from conversational speech. We included conversational speech as this type of speech material is most representative of everyday listening. Additionally, we investigated whether ANL outcomes, obtained with these three different speech materials, were associated with self-reported limitations due to hearing problems and listening effort in everyday life, as assessed by a questionnaire. ANL data were collected for 57 relatively good-hearing adult participants with an age range representative for hearing aid users. Results showed that meaningfulness, but not semantic coherence of the speech material affected ANL. Less noise was accepted for the non-meaningful ISTS signal than for the meaningful speech materials. ANL repeatability was comparable

  3. Genotypic variation in host response to infection affects parasite reproductive rate.

    PubMed

    Tavalire, Hannah F; Blouin, Michael S; Steinauer, Michelle L

    2016-02-01

    Parasite fitness is largely influenced by a variation in host response due to the host's genetic background. Here we investigated the impact of host genotype on pathogen success in the snail vector of its castrating parasite, Schistosoma mansoni. We infected five inbred lines of Biomphalaria glabrata with two infection doses and followed their growth, reproductive output and parasite production throughout the course of infection. There was no difference in resistance to infection among inbred lines, but lines varied in their responses to infection and the numbers of parasites produced. Snails did not compensate for castration by increasing their fecundity during the early phase of infection (fecundity compensation). However, some lines were able to delay parasite shedding for up to 30 weeks, thus prolonging reproduction before the onset of castration. Here we propose this strategy as a novel defense against castrating pathogens in snails. Gigantism, a predicted outcome of castration due to energy reallocation, occurred early in infection (<15 weeks) and was not universal among the snail lines. Lines that did not show gigantism were also characterised by a high parasite production rate and low survivorship, perhaps indicating energy reallocation into parasite production and costly immune defense. We observed no differences in total parasite production among lines throughout the entire course of infection, although lines differed in their parasite reproductive rate. The average rate of parasite production varied among lines from 1300 to 2450 cercariae within a single 2h shedding period, resulting in a total production of 6981-29,509 cercariae over the lifetime of a single snail. Regardless of genetic background, snail size was a strong predictor of parasite reproduction: each millimetre increase in snail size at the time of the first shed resulted in up to 3500 more cercariae over the lifetime of the snail. The results of this study provide a detailed picture of

  4. Melanin content in melanoma metastases affects the outcome of radiotherapy.

    PubMed

    Brożyna, Anna A; Jóźwicki, Wojciech; Roszkowski, Krzysztof; Filipiak, Jan; Slominski, Andrzej T

    2016-04-01

    Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma. PMID:26910282

  5. Melanin content in melanoma metastases affects the outcome of radiotherapy

    PubMed Central

    Brożyna, Anna A.; Jóźwicki, Wojciech; Roszkowski, Krzysztof; Filipiak, Jan; Slominski, Andrzej T.

    2016-01-01

    Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma. PMID:26910282

  6. COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

    PubMed Central

    Need, Anna C.; LaBar, Kevin S.; Waters-Metenier, Sheena; Cirulli, Elizabeth T.; Kragel, James; Goldstein, David B.; Cabeza, Roberto

    2010-01-01

    The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496–1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output. PMID:19641018

  7. Influence of genotype-dependent effects of covariates on the outcome of segregation analysis of the body mass index.

    PubMed Central

    Borecki, I B; Bonney, G E; Rice, T; Bouchard, C; Rao, D C

    1993-01-01

    Several recent studies of the body mass index (BMI) have provided support for a recessive major gene influencing heaviness in humans. Segregation analysis of the BMI was carried out recently in a series of randomly sampled French-Canadian families to determine whether we could replicate the major gene finding by using a residual phenotype adjusted for the effects of age and sex. The best model included a recessive major effect for high BMI values with residual familial resemblance; however, Mendelian transmission could not be confirmed, and the no-transmission hypothesis (where all the tau's are constrained to be equal) was not rejected. Considering that the BMI is a complex phenotype affected by many factors and that there are known variations in body composition during growth and aging, we undertook a reanalysis of the data, using a model that allowed the estimation of genotype-specific age and gender effects. New tests on the transmission parameters satisfy the criteria for interfering Mendelian segregation. The results suggest that individuals with the "high" recessive genotype show the greatest degree of heaviness at birth, with a subsequent trend toward lower values throughout life, while individuals with the dominant "normal" genotypes show no appreciable trends with age. In addition, the "high" genotype appears to confer a greater degree of heaviness in females as compared with males. These results, along with other observations from the data, suggest that, while a recessive single gene influence may be discernible, the phenotypic expression of the BMI is likely to be complicated by genotype x environment interactions and, possibly, by the action of other loci. Further, the data also are consistent with the hypothesis that modifying factors may include the adoption of a more prudent life-style by individuals genetically predisposed to heaviness and a secular increase in the incidence, prevalence, and potency of environmentally based triggers leading to a

  8. Learning Outcomes in Affective Domain within Contemporary Architectural Curricula

    ERIC Educational Resources Information Center

    Savic, Marko; Kashef, Mohamad

    2013-01-01

    Contemporary architectural education has shifted from the traditional focus on providing students with specific knowledge and skill sets or "inputs" to outcome based, student-centred educational approach. Within the outcome based model, students' performance is assessed against measureable objectives that relate acquired knowledge…

  9. Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients

    PubMed Central

    Grammatikos, Georgios; Lange, Christian; Susser, Simone; Schwendy, Susanne; Dikopoulos, Nektarios; Buggisch, Peter; Encke, Jens; Teuber, Gerlinde; Goeser, Tobias; Thimme, Robert; Klinker, Hartwig; Boecher, Wulf O.; Schulte-Frohlinde, Ewert; Penna-Martinez, Marissa; Badenhoop, Klaus; Zeuzem, Stefan; Berg, Thomas; Sarrazin, Christoph

    2014-01-01

    Background Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24–72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002–1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975–0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000–1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073–2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271–4.695, P = 0.007) constituted the strongest predictors of treatment response. Conclusions While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients. PMID:24516573

  10. Genotype at the PMEL17 locus affects social and explorative behaviour in chickens.

    PubMed

    Karlsson, A-C; Kerje, S; Andersson, L; Jensen, P

    2010-04-01

    1. We studied behaviour and brain gene expression in homozygous PMEL17 genotypes, using chickens originating from an advanced White Leghorn x red junglefowl intercross. The behavioural studies consisted of three social and one explorative behaviour test. There were significant differences between the genotypes in both social and explorative behaviour. 2. Gene expression studies showed no PMEL17 expression in brain, so the genotype differences must depend on extra-neural gene expression or expression during embryonic development. However, linkage or spurious family effects (genetic drift) can not be excluded. 3. The study strongly suggests a correlated effect between plumage colour and behaviour, and we conclude that PMEL17 may have a pleiotropic effect on social and explorative behaviour in chickens. PMID:20461577

  11. Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

    PubMed Central

    Rafiei, Alireza; Hosseini, Vahid; Janbabai, Ghasem; Fazli, Bahman; Ajami, Abulghasem; Hosseini-khah, Zahra; Gilbreath, Jeremy; Merrell, D Scott

    2012-01-01

    AIM: To investigate the association of the inducible nitric oxide synthetase (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and gastric cancer (GC) risk in Iran. METHODS: In order to determine whether there was a correlation between iNOS genotype and GC in Iran, we conducted a case-control study using samples from 329 individuals. For each sample, the C150T iNOS polymorphism was genotyped by polymerase chain reaction (PCR) and restriction digestion. Patients were grouped by cancer presence, demographic and behavior characteristics, and H. pylori infection status. Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population. RESULTS: In this population, we found that smoking, hot beverage consumption, a familial history of GC and H. pylori infection status were significantly associated with GC development (P = 0.015, P < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone, but was impacted by H. pylori infection status. When compared to the non-H. pylori infected group, cancer patients who had a heterozygous CT genotype and were also infected with H. pylori were 2.1 times more at risk of developing GC [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P = 0.029). In contrast, this association was not seen in patients in the control group. CONCLUSION: A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility. PMID:23002365

  12. Physiological traits and meat quality of pigs as affected by genotype and housing system.

    PubMed

    Lebret, B; Prunier, A; Bonhomme, N; Foury, A; Mormède, P; Dourmad, J Y

    2011-05-01

    The influence of pig housing system: alternative (bedding with outdoor area, BO) vs. conventional (slatted floor, SF) on growth performance, reactivity to pre-slaughter handling and meat quality was evaluated in two genotypes differing in the sire line, Duroc (CD) or synthetic (CS) with 40 pigs/genotype. Animal response to housing did not differ between genotypes. BO pigs had higher growth rate and feed intake, but similar carcass composition to SF pigs. Levels of stress related hormones and plasma metabolites at slaughter were not different between BO and SF pigs, suggesting that housing did not influence pig reactivity to pre-slaughter handling. Similar (Longissimus lumborum and Biceps femoris) or slightly reduced (Semimembranosus) pH values, higher drip, lipid content and juiciness were observed in BO compared with SF pork. CD pigs had more tender meat than CS. In conclusion, the BO system resulted in higher feed intake, faster growth rate, increased intramuscular fat, and improved eating quality in both genotypes. PMID:21185130

  13. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes.

    PubMed

    Zwart, Sara R; Gregory, Jesse F; Zeisel, Steven H; Gibson, Charles R; Mader, Thomas H; Kinchen, Jason M; Ueland, Per M; Ploutz-Snyder, Robert; Heer, Martina A; Smith, Scott M

    2016-01-01

    Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients. PMID:26316272

  14. How Different Genetically Manipulated Brassica Genotypes Affect Life Table Parameters of Plutella xylostella (Lepidoptera: Plutellidae).

    PubMed

    Nikooei, Mehrnoosh; Fathipour, Yaghoub; Jalali Javaran, Mokhtar; Soufbaf, Mahmoud

    2015-04-01

    The fitness of Plutella xylostella L. on different genetically manipulated Brassica plants, including canola's progenitor (Brassica rapa L.), two cultivated canola cultivars (Opera and RGS003), one hybrid (Hyula401), one gamma-ray mutant-RGS003, and one transgenic (PF) genotype was compared using two-sex and female-based life table parameters. All experiments were conducted in a growth chamber at 25±1°C, 65±5% relative humidity, and a photoperiod of 16:8 (L:D) h. There were significant differences in duration of different life stages of P. xylostella on different plant genotypes. The shortest (13.92 d) and longest (24.61 d) total developmental time were on Opera and PF, respectively. The intrinsic rate of increase of P. xylostella ranged between 0.236 (Opera) and 0.071 day(-1) (PF). The highest (60.79 offspring) and lowest (7.88 offspring) net reproductive rates were observed on Opera and PF, respectively. Comparison of intrinsic rate of increase, net reproductive rates, finite rate of increase, mean generation time, fecundity, and survivorship of P. xylostella on the plant genotypes suggested that this pest performed well on cultivars (RGS003 and Opera) and performed poorly on the other manipulated genotypes especially on mutant-RGS003 and PF. Glucosinolate levels were significantly higher in damaged plants than undamaged ones and the lowest and highest concentrations of glucosinolates were found in transgenic genotype and canola's progenitor, respectively. Interestingly, our results showed that performance and fitness of this pest was better on canola's progenitor and cultivated plants, which had high levels of glucosinolate. PMID:26470162

  15. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.

    PubMed

    Pan, Xiaoxia; Ouyang, Yan; Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  16. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

    PubMed Central

    Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  17. Factors affecting patient outcome in primary cutaneous aspergillosis

    PubMed Central

    Tatara, Alexander M.; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Abstract Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality). We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome. We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4 ± 22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3–120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality. Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome. PMID:27367980

  18. Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis

    PubMed Central

    Wiesner, Darin L.; Moskalenko, Oleksandr; Corcoran, Jennifer M.; McDonald, Tami; Rolfes, Melissa A.; Meya, David B.; Kajumbula, Henry; Kambugu, Andrew; Bohjanen, Paul R.; Knight, Joseph F.; Boulware, David R.; Nielsen, Kirsten

    2012-01-01

    ABSTRACT In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th2 response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality. PMID:23015735

  19. Race Affects Outcome among Infants with Intestinal Failure

    PubMed Central

    Squires, Robert H; Balint, Jane; Horslen, Simon; Wales, Paul W.; Soden, Jason; Duggan, Christopher; Li, Ruosha; Belle, Steven H

    2014-01-01

    Objective Intestinal failure is a rare, devastating condition associated with significant morbidity and mortality. We sought to determine if ethnic and racial differences were associated with patient survival and likelihood of receiving an intestinal transplant in a contemporary cohort of children with intestinal failure. Methods This was an analysis of a multicenter cohort study with data collected from chart review conducted by the Pediatric Intestinal Consortium (PIFCon). Entry criteria included infants < 12 mo receiving parenteral nutrition (PN) for > 60 continuous days and followed for at least 2 years. Outcomes included death and intestinal transplant (ITx). Race and ethnicity were recorded as they were in the medical record. For purposes of statistical comparisons and regression modeling, categories of race were consolidated into “white” and “non-white” children. Results Of 272 subjects enrolled, 204 white and 46 non-white children were available for analysis. The 48 month cumulative incidence probability (CIP) of death without ITx was 0.40 for non-white and 0.16 for white children (p<0.001); the CIP of ITx was 0.07 for non-white vs 0.31 for white children (p=0.003). The associations between race and outcomes remained after accounting for low-birth weight, diagnosis, and being seen at a transplant center. Conclusion Race is associated with death and receiving an ITx in a large cohort of children with intestinal failure. This study highlights the need to investigate reasons for this apparent racial disparity in outcome among children with intestinal failure. PMID:24918984

  20. How much do immigration and trade affect labor market outcomes?

    PubMed

    Borjas, G J; Freeman, R B; Katz, L F

    1997-01-01

    "This paper provides new estimates of the impact of immigration and trade on the U.S. labor market.... We examine the relation between economic outcomes for native workers and immigrant flows to regional labor markets.... We...use the factor proportions approach to examine the contributions of immigration and trade to recent changes in U.S. educational wage differentials and attempt to provide a broader assessment of the impact of immigration on the incomes of U.S. natives." Comments and discussion by John DiNardo, John M. Abowd, and others are included (pp. 68-85). PMID:12321914

  1. The Synergistic Effect of Affective Factors on Student Learning Outcomes

    ERIC Educational Resources Information Center

    Jack, Brady Michael; Lin, Huann-shyang; Yore, Larry D.

    2014-01-01

    This study investigates how affective and self-related factors impact participation in science learning and environmental awareness and responsibility. Using PISA 2006 datasets from Taiwan and Canada having similar level of science competency, the model for this study verifies and expands an earlier model by examining the relationships among…

  2. Cognitive and Affective Learning Outcomes of Gifted Elementary School Students

    ERIC Educational Resources Information Center

    Delcourt, Marcia A. B.; Cornell, Dewey G.; Goldberg, Marc D.

    2007-01-01

    This project was a 2-year investigation of elementary school children placed in programs for high-ability learners. The primary purpose of the study was to investigate academic and affective changes in students during their first 2 years in a gifted program. Students were assessed during the fall of one year and the spring of the next year.…

  3. Higher Education for Sustainability: Seeking Affective Learning Outcomes

    ERIC Educational Resources Information Center

    Shephard, Kerry

    2008-01-01

    Purpose: The purpose of this paper is to interpret aspects of education for sustainability in relation to educational theories of the affective domain (values, attitudes and behaviours) and suggest how the use of these theories, and relevant experience, in other educational areas could benefit education for sustainability.…

  4. Family-School Links: How Do They Affect Educational Outcomes?

    ERIC Educational Resources Information Center

    Booth, Alan, Ed.; Dunn, Judith F., Ed.

    This book explores issues related to the links between families and schools and how they affect children's educational achievement, and is organized as follows: Part 1, titled "Families and Schools: How Can They Work Together To Promote Children's School Success?" contains the following chapters: chapter 1, "Family Involvement in Chidrens' and…

  5. Characterization of high-yield performance as affected by genotype and environment in rice.

    PubMed

    Chen, Song; Zeng, Fang-rong; Pao, Zong-zhi; Zhang, Guo-ping

    2008-05-01

    We characterized yield-relevant characters and their variations over genotypes and environments (locations and years) by examining two rice varieties (9746 and Jinfeng) with high yield potential. 9746 and Jinfeng were planted in two locations of Shanghai, China, during 2005 and 2006. The results show that there was a large variation in grain yield between locations and years. The realization of high yield potential for the two types of rice was closely related to the improved sink size, such as more panicles per square meter or grains per panicle. Stem and leaf biomasses were mainly accumulated from tillering stage to heading stage, and showed slow decline during grain filling. Meanwhile, some photosynthetic characters including net photosynthesis rate (Pn), leaf area index (LAI), specific leaf area (SLA), fluorescence parameter (maximum quantum yield of PSII, Fv/Fm), chlorophyll content (expressed as SPAD value), as well as nutrient (N, P, K) uptake were also measured to determine their variations over genotypes and environments and their relationships with grain yield. Although there were significant differences between years or locations for most measurements, SLA at tillering and heading stages, Fv/Fm and LAI at heading stage, stem biomass at heading and maturity stages, and leaf nitrogen concentration at tillering and heading stages remained little changed, indicating their possible applications as selectable characters in breeding programs. It was also found that stem nitrogen accumulation at tillering stage is one of the most important and stable traits for high yield formation. PMID:18500775

  6. Secondary science classroom dissections: Informing policy by evaluating cognitive outcomes and exploring affective outcomes

    NASA Astrophysics Data System (ADS)

    Allspaw, Kathleen M.

    Animal protection organizations claim that dissection is pedagogically unsound and that it will cause students to lose respect for non-human animals. Science teacher organizations support curricula that teach respect for animal life and include dissection. Prior research compared dissection to dissection alternatives. Four of the six studies revealed no difference between groups on tests of cognitive outcomes. One study revealed that dissection was superior, and one revealed that the alternative was superior. No differences in attitudes toward science, dissection or school were found. Attitudes toward non-human animals were not measured. This study focused on the dissections of earthworms and frogs in middle and high school classrooms. Pre and post-tests of conceptual understanding revealed failing scores and no significant pre/post differences. Because these tests required critical thinking skills, and the dissection activities did not, it is difficult to determine if the poor performance on these tests indicates the inability of the students to think critically, and/or if it indicates the ineffectiveness of dissection. Further studies of dissections that focus on critical thinking would be necessary to make this distinction. Classroom observations, student written narratives, and student and adult interviews revealed mixed attitudes toward non-human animals. Student behaviors during dissection were similar to those behaviors exhibited during non-dissection activities. Most students and adults readily supported worm dissections while they expressed some trepidation about frog dissections. Students and adults universally expressed affection for their pets and opposed the use of their own pets for dissection/research. There was slight support for the use of dogs and cats for dissection/research, but only those students who expressed hate for cats said that they could dissect cats. None of the students or adults expressed a willingness to dissect dogs. Some students

  7. Angiotensin-Converting Enzyme Genotype Affects Skeletal Muscle Strength In Elite Athletes

    PubMed Central

    Costa, Aldo Matos; Silva, António José; Garrido, Nuno; Louro, Hugo; Marinho, Daniel Almeida; Cardoso Marques, Mário; Breitenfeld, Luiza

    2009-01-01

    Previous studies have associated angiotensin-converting enzyme (ACE) D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years) and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years). The athletes were classified as: short (≤ 200m) and middle (400m to 1500m) distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ) and counter movement jump (CMJ) were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland). DNA extraction was obtained with Chelex 100® and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote’s. We found that allelic frequency differs significantly by event distance specialization in both genders (p < 0.05). In fact, sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05), in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05). In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females. Key points DD homozygote’s and D allele carriers from both genders shows significantly higher right grip strength. Right grip strength remains significantly higher in the D allele carrier’s female endurance group. Female’s D allele

  8. Factors Affecting Phenotype Variability in a Family with CMT2B: Gender and LRSAM1 Genotype

    PubMed Central

    Peddareddygari, Leema Reddy; Oberoi, Kinsi; Vellore, Jaasrini Reddy; Grewal, Raji P.

    2016-01-01

    Charcot-Marie-Tooth disease type 2 (CMT2) is an autosomal dominant axonal neuropathy caused by mutations in various genes. The subtype CMT2B results from missense mutations in RAB7A, member RAS oncogene family gene, whereas missense mutations in the Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) gene cause CMT2P. We describe the genotype/phenotype analysis of a family in which a previously described mutation in the RAB7A gene and a novel mutation in the LRSAM1 gene were identified. In this family, none of the individuals had ulceromutilating features, and there was a marked variability in the age of onset. We discuss the possible etiology of the observed phenotypic variability including the role of gender and possible RAB7A/LRSAM1 gene interactions. PMID:27462242

  9. Genotyping of Toxoplasma gondii isolates in meningo-encephalitis affected striped dolphins (Stenella coeruleoalba) from Italy.

    PubMed

    Di Guardo, Giovanni; Di Cesare, Angela; Otranto, Domenico; Casalone, Cristina; Iulini, Barbara; Mignone, Walter; Tittarelli, Cristiana; Meloni, Silvana; Castagna, Giuseppe; Forster, Fiona; Kennedy, Seamus; Traversa, Donato

    2011-12-29

    This study reports the occurrence of Toxoplasma gondii in the brain of three striped dolphins (Stenella ceoruleoalba) found stranded on the Ligurian Sea coast of Italy between 2007 and 2008. These animals showed a severe, subacute to chronic, non-purulent, multifocal meningo-encephalitis, with the cerebral parenchyma of two dolphins harbouring protozoan cysts and zoites immunohistochemically linked to T. gondii. Molecular, phylogenetic and mutation scanning analyses showed the occurrence of Type II and of an atypical Type II T. gondii isolates in one and two dolphins, respectively. In spite of the different molecular patterns characterizing the above T. gondii genotypes, the brain lesions observed in the three animals showed common microscopic features, with no remarkable differences among them. The role of T. gondii in causing the meningo-encephalitis is herein discussed. PMID:21802209

  10. Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

    PubMed Central

    Zheng, Guoping; Ge, Menghua; Qiu, Guanguan; Shu, Qiang; Xu, Jianguo

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-α stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models. PMID:26257791

  11. Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization.

    PubMed

    Zheng, Guoping; Ge, Menghua; Qiu, Guanguan; Shu, Qiang; Xu, Jianguo

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-α stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models. PMID:26257791

  12. Hospital volume affects outcome after total knee arthroplasty

    PubMed Central

    Pamilo, Konsta J; Peltola, Mikko; Paloneva, Juha; Mäkelä, Keijo; Häkkinen, Unto; Remes, Ville

    2015-01-01

    Background and purpose The influence of hospital volume on the outcome of total knee joint replacement surgery is controversial. We evaluated nationwide data on the effect of hospital volume on length of stay, re-admission, revision, manipulation under anesthesia (MUA), and discharge disposition for total knee replacement (TKR) in Finland. Patients and methods 59,696 TKRs for primary osteoarthritis performed between 1998 and 2010 were identified from the Finnish Hospital Discharge Register and the Finnish Arthroplasty Register. Hospitals were classified into 4 groups according to the number of primary and revision knee arthroplasties performed on an annual basis throughout the study period: 1–99 (group 1), 100–249 (group 2), 250–449 (group 3), and ≥ 450 (group 4). The association between hospital procedure volume and length of stay (LOS), length of uninterrupted institutional care (LUIC), re-admissions, revisions, MUA, and discharge disposition were analyzed. Results The greater the volume of the hospital, the shorter was the average LOS and LUIC. Smaller hospital volume was not unambiguously associated with increased revision, re-admission, or MUA rates. The smaller the annual hospital volume, the more often patients were discharged home. Interpretation LOS and LUIC ought to be shortened in lower-volume hospitals. There is potential for a reduction in length of stay in extended institutional care facilities. PMID:25323798

  13. Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

    SciTech Connect

    D'Ambrosio, David J.; Li Tianyu; Horwitz, Eric M.; Chen, David Y.T.; Pollack, Alan; Buyyounouski, Mark K.

    2008-12-01

    Purpose: The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer. Methods and Materials: Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. Results: The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR {>=}33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR {>=}33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined. Conclusions: A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of {>=}33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

  14. Outcomes in cochlear implantation: variables affecting performance in adults and children.

    PubMed

    Cosetti, Maura K; Waltzman, Susan B

    2012-02-01

    This article highlights variables that affect cochlear implant performance, emerging factors warranting consideration, and variables shown not to affect performance. Research on the outcomes following cochlear implantation has identified a wide spectrum of variables known to affect pos0timplantation performance. These variables relate to the device itself as well as individual patient characteristics. Factors believed to affect spiral ganglion cell survival and function have been shown to influence postoperative performance. Binaural hearing affects performance. Social and educational factors also affect postoperative performance. Novel variables capable of affecting performance continue to emerge with increased understanding of auditory pathway development and neural plasticity. PMID:22115688

  15. Psychosocial Environment and Affective Outcomes in Technology-Rich Classrooms: Testing a Causal Model

    ERIC Educational Resources Information Center

    Dorman, Jeffrey P.; Fraser, Barry J.

    2009-01-01

    Research investigated classroom environment antecedent variables and student affective outcomes in Australian high schools. The Technology-Rich Outcomes-Focused Learning Environment Inventory (TROFLEI) was used to assess 10 classroom environment dimensions: student cohesiveness, teacher support, involvement, investigation, task orientation,…

  16. Hepatitis C virus genotype and HIV coinfection affect cytokine mRNA levels in unstimulated PBMC but do not shift the T1/T2 balance.

    PubMed

    Lee, Silvia; Watson, Mark W; Clark, Ben; Flexman, James P; Cheng, Wendy; French, Martyn A H; Price, Patricia

    2006-08-01

    Rapid progression of hepatitis C virus (HCV) disease in patients with HIV/HCV may reflect different cytokine responses and be influenced by HCV genotype. This is addressed by a study of patients with HIV/HCV coinfection and infection with HCV genotype 2 or 3 (2/3). They are compared with coinfected patients infected with genotype 1 and HCV monoinfected patients matched for HCV genotype. IFN-gamma, IL-10, IL-4 and IL-4delta2 mRNA were quantified by real-time PCR in unstimulated PBMC and after in vitro stimulation with HCV core or nonstructural 3/4A antigen. In unstimulated PBMC, levels of IFN-gamma and IL-4 mRNA were lowest in HIV/HCV genotype 1 patients, intermediate in HIV/HCV genotype 2/3 patients and highest in HCV genotype 2/3 patients. Neither HCV genotype nor HIV affected levels of IL-10 mRNA in unstimulated PBMC or IFN-gamma, IL-4 and IL-10 mRNA in PBMC stimulated with HCV antigens. Levels of IL-4 and IL-4delta2 mRNA correlated in mitogen-stimulated PBMC from all patient groups but both were low in HIV/HCV genotype 1 patients. Serum soluble CD30 levels (a putative marker of a T2 cytokine environment) did not differ between patient groups. The data do not suggest a shift in the T1/T2 balance driven by HIV coinfection or HCV genotype but either may affect IL-4 bioavailability. PMID:16834574

  17. Intervention Outcomes among HIV-affected Families Over 18 Months

    PubMed Central

    Rotheram-Borus, Mary Jane; Rice, Eric; Comulada, W. Scott; Best, Karin; Elia, Carla; Peters, Katherine; Li, Li; Green, Sara; Valladares, Ena

    2012-01-01

    We evaluate the efficacy of a family-based intervention over time among HIV-affected families. Mothers Living with HIV (MLH; n=339) in Los Angeles and their school-aged children were randomized to either an intervention or control condition and followed for 18 months. MLH and their children in the intervention received 16 cognitive-behavioral, small-group sessions designed to help them maintain physical and mental health, parent while ill, address HIV-related stressors, and reduce HIV-transmission behaviors. At recruitment, MLH reported few problem behaviors related to physical health, mental health, or sexual or drug transmission acts. Compared to MLH in the control condition, intervention MLH were significantly more likely to monitor their own CD4 cell counts and their children were more likely to decrease alcohol and drug use. Most MLH and their children had relatively healthy family relationships. Family-based HIV interventions should be limited to MLH who are experiencing substantial problems. PMID:22020758

  18. Prediction and diagnosis of clinical outcomes affecting restoration margins.

    PubMed

    Dennison, J B; Sarrett, D C

    2012-04-01

    The longevity of dental restorations is largely dependent on the continuity at the interface between the restorative material and adjacent tooth structure (the restoration margin). Clinical decisions on restoration repair or replacement are usually based upon the weakest point along that margin interface. Physical properties of a restorative material, such as polymerisation shrinkage, water sorption, solubility, elastic modulus and shear strength, all have an effect on stress distribution and can significantly affect margin integrity. This review will focus on two aspects of margin deterioration in the oral environment: the in vitro testing of margin seal using emersion techniques to simulate the oral environment and to predict clinical margin failure and the relationship between clinically observable microleakage and secondary caries. The many variables associated with in vitro testing of marginal leakage and the interpretation of the data are presented in detail. The most recent studies of marginal leakage mirror earlier methodology and lack validity and reliability. The lack of standardised testing procedures makes it impossible to compare studies or to predict the clinical performance of adhesive materials. Continual repeated in vitro studies contribute little to the science in this area. Clinical evidence is cited to refute earlier conclusions that clinical microleakage (penetrating margin discoloration) leads to caries development and is an indication for restoration replacement. Margin defects, without visible evidence of soft dentin on the wall or base of the defect, should be monitored, repaired or resealed, in lieu of total restoration replacement. PMID:22066463

  19. Midterm Outcome of Femoral Artery Stenting and Factors Affecting Patency

    PubMed Central

    Yu, Jae Seoung; Park, Keun-Myoung; Jeon, Yong Sun; Cho, Soon Gu; Hong, Kee Chun; Shin, Woo Young; Choe, Yun-Mee; Shin, Seok-Hwan; Kim, Kyung Rae

    2015-01-01

    Purpose: The purpose of this study was to evaluate the early and midterm results of superficial femoral artery (SFA) stenting with self-expanding nitinol stents and to identify the factors affecting patency. Materials and Methods: SFA stenting was performed in 165 limbs of 117 patients from January 2009 to December 2013. Patients were followed-up for the first occurrence of occlusion or stenosis based on computed tomography and duplex scan results and a decrease in ankle brachial index of >15%. Results: During the follow-up period (mean, 15.3±3.2 months), no early thrombotic reocclusions occurred within 30 days, but in-stent restenosis developed in 78 limbs. The primary patency rates at 6, 12, 18, and 24 months were 78%, 66%, 42%, and 22%, respectively, and the secondary patency rates were 85%, 72%, 58%, and 58%, respectively. TASC II C or D lesions, stent length >8 cm, number of patent tibial arteries and diabetes were significantly associated with reintervention. Conclusion: The midterm results of stenting for SFA occlusive disease were disappointing because the primary and secondary patency rates at two years were 22% and 58%, respectively. Reintervention after SFA stenting remains a major problem, particularly in patients with diabetes mellitus or long TASC II C or D lesions. PMID:26719837

  20. Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate

    PubMed Central

    INOUE, MASASHI; LI, XIA; McCAUGHEY, STUART A.; BEAUCHAMP, GARY K.; BACHMANOV, ALEXANDER A.

    2013-01-01

    In mice, behavioral acceptance of the bitter compound sucrose octaacetate (SOA) depends on allelic variation of a single gene, Soa. The SW.B6-Soab congenic mouse strain has the genetic background of an “SOA taster” SWR/J strain and an Soa-containing donor chromosome fragment from an “SOA nontaster” C57BL/6J strain. Using microsatellite markers polymorphic between the two parental strains, we determined that the donor fragment spans 5–10 cM of distal chromosome 6. The SWR/J mice avoided SOA in two-bottle tests with water and had strong responses to SOA in two gustatory nerves, the chorda tympani (CT) and glossopharyngeal (GL). In contrast, the SW.B6-Soab mice were indifferent to SOA in two-bottle tests and had very weak responses to SOA in both of these nerves. The SWR/J and SW.B6-Soab mice did not differ in responses of either nerve to sucrose, NaCl, HCl, or the bitter-tasting stimuli quinine, denatonium, strychnine, 6-n-propylthiouracil, phenylthiocarbamide, and MgSO4. Thus the effect of the Soa genotype on SOA avoidance is mediated by peripheral taste responsiveness to SOA, involving taste receptor cells innervated by both the CT and GL nerves. PMID:11328963

  1. COMT genotype affects prefrontal white matter pathways in children and adolescents

    PubMed Central

    Thomason, Moriah E.; Dougherty, Robert F.; Colich, Natalie L.; Perry, Lee M.; Rykhlevskaia, Elena I.; Louro, Hugo M.; Hallmayer, Joachim F.; Waugh, Christian E.; Bammer, Roland; Glover, Gary H.; Gotlib, Ian H.

    2010-01-01

    Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9–15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter. PMID:20083203

  2. Gender Affects Early Postoperative Outcomes of Rotator Cuff Repair

    PubMed Central

    Ye, Hee-Uk; Jung, Jae-Won; Lee, Young-Kuk

    2015-01-01

    Background The literature does not provide consistent information on the impact of patients' gender on recovery after rotator cuff repair. The purpose of this study was to determine whether gender affects pain and functional recovery in the early postoperative period after rotator cuff repair. Methods Eighty patients (40 men and 40 women) were prospectively enrolled. Pain intensity and functional recovery were evaluated, using visual analog scale (VAS) pain score and range of motion on each of the first 5 postoperative days, at 2 and 6 weeks and at 3, 6, and 12 months after surgery. Perioperative medication-related adverse effects and postoperative complications were also assessed. Results The mean VAS pain score was significantly higher for women than men at 2 weeks after surgery (p = 0.035). For all other periods, there was no significant difference between men and women in VAS pain scores, although women had higher scores than men. Mean forward flexion in women was significantly lower than men at 6 weeks after surgery (p = 0.033) and the mean degree of external rotation in women was significantly lower than men at 6 weeks (p = 0.007) and at 3 months (p = 0.017) after surgery. There was no significant difference in medication-related adverse effects or postoperative complications. Conclusions Women had more pain and slower recovery of shoulder motion than men during the first 3 months after rotator cuff repair. These findings can serve as guidelines for pain management and rehabilitation after surgery and can help explain postoperative recovery patterns to patients with scheduled rotator cuff repair. PMID:26217471

  3. APOE Genotype Predicts Extent of Bleeding and Outcome in Lobar Intracerebral Hemorrhage

    PubMed Central

    Biffi, Alessandro; Anderson, Christopher D.; Jagiella, Jeremiasz M.; Schmidt, Helena; Kissela, Brett; Hansen, Björn M.; Jimenez-Conde, Jordi; Pires, Caroline R.; Ayres, Alison M.; Schwab, Kristin; Cortellini, Lynelle; Pera, Joanna; Urbanik, Andrzej; Romero, Javier M.; Rost, Natalia S.; Goldstein, Joshua N.; Viswanathan, Anand; Pichler, Alexander; Enzinger, Christian; Rabionet, Raquel; Norrving, Bo; Tirschwell, David L.; Selim, Magdy; Brown, Devin L.; Silliman, Scott L.; Worrall, Bradford B.; Meschia, James F.; Kidwell, Chelsea S.; Broderick, Joseph P.; Greenberg, Steven M.; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Woo, Daniel; Rosand, Jonathan

    2011-01-01

    SUMMARY Background APOE alleles ε2/ε4 increase risk of intracerebral hemorrhage (ICH) in the lobar regions, presumably through their influence on risk of cerebral amyloid angiopathy. We investigated whether these variants also associate with ICH severity, specifically larger ICH volume at presentation. Methods We initially investigated the association of ε2/ε4 with ICH volume and outcome in a Discovery sample of 865 individuals of European ancestry. Replication was completed in two samples, comprising 946 Europeans (Replication I) and 214 African-Americans (Replication II) respectively. Admission ICH volume was quantified on CT scan. Poor functional outcome (modified Rankin Scale: 3 – 6) and mortality were assessed at 90 days. Findings Among patients with lobar ICH, APOE ε2 was associated with larger ICH volume: each allele copy increased hematoma size by 5·3 cc (95% CI 4·1 – 6·2 cc, p = 0.004), with replication in Europeans (p = 0·008) and African Americans (p = 0·016). Consistent with this, ε2 was associated with both mortality (OR = 1·50, 1·23 – 1·82, p = 2·45 × 10−5) and poor functional outcome (OR = 1·52, 1·25 – 1·85, p = 1·74 × 10−5). We were not able to replicate published associations between ε4 and overall ICH mortality in a meta-analysis of all available data (n = 2202 ICH cases, OR = 1·08, 95% CI: 0·86 – 1·36, p = 0·52). Interpretation In lobar ICH, APOE ε2 is associated with larger ICH volume at presentation, and hence increased mortality and disability. These findings suggest a role for the vasculopathic changes associated with the ε2 allele in influencing the severity and clinical course of lobar ICH. Funding This study was funded by NIH-NINDS, the American Heart Association, government agencies in Spain, Poland and Austria, academic institutions in Sweden and Austria, and philanthropic organizations. PMID:21741316

  4. Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation.

    PubMed

    Sobecks, Ronald M; Wang, Tao; Askar, Medhat; Gallagher, Meighan M; Haagenson, Michael; Spellman, Stephen; Fernandez-Vina, Marcelo; Malmberg, Karl-Johan; Müller, Carlheinz; Battiwalla, Minoo; Gajewski, James; Verneris, Michael R; Ringdén, Olle; Marino, Susana; Davies, Stella; Dehn, Jason; Bornhäuser, Martin; Inamoto, Yoshihiro; Woolfrey, Ann; Shaw, Peter; Pollack, Marilyn; Weisdorf, Daniel; Milller, Jeffrey; Hurley, Carolyn; Lee, Stephanie J; Hsu, Katharine

    2015-09-01

    Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. PMID:25960307

  5. Water temperature affects pathogenicity of different betanodavirus genotypes in experimentally challenged Dicentrarchus labrax.

    PubMed

    Toffan, Anna; Panzarin, Valentina; Toson, Marica; Cecchettin, Krizia; Pascoli, Francesco

    2016-05-26

    Betanodaviruses are the causative agents of a highly infectious disease of fish known as viral nervous necrosis (VNN). To date, 4 different nervous necrosis virus (NNV) genotypes have been described, but natural reassortant viruses have also been detected, which further increase viral variability. Water temperature plays an important role in determining the appearance and the severity of VNN disease. We assessed the effect of temperature (20°, 25° and 30°C) on mortality and virus load in the brain of European sea bass Dicentrarchus labrax experimentally infected with 4 genetically different betanodaviruses, namely red-spotted grouper NNV (RGNNV), striped jack NNV (SJNNV) and the reassortant strains RGNNV/SJNNV and SJNNV/RGNNV. The RGNNV/SJNNV virus possesses the polymerase gene of RGNNV and the coat protein gene of SJNNV, and vice versa for the SJNNV/RGNNV virus. The obtained results showed that the RGNNV strain is the most pathogenic for juvenile sea bass, but clinical disease and mortality appeared only at higher temperatures. The SJNNV strain is weakly pathogenic for D. labrax regardless of the temperature used, while virus replication was detected in the brain of survivors only at 20°C. Finally, reassortant strains caused low mortality, independent of the temperature used, but the viral load in the brain was strongly influenced by water temperature and the genetic type of the polymerase gene. Taken together, these data show that nodavirus replication in vivo is a composite process regulated by both the genetic features of the viral strain and water temperatures. PMID:27225206

  6. DETERMINATION OF GENOTYPE COMBINATIONS THAT CAN PREDICT THE OUTCOME OF THE TREATMENT OF ALCOHOL DEPENDENCE USING THE 5-HT3 ANTAGONIST ONDANSETRON

    PubMed Central

    Johnson, Bankole A.; Seneviratne, Chamindi; Wang, Xin-Qun; Ait-Daoud, Nassima; Li, Ming D.

    2013-01-01

    Objective Previously, we reported that the 5′-HTTLPR-LL and rs1042173-TT (SLC6A4-LL/TT) genotypes in the serotonin transporter gene predicted a significant reduction in the severity of alcohol consumption among alcoholics receiving the 5-HT3 antagonist ondansetron. In this study, we explored additional markers of ondansetron treatment response in alcoholics by examining polymorphisms in the HTR3A and HTR3B genes, which regulate directly the function and binding of 5-HT3 receptors to ondansetron. Method We genotyped 1 rare and 18 common single-nucleotide polymorphisms in HTR3A and HTR3B in the same sample that we had genotyped for SLC6A4-LL/TT in the previous randomized, double-blind, 11-week clinical trial. Participants were 283 European Americans who received oral ondansetron (4 μg/kg twice daily) or placebo along with weekly cognitive behavioral therapy. Associations of individual and combined genotypes with treatment response on drinking outcomes were analyzed. Results Individuals carrying one or more of genotypes rs1150226-AG and rs1176713-GG in HTR3A and rs17614942-AC in HTR3B showed a significant overall mean difference between ondansetron and placebo in drinks per drinking day (−2.50; effect size (ES)=0.867), percentage of heavy drinking days (−20.58%; ES=0.780), and percentage of days abstinent (18.18%; ES=0.683). Combining these HTR3A/HTR3B and SLC6A4-LL/TT genotypes increased the target cohort from approaching 20% (identified in our previous study) to 34%. Conclusions We present initial evidence suggesting that a combined 5-marker genotype panel can be used to predict the outcome of treatment of alcohol dependence with ondansetron. Additional, larger pharmacogenetic studies would help to validate our results. PMID:23897038

  7. Genotype and allele frequencies of drug-metabolizing enzymes and drug transporter genes affecting immunosuppressants in the Spanish white population.

    PubMed

    Bosó, Virginia; Herrero, María J; Buso, Enrique; Galán, Juan; Almenar, Luis; Sánchez-Lázaro, Ignacio; Sánchez-Plumed, Jaime; Bea, Sergio; Prieto, Martín; García, María; Pastor, Amparo; Sole, Amparo; Poveda, José Luis; Aliño, Salvador F

    2014-04-01

    Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug-induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy. PMID:24232128

  8. The effects of different sources of occupational stress on affective, motivational, and psychosomatic outcomes

    SciTech Connect

    Ovalle, N.K. II.

    1991-01-01

    The present study examined the effects of role conflict, role ambiguity, and five additional potential sources of occupational stress on an affective outcome (job satisfaction), a motivational outcome (intent to quit), and two psychosomatic outcomes (mental and physical anxiety). In addition to role conflict and role ambiguity, the five additional sources of occupational stress centered on job characteristics, work pressures, rewards and opportunities, interaction of the job and home life, and lack of job challenge. Data were collected from 85 technicians and managers in a service organization. The results of correlation and multiple regression analyses indicated that each of the sources of stress have significant yet different effects on the outcomes. Moreover, role conflict and ambiguity did not have as much of an effect across all outcomes as the other five sources of stress. These findings could be used to improve the measurement, understanding, and treatment of occupational stress. Other implications are discussed. 23 refs., 2 tabs.

  9. Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease.

    PubMed

    Habak, Claudine; Noreau, Anne; Nagano-Saito, Atsuko; Mejía-Constaín, Beatriz; Degroot, Clotilde; Strafella, Antonio P; Chouinard, Sylvain; Lafontaine, Anne-Louise; Rouleau, Guy A; Monchi, Oury

    2014-11-01

    Parkinson's disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinson's disease. Thirty patients (ages 53-68 years; 19 males, 11 females) at early stages of Parkinson's disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinson's disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism's effect on the clinical evolution of patients with Parkinson's disease, especially with cognitive decline. PMID:25212851

  10. How measurement artifacts affect cerebral autoregulation outcomes: A technical note on transfer function analysis.

    PubMed

    Meel-van den Abeelen, Aisha S S; de Jong, Daan L K; Lagro, Joep; Panerai, Ronney B; Claassen, Jurgen A H R

    2016-05-01

    Cerebral autoregulation (CA) is the mechanism that aims to maintain adequate cerebral perfusion during changes in blood pressure (BP). Transfer function analysis (TFA), the most reported method in literature to quantify CA, shows large between-study variability in outcomes. The aim of this study is to investigate the role of measurement artifacts in this variation. Specifically, the role of distortion in the BP and/or CBFV measurementon TFA outcomes was investigated. The influence of three types of artifacts on TFA outcomes was studied: loss of signal, motion artifacts, and baseline drifts. TFA metrics of signals without the simulated artifacts were compared with those of signals with artifacts. TFA outcomes scattered highly when more than 10% of BP signal or over 8% of the CBFV signal was lost, or when measurements contained one or more artifacts resulting from head movement. Furthermore, baseline drift affected interpretation of TFA outcomes when the power in the BP signal was 5 times the power in the LF band. In conclusion, loss of signal in BP and loss in CBFV, affects interpretation of TFA outcomes. Therefore, it is vital to validate signal quality to the defined standards before interpreting TFA outcomes. PMID:26935320

  11. Domestication-related variation in social preferences in chickens is affected by genotype on a growth QTL.

    PubMed

    Wirén, A; Wright, D; Jensen, P

    2013-04-01

    A growth-related QTL on chicken chromosome 1 has previously been shown to influence domestication behaviour in chickens. In this study, we used Red Junglefowl (RJF) and White Leghorn (WL) as well as the intercross between them to investigate whether stress affects the way birds allocate their time between familiar and unfamiliar conspecifics in a social preference test ('social support seeking'), and how this is related to genotype at specific loci within the growth QTL. Red Junglefowl males spent more time with unfamiliar chickens before the stressful event compared to the other birds, whereas all birds except WL males tended to spend less time with unfamiliar ones after stress. A significant QTL locus was found to influence both social preference under undisturbed circumstances and social support seeking. The WL allele at this QTL was associated not only with a preference for unfamiliar individuals but also with a shift towards familiar ones in response to stress (social support seeking). A second, suggestive QTL also affected social support seeking, but in the opposite direction; the WL allele was associated with increased time spent with unfamiliar individuals. The region contains several possible candidate genes, and gene expression analysis of a number of them showed differential expression between RJF and WL of AVPR2 (receptor for vasotocin), and possibly AVPR1a (another vasotocin receptor) and NRCAM (involved in neural development) in the lower frontal lobes of the brains of RJF and WL animals. These three genes continue to be interesting candidates for the observed behavioural effects. PMID:23331324

  12. Adolescents' Cognitive "Habitus", Learning Environments, Affective Outcomes of Schooling, and Young Adults' Educational Attainment

    ERIC Educational Resources Information Center

    Marjoribanks, Kevin

    2006-01-01

    A moderation-mediation model was constructed to examine relationships among adolescents' cognitive "habitus" (their cognitive dispositions), learning environments, affective outcomes of schooling, and young adults' educational attainment. Data were collected as part of a longitudinal survey of Australian youth (4,171 females, 3,718 males). The…

  13. School Factors Explaining Achievement on Cognitive and Affective Outcomes: Establishing a Dynamic Model of Educational Effectiveness

    ERIC Educational Resources Information Center

    Creemers, Bert; Kyriakides, Leonidas

    2010-01-01

    The dynamic model of educational effectiveness defines school level factors associated with student outcomes. Emphasis is given to the two main aspects of policy, evaluation, and improvement in schools which affect quality of teaching and learning at both the level of teachers and students: a) teaching and b) school learning environment. Five…

  14. Factors Affecting Academic Outcomes of Underprepared Community College Students. AIR 1999 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Zhao, J. Charles

    This study examined the factors affecting the four-year academic performance and outcomes of 1,249 underprepared students at Prince George's Community College (Maryland). The fall 1994 freshmen required remediation in reading, writing, or mathematics. Subjects were defined as achievers if, by summer 1998, they had earned a degree or certificate…

  15. Affective Learning Outcomes in Workplace Training: A Test of Synchronous vs. Asynchronous Online Learning Environments

    ERIC Educational Resources Information Center

    Cleveland-Innes, Martha; Ally, Mohamed

    2004-01-01

    Research employing an experimental design pilot-tested two delivery platforms, WebCT™ and vClass™, for the generation of affective learning outcomes in the workplace. Using a sample of volunteer participants in the help-desk industry, participants were randomly assigned to one of the two types of delivery software. Thirty-eight subjects…

  16. Teacher Interpersonal Behaviour and Secondary Students' Cognitive, Affective and Moral Outcomes in Hong Kong

    ERIC Educational Resources Information Center

    Sivan, Atara; Chan, Dennis W. K.

    2013-01-01

    This study validated the Chinese version of the Questionnaire on Teacher Interaction (QTI) in the Hong Kong context as well as examined the relationship between students' perceptions of interpersonal teacher behaviour and their cognitive, affective and moral learning outcomes. Data were collected with the QTI and four other measures of student…

  17. Technology Integration before Student Outcomes: Factors Affecting Teacher Adoption of Technology in India

    ERIC Educational Resources Information Center

    Bandyopadhyay, Alankar

    2013-01-01

    Since the 1920s, ICTs have been endorsed as solutions to challenges of access and quality in education. Proponents have also supported technology use in education on grounds that it could potentially impact cognitive, affective, and pedagogical outcomes. Based on these perceived benefits, many developed and developing countries have been…

  18. Coping with Challenge and Hindrance Stressors in Teams: Behavioral, Cognitive, and Affective Outcomes

    ERIC Educational Resources Information Center

    Pearsall, Matthew J.; Ellis, Aleksander P. J.; Stein, Jordan H.

    2009-01-01

    The purpose of this study was to utilize the challenge-hindrance framework to examine the discrete and combined effects of different environmental stressors on behavioral, cognitive, and affective outcomes at the team level. Results from 83 teams working on a command and control simulation indicated that the introduction of a challenge stressor…

  19. Genotype-environment interactions affecting preflowering physiological and morphological traits of Brassica rapa grown in two watering regimes.

    PubMed

    El-Soda, Mohamed; Boer, Martin P; Bagheri, Hedayat; Hanhart, Corrie J; Koornneef, Maarten; Aarts, Mark G M

    2014-02-01

    Plant growth and productivity are greatly affected by drought, which is likely to become more threatening with the predicted global temperature increase. Understanding the genetic architecture of complex quantitative traits and their interaction with water availability may lead to improved crop adaptation to a wide range of environments. Here, the genetic basis of 20 physiological and morphological traits is explored by describing plant performance and growth in a Brassica rapa recombinant inbred line (RIL) population grown on a sandy substrate supplemented with nutrient solution, under control and drought conditions. Altogether, 54 quantitative trait loci (QTL) were identified, of which many colocated in 11 QTL clusters. Seventeen QTL showed significant QTL-environment interaction (Q×E), indicating genetic variation for phenotypic plasticity. Of the measured traits, only hypocotyl length did not show significant genotype-environment interaction (G×E) in both environments in all experiments. Correlation analysis showed that, in the control environment, stomatal conductance was positively correlated with total leaf dry weight (DW) and aboveground DW, whereas in the drought environment, stomatal conductance showed a significant negative correlation with total leaf DW and aboveground DW. This correlation was explained by antagonistic fitness effects in the drought environment, controlled by a QTL cluster on chromosome A7. These results demonstrate that Q×E is an important component of the genetic variance and can play a great role in improving drought tolerance in future breeding programmes. PMID:24474811

  20. Genotype on the pigmentation regulating PMEL17 gene affects behavior in chickens raised without physical contact with conspecifics.

    PubMed

    Karlsson, Anna-Carin; Mormede, Pierre; Kerje, Susanne; Jensen, Per

    2011-03-01

    Chickens homozygous for the Dominant white or wild-type allele of PMEL17 were subjected to a broad phenotyping in order to detect consistent differences between genotypes. To exclude feather pecking, the chickens were individually housed without physical contact, from the day of hatching, and tested for social, aggressive, fear and exploratory behaviors, and corticosterone and testosterone levels were assessed. In a principal component analysis, 53.2% of the behavior variation was explained by two factors. Factor one was an activity and social factor, and there was a significant effect of genotype on the factor scores. On factor two, related to aggressive behavior, there were significant effects of genotype, sex and their interaction. There were no genotype effects on hormone levels or any other measured non-behavioral phenotypes. Hence, differences in behavior between PMEL17 genotypes remained when negative social experiences were excluded, indicating a direct pleiotropic effect of the gene on behavior. PMID:20623330

  1. Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

    SciTech Connect

    Hughes, Michael F.; Edwards, Brenda C.; Herbin-Davis, Karen M.; Saunders, Jesse; Styblo, Miroslav; Thomas, David J.

    2010-12-15

    Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to {approx} 35% and in wild-type mice to {approx} 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminished capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. Altered retention and tissue tropism of arsenic in As3mt knockout mice could affect the toxic or carcinogenic effects associated with exposure to this metalloid or its methylated metabolites.

  2. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  3. Pathways to poor educational outcomes for HIV/AIDS-affected youth in South Africa.

    PubMed

    Orkin, Mark; Boyes, Mark E; Cluver, Lucie D; Zhang, Yuning

    2014-01-01

    A recent systematic review of studies in the developing world has critically examined linkages from familial HIV/AIDS and associated factors such as poverty and child mental health to negative child educational outcomes. In line with several recommendations in the review, the current study modelled relationships between familial HIV/AIDS, poverty, child internalising problems, gender and four educational outcomes: non-enrolment at school, non-attendance, deficits in grade progression and concentration problems. Path analyses reveal no direct associations between familial HIV/AIDS and any of the educational outcomes. Instead, HIV/AIDS-orphanhood or caregiver HIV/AIDS-sickness impacted indirectly on educational outcomes via the poverty and internalising problems that they occasioned. This has implications for evidence-based policy inferences. For instance, by addressing such intervening variables generally, rather than by seeking to target families affected by HIV/AIDS, interventions could avoid exacerbating stigmatisation, while having a more direct and stronger impact on children's educational outcomes. This analytic approach also suggests that future research should seek to identify causal paths, and may include other intervening variables related to poverty (such as child housework and caring responsibilities) or to child mental health (such as stigma and abuse), that are linked to both familial HIV/AIDS and educational outcomes. PMID:23965029

  4. Examining intrinsic versus extrinsic exercise goals: cognitive, affective, and behavioral outcomes.

    PubMed

    Sebire, Simon J; Standage, Martyn; Vansteenkiste, Maarten

    2009-04-01

    Grounded in self-determination theory (SDT), this study had two purposes: (a) examine the associations between intrinsic (relative to extrinsic) exercise goal content and cognitive, affective, and behavioral outcomes; and (b) test the mediating role of psychological need satisfaction in the Exercise Goal Content --> Outcomes relationship. Using a sample of 410 adults, hierarchical regression analysis showed relative intrinsic goal content to positively predict physical self-worth, self-reported exercise behavior, psychological well-being, and psychological need satisfaction and negatively predict exercise anxiety. Except for exercise behavior, the predictive utility of relative intrinsic goal content on the dependent variables of interest remained significant after controlling for participants' relative self-determined exercise motivation. Structural equation modeling analyses showed psychological need satisfaction to partially mediate the effect of relative intrinsic goal content on the outcome variables. Our findings support further investigation of exercise goals commensurate with the goal content perspective advanced in SDT. PMID:19454771

  5. Comparing predicted and actual affective responses to process versus outcome: an emotion-as-feedback perspective.

    PubMed

    Kwong, Jessica Y Y; Wong, Kin Fai Ellick; Tang, Suki K Y

    2013-10-01

    One of the conjectures in affective forecasting literature is that people are advised to discount their anticipated emotions because their forecasts are often inaccurate. The present research distinguishes between emotional reactions to process versus those to outcome, and highlights an alternative view that affective misforecasts could indeed be adaptive to goal pursuit. Using an ultimatum game, Study 1 showed that people overpredicted how much they would regret and be disappointed by the amount of effort they exerted, should the outcomes turned out worse than expected; nonetheless, people could accurately predict their emotional responses to unfavorable outcomes per se. In a natural setting of a university examination, Study 2 demonstrated that actual regret and disappointment toward favorable outcomes were more intense than the level people expected, but this discrepancy was not observed in their emotional responses to efforts they had invested. These two distinct patterns of results substantiate the argument that the deviation between predicted and actual emotions is dependent on the referents of the emotional reactions. PMID:23831563

  6. Effects of acute psychosocial stress exposure on endocrine and affective reactivity in college students differing in the 5-HTTLPR genotype and trait neuroticism.

    PubMed

    Verschoor, Ellen; Markus, C Rob

    2011-07-01

    Enhanced stress vulnerability has been implicated in the pathogenesis of affective disorders. Although both genetic (5-HTTLPR) and cognitive (neuroticism) factors are known to increase stress vulnerability, no experimental study has investigated the interaction between these two factors on psychobiological reactivity following acute stress exposure. This study used a balanced experimental design to examine the interaction between the 5-HTTLPR genotype and trait neuroticism in neuroendocrine and affective stress responses. From a large group of 771 students, 48 carriers of the short/short (S/S) allele and 48 carriers of the long/long (L/L) allele with the lowest and the highest neuroticism scores (77 females, 19 males; mean age ± SD: 20.6 ± 2 years) were selected and exposed to an acute psychosocial stressor. Mood was assessed before and after the stressor, and salivary cortisol concentrations were measured before and at 20, 30, and 60 min after stressor onset. Acute stress increased salivary cortisol concentration regardless of either 5-HTTLPR genotype or neuroticism, but it caused a less profound negative mood change in L/L compared to S/S-allele carriers with the lowest neuroticism scores. The 5-HTTLPR genotype influences affective reactivity to acute stress conditional upon neuroticism, improving resilience to acute stress in L/L-allele carriers if they do not already possess high cognitive-affective (neuroticism) vulnerability. PMID:21438771

  7. Transmission and persistence of Ceratonova shasta genotypes in Chinook salmon.

    PubMed

    Hurst, Charlene N; Wong, Peter; Hallett, Sascha L; Ray, R Adam; Bartholomew, Jerri L

    2014-12-01

    Ceratonova shasta is a myxozoan parasite of salmon and trout transmitted by waterborne actinospores. Based on DNA sequence data and host specificity, 4 distinct parasite genotypes are recognized. Genotypes I and II are common in the lower reaches of the Klamath River, Oregon-California, but only infection by genotype I causes mortality in Chinook salmon. We conducted sentinel fish exposures and determined genotype composition in river water during exposure, and in fish gills, intestine, and tank water post-exposure to determine whether: (1) transmission of parasites having different genotypes is host-specific and (2) all transmitted genotypes persist in the host through to release as waterborne stages. Initial parasite transmission to the fish host appears indiscriminant, since we detected both genotypes I and II in 83.6% of the fish gills sampled. However, only genotype I was detected in fish that succumbed to infection, while both genotypes persisted in fish that survived. Persistence was likely dependent on exposure dose, initial infection type (mixed or single) and infection outcome (mortality or survival). The transmission of both genotypes to a majority of Chinook salmon and the persistence of multiple genotypes raises questions about how infection with mixed genotypes could result in within-host interactions that affect disease severity. PMID:24945751

  8. Genotype-by-Environment Interactions and Adaptation to Local Temperature Affect Immunity and Fecundity in Drosophila melanogaster

    PubMed Central

    Lazzaro, Brian P.; Flores, Heather A.; Lorigan, James G.; Yourth, Christopher P.

    2008-01-01

    Natural populations of most organisms harbor substantial genetic variation for resistance to infection. The continued existence of such variation is unexpected under simple evolutionary models that either posit direct and continuous natural selection on the immune system or an evolved life history “balance” between immunity and other fitness traits in a constant environment. However, both local adaptation to heterogeneous environments and genotype-by-environment interactions can maintain genetic variation in a species. In this study, we test Drosophila melanogaster genotypes sampled from tropical Africa, temperate northeastern North America, and semi-tropical southeastern North America for resistance to bacterial infection and fecundity at three different environmental temperatures. Environmental temperature had absolute effects on all traits, but there were also marked genotype-by-environment interactions that may limit the global efficiency of natural selection on both traits. African flies performed more poorly than North American flies in both immunity and fecundity at the lowest temperature, but not at the higher temperatures, suggesting that the African population is maladapted to low temperature. In contrast, there was no evidence for clinal variation driven by thermal adaptation within North America for either trait. Resistance to infection and reproductive success were generally uncorrelated across genotypes, so this study finds no evidence for a fitness tradeoff between immunity and fecundity under the conditions tested. Both local adaptation to geographically heterogeneous environments and genotype-by-environment interactions may explain the persistence of genetic variation for resistance to infection in natural populations. PMID:18369474

  9. The cosmetic outcome of external dacryocystorhinostomy scar and factors affecting it

    PubMed Central

    Waly, Mostafa A; Shalaby, Osama E; Elbakary, Molham A; Hashish, Aiman A

    2016-01-01

    Purpose: To study the cosmetic outcome of external dacryocystorhinostomy (Ex-DCR) and to detect the factors affecting it. Patients and Methods: Prospective randomized interventional study included forty patients who were treated by 40 Ex-DCRs. In twenty patients, medial canthal vertical incision was used and in the other twenty cases, subciliary incision was used. The skin was closed using vicryl 6-0 or prolene 6-0 interrupted sutures, and each one was randomly used in twenty patients (10 patients of each incision type). Cosmetic outcome was evaluated 6 months postoperative by the patients and by an oculoplastic surgeon on a four grades scale. Cosmetic results and its correlation to patients’ age, sex, skin complexion, type of incision, and type of skin sutures were studied. Results: The mean scar grading was 0.98 ± 1.0 and 1.3 ± 1.0 in patients’ and examiner's assessment. About 27.5% described their scars as cosmetically significant. The cosmetic outcome was significantly affected by the type of incision with only 5% significant scars in subciliary incision group. Prolene 6-0 suture was associated with better cosmetic results with 15% significant scars. 50% of dark-skinned patients showed cosmetically significant scars. Although no correlation was found between patients’ age and cosmetic outcome, pediatric patients showed higher tendency to scar visibility with mean scar grade 1.2 ± 1.0 and 1.5 ± 0.9 in patients’ and examiner's assessment. Conclusion: Dark skinned and pediatric patients are more prone to visible Ex-DCR scar. The use of subciliary approach and prolene 6-0 skin sutures is associated with more favorable cosmetic outcome. PMID:27221676

  10. Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis

    PubMed Central

    Mega, Jessica L.; Simon, Tabassome; Collet, Jean-Philippe; Anderson, Jeffrey L.; Antman, Elliott M.; Bliden, Kevin; Cannon, Christopher P.; Danchin, Nicolas; Giusti, Betti; Gurbel, Paul; Horne, Benjamin D.; Hulot, Jean-Sebastian; Kastrati, Adnan; Montalescot, Gilles; Neumann, Franz-Josef; Shen, Lei; Sibbing, Dirk; Steg, P. Gabriel; Trenk, Dietmar; Wiviott, Stephen D.; Sabatine, Marc S.

    2011-01-01

    Content Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. Objective In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants. Data Sources and Study Selection A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained. Data Extraction Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype. Results Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles

  11. Bad actions or bad outcomes? Differentiating affective contributions to the moral condemnation of harm.

    PubMed

    Miller, Ryan M; Hannikainen, Ivar A; Cushman, Fiery A

    2014-06-01

    Moral condemnation of harmful behavior is influenced by both cognitive and affective processes. However, despite much recent research, the proximate source of affect remains unclear. One obvious contender is empathy; simulating the victim's pain could lead one to judge an action as wrong ("outcome aversion"). An alternative, less obvious source is one's own aversion to performing the action itself ("action aversion"). To dissociate these alternatives, we developed a scale that assessed individual aversions to (a) witnessing others experience painful outcomes (e.g., seeing someone fall down stairs); and (b) performing actions that are harmless yet aversive (e.g., stabbing a fellow actor with a fake stage knife). Across 4 experiments, we found that moral condemnation of both first-person and third-party harmful behavior in the context of moral dilemmas is better predicted by one's aversion to action properties than by an affective response to victim suffering. In a fifth experiment, we manipulated both action aversion and the degree of expected suffering across a number of actions and found that both factors make large, independent contributions to moral judgment. Together, these results suggest we may judge others' actions by imagining what it would feel like to perform the action rather than experience the consequences of the action. Accordingly, they provide a counterpoint to a dominant but largely untested assumption that empathy is the key affective response governing moral judgments of harm. PMID:24512250

  12. Hepatitis C virus genotype 1: how genetic variability of the core protein affects the response to pegylated-interferon and ribavirin therapy.

    PubMed

    Alhamlan, F S; Al-Ahdal, M N; Khalaf, N Z; Abdo, A A; Sanai, F M; Al-Ashgar, H I; Elhefnawi, M; Zaid, A; Al-Qahtani, A A

    2014-02-01

    Hepatitis C virus subgenotypes 1a and 1b are found worldwide and cause 60% of all hepatitis C cases. It has been reported recently that viral genetic variations have a critical impact on the patient treatment outcome. In particular, polymorphisms of the HCV core protein have been linked to poor treatment response. However, most of these studies were conducted on Asian populations, Japanese in particular who are infected with HCV subgenotype 1b. Hence, we aimed in this study to examine the core protein polymorphisms in Saudi patients who are infected with chronic HCV genotype 1 (1a and 1b subtypes) and its association with treatment outcome. Direct sequencing of full-length core protein and data mining analyses were utilized. Results have shown that the response to treatment is dependent on subgenotypes. Indeed, HCV-1b showed different point mutations that are associated with treatment outcome where the point mutations at positions 70 (Arg(70) Gln) and 75 (Thr(75) Ala) in HCV-1b are significantly associated with PEG-IFN/RBV treatment response. In contrast, HCV-1a showed no significant association between core protein mutations and response to treatment. In addition, analyses of HCV-1a core protein sequences revealed a highly conserved region especially in the responder group. This study provides a new insight in the genetic variability of full-length core protein in HCV genotype 1 in Saudi infected patients. PMID:24166351

  13. New Avian Paramyxoviruses Type I Strains Identified in Africa Provide New Outcomes for Phylogeny Reconstruction and Genotype Classification

    PubMed Central

    Gil, Patricia; Briand, François-Xavier; Molia, Sophie; Gaidet, Nicolas; Cappelle, Julien; Chevalier, Véronique; Balança, Gilles; Traoré, Abdallah; Grillet, Colette; Maminiaina, Olivier Fridolin; Guendouz, Samia; Dakouo, Marthin; Samaké, Kassim; Bezeid, Ould El Mamy; Diarra, Abbas; Chaka, Hassen; Goutard, Flavie; Thompson, Peter; Martinez, Dominique; Jestin, Véronique; Albina, Emmanuel

    2013-01-01

    Newcastle disease (ND) is one of the most lethal diseases of poultry worldwide. It is caused by an avian paramyxovirus 1 that has high genomic diversity. In the framework of an international surveillance program launched in 2007, several thousand samples from domestic and wild birds in Africa were collected and analyzed. ND viruses (NDV) were detected and isolated in apparently healthy fowls and wild birds. However, two thirds of the isolates collected in this study were classified as virulent strains of NDV based on the molecular analysis of the fusion protein and experimental in vivo challenges with two representative isolates. Phylogenetic analysis based on the F and HN genes showed that isolates recovered from poultry in Mali and Ethiopia form new groups, herein proposed as genotypes XIV and sub-genotype VIf with reference to the new nomenclature described by Diel’s group. In Madagascar, the circulation of NDV strains of genotype XI, originally reported elsewhere, is also confirmed. Full genome sequencing of five African isolates was generated and an extensive phylogeny reconstruction was carried out based on the nucleotide sequences. The evolutionary distances between groups and the specific amino acid signatures of each cluster allowed us to refine the genotype nomenclature. PMID:24204623

  14. Environment and host genotype determine the outcome of a plant-virus interaction: from antagonism to mutualism.

    PubMed

    Hily, Jean-Michel; Poulicard, Nils; Mora, Miguel-Ángel; Pagán, Israel; García-Arenal, Fernando

    2016-01-01

    It has been hypothesized that plant-virus interactions vary between antagonism and conditional mutualism according to environmental conditions. This hypothesis is based on scant experimental evidence, and to test it we examined the effect of abiotic factors on the Arabidopsis thaliana-Cucumber mosaic virus (CMV) interaction. Four Arabidopsis genotypes clustering into two allometric groups were grown under six environments defined by three temperature and two light-intensity conditions. Plants were either CMV-infected or mock-inoculated, and the effects of environment and infection on temporal and resource allocation life-history traits were quantified. Life-history traits significantly differed between allometric groups over all environments, with group 1 plants tolerating abiotic stress better than those of group 2. The effect of CMV infection on host fitness (virulence) differed between genotypes, being lower in group 1 genotypes. Tolerance to abiotic stress and to infection was similarly achieved through life-history trait responses, which resulted in resource reallocation from growth to reproduction. Effects of infection varied according to plant genotype and environment from detrimental to beneficial for host fitness. These results are highly relevant and demonstrate that plant viruses can be pleiotropic parasites along the antagonism-mutualism continuum, which should be considered in analyses of the evolution of plant-virus interactions. PMID:26365599

  15. Does Augmented Reality Affect High School Students' Learning Outcomes in Chemistry?

    NASA Astrophysics Data System (ADS)

    Renner, Jonathan Christopher

    Some teens may prefer using a self-directed, constructivist, and technologic approach to learning rather than traditional classroom instruction. If it can be demonstrated, educators may adjust their teaching methodology. The guiding research question for this study focused on how augmented reality affects high school students' learning outcomes in chemistry, as measured by a pretest and posttest methodology when ensuring that the individual outcomes were not the result of group collaboration. This study employed a quantitative, quasi-experimental study design that used a comparison and experimental group. Inferential statistical analysis was employed. The study was conducted at a high school in southwest Colorado. Eighty-nine respondents returned completed and signed consent forms, and 78 participants completed the study. Results demonstrated that augmented reality instruction caused posttest scores to significantly increase, as compared to pretest scores, but it was not as effective as traditional classroom instruction. Scores did improve under both types of instruction; therefore, more research is needed in this area. The present study was the first quantitative experiment controlling for individual learning to validate augmented reality using mobile handheld digital devices that affected individual students' learning outcomes without group collaboration. This topic was important to the field of education as it may help educators understand how students learn and it may also change the way students are taught.

  16. Paternal investment and status-related child outcomes: timing of father's death affects offspring success.

    PubMed

    Shenk, Mary K; Scelza, Brooke A

    2012-09-01

    Recent work in human behavioural ecology has suggested that analyses focusing on early childhood may underestimate the importance of paternal investment to child outcomes since such investment may not become crucial until adolescence or beyond. This may be especially important in societies with a heritable component to status, as later investment by fathers may be more strongly related to a child's adult status than early forms of parental investment that affect child survival and child health. In such circumstances, the death or absence of a father may have profoundly negative effects on the adult outcomes of his children that cannot be easily compensated for by the investment of mothers or other relatives. This proposition is tested using a multigenerational dataset from Bangalore, India, containing information on paternal mortality as well as several child outcomes dependent on parental investment during adolescence and young adulthood. The paper examines the effects of paternal death, and the timing of paternal death, on a child's education, adult income, age at marriage and the amount spent on his or her marriage, along with similar characteristics of spouses. Results indicate that a father's death has a negative impact on child outcomes, and that, in contrast to some findings in the literature on father absence, the effects of paternal death are strongest for children who lose their father in late childhood or adolescence. PMID:22429791

  17. Antigenic differences among NDV strains of different genotypes used in vaccine formulation affects viral shedding after a virulent challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Strains of Newcastle disease virus (NDV) can be separated into genotypes based on genome differences even though they are antigenically considered to be of a single serotype. It is widely recognized that an efficacious Newcastle disease (ND) vaccine made with any NDV does induce protection against ...

  18. Analysis of donor heterogeneity as a factor affecting the clinical outcome of oocyte donation.

    PubMed

    Harris, Sarah E; Faddy, Malcolm; Levett, Stephen; Sharma, Vinay; Gosden, Roger

    2002-11-01

    This study investigated factors that may affect the clinical outcome of oocyte donation on the basis of data from a clinical programme involving 243 treatment cycles analysed retrospectively. In each cohort, oocytes were distributed randomly to one, two or three recipients, which enabled the outcomes in terms of pregnancy and live birth rates to be compared among donors. The results were compared with respect to age of the donor and recipient, number of oocytes collected, fertilization and cleavage rates, qualitative embryo criteria (morphological grade) and other clinical criteria. Most variables had no significant effect on either outcome, although the live birth rate varied inversely with recipient age. Unsurprisingly, the pregnancy rate was correlated positively with the number of embryos transferred. Most of the variation in pregnancy and live birth rates (85-90%) could not be accounted for by any specific donation characteristic, indicating that interdonor heterogeneity was the result of idiopathic factors. The factor most predictive of a recipient's cycle outcome was a history of previous success of the donor, which accounted for approximately 30% of the variation in live birth rates. Pregnancy success rates varied widely among oocyte donors, as has been found among sperm donors. This observation highlights the need to identify markers that predict developmental competence and help to identify the genetic and environmental bases of differential fertility. In conclusion, the quality of oocytes varied widely among women presumed to be fertile by clinical criteria, and the causative factors set a major limitation on the prospects of improving the outcome of egg donation. PMID:12477962

  19. Conceptualising the Impact of Arousal and Affective State on Training Outcomes of Operant Conditioning

    PubMed Central

    Starling, Melissa J.; Branson, Nicholas; Cody, Denis; McGreevy, Paul D.

    2013-01-01

    Simple Summary This article discusses the impacts of arousal and emotional state on training animals using methods based on reward and punishment. Three-dimensional graphs are provided to offer a visual means to illustrate how arousal and emotional state may influence the effectiveness of reward and punishment depending on the behaviour being trained. Dogs and horses are used to illustrate this with reference to commonly trained behaviours in a predatory and a prey animal. Abstract Animal training relies heavily on an understanding of species-specific behaviour as it integrates with operant conditioning principles. Following on from recent studies showing that affective states and arousal levels may correlate with behavioural outcomes, we explore the contribution of both affective state and arousal in behavioural responses to operant conditioning. This paper provides a framework for assessing how affective state and arousal may influence the efficacy of operant training methods. It provides a series of three-dimensional conceptual graphs as exemplars to describing putative influences of both affective state and arousal on the likelihood of dogs and horses performing commonly desired behaviours. These graphs are referred to as response landscapes, and they highlight the flexibility available for improving training efficacy and the likely need for different approaches to suit animals in different affective states and at various levels of arousal. Knowledge gaps are discussed and suggestions made for bridging them. PMID:26487403

  20. Predicted and experienced affective responses to the outcome of the 2008 U.S. presidential election.

    PubMed

    Kitchens, Michael B; Corser, Grant C; Gohm, Carol L; VonWaldner, Kristen L; Foreman, Elizabeth L

    2010-12-01

    People typically have intense feelings about politics. Therefore, it was no surprise that the campaign and eventual election of Barack Obama were highly anticipated and emotionally charged events, making it and the emotion experienced afterward a useful situation in which to replicate prior research showing that people typically overestimate the intensity and duration of their future affective states. Consequently, it was expected that Obama supporters and McCain supporters might overestimate the intensity of their affective responses to the outcome of the election. Data showed that while McCain supporters underestimated how happy they would be following the election, Obama supporters accurately predicted how happy they would be following the election. These data provide descriptive information on the accuracy of people's predicted reactions to the 2008 U.S. presidential election. The findings are discussed in the context of the broad literature and this specific and unique event. PMID:21323142

  1. Paraoxonase 1 Gene Polymorphism Does Not Affect Clopidogrel Response Variability but Is Associated with Clinical Outcome after PCI

    PubMed Central

    Kang, Jeehoon; Jeon, Ki-Hyun; Kang, Si-Hyuck; Han, Jung-Kyu; Lee, Sang Eun; Yang, Han-Mo; Lee, Hae-Young; Kang, Hyun-Jae; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

    2013-01-01

    Background Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation. Methods A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months. Results PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55–87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78–1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients. Conclusion PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C. PMID:23418418

  2. Lifestyle-Related Diseases Affect Surgical Outcomes after Posterior Lumbar Interbody Fusion.

    PubMed

    Sakaura, Hironobu; Miwa, Toshitada; Yamashita, Tomoya; Kuroda, Yusuke; Ohwada, Tetsuo

    2016-02-01

    Study Design Retrospective study. Objective Hyperlipidemia (HL) and hypertension (HT) lead to systemic atherosclerosis. Not only atherosclerosis but also bone fragility and/or low bone mineral density result from diabetes mellitus (DM) and chronic kidney disease (CKD). The purpose of this study was to examine whether these lifestyle-related diseases affected surgical outcomes after posterior lumbar interbody fusion (PLIF). Methods The subjects comprised 122 consecutive patients who underwent single-level PLIF for degenerative lumbar spinal disorders. The clinical results were assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2 years postoperatively. The fusion status was graded as union in situ, collapsed union, or nonunion at 2 years after surgery. The abdominal aorta calcification (AAC) score was assessed using preoperative lateral radiographs of the lumbar spine. Results HL did not significantly affect the JOA score recovery rate. On the other hand, HT and CKD (stage 3 to 4) had a significant adverse effect on the recovery rate. The recovery rate was also lower in the DM group than in the non-DM group, but the difference was not significant. The AAC score was negatively correlated with the JOA score recovery rate. The fusion status was not significantly affected by HL, HT, DM, or CKD; however, the AAC score was significantly higher in the collapsed union and nonunion group than in the union in situ group. Conclusions At 2 years after PLIF, the presence of HT, CKD, and AAC was associated with significantly worse clinical outcomes, and advanced AAC significantly affected fusion status. PMID:26835195

  3. Mechanisms of Behavioral and Affective Treatment Outcomes in a Cognitive Behavioral Intervention for Boys.

    PubMed

    Burke, Jeffrey D; Loeber, Rolf

    2016-01-01

    Evidence for effective treatment for behavioral problems continues to grow, yet evidence about the effective mechanisms underlying those interventions has lagged behind. The Stop Now and Plan (SNAP) program is a multicomponent intervention for boys between 6 and 11. This study tested putative treatment mechanisms using data from 252 boys in a randomized controlled trial of SNAP versus treatment as usual. SNAP includes a 3 month group treatment period followed by individualized intervention, which persisted through the 15 month study period. Measures were administered in four waves: at baseline and at 3, 9 and 15 months after baseline. A hierarchical linear modeling strategy was used. SNAP was associated with improved problem-solving skills, prosocial behavior, emotion regulation skills, and reduced parental stress. Prosocial behavior, emotion regulation skills and reduced parental stress partially mediated improvements in child aggression. Improved emotion regulation skills partially mediated treatment-related child anxious-depressed outcomes. Improvements in parenting behaviors did not differ between treatment conditions. The results suggest that independent processes may drive affective and behavioral outcomes, with some specificity regarding the mechanisms related to differing treatment outcomes. PMID:25619927

  4. High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.

    PubMed

    Rojnueangnit, Kitiwan; Xie, Jing; Gomes, Alicia; Sharp, Angela; Callens, Tom; Chen, Yunjia; Liu, Ying; Cochran, Meagan; Abbott, Mary-Alice; Atkin, Joan; Babovic-Vuksanovic, Dusica; Barnett, Christopher P; Crenshaw, Melissa; Bartholomew, Dennis W; Basel, Lina; Bellus, Gary; Ben-Shachar, Shay; Bialer, Martin G; Bick, David; Blumberg, Bruce; Cortes, Fanny; David, Karen L; Destree, Anne; Duat-Rodriguez, Anna; Earl, Dawn; Escobar, Luis; Eswara, Marthanda; Ezquieta, Begona; Frayling, Ian M; Frydman, Moshe; Gardner, Kathy; Gripp, Karen W; Hernández-Chico, Concepcion; Heyrman, Kurt; Ibrahim, Jennifer; Janssens, Sandra; Keena, Beth A; Llano-Rivas, Isabel; Leppig, Kathy; McDonald, Marie; Misra, Vinod K; Mulbury, Jennifer; Narayanan, Vinodh; Orenstein, Naama; Galvin-Parton, Patricia; Pedro, Helio; Pivnick, Eniko K; Powell, Cynthia M; Randolph, Linda; Raskin, Salmo; Rosell, Jordi; Rubin, Karol; Seashore, Margretta; Schaaf, Christian P; Scheuerle, Angela; Schultz, Meredith; Schorry, Elizabeth; Schnur, Rhonda; Siqveland, Elizabeth; Tkachuk, Amanda; Tonsgard, James; Upadhyaya, Meena; Verma, Ishwar C; Wallace, Stephanie; Williams, Charles; Zackai, Elaine; Zonana, Jonathan; Lazaro, Conxi; Claes, Kathleen; Korf, Bruce; Martin, Yolanda; Legius, Eric; Messiaen, Ludwine

    2015-11-01

    Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients. PMID:26178382

  5. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

    PubMed Central

    Thomsen, Christian; Theilig, Dorothea; Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schreiter, Nils; Schreiter, Vera; Schürmann, Dirk; Temmesfeld-Wollbrueck, Bettina; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2016-01-01

    The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID:27354783

  6. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy.

    PubMed

    Thomsen, Christian; Theilig, Dorothea; Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schreiter, Nils; Schreiter, Vera; Schürmann, Dirk; Temmesfeld-Wollbrueck, Bettina; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2016-01-01

    The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George's Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID:27354783

  7. Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.

    PubMed

    Clelland, C L; Drouet, V; Rilett, K C; Smeed, J A; Nadrich, R H; Rajparia, A; Read, L L; Clelland, J D

    2016-01-01

    Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions. PMID:27622935

  8. Critical Factors Affecting the Assessment of Student Learning Outcomes: A Delphi Study of the Opinions of Community College Personnel

    ERIC Educational Resources Information Center

    Somerville, Jerry

    2008-01-01

    The purpose of this qualitative study was to identify critically important factors that affect the meaningful assessment of student learning outcomes and study why these factors were critically important. A three-round Delphi process was used to solicit the opinions of individuals who were actively involved in student learning outcomes assessment…

  9. Learning science in a cooperative setting: Academic achievement and affective outcomes

    NASA Astrophysics Data System (ADS)

    Lazarowitz, Reuven; Hertz-Lazarowitz, Rachel; Baird, J. Hugh

    A learning unit in earth science was taught to high school students, using a jigsaw-group mastery learning approach. The sample consisted of 73 students in the experimental group and 47 students who learned the topic in an individualized mastery learning approach. The study lasted 5 weeks. Pretests and posttests on academic achievement and affective outcomes were administered. Data were treated with an analysis of covariance. The results show that students of the experimental group achieved significantly higher on academic outcomes, both normative and objective scores. On the creative essay test, the differences in number of ideas and total essay score were not significant between the groups, although the mean scores for number of words were higher for the individualized mastery learning group. On the affective domain, jigsaw-group mastery learning students scored significantly higher on self-esteem, number of friends, and involvement in the classroom. No differences were found in cohesiveness, cooperation, competition, and attitudes toward the subject learned. The results are discussed through the evaluation and comparison of the two methods of instruction used in this study.The cooperative learning movement began in junior high schools as part of the desegregation process, aiming at facilitating positive ethnic relations and increasing academic achievement and social skills among diverse students (Aronson, Stephan, Sikes, Blaney, & Snapp, 1978; Sharan & Hertz-Lazarowitz, 1980; Slavin, 1980). However, elementary teachers quickly recognized the potential of cooperative methods, and such methods were adopted freely in elementary schools before becoming widespread on the junior and senior high level. It has only been during the past few years that application of cooperative learning has been studied extensively with these older students.Cooperative learning methods generally involve heterogeneous groups working together on tasks that are deliberately structured to

  10. The Host Genotype and Environment Affect Strain Types of Bifidobacterium longum subsp. longum Inhabiting the Intestinal Tracts of Twins

    PubMed Central

    Zhang, Min; Hang, Xiaomin; Tan, Jing

    2015-01-01

    To investigate the influences of host genotype and environment on Bifidobacterium longum subsp. longum inhabiting human intestines at the strain level, six pairs of twins, divided into two groups (children and adults), were recruited. Each group consisted of two monozygotic (MZ) twin pairs and one dizygotic (DZ) twin pair. Child twins had been living together from birth, while adult twins had been living separately for 5 to 10 years. A total of 345 B. longum subsp. longum isolates obtained from 60 fecal samples from these twins were analyzed by multilocus sequence typing (MLST), and 35 sequence types (STs) were finally acquired. Comparison of strains within and between the twin pairs showed that no strains with identical STs were observed between unrelated individuals or within adult DZ twin pairs. Eight STs were found to be monophyletic, existing within MZ twins and child DZ twins. The similarity of strain types within child cotwins was significantly higher than that within adult cotwins, which indicated that environment was one of the important determinants in B. longum subsp. longum strain types inhabiting human intestines. However, although these differences between MZ and DZ twins were observed, it is still difficult to reach an exact conclusion about the impact of host genotype. This is mainly because of the limited number of subjects tested in the present study and the lack of strain types tracing in the same twin pairs from birth until adulthood. PMID:25956768

  11. Visual Acuity Testing: Feedback Affects Neither Outcome nor Reproducibility, but Leaves Participants Happier

    PubMed Central

    Bach, Michael; Schäfer, Kerstin

    2016-01-01

    Assessment of visual acuity is a well standardized procedure at least for expert opinions and clinical trials. It is often recommended not giving patients feedback on the correctness of their responses. As this viewpoint has not been quantitatively examined so far, we quantitatively assessed possible effects of feedback on visual acuity testing. In 40 normal participants we presented Landolt Cs in 8 orientations using the automated Freiburg Acuity Test (FrACT, outcome measures were absolute visual acuity (logMAR), its test-retest agreement (limits of agreement) and participants’ comfort estimates on a 5-step symmetric Likert scale. Feedback influenced acuity outcome significantly (p = 0.02), but with a tiny effect size: 0.02 logMAR poorer acuity for (D) compared to (A), even weaker effects for (B) and (C). Test-retest agreement was high (limits of agreement: ± 1.0 lines) and did not depend on feedback (p>0.5). The comfort ranking clearly differed, by 2 steps on the Likert scale: the condition (A)–no feedback–was on average “slightly uncomfortable”, the other three conditions were “slightly comfortable” (p<0.0001). Feedback affected neither reproducibility nor the acuity outcome to any relevant extent. The participants, however, reported markedly greater comfort with any kind of feedback. We conclude that systematic feedback (as implemented in FrACT) offers nothing but advantages for routine use. PMID:26824693

  12. Visual Acuity Testing: Feedback Affects Neither Outcome nor Reproducibility, but Leaves Participants Happier.

    PubMed

    Bach, Michael; Schäfer, Kerstin

    2016-01-01

    Assessment of visual acuity is a well standardized procedure at least for expert opinions and clinical trials. It is often recommended not giving patients feedback on the correctness of their responses. As this viewpoint has not been quantitatively examined so far, we quantitatively assessed possible effects of feedback on visual acuity testing. In 40 normal participants we presented Landolt Cs in 8 orientations using the automated Freiburg Acuity Test (FrACT, outcome measures were absolute visual acuity (logMAR), its test-retest agreement (limits of agreement) and participants' comfort estimates on a 5-step symmetric Likert scale. Feedback influenced acuity outcome significantly (p = 0.02), but with a tiny effect size: 0.02 logMAR poorer acuity for (D) compared to (A), even weaker effects for (B) and (C). Test-retest agreement was high (limits of agreement: ± 1.0 lines) and did not depend on feedback (p>0.5). The comfort ranking clearly differed, by 2 steps on the Likert scale: the condition (A)-no feedback-was on average "slightly uncomfortable", the other three conditions were "slightly comfortable" (p<0.0001). Feedback affected neither reproducibility nor the acuity outcome to any relevant extent. The participants, however, reported markedly greater comfort with any kind of feedback. We conclude that systematic feedback (as implemented in FrACT) offers nothing but advantages for routine use. PMID:26824693

  13. Learning science in a cooperative setting: Academic achievement and affective outcomes

    NASA Astrophysics Data System (ADS)

    Lazarowitz, Reuven; Hertz-Lazarowitz, Rachel; Baird, J. Hugh

    A learning unit in earth science was taught to high school students, using a jigsaw-group mastery learning approach. The sample consisted of 73 students in the experimental group and 47 students who learned the topic in an individualized mastery learning approach. The study lasted 5 weeks. Pretests and posttests on academic achievement and affective outcomes were administered. Data were treated with an analysis of covariance. The results show that students of the experimental group achieved significantly higher on academic outcomes, both normative and objective scores. On the creative essay test, the differences in number of ideas and total essay score were not significant between the groups, although the mean scores for number of words were higher for the individualized mastery learning group. On the affective domain, jigsaw-group mastery learning students scored significantly higher on self-esteem, number of friends, and involvement in the classroom. No differences were found in cohesiveness, cooperation, competition, and attitudes toward the subject learned. The results are discussed through the evaluation and comparison of the two methods of instruction used in this study.The cooperative learning movement began in junior high schools as part of the desegregation process, aiming at facilitating positive ethnic relations and increasing academic achievement and social skills among diverse students (Aronson, Stephan, Sikes, Blaney, & Snapp, 1978; Sharan & Hertz-Lazarowitz, 1980; Slavin, 1980). However, elementary teachers quickly recognized the potential of cooperative methods, and such methods were adopted freely in elementary schools before becoming widespread on the junior and senior high level. It has only been during the past few years that application of cooperative learning has been studied extensively with these older students.Cooperative learning methods generally involve heterogeneous groups working together on tasks that are deliberately structured to

  14. Through what mechanisms do protected areas affect environmental and social outcomes?

    PubMed Central

    Ferraro, Paul J.; Hanauer, Merlin M.

    2015-01-01

    To develop effective protected area policies, scholars and practitioners must better understand the mechanisms through which protected areas affect social and environmental outcomes. With strong evidence about mechanisms, the key elements of success can be strengthened, and the key elements of failure can be eliminated or repaired. Unfortunately, empirical evidence about these mechanisms is limited, and little guidance for quantifying them exists. This essay assesses what mechanisms have been hypothesized, what empirical evidence exists for their relative contributions and what advances have been made in the past decade for estimating mechanism causal effects from non-experimental data. The essay concludes with a proposed agenda for building an evidence base about protected area mechanisms. PMID:26460122

  15. Relationship of Negative Affect and Outcome of an Opioid Therapy Trial Among Low Back Pain Patients

    PubMed Central

    Jamison, Robert N.; Edwards, Robert R.; Liu, Xiaoxia; Ross, Edgar L.; Michna, Edward; Warnick, Meredith; Wasan, Ajay D.

    2013-01-01

    Objectives Patients with chronic noncancer pain frequently report symptoms of depression and anxiety (negative affect), which are associated with higher ratings of pain intensity and a greater likelihood of being prescribed chronic opioid therapy. The purpose of this secondary analysis was to test the hypothesis that initial levels of negative affect can predict treatment-related outcomes in a double-blind, placebo-controlled study of extended-release (ER) hydromorphone among opioid-tolerant patients with chronic low back pain. Methods Four hundred fifty-nine (N = 459) patients participated in the titration/conversion phase of a multicenter study, of which 268 were randomized to receive once-daily hydromorphone or placebo. All patients completed the Hospital Anxiety and Depression Scale (HADS) at baseline and were divided evenly into Low (N = 157), Moderate (N = 155), and High (N = 147) negative affect groups based on their scores. Group differences in numerical pain intensity measures at home and in the clinic, Roland–Morris Disability ratings, and measures of symptoms from the Subjective Opiate Withdrawal Scale (SOWS) throughout the trial were analyzed. Results Two hundred sixty-eight of the initial 459 subjects who entered the 2 to 4-week titration/conversion phase (pretreatment) were successfully randomized to either placebo or ER hydromorphone; a total of 110 patients then completed this double-blind phase of the study. Those in the Moderate and High negative affect groups tended to drop out more often during the titration/conversion phase because of the adverse effects or lack of efficacy of their prescribed opioid than those in the Low negative mood group (P < 0.05). Overall, those patients in the Moderate and High groups reported significantly higher pain intensity scores in at-home and in-clinic pain intensity ratings (P < 0.05), greater disability on the Roland–Morris Scale (P < 0.01), and more withdrawal symptoms on the SOWS (P < 0.05) than those in

  16. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

  17. Spirituality and religiousness as predictive factors of outcome in schizophrenia and schizo-affective disorders.

    PubMed

    Mohr, Sylvia; Perroud, Nader; Gillieron, Christiane; Brandt, Pierre-Yves; Rieben, Isabelle; Borras, Laurence; Huguelet, Philippe

    2011-04-30

    Spirituality and religiousness have been shown to be highly prevalent in patients with schizophrenia. This study assesses the predictive value of helpful vs. harmful use of religion to cope with schizophrenia or schizo-affective disorder at 3 years. From an initial cohort of 115 outpatients, 80% were reassessed for positive, negative and general symptoms, clinical global impression, social adaptation and quality of life. For patients with helpful religion at baseline, the importance of spirituality was predictive of fewer negative symptoms, better clinical global impression, social functioning and quality of life. The frequencies of religious practices in community and support from religious community had no effect on outcome. For patients with harmful religion at baseline, no relationships were elicited. This result may be due to sample size. Indeed, helpful spiritual/religious coping concerns 83% of patients, whereas harmful spiritual/religious coping concerns only 14% of patients. Our study shows that helpful use of spirituality is predictive of a better outcome. Spirituality may facilitate recovery by providing resources for coping with symptoms. In some cases, however, spirituality and religiousness are a source of suffering. Helpful vs. harmful spiritual/religious coping appears to be of clinical significance. PMID:20869123

  18. Parenting Cognition and Affective Outcomes Following Parent Management Training: A Systematic Review.

    PubMed

    Colalillo, Sara; Johnston, Charlotte

    2016-09-01

    Parent management training (PMT) is considered the gold standard in the treatment of child behavior problems. The secondary effects of these interventions, particularly on parent well-being, are infrequently studied, despite evidence that parents of children with behavior problems often experience personal difficulties. This narrative review examined the affective and parenting cognition outcomes of PMT for mothers and fathers of children ages 2-13 years, across 48 controlled treatment studies. Substantial support was found for reductions in parenting stress, and increases in perceived parenting competence following PMT. Evidence indicated fewer improvements in domains more distal from parenting, including parent depressive symptoms and marital relationship dysfunction. A number of studies suggested parent gender as a moderator of parent outcomes of PMT; however, the underrepresentation of fathers in existing research limits conclusions in this regard. Avenues for future research are highlighted to address current gaps in the literature, and to further our understanding of the ways in which both children and parents may benefit from PMT. PMID:27389605

  19. Improving the outcomes of children affected by parental substance abuse: a review of randomized controlled trials

    PubMed Central

    Calhoun, Stacy; Conner, Emma; Miller, Melodi; Messina, Nena

    2015-01-01

    Substance abuse is a major public health concern that impacts not just the user but also the user’s family. The effect that parental substance abuse has on children has been given substantial attention over the years. Findings from the literature suggest that children of substance-abusing parents have a high risk of developing physical and mental health and behavioral problems. A number of intervention programs have been developed for parents who have a substance abuse problem. There have also been a number of interventions that have been developed for children who have at least one parent with a substance abuse problem. However, it remains unclear how we can best mitigate the negative effects that parental substance abuse has on children due to the scarcity of evaluations that utilize rigorous methodologies such as experimental designs. The purpose of this study is to review randomized controlled trials of intervention programs targeting parents with substance abuse problems and/or children with at least one parent with a substance abuse problem in order to identify programs that show some promise in improving the behavioral and mental health outcomes of children affected by parental substance abuse. Four randomized controlled trials that met our eligibility criteria were identified using major literature search engines. The findings from this review suggest that interventions that focus on improving parenting practices and family functioning may be effective in reducing problems in children affected by parental substance abuse. However, further research utilizing rigorous methodologies are needed in order to identify other successful interventions that can improve the outcomes of these children long after the intervention has ended. PMID:25670915

  20. Factors affecting the outcome of related allogeneic hematopoietic cell transplantation in patients with Fanconi Anemia.

    PubMed

    Ayas, Mouhab; Siddiqui, Khawar; Al-Jefri, Abdullah; El-Solh, Hassan; Al-Ahmari, Ali; Khairy, Ashraf; Markiz, Samer; Shahin, Hasan; Al-Musa, Abdulrahman; Al-Seraihy, Amal

    2014-10-01

    Hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi Anemia (FA), and it is generally accepted that these patients should receive low-intensity conditioning because of the underlying DNA repair defect in their cells. Outcomes for recipients of matched related HCT have generally been favorable, but only a few studies have scrutinized the factors that may affect the eventual outcome of these patients. This retrospective analysis of 94 pediatric patients with FA who underwent related HCT at King Faisal Specialist Hospital & Research Center was carried out to attempt to identify factors that may affect outcome. Results showed overall survival (OS) probabilities of 92.5%, 89%, and 86% at 1, 5, and 10 years, respectively. In univariate analysis, use of higher dose cyclophosphamide (CY) (60 mg/kg) conditioning was associated with a better 10-year OS than lower dose CY (20 mg/kg) conditioning (91% versus 82%, respectively; P = .035), and use of radiation-containing regimens was associated with a significantly lower 10-year OS than nonradiation regimens (76% versus 91%, respectively; P = .005). Of the 4 regimens used in this study, the fludarabine-based regimen was associated with the highest survival (95.2%; P = .034). The use of the higher dose CY (60 mg/kg) was associated with a significantly increased incidence of hemorrhagic cystitis (HC) (20% versus 5.6% respectively; P = .049). Three patients (3%) developed squamous cell carcinoma (2 oropharyngeal and 1 genitourinary), at 9.4, 5.4, and 13.3 years after HCT; 2 of them had radiation-containing conditioning. In conclusion, our data suggest that although using a higher dose CY (60 mg/kg) conditioning regimen may be associated with better survival, it is also associated with a significantly increased risk of HC. The addition of fludarabine to the low-dose CY (20 mg/kg) is associated with the best survival. On the other hand, radiation-containing regimens are associated with

  1. Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype

    PubMed Central

    Bodden, Carina; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Gerß, Joachim; Palme, Rupert; Lesch, Klaus-Peter; Lewejohann, Lars; Kaiser, Sylvia; Sachser, Norbert

    2015-01-01

    Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered

  2. Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients.

    PubMed

    Feng, Bo; Yang, Rui-Feng; Zhang, Hai-Ying; Luo, Bi-Fen; Kong, Fan-Yun; Rao, Hui-Ying; Jin, Qian; Cong, Xu; Wei, Lai

    2015-01-01

    Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expensive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1log10IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.2%). Analysis on the validation group demonstrated a positive predictive value of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in

  3. Gender-related affecting factors of prediabetes on its 10-year outcome

    PubMed Central

    Song, Xiaomin; Qiu, Miaoyan; Zhang, Xuan'e; Wang, Haiyan; Tong, Wenxin; Ju, Liping; Gu, Lei; Sun, Siming; Zhang, Hongli; Wang, Weiqing; Tian, Jingyan

    2016-01-01

    Objective To investigate the gender-related affecting factors of prediabetes on its 10-year outcome, in a longitudinal study. Methods and results This longitudinal population-based study was performed in the Ping Liang community, Yangpu district, Shanghai, between November 2002 and October 2014. There were 334 participants with prediabetes enrolled in the final analysis. While a certain proportion of the prediabetic population progress to diabetes, the majority remain at the same level or even revert to normal glucose regulation. No gender difference was observed in the change of glucose regulation. However, results from an adjusted logistic regression analysis in males showed that physical activity was significantly associated with both elevated odds of reverting to normal glucose regulation (active vs inactive, OR 3.00, 95% CI 1.09 to 8.30) and developing diabetes (OR 0.34, 95% CI 0.13 to 0.92). Age, baseline 2 h glucose, triglycerides and smoking status were also risk factors significantly associated with diabetes development; while for females, waist circumference played a key role in the outcome. Every unit elevation of waist circumference was associated with lower odds of reverting to normal glucose regulation (OR, 0.94; 95% CI 0.89 to 0.98) and higher odds of progressing to diabetes (OR, 1.05; 95% CI 1.01 to 1.10). Baseline hypertension and family history of diabetes carried higher risk for developing diabetes as well. Conclusions Physical activity in males and waist circumference in females are important factors predicting both progression to diabetes and regression to normal glucose regulation, indicating that more exercise for males and lower waist circumference for females are beneficial for prediabetes to achieve reversion. PMID:27239315

  4. Climate change affects the outcome of competitive interactions-an application of principal response curves.

    PubMed

    Heegaard, Einar; Vandvik, Vigdis

    2004-05-01

    It has been hypothesised that climate change may affect vegetation by changing the outcome of competitive interactions. We use a space-for-time approach to evaluate this hypothesis in the context of alpine time-of-snowmelt gradients. Principal response curves, a multivariate repeated-measurement analysis technique, are used to analyse for compositional differences in local ridge-to-snowbed gradients among 100 m altitudinal bands from 1,140 to 1,550 m a.s.l., corresponding to a temperature gradient of 2.5 degrees C (local lapse rate is 0.6 degrees C). The interaction between time-of-snowmelt and altitude is strongly significant statistically, indicating that the altitudinal gradient cannot be explained simply by the physiological responses of the species, but that there are also changes in the outcome of competitive interactions. At higher altitudes, there is a decrease in the time-of-snowmelt ranges of species which have intermediate times-of-snowmelt optima, whereas snowbed (chinophilous) species have wider time-of-snowmelt ranges. As snowbed species can survive, grow and reproduce at very early snow-free sites at high altitudes, the most likely explanation for their absence from all but the latest time-of-snowmelt habitats at lower altitudes is competitive exclusion by more vigorous lee-side species. This suggests that with future climate change snowbed species will experience, in addition to habitat fragmentation and reduced size of habitats due to increased temperature and snowmelt, an indirect effect due to competitive exclusion from late-snowmelt sites by species that have their optima outside snowbeds. PMID:15021981

  5. Does therapist’s attitude affect clinical outcome of lumbar facet joint injections?

    PubMed Central

    Middendorp, Marcus; Kollias, Konstantinos; Ackermann, Hanns; Splettstößer, Annina; Vogl, Thomas J; Khan, M Fawad; Maataoui, Adel

    2016-01-01

    AIM: To investigate if the clinical outcome of intra-articular lumbar facet joint injections is affected by the therapist’s attitude. METHODS: A total of 40 patients with facet joint-associated chronic low back pain were randomly divided into two groups. All patients received computed tomography-guided, monosegmental intra-articular facet joint injections. Following the therapeutic procedure, the patients of the experimental group (EG) held a conversation with the radiologist in a comfortable atmosphere. During the dialog, the patients were encouraged to ask questions and were shown four images. The patients of the control group (CG) left the clinic without any further contact with the radiologist. Outcome was assessed using a pain-based Verbal Numeric Scale at baseline, at 1 wk and at 1, 3, and 6 mo after first treatment. RESULTS: The patient demographics showed no differences between the groups. The patients of the EG received 57 interventional procedures in total, while the patients of the CG received 70 interventional procedures. In both groups, the pain scores decreased significantly over the entire observation period. Compared to the CG, the EG showed a statistically significant reduction of pain at 1 wk and 1 mo post-treatment, while at 3 and 6 mo after treatment, there were no significant differences between both groups. CONCLUSION: Our results show a significant effect on pain relief during the early post-interventional period in the EG as compared to the CG. The basic principle behind the higher efficacy might be the phenomenon of hetero-suggestion. PMID:27358691

  6. Does Family Structure Affect Children's Educational Outcomes? NBER Working Paper Series.

    ERIC Educational Resources Information Center

    Pollak, Robert A.; Ginther, Donna K.

    This paper examines correlations between children's educational outcomes and family structure. Although popular discussions focus on distinctions between two-parent and single-parent families, earlier research shows that outcomes for stepchildren are similar to outcomes for children in single-parent families, and earlier researchers suggested that…

  7. Cardiovascular and Affective Outcomes of Active Gaming: Using the Nintendo Wii as a Cardiovascular Training Tool

    PubMed Central

    Naugle, Keith E.; Naugle, Kelly M.; Wikstrom, Erik A.

    2014-01-01

    Naugle, KE, Naugle, KM, and Wikstrom, EA. Cardiovascular and affective outcomes of active gaming: Using the Nintendo Wii as a cardiovascular training tool. J Strength Cond Res 28(2): 443–451, 2014–Active-video gaming is purported to produce similar cardiovascular responses as aerobic fitness activities. This study compared the emotional and cardiovascular effects of Wii games with those of traditional exercise in college-aged adults with different exercise backgrounds. Specifically, the percentage of heart rate reserve, rate of perceived exertion (RPE), level of enjoyment, and Positive and Negative Affect Schedule scores were compared between subjects who reported exercising frequently at high intensities (high-intensity exerciser group: age = 20.18 years [0.87]; Height = 165.23 cm [9.97]; Mass = 62.37 kg [11.61]), N = 11 and those who exercise more often at lower intensities (low-intensity exercisers group: age = 20.72 years [1.19]; Height = 164.39 cm [8.05]; Mass = 68.04 kg [10.71]), N = 11. The subjects completed six 20-minute exercises sessions: treadmill walking, stationary cycling, and Wii's Tennis, Boxing, Cycling, and Step. The low-intensity exerciser group achieved a greater percentage of heart rate reserve (a) during traditional exercise compared with that during Wii boxing, (b) playing Wii boxing compared with that for Wii tennis, and (c) playing Wii boxing compared with that when the high-intensity exercisers group played any Wii games (p < 0.05). The RPE was greater for boxing and cycling compared with that for tennis and step (p < 0.05). Ratings of enjoyment and the increase in positive emotion were greater for boxing and for tennis compared with those for traditional exercises (p < 0.05). Results suggest that Wii boxing shows the greatest potential as a cardiovascular fitness tool among the Wii games, particularly for individuals who typically exercise at lower intensities. PMID:23660574

  8. Variable Gene Dispersal Conditions and Spatial Deforestation Patterns Can Interact to Affect Tropical Tree Conservation Outcomes

    PubMed Central

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H.

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with ‘Near’ distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  9. Do different reperfusion methods affect the outcomes of stroke induced by MCAO in adult rats?

    PubMed

    Zuo, Xia-Lin; Deng, Hou-Liang; Wu, Ping; Xu, En

    2016-09-01

    There are two patterns of ischemia/reperfusion (I/R) models used in rat middle cerebral artery occlusion (MCAO) I/R models, which differ in the use of unilateral or bilateral carotid artery reperfusion. The primary difference between the two patterns of I/R models is the complexity of the surgery procedure. However, researchers in this field have no idea whether there are any differences in outcomes of these two methods. In this study, we investigated the effects of the two methods on neurological deficits, infarct volume, blood-brain barrier (BBB) integrity and brain derived neurotrophic factor (BDNF) expression. Through evaluating the current way of bilateral common carotid artery reperfusion, we tried to find whether it could be replaced by an easier way. We found that there were no statistical significant differences between the different methods in infarct volume, neurological deficits, BBB integrity, and the level of BDNF (P > 0.05). These data demonstrated that different methods did not affect the neurological deficits, infarct volume, BBB integrity, and the BDNF protein level, which provides reference when we use an experimental stroke. These results suggest that the two methods have similar capability for inducing cerebral I/R injury and can be interchanged. PMID:26268737

  10. Perceptions of Intragroup Rejection and Coping Strategies: Malleable Factors Affecting Hispanic Adolescents’ Emotional and Academic Outcomes

    PubMed Central

    Warren, Michael T.; Crano, William D.; Unger, Jennifer B.

    2015-01-01

    Understanding psychosocial factors that affect the academic achievement of Hispanic adolescents remains a nationwide priority in the United States. Extending previous studies of the stressful effects of perceived discrimination, this year-long longitudinal study examined the correlates of perceived ethnic in-group rejection, coping strategies and fatalistic beliefs, on depressive symptoms, grades, and college aspirations of 2,214 Hispanic adolescents (54 % female) in Southern California. Based on the transactional model of stress and coping and on self-perception theory, structural equation models revealed that high perceived intragroup rejection (10th grade) and low levels of active coping (11th grade) were associated with depressive symptoms in 11th grade. Also, depressive symptoms partially mediated the link between intragroup rejection and both academic outcomes. Avoidant coping strategies (e.g., watching TV) also predicted depressive symptoms and were positively related to fatalism. In addition, fatalism was negatively related to grades and aspiration to attend college. The findings suggest the need to help adolescents find adequate outlets for communication and to create awareness about the potential effects of intragroup rejection. PMID:24234042

  11. Outcomes and Risk Factors Affecting Mortality in Patients Who Underwent Colorectal Emergency Surgery

    PubMed Central

    Oh, Nam Ho

    2016-01-01

    Purpose Emergency colorectal surgery has a high risk of mortality and morbidity because of incomplete bowel preparation, bacterial proliferation, and contamination. In this study, we investigated the outcomes and the risk factors affecting mortality in patients who had undergone emergency surgery for the treatment of various colorectal diseases. Methods This study is a retrospective analysis of prospectively collected data to survey the clinical results for patients who had undergone emergency colorectal surgery from January 2014 to December 2014. We analyzed various clinicopathologic factors, which were divided into 3 categories: preoperative, intraoperative, and postoperative. Results A total of 50 patients had undergone emergency colorectal surgery during the time period covered by this study. Among them, 10 patients (20%) died during the postoperative period. A simple linear regression analysis showed that the risk factors for mortality were old age, preoperative hypotension, and a high American Society of Anesthesiologist (ASA) score. Moreover, a multiple linear regression analysis showed a high ASA score and preoperative hypotension to be independent risk factors. Conclusion In this study, emergency colorectal surgery showed a relatively high mortality rate. Furthermore, the independent risk factors for mortality were preoperative hypotension and high ASA score; thus, patients with these characteristics need to be evaluated more carefully and receive better care if the mortality rate is to be reduced.

  12. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  13. A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Cardiac surgery is one of the most commonly performed surgical procedures worldwide with >700,000 surgeries in 2006 in the US alone. Cardiac surgery results in a considerable exposure to physical and emotional stress; stress-related disorders such as depression or post-traumatic stress disorder are the most common adverse outcomes of cardiac surgery, seen in up to 20% of patients. Using information from a genome-wide association study to characterize genetic effects on emotional memory, we recently identified a single nucleotide polymorphism of the glucocorticoid receptor gene (the Bcll single nucleotide polymorphism) as a significant genetic risk factor for traumatic memories from cardiac surgery and symptoms of post-traumaticstress disorder. The Bcll high-risk genotype (Bcll GG) has a prevalence of 16.6% in patients undergoing cardiac surgery and is associated with increased glucocorticoid receptor signaling under stress. Concomitant animal experiments have confirmed an essential role of glucocorticoid receptor activation for traumatic memory formation during stressful experiences. Early cognitive behavioral intervention has been shown to prevent stress-related disorders after heart surgery. Methods/Design The proposed study protocol is based on the above mentioned earlier findings from animal experiments and preclinical studies in volunteers. Patients (n = 872) will be genotyped for the Bcll single nucleotide polymorphism before surgery, which should result in 120 homozygous high-risk carriers of the Bcll GG allele and 240 randomly selected low-risk heterozygous or non-carriers of the single nucleotide polymorphism. All patients will then undergo randomization to either cognitive behavioral intervention or a control intervention consisting of non-specific general information about the role of stress in heart disease. The primary efficacy endpoint will be post-traumatic stress levels at one year after surgery as determined by a standardized

  14. Oocyte donation in Turner's syndrome: an analysis of the factors affecting the outcome.

    PubMed

    Khastgir, G; Abdalla, H; Thomas, A; Korea, L; Latarche, L; Studd, J

    1997-02-01

    A total of 29 women with Turner's syndrome (19 monosomy and 10 mosaic) had 68 cycles of oocyte donation that included 29 cycles of initial attempt and 39 cycles of subsequent attempts. Oral oestradiol valerate was used either in a variable dose (42 cycles) or in a constant dose (26 cycles) regimen for the endometrial preparation which was monitored by pelvic ultrasonography. The embryos/zygotes were transferred either fresh (50 cycles) or after cryopreservation (18 cycles) into the Fallopian tube (41 cycles) and uterine cavity (27 cycles) as appropriate. There were 28 clinical pregnancies including two sets of triplets resulting in a pregnancy rate of 41.2% per treatment cycle and an implantation rate of 17.1% per embryo transferred. The recipient's age, chromosomal constitution or associated uterine or tubal anomaly had no influence on the treatment outcome. The implantation and pregnancy rates were higher in the subsequent than initial cycles (22.6 versus 9.99%, P < 0.05; 51.3 versus 27.6%, P < 0.05). An endometrial thickness of > or = 6.5 mm was an important predictor of pregnancy but the endometrial echo pattern failed to predict the outcome. Although the total dose of oestradiol before embryo transfer was higher in the pregnant cycles than the non-pregnant ones and its gradation (< 50 mg, 50-100 mg, < 100 mg) influenced the implantation (3.4, 17.5, 26.3% respectively, P < 0.05) and pregnancy rates (10, 42.2, 61.5% respectively, P < 0.05), the effect was indirect by altering the endometrial thickness. The number of oocytes fertilized affected the pregnancy rate irrespective of the number of embryos transferred. The implantation and pregnancy rates were higher when fresh rather than frozen-thawed embryos were transferred (20.3 versus 8.2%, P < 0.05; 48 versus 22.2%, P < 0.05) but the route of transfer was of no statistical importance. The overall miscarriage rate was higher (50%), and was related to the presence of hypoplastic or bicornuate uterus and to a low

  15. Virus and Host Factors Affecting the Clinical Outcome of Bluetongue Virus Infection

    PubMed Central

    Caporale, Marco; Di Gialleonorado, Luigina; Janowicz, Anna; Wilkie, Gavin; Shaw, Andrew; Savini, Giovanni; Van Rijn, Piet A.; Mertens, Peter; Di Ventura, Mauro

    2014-01-01

    ABSTRACT Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence. IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected

  16. Personality and serotonin transporter genotype interact with social context to affect immunity and viral set-point in simian immunodeficiency virus disease.

    PubMed

    Capitanio, John P; Abel, Kristina; Mendoza, Sally P; Blozis, Shelley A; McChesney, Michael B; Cole, Steve W; Mason, William A

    2008-07-01

    From the beginning of the AIDS epidemic, stress has been a suspected contributor to the wide variation seen in disease progression, and some evidence supports this idea. Not all individuals respond to a stressor in the same way, however, and little is known about the biological mechanisms by which variations in individuals' responses to their environment affect disease-relevant immunologic processes. Using the simian immunodeficiency virus/rhesus macaque model of AIDS, we explored how personality (Sociability) and genotype (serotonin transporter promoter) independently interact with social context (Stable or Unstable social conditions) to influence behavioral expression, plasma cortisol concentrations, SIV-specific IgG, and expression of genes associated with Type I interferon early in infection. SIV viral RNA set-point was strongly and negatively correlated with survival as expected. Set-point was also associated with expression of interferon-stimulated genes, with CXCR3 expression, and with SIV-specific IgG titers. Poorer immune responses, in turn, were associated with display of sustained aggression and submission. Personality and genotype acted independently as well as in interaction with social condition to affect behavioral responses. Together, the data support an "interactionist" perspective [Eysenck, H.J., 1991. Personality, stress and disease: an interactionist perspective. Psychol. Inquiry 2, 221-232] on disease. Given that an important goal of HIV treatment is to maintain viral set-point as low as possible, our data suggest that supplementing anti-retroviral therapy with behavioral or pharmacologic modulation of other aspects of an organism's functioning might prolong survival, particularly among individuals living under conditions of threat or uncertainty. PMID:17719201

  17. Factors affecting the outcome of maternity care. II. Neonatal outcomes and resources beyond the hospital of birth.

    PubMed Central

    Mugford, M; Szczepura, A; Lodwick, A; Stilwell, J

    1988-01-01

    Analysis of data about perinatal mortality and indicators of resources at maternity hospitals in the West Midlands region between 1977 and 1983 showed that paediatric staff ratios were inversely related to in-house mortality rates. In this paper, the outcomes for and resources used by transferred babies are added to those of the hospital of birth for three of the study years--1978, 1980, and 1982. Patterns of transfer differ between units and over time in the region, and a regional neonatal intensive care policy was introduced in 1980. Analysis of the new variables showed that in 1978 paediatric staffing was significantly inversely related to neonatal mortality. In later years, neonatal mortality of births at maternity units is explained entirely by the proportion of low or very low weight births. PMID:3221167

  18. The effect of playing a science center-based mobile game: Affective outcomes and gender differences

    NASA Astrophysics Data System (ADS)

    Atwood-Blaine, Dana

    Situated in a hands-on science center, The Great STEM Caper was a collaborative mobile game built on the ARIS platform that was designed to engage 5th-9th grade players in NGSS science and engineering practices while they interacted with various exhibits. Same gender partners sharing one iPad would search for QR codes placed at specific exhibits; scanning a code within the game would launch a challenge for that exhibit. The primary hypothesis was that in- game victories would be equivalent to "mastery experiences" as described by Bandura (1997) and would result in increased science self-efficacy. Gender differences in gameplay behaviors and perceptions were also studied. The study included two groups, one that played the game during their visit and one that explored the science center in the traditional way. The Motivation to Learn Science Questionnaire was administered to participants in both groups both before and after their visit to the science center. Participants wore head-mounted GoPro cameras to record their interactions within the physical and social environment. No differences in affective outcomes were found between the game and comparison groups or between boys and girls in the game group. The MLSQ was unable to measure any significant change in science self-efficacy, interest and enjoyment of science, or overall motivation to learn science in either group. However, girls outperformed boys on every measure of game achievement. Lazzaro's (2004) four types of fun were found to be a good fit for describing the gender differences in game perceptions and behaviors. Girls tended to enjoy hard fun and collaborative people fun while boys enjoyed easy fun and competitive people fun. While boys associated game achievement with enjoyment and victory, girls perceived their game achievement as difficult, rather than enjoyable or victorious.

  19. Fighting while parasitized: can nematode infections affect the outcome of staged combat in beetles?

    PubMed

    Vasquez, David; Willoughby, Anna; Davis, Andrew K

    2015-01-01

    The effects of non-lethal parasites may be felt most strongly when hosts engage in intense, energy-demanding behaviors. One such behavior is fighting with conspecifics, which is common among territorial animals, including many beetle species. We examined the effects of parasites on the fighting ability of a saproxylic beetle, the horned passalus (Odontotaenius disjunctus, Family: Passalidae), which is host to a non-lethal nematode, Chondronema passali. We pitted pairs of randomly-chosen (but equally-weighted) beetles against each other in a small arena and determined the winner and aggression level of fights. Then we examined beetles for the presence, and severity of nematode infections. There was a non-significant tendency (p = 0.065) for the frequency of wins, losses and draws to differ between beetles with and without C. passali; non-parasitized individuals (n = 104) won 47% of their fights while those with the parasite (n = 88) won 34%, a 13% difference in wins. The number of nematodes in a beetle affected the outcome of fights between infected and uninfected individuals in an unexpected fashion: fighting ability was lowest in beetles with the lowest (p = 0.033), not highest (p = 0.266), nematode burdens. Within-fight aggression was highest when both beetles were uninfected and lowest when both were infected (p = 0.034). Collectively, these results suggest the nematode parasite, C. passali, is associated with a modest reduction in fighting ability in horned passalus beetles, consistent with the idea that parasitized beetles have lower energy available for fighting. This study adds to a small but growing body of evidence showing how parasites negatively influence fighting behavior in animals. PMID:25830367

  20. Obstructive sleep apnea affects the clinical outcomes of patients undergoing percutaneous coronary intervention

    PubMed Central

    Zhang, Jun-jie; Gao, Xiao-fei; Ge, Zhen; Jiang, Xiao-Min; Xiao, Ping-xi; Tian, Nai-liang; Kan, Jing; Lee, Chi-Hang; Chen, Shao-Liang

    2016-01-01

    Background There is a paucity of evidence regarding the association between obstructive sleep apnea (OSA) and patients undergoing percutaneous coronary intervention (PCI) for coronary artery disease. We sought to investigate whether OSA affects the clinical outcomes of patients undergoing PCI. Patients and methods All enrolled individuals treated with PCI were evaluated for OSA by polysomnography. The primary end point was defined as major adverse cardiac events (MACEs) at 2 years, including cardiac death, myocardial infarction (MI), and/or target vessel revascularization. Results A total of 340 consecutive patients undergoing PCI were assigned to the OSA (n=152, apnea–hypopnea index ≥15) and non-OSA (n=188, apnea–hypopnea index <15) groups. The incidence of OSA in patients with coronary artery disease undergoing PCI was 44.7%. Patients in the OSA group had more three-vessel disease (34.9%), increased number of total implanted stents (3.3±2.0), and longer total stent length (83.8±53.1 mm) when compared to the non-OSA group (23.4%, P=0.020; 2.8±1.9, P=0.007; 68.7±48.4, P=0.010). After a median follow-up of 2 years, the incidence of MACEs was significantly higher in patients with OSA (25.0% vs 16.0%, P=0.038), mainly driven by the increased periprocedural MI (19.2% vs 11.2%, P=0.038) in the OSA group. By Cox regression multivariable analysis, the independent predictor of MACEs was OSA (hazard ratio: 1.962, 95% confidence interval: 1.036–3.717, P=0.039). Conclusion There was a high prevalence of moderate-to-severe OSA in patients undergoing PCI, and OSA was associated with significantly increased MACE rate, mainly due to the increase in periprocedural MI rate. PMID:27284240

  1. Linking Affective Commitment, Career Self-Efficacy, and Outcome Expectations: A Test of Social Cognitive Career Theory

    ERIC Educational Resources Information Center

    Conklin, Amanda M.; Dahling, Jason J.; Garcia, Pablo A.

    2013-01-01

    The authors tested a model based on the satisfaction model of social cognitive career theory (SCCT) that links college students' affective commitment to their major (the emotional identification that students feel toward their area of study) with career decision self-efficacy (CDSE) and career outcome expectations. Results indicate that CDSE…

  2. Cognitive and Socio-Affective Outcomes of Project-Based Learning: Perceptions of Greek Second Chance School Students

    ERIC Educational Resources Information Center

    Koutrouba, Konstantina; Karageorgou, Elissavet

    2013-01-01

    The present questionnaire-based study was conducted in 2010 in order to examine 677 Greek Second Chance School (SCS) students' perceptions about the cognitive and socio-affective outcomes of project-based learning. Data elaboration, statistical and factor analysis showed that the participants found that project-based learning offered a second…

  3. Culture Matters. Factors Affecting the Outcomes of Participation in Vocational Education and Training by Australian Indigenous Peoples.

    ERIC Educational Resources Information Center

    McIntyre, John; Ardler, William; Morley-Warner, Terri; Solomon, Nicky; Spindler, Laraine

    The factors affecting the outcomes of indigenous Australians' participation in vocational education and training (VET) were examined in a study in which 7 Aboriginal researchers in 5 Australian states and territories interviewed 70 indigenous Australians enrolled in VET and 48 coordinators and teachers in technical and further education (TAFE)…

  4. NS5A sequence heterogeneity of hepatitis C virus genotype 4a predicts clinical outcome of pegylated-interferon-ribavirin therapy in Egyptian patients.

    PubMed

    El-Shamy, Ahmed; Shoji, Ikuo; El-Akel, Wafaa; Bilasy, Shymaa E; Deng, Lin; El-Raziky, Maissa; Jiang, Da-peng; Esmat, Gamal; Hotta, Hak

    2012-12-01

    Hepatitis C virus genotype 4 (HCV-4) is the cause of approximately 20% of the 180 million cases of chronic hepatitis C in the world. HCV-4 infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. Viral genetic polymorphisms, especially within core and NS5A regions, have been implicated in influencing the response to pegylated-interferon and ribavirin (PEG-IFN/RBV) combination therapy in HCV-1 infection. However, this has not been confirmed in HCV-4 infection. Here, we investigated the impact of heterogeneity of NS5A and core proteins of HCV-4, mostly subtype HCV-4a, on the clinical outcomes of 43 Egyptian patients treated with PEG-IFN/RBV. Sliding window analysis over the carboxy terminus of NS5A protein identified the IFN/RBV resistance-determining region (IRRDR) as the most prominent region associated with sustained virological response (SVR). Indeed, 21 (84%) of 25 patients with SVR, but only 5 (28%) of 18 patients with non-SVR, were infected with HCV having IRRDR with 4 or more mutations (IRRDR ≥ 4) (P = 0.0004). Multivariate analysis identified IRRDR ≥ 4 as an independent SVR predictor. The positive predictive value of IRRDR ≥ 4 for SVR was 81% (21/26; P = 0.002), while its negative predictive value for non-SVR was 76% (13/17; P = 0.02). On the other hand, there was no significant correlation between core protein polymorphisms, either at residue 70 or at residue 91, and treatment outcome. In conclusion, the present results demonstrate for the first time that IRRDR ≥ 4, a viral genetic heterogeneity, would be a useful predictive marker for SVR in HCV-4 infection when treated with PEG-IFN/RBV. PMID:22993188

  5. How Group Experience Affects Outcomes from NOLS Programs: A Means-End Investigation

    ERIC Educational Resources Information Center

    Goldenberg, Marni; Soule, Katherine

    2011-01-01

    Using means-end theory, this study evaluates how being part of a group influences outcomes of National Outdoor Leadership School (NOLS) participants. This study examines outcomes from NOLS courses during the summer of 2006 in the Wind River Mountain Range of Wyoming. Immediately following 2006 course completion, a convenience sample of 345…

  6. Environmental Conditions Affect Botrytis cinerea Infection of Mature Grape Berries More Than the Strain or Transposon Genotype.

    PubMed

    Ciliberti, Nicola; Fermaud, Marc; Roudet, Jean; Rossi, Vittorio

    2015-08-01

    Effects of environment, Botrytis cinerea strain, and their interaction on the infection of mature grape berries were investigated. The combined effect of temperature (T) of 15, 20, 25, and 30°C and relative humidity (RH) of 65, 80, 90, and 100% was studied by inoculating berries with mycelium plugs. Regardless of the T, no disease occurred at 65% RH, and both disease incidence and severity increased with increasing RH. The combined effect of T (5 to 30°C) and wetness duration (WD) of 3, 6, 12, 24, and 36 h was studied by inoculating berries with conidia. At WD of 36 h, disease incidence was approximately 75% of affected berries at 20 or 25°C, 50% at 15°C, and 30 to 20% at 30 and 10°C; no infection occurred at 5°C. Under favorable conditions (100% RH or 36 h of WD) and unfavorable conditions (65% RH or 3 h of WD), berry wounding did not significantly affect disease incidence; under moderately favorable conditions (80% RH or 6 to 12 h of WD), disease incidence was approximately 1.5 to 5 times higher in wounded than in intact berries. Our data collectively showed that (i) T and RH or WD were more important than strain for mature berry infection by either mycelium or conidia and (ii) the effect of the environment on the different strains was similar. Two equations were developed describing the combined effect of T and RH, or T and WD, on disease incidence following inoculation by mycelium (R2=0.99) or conidia (R2=0.96), respectively. These equations may be useful in the development of models used to predict and control Botrytis bunch rot during berry ripening. PMID:26218433

  7. Does Alcohol Consumption during Multidrug-resistant Tuberculosis Treatment Affect Outcome?

    PubMed Central

    Duraisamy, Karthickeyan; Mrithyunjayan, Sunilkumar; Ghosh, Smita; Nair, Sreenivas Achuthan; Balakrishnan, Shibu; Subramoniapillai, Jayasankar; Oeltmann, John E.; Moonan, Patrick K.; Kumar, Ajay M. V.

    2015-01-01

    Rationale India reports the largest number of multidrug-resistant tuberculosis cases in the world; yet, no longitudinal study has assessed factors related to treatment outcomes under programmatic conditions in the public sector. Objectives To describe demographic, clinical, and risk characteristics associated with treatment outcomes for all patients with multidrug-resistant tuberculosis registered in the Revised National Tuberculosis Control Programme, Kerala State, India from January 1, 2009 to June 30, 2010. Methods Cox regression methods were used to calculate adjusted hazard ratios with 95% confidence intervals (CIs) to assess factors associated with an unsuccessful treatment outcome. Measurements and Main Results Of 179 patients with multidrug-resistant tuberculosis registered, 112 (63%) had successful treatment outcomes (77 bacteriologically cured, 35 treatment completed) and 67 (37%) had unsuccessful treatment outcomes (30 died, 26 defaulted, 9 failed treatment, 1 stopped treatment because of drug-related adverse events, and 1 developed extensively drug-resistant tuberculosis). The hazard for unsuccessful outcome was significantly higher among patients who consumed alcohol during treatment (adjusted hazard ratio, 4.3; 95% CI, 1.1–17.6) than those who did not. Persons who consumed alcohol during treatment, on average, missed 18 more intensive-phase doses (95% CI, 13–22) than those who did not. Although many patients had diabetes (33%), were ever smokers (39%), or had low body mass index (47%), these factors were not associated with outcome. Conclusion Overall treatment success was greater than global and national averages; however, outcomes among patients consuming alcohol remained poor. Integration of care for multidrug-resistant tuberculosis and alcoholism should be considered to improve treatment adherence and outcomes. PMID:24735096

  8. Chronic urinary retention in men: how we define it, and how does it affect treatment outcome.

    PubMed

    Negro, Carlo L A; Muir, Gordon H

    2012-12-01

    What's known on the subject? and What does the study add? Chronic urinary retention (CUR) is a poorly defined entity, as the key element of definition, significant postvoid residual urine volume (PVR), has not a worldwide and moreover evidenced-based definition. There is no agreement on which is the threshold value to define a significant PVR and different society produced guidelines with different thresholds ranging from 300 mL to 1000 mL. Diagnosis is difficult, and management has not been defined yet. There is a lack of studies on the best management of these patients, as this group of patients has always been considered at high risk of failure. Only one study compares conservative with the surgical management but it is not a randomised controlled trail. This review offers a systematic appraisal of the most recent publications on CUR. It indicates the absence of a real worldwide agreed definition, as the two keys element of it are not satisfactorily defined yet: significant PVR, is suffering from a lack of evidenced-based definition, and percussable or palpable bladder is a very nebulous concept as it is not a criteria of certainty as different individual variables affect it. This has an important effect on management which is not structured. Most of the trials involving benign prostatic hyperplasia treatments (either medical or surgical) tend to exclude this group of patients, which is a clinically important group, comprising up to a quarter of men undergoing TURP in the UK. Urinary retention describes a bladder that does not empty completely or does not empty at all. Historically, urinary retention has been classified as either acute or chronic the latter is generally classified as high pressure or low pressure according to the bladder filling pressure on urodynamic. A MEDLINE® search for articles written in English and published before January 2010 was done using a list of terms related to urinary retention: 'urinary retention', 'chronic urinary retention

  9. Quantitative trait loci affecting survival and fertility-related traits in Caenorhabditis elegans show genotype-environment interactions, pleiotropy and epistasis.

    PubMed Central

    Shook, D R; Johnson, T E

    1999-01-01

    We have identified, using composite interval mapping, quantitative trait loci (QTL) affecting a variety of life history traits (LHTs) in the nematode Caenorhabditis elegans. Using recombinant inbred strains assayed on the surface of agar plates, we found QTL for survival, early fertility, age of onset of sexual maturity, and population growth rate. There was no overall correlation between survival on solid media and previous measures of survival in liquid media. Of the four survival QTL found in these two environments, two have genotype-environment interactions (GEIs). Epistatic interactions between markers were detected for four traits. A multiple regression approach was used to determine which single markers and epistatic interactions best explained the phenotypic variance for each trait. The amount of phenotypic variance accounted for by genetic effects ranged from 13% (for internal hatching) to 46% (for population growth). Epistatic effects accounted for 9-11% of the phenotypic variance for three traits. Two regions containing QTL that affected more than one fertility-related trait were found. This study serves as an example of the power of QTL mapping for dissecting the genetic architecture of a suite of LHTs and indicates the potential importance of environment and GEIs in the evolution of this architecture. PMID:10545455

  10. BAY61-3606 Affects the Viability of Colon Cancer Cells in a Genotype-Directed Manner

    PubMed Central

    Lau, Ken S.; Zhang, Tinghu; Kendall, Krystle R.; Lauffenburger, Douglas; Gray, Nathanael S.; Haigis, Kevin M.

    2012-01-01

    Background K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value. Methods We searched for small molecule kinase inhibitors that preferentially affect the growth of colorectal cancer cells expressing mutant K-RAS. The mechanism of action of one inhibitor was explored using chemical and genetic approaches. Results We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF. As a result of MAP4K2 inhibition, wild-type cells became sensitive to AZ-628, a RAF inhibitor, when also treated with BAY61-3606. Conclusions These studies indicate that BAY61-3606 exerts distinct biological activities in different genetic contexts. PMID:22815993

  11. Foreign language affects the contribution of intentions and outcomes to moral judgment.

    PubMed

    Geipel, Janet; Hadjichristidis, Constantinos; Surian, Luca

    2016-09-01

    We examine whether the use of a foreign language, as opposed to the native language, influences the relative weight intentions versus outcomes carry in moral evaluations. In Study 1, participants were presented with actions that had positive outcomes but were motivated by dubious intentions, while in Study 2 with actions that had negative outcomes but were motivated by positive intentions. Participants received the materials either in their native or a foreign language. Foreign language prompted more positive moral evaluations in Study 1 and less positive evaluations in Study 2. These results show that foreign language reduces the relative weight placed on intentions versus outcomes. We discuss several theoretical accounts that are consistent with the results such as that foreign language attenuates emotions (triggered by intentions) or it depletes cognitive resources. PMID:27232522

  12. Does family group decision making affect child welfare outcomes? Findings from a randomized control study.

    PubMed

    Berzin, Stephanie Cosner; Cohen, Ed; Thomas, Karen; Dawson, William C

    2008-01-01

    This article describes the evaluation of two family group decision-making programs (FGDM; Fresno n = 60; Riverside n = 50) administered under the California Title IV-E Waiver Demonstration Project. This is the only evaluation using random assignment to examine FGDM. Overall, results did not indicate more positive outcomes for children receiving the intervention, but did indicate that children were not worse than those receiving traditional services; outcomes examined were related to child safety, placement stability, and permanence. PMID:19391466

  13. Yield and quality grade outcomes as affected by molecular breeding values for commercial beef cattle.

    PubMed

    Thompson, N M; DeVuyst, E A; Brorsen, B W; Lusk, J L

    2015-05-01

    Although genetic tests for many economically important beef cattle traits are commercially available, additional information is needed to help the industry better understand how the results from these tests translate into phenotypic outcomes. This information has important implications for marker-assisted management. The objective of this research was to determine the relationship between molecular breeding values (MBV) characterizing yield grade and marbling and distributions of phenotypic outcomes for yield grade and quality grade. Using data collected from commercially-fed cattle, mixed-model regression equations were estimated for yield grade and quality grade outcomes for both the full sample of commercial cattle (n= 8,995) and a subsample of black-hided steers (n = 4,790). Significant yield grade (P < 0.01) and marbling (P < 0.01) MBV effects were found. However, the yield grade MBV held up better at predicting phenotypic outcomes than the marbling MBV. Estimated conditional probability mass functions of yield and quality grade outcomes for the general population and black-hided steers were similar. Since distributions for black-hided steers were expected to be more applicable from a management perspective, we focused our analysis on these animals. For example, black-hided steers with "low" genetic potential for yield grade and marbling had about a 29% chance of achieving the base price or better on a price grid (yield grade 3 or lower and quality grade Low Choice or better). Increasing genetic potential for marbling increased the likelihood of achieving this same outcome. However, increasing genetic potential for yield grade was unlikely to increase overall carcass quality given its large deleterious effect on quality grade outcomes. Instead, simultaneous improvements in genetic potential for yield grade and marbling offered much more reliable improvements in overall carcass quality. For example, an animal with "moderate" genetic potential for both yield

  14. Proteome Differences between Hepatitis B Virus Genotype-B- and Genotype-C-Induced Hepatocellular Carcinoma Revealed by iTRAQ-Based Quantitative Proteomics.

    PubMed

    Wei, Dahai; Zeng, Yongyi; Xing, Xiaohua; Liu, Hongzhi; Lin, Minjie; Han, Xiao; Liu, Xiaolong; Liu, Jingfeng

    2016-02-01

    Hepatitis B virus (HBV) is the main cause of hepatocellular carcinoma (HCC) in southeast Asia where HBV genotype B and genotype C are the most prevalent. Viral genotypes have been reported to significantly affect the clinical outcomes of HCC. However, the underlying molecular differences among different genotypes of HBV virus infected HCC have not been revealed. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify the proteome differences between the HBV genotypes B- and C-induced HCC. In brief, a total of 83 proteins in the surrounding noncancerous tissues and 136 proteins in the cancerous tissues between HBV genotype-B- and genotype-C-induced HCC were identified, respectively. This information revealed that there might be different molecular mechanisms of the tumorigenesis and development of HBV genotypes B- and C-induced HCC. Furthermore, our results indicate that the two proteins ARFIP2 and ANXA1 might be potential biomarkers for distinguishing the HBV genotypes B- and C-induced HCC. Thus, the quantitative proteomic analysis revealed molecular differences between the HBV genotypes B- and C-induced HCC, and might provide fundamental information for further deep study. PMID:26709725

  15. Do Neighbours Affect Teenage Outcomes? Evidence from Neighbourhood Changes in England. CEE DP 122

    ERIC Educational Resources Information Center

    Gibbons, Stephen; Silva, Olmo; Weinhardt, Felix

    2010-01-01

    There are large disparities between the achievements, behaviour and aspirations of children growing up in different neighbourhoods. This has contributed to the view that neighbourhoods can determine individuals' outcomes. Notably, in the long run these effects could lead to larger social inequality and reduce social mobility, which is why they…

  16. The Mediating Role of Affective Commitment in the Relation of the Feedback Environment to Work Outcomes

    ERIC Educational Resources Information Center

    Norris-Watts, Christina; Levy, Paul E.

    2004-01-01

    The Feedback Environment, as opposed to the formal performance appraisal process, is comprised of the daily interactions between members of an organization (Steelman, Levy, & Snell, in press). Relations between the feedback environment and work outcome variables such as Organizational Citizenship Behavior (OCB) were examined through the mediating…

  17. Neighborhoods and Youth: How Neighborhood Demographics and Social Processes Affect Youth Outcomes

    ERIC Educational Resources Information Center

    Swisher, Ray

    2008-01-01

    Researchers over the past two decades have increasingly recognized the importance of neighborhood contexts for youth development. For example, living in a disadvantaged neighborhood has been associated with a wide range of negative outcomes throughout the early years of the life course. However, neighborhoods likely have very different effects,…

  18. Organizational and individual factors affecting consumer outcomes of care in mental health services.

    PubMed

    Morris, Anne; Bloom, Joan R; Kang, Soo

    2007-05-01

    The impact of organizational and individual factors on outcomes of care were assessed for 424 adult consumers with chronic mental illness who were receiving services from one of 14 Community Mental Health Organizations (CMHOs) in Colorado over a 30-month period, as part of a larger statewide evaluation of the impact of Medicaid capitation on mental health services. Data on organizational culture and climate were aggregated from surveys of staff and administrators conducted within CMHOs over a two-year period corresponding to the collection of consumer outcome and service utilization data. Growth curve analyses were conducted on consumer perceptions of physical and mental health, and on quality of life (QOL). Analyses indicated a significant cross-level effect of organizational culture and climate on improvements in consumer perceptions of physical and mental health, but not on a "quasi-objective" index of QOL. Individual characteristics, such as age, diagnosis, gender, and ethnicity, were significant predictors of outcomes. Being older, female, an ethnic minority, and having a diagnosis of schizophrenia all predicted poorer outcomes among consumers. These findings are discussed in terms of their implications for policy and future research. PMID:17096194

  19. Can a future choice affect a past measurement’s outcome?

    SciTech Connect

    Aharonov, Yakir; Cohen, Eliahu; Elitzur, Avshalom C.

    2015-04-15

    An EPR experiment is studied where each particle within the entangled pair undergoes a few weak measurements (WMs) along some pre-set spin orientations, with the outcomes individually recorded. Then the particle undergoes one strong measurement along an orientation chosen at the last moment. Bell-inequality violation is expected between the two final measurements within each EPR pair. At the same time, statistical agreement is expected between these strong measurements and the earlier weak ones performed on that pair. A contradiction seemingly ensues: (i) Bell’s theorem forbids spin values to exist prior to the choice of the orientation measured; (ii) A weak measurement is not supposed to determine the outcome of a successive strong one; and indeed (iii) Almost no disentanglement is inflicted by the WMs; and yet (iv) The outcomes of weak measurements statistically agree with those of the strong ones, suggesting the existence of pre-determined values, in contradiction with (i). Although the conflict can be solved by mere mitigation of the above restrictions, the most reasonable resolution seems to be that of the Two-State-Vector Formalism (TSVF), namely, that the choice of the experimenter has been encrypted within the weak measurement’s outcomes, even before the experimenters themselves know what their choice will be.

  20. Culture-Specific Variables That May Affect Employment Outcomes for Mexican-American Youth with Disabilities.

    ERIC Educational Resources Information Center

    Meier-Kronick, Nancy

    This paper reviews variables specific to the Mexican-American culture that might influence work-related behavior and outcomes for youths with disabilities from this population. Areas covered include: parental/family network; cultural view of disability; religious influences; acculturation levels; language issues; education and employment…

  1. Does Year Round Schooling Affect the Outcome and Growth of California's API Scores?

    ERIC Educational Resources Information Center

    Wu, Amery D.; Stone, Jake E.

    2010-01-01

    This paper examined whether year round schooling (YRS) in California had an effect upon the outcome and growth of schools' Academic Performance Index (API) scores. While many previous studies had examined the connection between YRS and academic achievement, most had lacked the statistical rigour required to provide reliable interpretations. As a…

  2. Does Surgical Management of the Hand in Children with Spastic Unilateral Cerebral Palsy Affect Functional Outcome?

    ERIC Educational Resources Information Center

    van Munster, Judith C.; Maathuis, Karel G. B.; Haga, Nienke; Verheij, Nienke P.; Nicolai, Jean-Philippe A.; Hadders-Algra, Mijna

    2007-01-01

    The aim of this review was to examine the literature on the effects of surgery of the spastic hand in children with cerebral palsy on functional outcome and muscle coordination. We performed a search of the relevant literature in Medline, Embase, and Biological Abstracts from 1966 to June 2006. The search resulted in eight studies on the effect of…

  3. Does Family Group Decision Making Affect Child Welfare Outcomes? Findings from a Randomized Control Study

    ERIC Educational Resources Information Center

    Berzin, Stephanie Cosner; Cohen, Ed; Thomas, Karen; Dawson, William C.

    2008-01-01

    This article describes the evaluation of two family group decision-making programs administered under the California Title IV-E Waiver Demonstration Project. This is the only evaluation using random assignment to examine FGDM. Overall, results did not indicate more positive outcomes for children receiving the intervention, but did indicate that…

  4. Affective Commitment to the Organization, Supervisor, and Work Group: Antecedents and Outcomes

    ERIC Educational Resources Information Center

    Vandenberghe, Christian; Bentein, Kathleen; Stinglhamber, Florence

    2004-01-01

    Three longitudinal studies investigated the usefulness of distinguishing among employees' affective commitments to the organization, the supervisor, and the work group. Study 1, with 199 employees from various organizations, found that affective commitments to these entities were factorially distinct and related differentially to their theorized…

  5. An update to the HIV-TRePS system: the development of new computational models that do not require a genotype to predict HIV treatment outcomes

    PubMed Central

    Revell, Andrew D.; Wang, Dechao; Wood, Robin; Morrow, Carl; Tempelman, Hugo; Hamers, Raph; Alvarez-Uria, Gerardo; Streinu-Cercel, Adrian; Ene, Luminita; Wensing, Annemarie; Reiss, Peter; van Sighem, Ard I.; Nelson, Mark; Emery, Sean; Montaner, Julio S. G.; Lane, H. Clifford; Larder, Brendan A.; Reiss, Peter; van Sighem, Ard; Montaner, Julio; Harrigan, Richard; Rinke de Wit, Tobias; Hamers, Raph; Sigaloff, Kim; Agan, Brian; Marconi, Vincent; Wegner, Scott; Sugiura, Wataru; Zazzi, Maurizio; Streinu-Cercel, Adrian; Alvarez-Uria, Gerardo; Gatell, Jose; Lazzari, Elisa; Gazzard, Brian; Nelson, Mark; Pozniak, Anton; Mandalia, Sundhiya; Ruiz, Lidia; Clotet, Bonaventura; Staszewski, Schlomo; Torti, Carlo; Lane, Cliff; Metcalf, Julie; Perez-Elias, Maria-Jesus; Carr, Andrew; Norris, Richard; Hesse, Karl; Vlahakis, Emanuel; Tempelman, Hugo; Barth, Roos; Morrow, Carl; Wood, Robin; Ene, Luminita; Dragovic, Gordana; Emery, Sean; Cooper, David; Torti, Carlo; Baxter, John; Monno, Laura; Torti, Carlo; Gatell, Jose; Clotet, Bonventura; Picchio, Gaston; deBethune, Marie-Pierre; Perez-Elias, Maria-Jesus

    2014-01-01

    Objectives The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings. Methods Random forest models were trained to predict the probability of a virological response to therapy (<50 copies HIV RNA/mL) following virological failure using the following data from 22 567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models' accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available. Results The models achieved AUCs of 0.79–0.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.56–0.57) for genotyping. Conclusions The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available. PMID:24275116

  6. Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson’s Disease?

    PubMed Central

    Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Giladi, Nir; Ghilardi, Maria Felice; Pezzoli, Gianni; Frazzitta, Giuseppe

    2016-01-01

    Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive impairment (score 21–26), group 3—moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). Results: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. Conclusions: Patients gain benefit in the rehabilitative outcomes, regardless of cognition

  7. Idiosyncratic Variables Affecting Functional Analysis Outcomes: A Review (2001–2010)

    PubMed Central

    Schlichenmeyer, Kevin J.; Roscoe, Eileen M.; Rooker, Griffin W.; Wheeler, Emily E.; Dube, William V.

    2013-01-01

    Although typical functional analyses often produce clear outcomes, some studies have reported ambiguous results that cannot be interpreted. Such undifferentiated outcomes may occur if test conditions do not include relevant antecedent or consequent events. Clinicians then may try to modify the functional analysis conditions to include those events. Hanley, Iwata, and McCord (2003) reviewed the functional analysis literature through the year 2000 and described idiosyncratic variables included in modified functional analyses. The objective of the present review was to present a quantitative analysis of idiosyncratic antecedents and consequences in modified functional analyses during the past decade (2001 to 2010). We discuss the range of stimulus parameters tested and the assessment strategies used for informing the modified analysis conditions. PMID:24114110

  8. Psychosocial outcome following genetic risk counselling for familial colorectal cancer. A comparison of affected patients and family members.

    PubMed

    Keller, M; Jost, R; Haunstetter, C M; Sattel, H; Schroeter, C; Bertsch, U; Cremer, F; Kienle, P; Tariverdian, M; Kloor, M; Gebert, J; Brechtel, A

    2008-11-01

    Few studies have reported prospective data on psychosocial outcomes after genetic counselling in families with suspected hereditary non-polyposis colorectal cancer (HNPCC). This prospective study examines the impact of multidisciplinary risk counselling on the psychosocial outcome of 139 affected cancer patients and 233 family members without cancer at risk for HNPCC. Participants completed questionnaires specific to HNPCC before and 8 weeks after attending the familial cancer clinic. Affected patients' levels of distress were closely related to their health status and exceeded that of unaffected individuals, as did worry regarding their relatives' risk. A significant reduction in general anxiety (Hospital Anxiety and Depression Scale), distress specific to familial CRC (Impact of Events Scale) and general cancer worry (Distress Hereditary Disorder) was demonstrated after counselling in both affected patients and unaffected individuals. Reduction in distress was more pronounced in affected patients given a high risk of HNPCC compared with those at intermediate risk. Among unaffected individuals, distress declined regardless of what clinical risk they were assigned. Their perceptions of risk and cancer-related threat declined, while confidence in effective surveillance increased. These results suggest the beneficial effects of multidisciplinary counselling even when high-risk information is conveyed. A patient's previous cancer experience is likely to contribute to clinically relevant distress (15% of those patients), indicating the need for appropriate counselling. PMID:18954412

  9. Method of induction could affect emotional outcomes: comment on markey, chin, vanepps, and loewenstein (2014 ).

    PubMed

    Bench, Shane W; Yaugher, Ashley C; Lench, Heather C

    2015-04-01

    Markey, Chin, Vanepps, and Loewenstein (2014) demonstrated six methods for the induction of boredom. However, a clear and testable definition of boredom should be established prior to experimental manipulation of the construct. Defining boredom from a functional emotion perspective is one approach that affords a definition separable from the outcomes associated with boredom and insight into which manipulations may effectively target the construct. PMID:25730196

  10. Predictive Factors Affecting Long-Term Outcome of Unilateral Lateral Rectus Recession

    PubMed Central

    Yang, Hee Kyung; Kim, Mi-Jin; Hwang, Jeong-Min

    2015-01-01

    Background There are few long-term outcome reports of unilateral lateral rectus (LR) recession for exotropia including a large number of subjects. Previous reports on unilateral LR recession commonly show extremely low rates of initial overcorrection and large exodrifts after surgery suggesting that the surgical dose may be increased. However, little is known of the long-term outcome of a large unilateral LR recession for exotropia. Objectives To determine long-term outcomes and predictive factors of recurrence after a large unilateral LR recession in patients with exotropia. Data Extraction Retrospective analysis was performed on 92 patients aged 3 to 17 years who underwent 10 mm unilateral LR recession for exotropia of ≤ 25 prism diopters (Δ) with prism and alternate cover testing and were followed up for more than 2 years after surgery. Final success rates within 10Δ of exophoria/tropia and 5Δ of esophoria/tropia at distance in the primary position, improvement in stereopsis and the predictive factors for recurrence were evaluated. Results At 24 months after surgery, 54% of patients had ocular alignment meeting the defined criteria of success, 45% had recurrence and 1% had overcorrection. After a mean follow-up of 39 months, 36% showed success, 63% showed recurrence and 1% resulted in overcorrection. The average time of recurrence was 23.4±14.7 months (range, 1–60 months) and the rate of recurrence per person-year was 23% after unilateral LR recession. Predictive factors of recurrence were a larger preoperative near angle of deviation (>16Δ) and larger initial postoperative exodeviation (>5Δ) at distance. Conclusions Long-term outcome of unilateral LR recession for exotropia showed low success rates with high recurrence, thus should be reserved for patients with a small preoperative near angle of exodeviation. PMID:26418819

  11. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.

    PubMed

    Kishnani, Priya S; Goldenberg, Paula C; DeArmey, Stephanie L; Heller, James; Benjamin, Danny; Young, Sarah; Bali, Deeksha; Smith, Sue Ann; Li, Jennifer S; Mandel, Hanna; Koeberl, Dwight; Rosenberg, Amy; Chen, Y-T

    2010-01-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were 6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc(4). Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p<0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein. PMID:19775921

  12. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants

    PubMed Central

    Kishnani, Priya S.; Goldenberg, Paula C.; DeArmey, Stephanie L.; Heller, James; Benjamin, Danny; Young, Sarah; Bali, Deeksha; Smith, Sue Ann; Li, Jennifer S.; Mandel, Hanna; Koeberl, Dwight; Rosenberg, Amy; Chen, Y-T

    2013-01-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were ≤6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc4. Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p < 0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein. PMID:19775921

  13. Nonsurgical scar management of the face: does early versus late intervention affect outcome?

    PubMed

    Parry, Ingrid; Sen, Soman; Palmieri, Tina; Greenhalgh, David

    2013-01-01

    Special emphasis is placed on the clinical management of facial scarring because of the profound physical and psychological impact of facial burns. Noninvasive methods of facial scar management include pressure therapy, silicone, massage, and facial exercises. Early implementation of these scar management techniques after a burn injury is typically accepted as standard burn rehabilitation practice, however, little data exist to support this practice. This study evaluated the timing of common noninvasive scar management interventions after facial skin grafting in children and the impact on outcome, as measured by scar assessment and need for facial reconstructive surgery. A retrospective review of 138 patients who underwent excision and grafting of the face and subsequent noninvasive scar management during a 10-year time frame was conducted. Regression analyses were used to show that earlier application of silicone was significantly related to lower Modified Vancouver Scar Scale scores, specifically in the subscales of vascularity and pigmentation. Early use of pressure therapy and implementation of facial exercises were also related to lower Modified Vancouver Scar Scale vascularity scores. No relationship was found between timing of the interventions and facial reconstructive outcome. Early use of silicone, pressure therapy, and exercise may improve scar outcome and accelerate time to scar maturity. PMID:23816994

  14. Do nonsteroidal anti-inflammatory drugs affect the outcome of arthroscopic Bankart repair?

    PubMed

    Blomquist, J; Solheim, E; Liavaag, S; Baste, V; Havelin, L I

    2014-12-01

    To achieve pain control after arthroscopic shoulder surgery, nonsteroidal anti-inflammatory drugs (NSAIDs) are a complement to other analgesics. However, experimental studies have raised concerns that these drugs may have a detrimental effect on soft tissue-to-bone healing and, thus, have a negative effect on the outcome. We wanted to investigate if there are any differences in the clinical outcome after the arthroscopic Bankart procedure for patients who received NSAIDs prescription compared with those who did not. 477 patients with a primary arthroscopic Bankart procedure were identified in the Norwegian shoulder instability register and included in the study. 32.5% received prescription of NSAIDs post-operatively. 370 (78%) of the patients answered a follow-up questionnaire containing the Western Ontario Shoulder Instability index (WOSI). Mean follow-up was 21 months. WOSI at follow-up were 75% in the NSAID group and 74% in the control group. 12% of the patients in the NSAID group and 14% in the control group reported recurrence of instability. The reoperation rate was 5% in both groups. There were no statistically significant differences between the groups. Prescription of short-term post-operative NSAID treatment in the post-operative period did not influence on the functional outcome after arthroscopic Bankart procedures. PMID:24750379

  15. Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer.

    PubMed

    Argalácsová, S; Slanař, O; Vítek, P; Tesařová, P; Bakhouche, H; DraŽďáková, M; Bartošová, O; Zima, T; PertuŽelka, L

    2015-01-01

    Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity. PMID:26681084

  16. Social Variables Affecting Mate Preferences, Copulation and Reproductive Outcome in a Pack of Free-Ranging Dogs

    PubMed Central

    Valsecchi, Paola; Natoli, Eugenia

    2014-01-01

    Mating and reproductive outcome is often determined by the simultaneous operation of different mechanisms like intra-sexual competition, mating preferences and sexual coercion. The present study investigated how social variables affected mating outcome in a pack of free-ranging dogs, a species supposed to have lost most features of the social system of wolves during domestication. We found that, although the pack comprised multiple breeding individuals, both male copulation success and female reproductive success were positively influenced by a linear combination of dominance rank, age and leadership. Our results also suggest that mate preferences affect mating outcome by reinforcing the success of most dominant individuals. In particular, during their oestrous period bitches clearly searched for the proximity of high-ranking males who displayed affiliative behaviour towards them, while they were more likely to reject the males who intimidated them. At the same time, male courting effort and male-male competition for receptive females appeared to be stronger in the presence of higher-ranking females, suggesting a male preference for dominant females. To our knowledge, these results provide the first clear evidence of social regulation of reproductive activities in domestic dogs, and suggest that some common organizing mechanisms may contribute to shape the social organization of both dogs and wolves. PMID:24905360

  17. Social variables affecting mate preferences, copulation and reproductive outcome in a pack of free-ranging dogs.

    PubMed

    Cafazzo, Simona; Bonanni, Roberto; Valsecchi, Paola; Natoli, Eugenia

    2014-01-01

    Mating and reproductive outcome is often determined by the simultaneous operation of different mechanisms like intra-sexual competition, mating preferences and sexual coercion. The present study investigated how social variables affected mating outcome in a pack of free-ranging dogs, a species supposed to have lost most features of the social system of wolves during domestication. We found that, although the pack comprised multiple breeding individuals, both male copulation success and female reproductive success were positively influenced by a linear combination of dominance rank, age and leadership. Our results also suggest that mate preferences affect mating outcome by reinforcing the success of most dominant individuals. In particular, during their oestrous period bitches clearly searched for the proximity of high-ranking males who displayed affiliative behaviour towards them, while they were more likely to reject the males who intimidated them. At the same time, male courting effort and male-male competition for receptive females appeared to be stronger in the presence of higher-ranking females, suggesting a male preference for dominant females. To our knowledge, these results provide the first clear evidence of social regulation of reproductive activities in domestic dogs, and suggest that some common organizing mechanisms may contribute to shape the social organization of both dogs and wolves. PMID:24905360

  18. Class IIa histone deacetylases affect neuronal remodeling and functional outcome after stroke.

    PubMed

    Kassis, Haifa; Shehadah, Amjad; Li, Chao; Zhang, Yi; Cui, Yisheng; Roberts, Cynthia; Sadry, Neema; Liu, Xianshuang; Chopp, Michael; Zhang, Zheng Gang

    2016-06-01

    We have previously demonstrated that stroke induces nuclear shuttling of class IIa histone deacetylase 4 (HDAC4). Stroke-induced nuclear shuttling of HDAC4 is positively and significantly correlated with improved indices of neuronal remodeling in the peri-infarct cortex. In this study, using a rat model for middle cerebral artery occlusion (MCAO), we tested the effects of selective inhibition of class IIa HDACs on functional recovery and neuronal remodeling when administered 24hr after stroke. Adult male Wistar rats (n = 15-17/group) were subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO. A battery of behavioral tests was performed. Lesion volume measurement and immunohistochemistry were performed 28 days after MCAO. We found that stroke increased total HDAC activity in the ipsilateral hemisphere compared to the contralateral hemisphere. Stroke-increased HDAC activity was significantly decreased by the administration of SAHA as well as by MC1568. However, SAHA significantly improved functional outcome compared to vehicle control, whereas selective class IIa inhibition with MC1568 increased mortality and lesion volume and did not improve functional outcome. In addition, MC1568 decreased microtubule associated protein 2 (MAP2, dendrites), phosphorylated neurofilament heavy chain (pNFH, axons) and myelin basic protein (MBP, myelination) immunoreactivity in the peri-infarct cortex. Quantitative RT-PCR of cortical neurons isolated by laser capture microdissection revealed that MC1568, but not SAHA, downregulated CREB and c-fos expression. Additionally, MC1568 decreased the expression of phosphorylated CREB (active) in neurons. Taken together, these findings demonstrate that selective inhibition of class IIa HDACs impairs neuronal remodeling and neurological outcome. Inactivation of CREB and c-fos by MC1568 likely contributes to

  19. Maternal First Trimester TSH Concentrations: Do They Affect Perinatal and Endocrine Outcomes?

    PubMed

    Fraenkel, M; Shafat, T; Erez, O; Lichtenstein, Y; Awesat, J; Novack, V; Tsur, A

    2016-07-01

    We aimed to examine the distribution of 1(st) trimester TSH and evaluate its association with perinatal outcomes and future development of maternal thyrotoxicosis. This retrospective cohort study included data of all women without prior thyroid disease who delivered a singleton at our medical center from 1/2001 to 12/2011 and had a 1(st) trimester TSH<4.0 mU/l. Women were divided according to 1(st) trimester TSH concentrations into quartiles and by predefined TSH values (mU/l): 1) TSH<0.1; 2) TSH 0.11-0.2; 3) TSH 0.21-0.4; and 4) TSH 0.4-4. Obstetrical outcomes, hCG concentrations, and future thyroid status were collected from electronic medical records. A total of 13 841 women fulfilled the inclusion criteria. Mean maternal TSH concentration at 5 weeks of gestation was 2.09±0.83 mU/l and decreased to 1.29±0.87 mU/l in weeks 8-9 with an increase towards the end of the 1(st) trimester. Odds ratio for future thyrotoxicosis was 3.64 in the lowest compared to the highest TSH quartile and 10.03 in those with TSH<0.1 compared to TSH 0.41-4 mU/l. Rates of female fetuses were higher in the low TSH quartiles and in the lower TSH groups, however baby gender was not associated with increased risk of future thyrotoxicosis. Low maternal 1(st) trimester TSH quartiles or concentrations were not associated with adverse pregnancy outcome. Only a minor fraction of pregnant women with a low first tirmester TSH subsequently developed future thyrotoxicosis. PMID:27351808

  20. Older Age Does Not Affect Healing Time and Functional Outcomes After Fracture Nonunion Surgery

    PubMed Central

    Taormina, David P.; Shulman, Brandon S.; Karia, Raj; Spitzer, Allison B.; Konda, Sanjit R.

    2014-01-01

    Introduction: Elderly patients are at risk of fracture nonunion, given the potential setting of osteopenia, poorer fracture biology, and comorbid medical conditions. Risk factors predicting fracture nonunion may compromise the success of fracture nonunion surgery. The purpose of this study was to investigate the effect of patient age on clinical and functional outcome following long bone fracture nonunion surgery. Materials and Methods: A retrospective analysis of prospectively collected data identified 288 patients (aged 18-91) who were indicated for long bone nonunion surgery. Two-hundred and seventy-two patients satisfied study inclusion criteria and analyses were performed comparing elderly patients aged ≥65 years (n = 48) with patients <65 years (n = 224) for postoperative wound complications, Short Musculoskeletal Functional Assessment (SMFA) functional status, healing, and surgical revision. Regression analyses were performed to look for associations between age, smoking status, and history of previous nonunion surgery with healing and functional outcome. Twelve-month follow-up was obtained on 91.5% (249 of 272) of patients. Results: Despite demographic differences in the aged population, including a predominance of medical comorbidities (P < .01) and osteopenia (P = .02), there was no statistical differences in the healing rate of elderly patients (95.8% vs 95.1%, P = .6) or time to union (6.2 ± 4.1 months vs. 7.2 ± 6.6, P = .3). Rates of postoperative wound complications and surgical revision did not statistically differ. Elderly patients reported similar levels of function up to 12 months after surgery. Regression analyses failed to show any significant association between age and final union or time to union. There was a strong positive association between smoking and history of previous nonunion surgery with time to union. Age was associated (positively) with 12-month SMFA activity score. Conclusions: Smoking and failure of previous surgical

  1. Favorable outcome of patients affected by rhabdoid tumors due to rhabdoid tumor predisposition syndrome (RTPS).

    PubMed

    Kordes, Uwe; Bartelheim, Kerstin; Modena, Piergiorgio; Massimino, Maura; Biassoni, Veronica; Reinhard, Harald; Hasselblatt, Martin; Schneppenheim, Reinhard; Frühwald, Michael C

    2014-05-01

    Rhabdoid tumor predisposition syndrome is usually associated with shorter survival in patients with malignant rhabdoid tumors regardless of anatomical origin. Here we present four children harboring truncating heterozygous SMARCB1/INI1 germline mutations with favorable outcome. All four patients received multi-modality treatment, three according to therapeutic recommendations by the EU-RHAB registry, two without radiotherapy, and mean event-free survival accounts for 7 years. In conclusion, intensive treatment with curative intent is justified for children with rhabdoid tumors even if an underlying rhabdoid predisposition syndrome is demonstrated. PMID:24123847

  2. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation

    PubMed Central

    Isernhagen, Antje; Malzahn, Dörthe; Viktorova, Elena; Elsner, Leslie; Monecke, Sebastian; von Bonin, Frederike; Kilisch, Markus; Wermuth, Janne Marieke; Walther, Neele; Balavarca, Yesilda; Stahl-Hennig, Christiane; Engelke, Michael; Walter, Lutz; Bickeböller, Heike; Kube, Dieter; Wulf, Gerald; Dressel, Ralf

    2015-01-01

    The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n = 452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR] = 0.77, P = 0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR] = 0.57, P = 0.0400) although homozygous carriers had an increased risk to experience this complication (OR = 1.92, P = 0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR = 0.54, P = 0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon-γ release, and faster co-stimulation of CD8+ T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8+ T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD. PMID:26483398

  3. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  4. Pediatric hydrocephalus: Does the shunt device pressure selection affect the outcome?

    PubMed Central

    Sinha, Arvind; Sharma, Anuj; Gupta, Charitesh

    2012-01-01

    Aim: To compare the efficacy of low- versus medium-pressure shunts in pediatric hydrocephalus in a randomized controlled trial. Materials and Methods: Forty patients of pediatric hydrocephalus were randomized into two groups. The Chhabra differential pressure VP shunt (low or medium) was inserted in every patient. Postoperative follow-up was performed for symptomatic improvement and radiological evaluation (by sonography or computed tomography scan) for ventricle hemispheric ratio (VHR). Comparative analysis of pre- and postoperative VHR and need of redo surgery for shunt malformation were carried out to establish outcomes. Results: Nineteen patients had a low-pressure and 21 patients had a medium-pressure shunt inserted. The age of the patients ranged from 1 day to 10 years. The average preoperative VHR in group A was 55.37%, which reduced to 40% postoperatively (P = 0.00005); likewise, the pre- and postoperative VHR in group B were 61.57% and 42%, respectively, which was statistically significant (P = 0.0006). The complications of shunts and incidence of redo shunt surgery in both groups were not found to be statistically significant (P = 0.5614). Conclusions: The study found no significant difference in the outcome of patients with low- or medium-pressure shunt placement in pediatric hydrocephalus. PMID:22529548

  5. Pretransfer computed tomography delays arrival to definitive care without affecting pediatric trauma outcomes

    PubMed Central

    Fahy, Aodhnait S.; Antiel, Ryan M.; Polites, Stephanie F.; Ishitani, Michael B.; Moir, Christopher R.; Zielinski, Martin D.

    2016-01-01

    Purpose Children with thoracic or abdominal trauma, presenting to referring hospitals, may undergo CT imaging prior to transfer to a pediatric trauma center (PTC). We sought to determine if children who undergo pretransfer imaging experience a delay in definitive care and worse clinical outcomes. Methods Pediatric blunt trauma patients transferred to our level I PTC were identified in this IRB approved study. Those transferred with CT imaging of the chest or abdomen/pelvis prior to transfer were compared to those transferred without imaging. Results Of 246 patients with a mean age of 12.4 ± 5.3 years (64% male), 128 patients (52%) underwent chest (n = 85) and/or abdominal (n = 115) CT studies prior to transfer. Among those patients with pretransfer CT, 14% of CT scans were repeated. On multivariate analysis accounting for distance, time from injury to arrival at our PTC was significantly greater in children who underwent pretransfer CT (320 ± 216 vs. 208 ± 149 minutes, p < 0.001). Median length of stay (3 vs. 3 days) and mortality (3% vs. 3%) were similar between groups (all p > 0.05). Conclusions A substantial number of pediatric blunt trauma patients underwent CT scans prior to transfer, which is associated with a delay in transfer but not worse outcomes. PMID:26778842

  6. How does family drug treatment court participation affect child welfare outcomes?

    PubMed

    Gifford, Elizabeth Joanne; Eldred, Lindsey Morgan; Vernerey, Allison; Sloan, Frank Allen

    2014-10-01

    Parental substance use is a risk factor for child maltreatment. Family drug treatment courts (FDTCs) have emerged in the United States as a policy option to treat the underlying condition and promote family preservation. This study examines the effectiveness of FDTCs in North Carolina on child welfare outcomes. Data come from North Carolina records from child protection services, court system, and birth records. Three types of parental participation in a FDTC are considered: referral, enrolling, and completing an FDTC. The sample includes 566 children who were placed into foster care and whose parents participated in a FDTC program. Findings indicate that children of parents who were referred but did not enroll or who enrolled but did not complete had longer stays in foster care than children of completers. Reunification rates for children of completers were also higher. Outcomes for children in the referred and enrolled groups did not differ in the multivariate analyses. While effective substance use treatment services for parents may help preserve families, future research should examine factors for improving participation and completion rates as well as factors involved in scaling programs so that more families are served. PMID:24736039

  7. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  8. Client Preferences Affect Treatment Satisfaction, Completion, and Clinical Outcome: A Meta-Analysis

    PubMed Central

    Lindhiem, Oliver; Bennett, Charles B.; Trentacosta, Christopher J.; McLear, Caitlin

    2014-01-01

    We conducted a meta-analysis on the effects of client preferences on treatment satisfaction, completion, and clinical outcome. Our search of the literature resulted in 34 empirical articles describing 32 unique clinical trials that either randomized some clients to an active choice condition (shared decision making condition or choice of treatment) or assessed client preferences. Clients who were involved in shared decision making, chose a treatment condition, or otherwise received their preferred treatment evidenced higher treatment satisfaction (ESd = .34; p < .001), increased completion rates (ESOR = 1.37; ESd = .17; p < .001), and superior clinical outcome (ESd = .15; p < .0001), compared to clients who were not involved in shared decision making, did not choose a treatment condition, or otherwise did not receive their preferred treatment. Although the effect sizes are modest in magnitude, they were generally consistent across several potential moderating variables including study design (preference versus active choice), psychoeducation (informed versus uninformed), setting (inpatient versus outpatient), client diagnosis (mental health versus other), and unit of randomization (client versus provider). Our findings highlight the clinical benefit of assessing client preferences, providing treatment choices when two or more efficacious options are available, and involving clients in treatment-related decisions when treatment options are not available. PMID:25189522

  9. How Group Factors Affect Adolescent Change Talk and Substance Use Outcomes: Implications for Motivational Interviewing Training

    PubMed Central

    Osilla, Karen Chan; Ortiz, J. Alexis; Miles, Jeremy N.V.; Pedersen, Eric R.; Houck, Jon M.; D'Amico, Elizabeth J.

    2014-01-01

    Clients who verbalize statements arguing for change (change talk, CT) in psychotherapy are more likely to decrease alcohol and other drug use (AOD) compared to clients who voice statements in opposition of change (sustain talk, ST). Little is known about how CT and ST are expressed in groups where adolescents may vary in their AOD use severity and readiness to change. First, we examined how session content was associated with CT/ST, and then we looked at whether different subtypes of CT/ST were associated with subsequent AOD outcomes three months later. Audio recordings (N=129 sessions) of a 6-session group motivational interviewing (MI) intervention, Free Talk, were coded. Session content was not associated with CT; however, some session content was associated with higher percentages of ST (e.g., normative feedback). Subtypes of CT (Commitment and Reason) were associated with improved AOD outcomes, whereas Ability subtype remarks were related to increased marijuana use, intentions, and consequences. Findings offer helpful guidance for clinical training and narrow in on the type of CT to try to elicit in group MI sessions. Regardless of session content, adolescents can benefit from hearing CT during the group. PMID:25602608

  10. The Effects of Trauma History and Prenatal Affective Symptoms on Obstetric Outcomes.

    PubMed

    Blackmore, Emma Robertson; Putnam, Frank W; Pressman, Eva K; Rubinow, David R; Putnam, Karen T; Matthieu, Monica M; Gilchrist, Michelle A; Jones, Ian; O'Connor, Thomas G

    2016-06-01

    Prenatal maternal mood may inform the adverse obstetric outcomes seen in disadvantaged populations. The contribution of having a trauma history is not well studied. We examined the impact of trauma exposure and mood symptoms on obstetric outcomes in 358 women. Women with antecedent trauma were more likely to have a history of depression, odds ratio = 2.83, 95% confidence interval [1.81, 4.42], were younger at their first pregnancy, 18.86 years versus 20.10 years, and had a higher number of previous pregnancies, 2.01 versus 1.54, compared to those with no trauma exposure. Women with prenatal anxiety had significantly smaller babies than nonanxious women, 3,313.17 g, (SD = 441.58) versus 3,429.27 g, (SD = 437.82) Trauma history magnified the effects of maternal prenatal mood on birthweight; the moderating effect was limited to those who first experienced a trauma under 18 years of age. Childhood trauma exposure increased vulnerability for low birthweight delivery associated with prenatal mood disturbance. Screening pregnant women for trauma history and current mood symptoms is indicated. PMID:27276162

  11. User Experience of Mobile Interactivity: How Do Mobile Websites Affect Attitudes and Relational Outcomes?

    ERIC Educational Resources Information Center

    Dou, Xue

    2013-01-01

    Mobile media offer new opportunities for fostering communications between individuals and companies. Corporate websites are being increasingly accessed via smart phones and companies are scrambling to offer a mobile-friendly user experience on their sites. However, very little is known about how interactivity in the mobile context affects user…

  12. Affecting Factors and Outcome on Intermittent Internet Pulling Behavior in Taiwan's Undergraduate Students

    ERIC Educational Resources Information Center

    Yang, Hui-Jen; Lay, Yun-Long

    2011-01-01

    Nowadays people's lives heavily rely on Internet facilities. Internet users generally have constant Internet connectivity and intermittently click on sites they want to access even amidst studying or working. In this study, we sought to examine the factors affecting intermittent Internet pulling behavior on undergraduate students. Furthermore, the…

  13. Marital Conflict and Child Outcomes: The Role of Children's Affect and Coping Processes.

    ERIC Educational Resources Information Center

    Martin, Sarah E.; Clements, Mari L.

    This study examined young children's affective distress and behavioral responses to parental marital conflict. Forty-eight 4-year-olds and their parents participated in the study. Mothers and fathers independently completed measures of marital conflict, children's reactions to marital conflict, and child behavior problems, while the children…

  14. Activation of less affected corticospinal tract and poor motor outcome in hemiplegic pediatric patients: a diffusion tensor tractography imaging study

    PubMed Central

    Kim, Jin Hyun; Son, Su Min

    2015-01-01

    The less affected hemisphere is important in motor recovery in mature brains. However, in terms of motor outcome in immature brains, no study has been reported on the less affected corticospinal tract in hemiplegic pediatric patients. Therefore, we examined the relationship between the condition of the less affected corticospinal tract and motor function in hemiplegic pediatric patients. Forty patients with hemiplegia due to perinatal or prenatal injury (13.7 ± 3.0 months) and 40 age-matched typically developing controls were recruited. These patients were divided into two age-matched groups, the high functioning group (20 patients) and the low functioning group (20 patients) using functional level of hemiplegia scale. Diffusion tensor tractography images showed that compared with the control group, the patient group of the less affected corticospinal tract showed significantly increased fiber number and significantly decreased fractional anisotropy value. Significantly increased fiber number and significantly decreased fractional anisotropy value in the low functioning group were observed than in the high functioning group. These findings suggest that activation of the less affected hemisphere presenting as increased fiber number and decreased fractional anisotropy value is related to poor motor function in pediatric hemiplegic patients. PMID:26889198

  15. Social-Emotional Factors Affecting Achievement Outcomes Among Disadvantaged Students: Closing the Achievement Gap.

    PubMed

    Becker, Bronwyn E; Luthar, Suniya S

    2002-01-01

    Despite concentrated efforts at improving inferior academic outcomes among disadvantaged students, a substantial achievement gap between the test scores of these students and others remains (Jencks & Phillips, 1998; National Center for Education Statistics, 2000a, 2000b; Valencia & Suzuki, 2000). Existing research used ecological models to document social-emotional factors at multiple levels of influence that undermine academic performance. This article integrates ideas from various perspectives in a comprehensive and interdisciplinary model that will inform policy makers, administrators, and schools about the social-emotional factors that act as both risk and protective factors for disadvantaged students' learning and opportunities for academic success. Four critical social-emotional components that influence achievement performance (academic and school attachment, teacher support, peer values, and mental health) are reviewed. PMID:23255834

  16. Social–Emotional Factors Affecting Achievement Outcomes Among Disadvantaged Students: Closing the Achievement Gap

    PubMed Central

    Becker, Bronwyn E.; Luthar, Suniya S.

    2012-01-01

    Despite concentrated efforts at improving inferior academic outcomes among disadvantaged students, a substantial achievement gap between the test scores of these students and others remains (Jencks & Phillips, 1998; National Center for Education Statistics, 2000a, 2000b; Valencia & Suzuki, 2000). Existing research used ecological models to document social–emotional factors at multiple levels of influence that undermine academic performance. This article integrates ideas from various perspectives in a comprehensive and interdisciplinary model that will inform policy makers, administrators, and schools about the social–emotional factors that act as both risk and protective factors for disadvantaged students’ learning and opportunities for academic success. Four critical social–emotional components that influence achievement performance (academic and school attachment, teacher support, peer values, and mental health) are reviewed. PMID:23255834

  17. Factors affecting the postoperative limb alignment and clinical outcome after Oxford unicompartmental knee arthroplasty.

    PubMed

    Kim, Seung-Ju; Bae, Ji-Hoon; Lim, Hong Chul

    2012-06-01

    We evaluated the postoperative mechanical axis deviation and clinical outcome according to bearing size, femoral component position, and tibial resection angle after unicompartmental knee arthroplasty (UKA). A total of 104 patients with 124 knees underwent Oxford phase 3 UKA. The overall changes in mechanical axis deviation and tibiofemoral angle were significantly different according to bearing size (P = .001 and < .001), but they were not significantly different according to the tibial resection angle and femoral component position. The postoperative mechanical axis fell into the zone C or zone 2 in 108 knees (87%) and into the zone 3 or zone 4 in 16 cases (13%). One hundred eight cases, which had the mechanical axis passing the zone C or zone 2, did not show any progression of arthritis. Limb alignment is a function of the thickness of the bearing rather than alignments of femoral and tibial implant. PMID:22285234

  18. Factors affecting treatment outcome in congenital nasolacrimal duct obstruction: A retrospective analysis from South India

    PubMed Central

    Bhandari, Sahil; Sengupta, Sabyasachi; Yadalla, Dayakar; Rajagopalan, Jayagayathri; Velis, Girish Bharat; Talele, Deepti; Kushwaha, Sameer

    2015-01-01

    Purpose: To investigate outcomes for different treatment modalities in congenital nasolacrimal duct obstruction (CNLDO) in an Indian population. Design: Retrospective, interventional, case series. Materials and Methods: In an institutional setting, case records of patients with CNLDO from January 2008 to 2012, were reviewed, and data on patient demographics, clinical presentation, and treatment details (sac massage, probing, and/or dacryocystorhinostomy) were recorded. Success of treatment was defined as complete resolution of symptoms and negative regurgitation on pressure over lacrimal sac (ROPLAS) area. Results: Two hundred and ninety-eight eyes of 240 patients with a mean age of 22.2 ± 26.14 months (median = 12 months, interquartile range = 17) were analyzed. Sac massage (n = 226) was successful in 67 eyes (30%). Multivariable logistic regression analyses showed that children with mucoid ROPLAS were almost 6 times more likely (odds ratio [OR] = 5.55 vs. clear ROPLAS, 95% confidence interval [CI] = 2.35–13.09, P < 0.001) to experience failure of sac massage. Overall probing (n = 193) was successful for 143 (74%) eyes. Multivariable logistic regression showed that older children were 25% more likely to experience probing failure (OR = 1.25 for every 6 months increment in age, 95%, CI = 1.09–1.42, P = 0.001). Conclusion: Sac massage is successful in only a third of our patients and those with mucoid ROPLAS are more likely to experience failure. Probing is successful in three-quarter of our subjects, and its success declines with a progressive increase in age. Lower socioeconomic status, poor general health, and recurrent respiratory infections are unique to our population and may influence outcomes. PMID:26654998

  19. Correlating Cleaning Thoroughness with Effectiveness and Briefly Intervening to Affect Cleaning Outcomes: How Clean Is Cleaned?

    PubMed Central

    Hosford, Eve; Ong, Ana; Richesson, Douglas; Fraser, Susan; Kwak, Yoon; Miller, Sonia; Julius, Michael; McGann, Patrick; Lesho, Emil

    2016-01-01

    Objectives The most efficient approach to monitoring and improving cleaning outcomes remains unresolved. We sought to extend the findings of a previous study by determining whether cleaning thoroughness (dye removal) correlates with cleaning efficacy (absence of molecular or cultivable biomaterial) and whether one brief educational intervention improves cleaning outcomes. Design Before-after trial. Setting Newly built community hospital. Intervention 90 minute training refresher with surface-specific performance results. Methods Dye removal, measured by fluorescence, and biomaterial removal and acquisition, measured with culture and culture-independent PCR-based assays, were clandestinely assessed for eight consecutive months. At this midpoint, results were presented to the cleaning staff (intervention) and assessments continued for another eight consecutive months. Results 1273 surfaces were sampled before and after terminal room cleaning. In the short-term, dye removal increased from 40.3% to 50.0% (not significant). For the entire study period, dye removal also improved but not significantly. After the intervention, the number of rooms testing positive for specific pathogenic species by culturing decreased from 55.6% to 36.6% (not significant), and those testing positive by PCR fell from 80.6% to 53.7% (P = 0.016). For nonspecific biomaterial on surfaces: a) removal of cultivable Gram-negatives (GN) trended toward improvement (P = 0.056); b) removal of any cultivable growth was unchanged but acquisition (detection of biomaterial on post-cleaned surfaces that were contaminant-free before cleaning) worsened (P = 0.017); c) removal of PCR-based detection of bacterial DNA improved (P = 0.046), but acquisition worsened (P = 0.003); d) cleaning thoroughness and efficacy were not correlated. Conclusion At this facility, a minor intervention or minimally more aggressive cleaning may reduce pathogen-specific contamination, but not without unintended consequences. PMID

  20. Data on IL-6 c.-174 G>C genotype and allele frequencies in patients with coronary heart disease in dependence of cardiovascular outcome.

    PubMed

    Reichert, Stefan; Schlitt, Axel; Benten, Ann-Christin; Hofmann, Britt; Schaller, Hans-Günter; Schulz, Susanne

    2016-09-01

    In this data article we present data on the distribution of alleles and genotypes of the interleukin (IL)-6 c.-174 G>C polymorphism (rs 1800795) in patients with coronary heart disease (CHD) in dependence of the incidence of new cardiovascular events (combined endpoint: myocardial infarction, stroke/TIA, cardiac death, death according to stroke) within three years follow-up. Moreover, we investigated putative associations between individual expression of IL-6 genotypes and IL-6 serum level. This investigation is a subanalysis of the article entitled "The Interleukin 6 c.-174 CC genotype is a predictor for new cardiovascular events in patients with coronary heart disease within three years follow-up" (ClinicalTrials.gov identifier: NCT01045070) (Reichert et al., 2016) [1]. PMID:27570807

  1. Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis

    PubMed Central

    Sabiiti, Wilber; Robertson, Emma; Beale, Mathew A.; Johnston, Simon A.; Brouwer, Annemarie E.; Loyse, Angela; Jarvis, Joseph N.; Gilbert, Andrew S.; Fisher, Matthew C.; Harrison, Thomas S.; May, Robin C.; Bicanic, Tihana

    2014-01-01

    Background. Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis and poor fungal clearance during treatment are recognized adverse prognostic markers; however, the underlying pathogenic factors that drive these clinical manifestations are incompletely understood. We profiled a large set of clinical isolates for established cryptococcal virulence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentation and outcome in human cryptococcosis. Methods. Sixty-five C. neoformans isolates from clinical trial patients with matched clinical data were assayed in vitro to determine murine macrophage uptake, intracellular proliferation rate (IPR), capsule induction, and laccase activity. Analysis of the correlation between prognostic clinical and host immune parameters and fungal phenotypes was performed using Spearman’s r, while the fungal-dependent impact on long-term survival was determined by Cox regression analysis. Results. High levels of fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio [HR] 2.6, 95% CI 1.2–5.5, P = 0.012). High-uptake strains were hypocapsular (r = –0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003). Fungal isolates with greater laccase activity exhibited heightened survival ex vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following patient antifungal treatment (r = 0.39, P = 0.003). Conclusion. These findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependent melanin pathways to human clinical presentation and outcome. Furthermore, characterization of fungal-specific pathways that drive clinical manifestation provide potential targets for the development of therapeutics and the management of CM. Funding. This work

  2. Nonambulatory cows: Duration of recumbency and quality of nursing care affect outcome of flotation therapy.

    PubMed

    Stojkov, J; Weary, D M; von Keyserlingk, M A G

    2016-03-01

    Cows that are unable or unwilling to stand and remain recumbent for ≥ 12 h are defined as nonambulatory. Care and management of nonambulatory cattle is considered a major animal welfare concern facing the livestock industry, particularly the dairy sector. Flotation therapy has gained interest as a means to promote recovery in nonambulatory cows and is based on the concept that by floating the cow in warm water, secondary pressure damage to muscles and nerves will be reduced. The objective of this study was to assess the physiological responses to stress related to the flotation therapy and to evaluate the effect of recumbency duration and nursing care on the outcome of the flotation therapy. The outcomes of 34 nonambulatory Holstein dairy cows were analyzed after they were subjected to flotation therapy. The duration of recumbency and quality of nursing care provided before initiation of the flotation treatment were assessed based on producer responses to survey questions, and from on-site observations by the researchers. A veterinarian examined all cows before flotation therapy began. The treatment was divided into 5 phases: baseline (before filling), manipulation (placing the cow into the tank), filling (the tank was filled with water), flotation (the cow was confined in the filled tank), and draining (water was removed from the tank). Stress responses to the procedure, excluding the manipulation portion, were assessed using heart rate variability. The high-frequency component (HF normalized units) decreased during the filling and draining phases (2.8 ± 0.2 and 3.1 ± 0.4, respectively) compared with the baseline and floating phase (5.1 ± 0.6 and 4.9 ± 0.3, [corrected] respectively). These results indicate that the stress related to the flotation therapy is greatest during the filling and draining phases of the treatment, when cows likely have to exert increased effort to transition to a standing position. The flotation therapy was less likely to be

  3. EEG-neurofeedback for optimising performance. I: a review of cognitive and affective outcome in healthy participants.

    PubMed

    Gruzelier, John H

    2014-07-01

    A re-emergence of research on EEG-neurofeedback followed controlled evidence of clinical benefits and validation of cognitive/affective gains in healthy participants including correlations in support of feedback learning mediating outcome. Controlled studies with healthy and elderly participants, which have increased exponentially, are reviewed including protocols from the clinic: sensory-motor rhythm, beta1 and alpha/theta ratios, down-training theta maxima, and from neuroscience: upper-alpha, theta, gamma, alpha desynchronisation. Outcome gains include sustained attention, orienting and executive attention, the P300b, memory, spatial rotation, RT, complex psychomotor skills, implicit procedural memory, recognition memory, perceptual binding, intelligence, mood and well-being. Twenty-three of the controlled studies report neurofeedback learning indices along with beneficial outcomes, of which eight report correlations in support of a meditation link, results which will be supplemented by further creativity and the performing arts evidence in Part II. Validity evidence from optimal performance studies represents an advance for the neurofeedback field demonstrating that cross fertilisation between clinical and optimal performance domains will be fruitful. Theoretical and methodological issues are outlined further in Part III. PMID:24125857

  4. Maternal Prenatal Positive Affect, Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study

    PubMed Central

    Kuusinen, Tiina; Tuovinen, Soile; Villa, Pia; Hämäläinen, Esa; Laivuori, Hannele; Kajantie, Eero; Räikkönen, Katri

    2016-01-01

    Background We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation. Methods Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records. Results One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions. Conclusions This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight. PMID:26919119

  5. Parents' Readiness to Change Affects BMI Reduction Outcomes in Adolescents with Polycystic Ovary Syndrome

    PubMed Central

    Jakubowski, Karen P.; Black, Jessica J.; El Nokali, Nermeen E.; Belendiuk, Katherine A.; Hannon, Tamara S.; Arslanian, Silva A.; Rofey, Dana L.

    2012-01-01

    Evidence supports the importance of parental involvement for youth's ability to manage weight. This study utilized the stages of change (SOC) model to assess readiness to change weight control behaviors as well as the predictive value of SOC in determining BMI outcomes in forty adolescent-parent dyads (mean adolescent age = 15 ± 1.84 (13–20), BMI = 37 ± 8.60; 70% white) participating in a weight management intervention for adolescent females with polycystic ovary syndrome (PCOS). Adolescents and parents completed a questionnaire assessing their SOC for the following four weight control domains: increasing dietary portion control, increasing fruit and vegetable consumption, decreasing dietary fat, and increasing usual physical activity. Linear regression analyses indicated that adolescent change in total SOC from baseline to treatment completion was not predictive of adolescent change in BMI from baseline to treatment completion. However, parent change in total SOC from baseline to treatment completion was predictive of adolescent change in BMI, (t(24) = 2.15, p = 0.043). Findings support future research which carefully assesses adolescent and parent SOC and potentially develops interventions targeting adolescent and parental readiness to adopt healthy lifestyle goals. PMID:22970350

  6. Developmental Exposure to TCDD Reduces Fertility and Negatively Affects Pregnancy Outcomes across Multiple Generations

    PubMed Central

    Bruner-Tran, Kaylon L.; Osteen, Kevin G.

    2010-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Since humans and animals are most sensitive to toxicant exposure during development, we previously developed a mouse model of in utero TCDD exposure in order to examine the impact of this toxicant on adult reproductive function. Our initial in utero toxicant-exposure study revealed a dose-dependent reduction in uterine sensitivity to progesterone; however, we did not previously explore establishment or maintenance of pregnancy. Thus, in the current study, we examined pregnancy outcomes in adult C57BL/6 mice with a history of developmental TCDD exposure. Herein we demonstrate reduced fertility and an increased incidence of premature birth (PTB) in F1 mice exposed in utero to TCDD as well as in three subsequent generations. Finally, our studies revealed that mice with a history of developmental TCDD exposure exhibit an increased sensitivity to inflammation which further negatively impacted gestation length in all generations examined. PMID:20955784

  7. Dose impaired relaxation of left ventricle affect early outcomes in CABG patients?

    PubMed

    Bagheri, Jamshid; Rezakhanloo, Fereshteh

    2010-01-01

    Although systolic dysfunction is revealed as a prognostic factor in cardiac surgery, the role of diastolic dysfunction as a predictive factor is less evaluated. In this retrospective study from 872 patients that underwent isolated coronary artery bypass graft (Jan 2008-Feb 2009), 388 patients had normal left ventricular ejection fraction (>50%). These are divided in two groups, Group 1: 361 patients without diastolic dysfunction (impaired relaxation) and Group 2: 27 patients with diastolic dysfunction (impaired relaxation). Mean age in group 1 was 57.72 year and in group 2 was 61.16 year (P = 0.07). Risk factors such as diabetes mellitus, hypertention and dyslipidemia were similar. Although overall complication rate was higher in group 2 (11.1% vs. 2.8% P value 0.05), but when each complication was studied individually no significant statistical difference was found. Also no significant statistical difference was found in mortality (2.2% in group 1 vs 7.4% in group 2 P = 0.1). In conclusion, from clinical standpoint diastolic dysfunction can be an important factor in assessing surgical outcome in patients whom underwent coronary artery bypass grafting. PMID:21137652

  8. Factors affecting short- and long-term outcomes of manipulation under anaesthesia in patients with adhesive capsulitis of the shoulder

    PubMed Central

    Owen, John M; Sayers, Adrian E; Woods, David A

    2014-01-01

    Background The present study aimed to evaluate and determine the factors that affect short- and long-term outcome following manipulation under anaesthesia (MUA) of patients with adhesive capsulitis. Methods Patients recruited from January 1999 to January 2010 were retrospectively analyzed and classified as having primary or secondary adhesive capsulitis. All patients were assessed for range of movement (ROM) and Oxford Shoulder Scores (OSS) before and immediately postoperatively, as well as for OSS more than 1 year post MUA. Results In total, 295 patients (315 shoulders) were sequentially recruited, and information was collected at baseline, as well as at a mean follow-up of 28 days and 3.6 years. A significant improvement in OSS and ROM was noted 1 month post MUA (p < 0.0001) with females benefiting more than males (p < 0.0025). Long-term follow-up revealed that the improvement in OSS was maintained (p < 0.0001). Secondary adhesive capsulitis significantly reduced the efficacy of MUA as assessed by ROM (p < 0.0001). Other factors (age, initial ROM and OSS, and length of symptoms prior to MUA) did not significantly affect the outcome over the short- or long-term. Conclusions The findings of the present study show that all patient groups had a significantly improved ROM and OSS in the short-term with long-term maintenance of improved OSS.

  9. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    PubMed

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC. PMID:27442681

  10. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program

    PubMed Central

    Mengesha, Melkamu Merid; Deyessa, Negussie; Tegegne, Balewgizie Sileshi; Dessie, Yadeta

    2016-01-01

    Background The outpatient therapeutic care program (OTP) of children with severe acute malnutrition (SAM) has been decentralized to health post level in Ethiopia since 2008–2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. Objective This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. Design Health facility–based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. Result 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97)]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56)]. However, children who gained Mid-Upper Arm Circumference (MUAC) ≥ 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06)]. Conclusions Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome. PMID:27396484

  11. Assessment of two different types of bias affecting the results of outcome-based evaluation in undergraduate medical education

    PubMed Central

    2014-01-01

    Background Estimating learning outcome from comparative student self-ratings is a reliable and valid method to identify specific strengths and shortcomings in undergraduate medical curricula. However, requiring students to complete two evaluation forms (i.e. one before and one after teaching) might adversely affect response rates. Alternatively, students could be asked to rate their initial performance level retrospectively. This approach might threaten the validity of results due to response shift or effort justification bias. Methods Two consecutive cohorts of medical students enrolled in a six-week cardio-respiratory module were enrolled in this study. In both cohorts, performance gain was estimated for 33 specific learning objectives. In the first cohort, outcomes calculated from ratings provided before (pretest) and after (posttest) teaching were compared to outcomes derived from comparative self-ratings collected after teaching only (thentest and posttest). In the second cohort, only thentests and posttests were used to calculate outcomes, but data collection tools differed with regard to item presentation. In one group, thentest and posttest ratings were obtained sequentially on separate forms while in the other, both ratings were obtained simultaneously for each learning objective. Results Using thentest ratings to calculate performance gain produced slightly higher values than using true pretest ratings. Direct comparison of then- and posttest ratings also yielded slightly higher performance gain than sequential ratings, but this effect was negligibly small. Conclusions Given the small effect sizes, using thentests appears to be equivalent to using true pretest ratings. Item presentation in the posttest does not significantly impact on results. PMID:25043503

  12. Psychosocial co-morbidity affects treatment outcome in children with fecal incontinence.

    PubMed

    van Everdingen-Faasen, Els Q; Gerritsen, Bert J; Mulder, Paul G H; Fliers, Ellen A; Groeneweg, Michael

    2008-09-01

    Fecal incontinence is a common disorder in children. Many children with fecal incontinence have psychosocial co-morbidity. In this study, the effect of psychosocial co-morbidity on the treatment outcome of children with fecal incontinence was evaluated. One hundred and fifty children with fecal incontinence were treated in a multidisciplinary program. All children had been treated unsuccessfully for at least one year before entering the program. The treatment consisted of laxative treatment, psychosocial interventions, and biofeedback training. Psychosocial co-morbidity was classified according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). One hundred and forty-one children were completely analyzed (102 boys, mean age 9.6 (range 6.5-16.5) years). Of these, 31 (22%) children had fecal incontinence without constipation and 110 (78%) children had fecal incontinence associated with constipation. In 95% of children, at least one psychosocial co-morbidity was present. Treatment was successful at 12 months in 69% of patients. Treatment was less successful in children with attention deficit hyperactivity disorder (ADHD), in children with parent-child relational problems, and in mentally retarded children. The results indicate that the early assessment and treatment of psychosocial co-morbidity might improve treatment response in children with fecal incontinence. Children with fecal incontinence are treated less successfully in the first year if they have ADHD, parent-child relational problems, or mental retardation. Psychosocial evaluation and the early assessment and treatment of psychosocial co-morbidity is indicated in order to improve response rate. Family counseling--aimed at improving parent-child relations--should be an integral part of a multidisciplinary treatment program for fecal incontinence. PMID:17952465

  13. Stress Management Affects Outcomes in the Pathophysiology of an Endometriosis Model

    PubMed Central

    Cruz, Myrella L.; Hernández, Siomara; Thompson, Kenira J.; Bayona, Manuel; Flores, Idhaliz

    2014-01-01

    We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions. PMID:25015902

  14. Video games do affect social outcomes: a meta-analytic review of the effects of violent and prosocial video game play.

    PubMed

    Greitemeyer, Tobias; Mügge, Dirk O

    2014-05-01

    Whether video game play affects social behavior is a topic of debate. Many argue that aggression and helping are affected by video game play, whereas this stance is disputed by others. The present research provides a meta-analytical test of the idea that depending on their content, video games do affect social outcomes. Data from 98 independent studies with 36,965 participants revealed that for both violent video games and prosocial video games, there was a significant association with social outcomes. Whereas violent video games increase aggression and aggression-related variables and decrease prosocial outcomes, prosocial video games have the opposite effects. These effects were reliable across experimental, correlational, and longitudinal studies, indicating that video game exposure causally affects social outcomes and that there are both short- and long-term effects. PMID:24458215

  15. Differential outcomes of type A dissection with malperfusion according to affected organ system

    PubMed Central

    Grimm, Joshua C.; Magruder, J. Trent; Crawford, Todd C.; Sciortino, Christopher M.; Zehr, Kenton J.; Mandal, Kaushik; Conte, John V.; Cameron, Duke E.; Black, James H.

    2016-01-01

    type A dissection can be managed in many patients by aortic replacement alone with low overall mortality. Most cases of renal and cerebral malperfusion resolved following aortic surgery. Revascularization was frequently necessary in patients with extremity malperfusion. Patients presenting with intestinal ischemia had very poor outcomes. A patient-specific approach is recommended in such complex patients.

  16. Cellular Intrinsic Mechanism Affecting the Outcome of AML Treated with Ara-C in a Syngeneic Mouse Model

    PubMed Central

    Tan, Dongming; Su, Guangsong; Zheng, Yanwen; He, Chao; Mao, Zhengwei J.; Singleton, Timothy P.; Yin, Bin

    2014-01-01

    The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. PMID:25314317

  17. Factors affecting the outcome of artificial insemination using cryopreserved spermatozoa in the giant panda (Ailuropoda melanoleuca).

    PubMed

    Huang, Yan; Li, Desheng; Zhou, Yingmin; Zhou, Qiang; Li, Rengui; Wang, Chengdong; Huang, Zhi; Hull, Vanessa; Zhang, Hemin

    2012-01-01

    Artificial insemination (AI) is an important component of captive breeding programs for endangered species, such as the giant panda. The panda has been the subject of increasingly successful captive breeding programs involving a compilation of assisted breeding techniques, including AI using cryopreserved spermatozoa. AI implementation is currently hampered by a lack of understanding of the factors that may cause failure. We investigated factors influencing the probability of success of AI for 14 giant panda females housed at the China Center for Research and Conservation of the Giant Panda (CCRCGP) inseminated in a total of 20 instances using cryopreserved spermatozoa from 11 males currently residing in 6 different captive breeding institutions. One of the pandas was the oldest giant panda female to ever successfully conceive from AI (20.5 years old). The success of AI was significantly affected by the timing of AI in relationship to both timing of peak urinary estrogen of the female and percent decline in urinary estrogen between the peak level and the first AI attempt. Our results suggest that the window for successful AI in giant pandas may be narrower than previously suspected, although individual differences in rates of decline in urinary estrogen may reflect some degree of variation in this crucial window across females. Our results are consistent with recent research on pandas and other species that demonstrates the efficacy of cryopreserved spermatozoa for AI and highlights the need for more in-depth analysis of factors related to female physiology that may influence its success. PMID:21932329

  18. Understanding the local socio-political processes affecting conservation management outcomes in Corbett Tiger Reserve, India.

    PubMed

    Rastogi, Archi; Hickey, Gordon M; Badola, Ruchi; Hussain, Syed Ainul

    2014-05-01

    Several measures have been recommended to guarantee a sustainable population of tigers: sufficient inviolate spaces for a viable population, sufficient prey populations, trained and skilled manpower to guard against poaching and intrusion, banning trade in tiger products to reduce poaching, and importantly, the political will to precipitate these recommendations into implementation. Of these, the creation of sufficient inviolate spaces (generally in the form of protected areas) has created the most issues with local resource-dependent communities, often resulting in significant challenges for tiger conservation policy and management. Very little empirical research has, however, been done to understand and contextualize the local-level socio-political interactions that may influence the efficacy of tiger conservation in India. In this paper, we present the results of exploratory research into the ways in which local-stakeholder groups affect the management of Corbett Tiger Reserve (CTR). Using a combined grounded theory-case study research design, and the Institutional Analysis and Development framework for analysis, we identify the socio-political processes through which local-stakeholder groups are able to articulate their issues and elicit desirable actions from the management of CTR. Increasing our awareness of these processes can help inform the design and implementation of more effective tiger conservation management and policy strategies that have the potential to create more supportive coalitions of tiger conservation stakeholders at the local level. PMID:24522894

  19. Understanding the Local Socio-political Processes Affecting Conservation Management Outcomes in Corbett Tiger Reserve, India

    NASA Astrophysics Data System (ADS)

    Rastogi, Archi; Hickey, Gordon M.; Badola, Ruchi; Hussain, Syed Ainul

    2014-05-01

    Several measures have been recommended to guarantee a sustainable population of tigers: sufficient inviolate spaces for a viable population, sufficient prey populations, trained and skilled manpower to guard against poaching and intrusion, banning trade in tiger products to reduce poaching, and importantly, the political will to precipitate these recommendations into implementation. Of these, the creation of sufficient inviolate spaces (generally in the form of protected areas) has created the most issues with local resource-dependent communities, often resulting in significant challenges for tiger conservation policy and management. Very little empirical research has, however, been done to understand and contextualize the local-level socio-political interactions that may influence the efficacy of tiger conservation in India. In this paper, we present the results of exploratory research into the ways in which local-stakeholder groups affect the management of Corbett Tiger Reserve (CTR). Using a combined grounded theory-case study research design, and the Institutional Analysis and Development framework for analysis, we identify the socio-political processes through which local-stakeholder groups are able to articulate their issues and elicit desirable actions from the management of CTR. Increasing our awareness of these processes can help inform the design and implementation of more effective tiger conservation management and policy strategies that have the potential to create more supportive coalitions of tiger conservation stakeholders at the local level.

  20. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice.

    PubMed

    Niermann, Sarah; Rattan, Saniya; Brehm, Emily; Flaws, Jodi A

    2015-06-01

    This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20 μg/kg/day-750 mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities. PMID:25765777

  1. Interconverting Conformations of Slipped-DNA Junctions Formed by Trinucleotide Repeats Affect Repair Outcome

    PubMed Central

    2013-01-01

    Expansions of (CTG)·(CAG) repeated DNAs are the mutagenic cause of 14 neurological diseases, likely arising through the formation and processing of slipped-strand DNAs. These transient intermediates of repeat length mutations are formed by out-of-register mispairing of repeat units on complementary strands. The three-way slipped-DNA junction, at which the excess repeats slip out from the duplex, is a poorly understood feature common to these mutagenic intermediates. Here, we reveal that slipped junctions can assume a surprising number of interconverting conformations where the strand opposite the slip-out either is fully base paired or has one or two unpaired nucleotides. These unpaired nucleotides can also arise opposite either of the nonslipped junction arms. Junction conformation can affect binding by various structure-specific DNA repair proteins and can also alter correct nick-directed repair levels. Junctions that have the potential to contain unpaired nucleotides are repaired with a significantly higher efficiency than constrained fully paired junctions. Surprisingly, certain junction conformations are aberrantly repaired to expansion mutations: misdirection of repair to the non-nicked strand opposite the slip-out leads to integration of the excess slipped-out repeats rather than their excision. Thus, slipped-junction structure can determine whether repair attempts lead to correction or expansion mutations. PMID:23339280

  2. Cardiovascular and affective outcomes of active gaming: using the nintendo wii as a cardiovascular training tool.

    PubMed

    Naugle, Keith E; Naugle, Kelly M; Wikstrom, Erik A

    2014-02-01

    Active-video gaming is purported to produce similar cardiovascular responses as aerobic fitness activities. This study compared the emotional and cardiovascular effects of Wii games with those of traditional exercise in college-aged adults with different exercise backgrounds. Specifically, the percentage of heart rate reserve, rate of perceived exertion (RPE), level of enjoyment, and Positive and Negative Affect Schedule scores were compared between subjects who reported exercising frequently at high intensities (high-intensity exerciser group: age = 20.18 years [0.87]; Height = 165.23 cm [9.97]; Mass = 62.37 kg [11.61]), N = 11 and those who exercise more often at lower intensities (low-intensity exercisers group: age = 20.72 years [1.19]; Height = 164.39 cm [8.05]; Mass = 68.04 kg [10.71]), N = 11. The subjects completed six 20-minute exercises sessions: treadmill walking, stationary cycling, and Wii's Tennis, Boxing, Cycling, and Step. The low-intensity exerciser group achieved a greater percentage of heart rate reserve (a) during traditional exercise compared with that during Wii boxing, (b) playing Wii boxing compared with that for Wii tennis, and (c) playing Wii boxing compared with that when the high-intensity exercisers group played any Wii games (p < 0.05). The RPE was greater for boxing and cycling compared with that for tennis and step (p < 0.05). Ratings of enjoyment and the increase in positive emotion were greater for boxing and for tennis compared with those for traditional exercises (p < 0.05). Results suggest that Wii boxing shows the greatest potential as a cardiovascular fitness tool among the Wii games, particularly for individuals who typically exercise at lower intensities. PMID:23660574

  3. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  4. Resolving the Effects of Maternal and Offspring Genotype on Dyadic Outcomes in Genome Wide Complex Trait Analysis (“M-GCTA”)

    PubMed Central

    Pourcain, Beate St.; Smith, George Davey; York, Timothy P.; Evans, David M.

    2014-01-01

    Genome wide complex trait analysis (GCTA) is extended to include environmental effects of the maternal genotype on offspring phenotype (“maternal effects”, M-GCTA). The model includes parameters for the direct effects of the offspring genotype, maternal effects and the covariance between direct and maternal effects. Analysis of simulated data, conducted in OpenMx, confirmed that model parameters could be recovered by full information maximum likelihood (FIML) and evaluated the biases that arise in conventional GCTA when indirect genetic effects are ignored. Estimates derived from FIML in OpenMx showed very close agreement to those obtained by restricted maximum likelihood using the published algorithm for GCTA. The method was also applied to illustrative perinatal phenotypes from ∼4,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children. The relative merits of extended GCTA in contrast to quantitative genetic approaches based on analyzing the phenotypic covariance structure of kinships are considered. PMID:25060210

  5. 48 week outcomes of maraviroc-containing regimens following the genotypic or Trofile assay in HIV-1 failing subjects: the OSCAR Study.

    PubMed

    Nozza, Silvia; Pignataro, Angela Rosa; Galli, Laura; Svicher, Valentina; Alteri, Claudia; Boeri, Enzo; Ripa, Marco; Castagna, Antonella; Sampaolo, Michela; Clementi, Massimo; Perno, Carlo Federico; Lazzarin, Adriano

    2016-09-01

    This study assessed the 48-week efficacy of an antiretroviral therapy including maraviroc following the assessment of co-receptor tropism by use of Geno2Pheno algorithm or the Trofile phenotypic assay in failing treatment-experienced HIV-1 patients. This was a multicenter, randomized, open-label, non-inferiority trial. Treatment-experienced subjects with HIV-RNA ≥500 copies/mL were randomized (1:1) to undergo co-receptor tropism testing by the Geno- 2Pheno algorithm (with a false positive rate >10%) or the Trofile assay before starting a new antiretroviral treatment which included maraviroc. The primary endpoint was the 48 week proportion of patients with treatment success (TS). Intention-to-treat analyses are also reported. One hundred and fifty-five experienced patients were analysed: 77 patients in the Trofile arm and 78 in the Genotype arm. The 48-week proportion of TS was 87% in the Trofile arm and 89% in the Genotype arm (difference: 1.5%, 95%CI: -8.9% to 11.8%) suggesting non-inferiority. In the Trofile arm, 10 patients had treatment failure: 5 viral rebound, 5 discontinuations. In the Genotype arm, 9 patients had treatment failure: 7 viral rebound, 2 lost to follow-up. CD4+ significantly increased from baseline to week 48 in both arms. 48-week treatment success was similar for maraviroc-including therapy prescribed following the Trofile phenotypic assay or Geno2Pheno algorithm. PMID:27602417

  6. Cognitive and Affective Predictors of Treatment Outcome in Cognitive Processing Therapy and Prolonged Exposure for Posttraumatic Stress Disorder

    PubMed Central

    Rizvi, Shireen L.; Vogt, Dawne S.; Resick, Patricia A.

    2009-01-01

    This study examined cognitive and affective predictors of treatment dropout and treatment efficacy in Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) for PTSD. Study participants were women with PTSD from a sexual assault who received at least one session of either treatment (n=145) as part of a randomized clinical trial. Results revealed that younger age, lower intelligence, and less education were associated with higher treatment dropout, whereas higher depression and guilt at pretreatment were associated with greater improvement in PTSD symptomatology. Results by treatment condition indicated that women with higher anger at pretreatment were more likely to drop out of PE and that older women in PE and younger women in CPT had the best overall outcomes. These findings have implications for efforts to enhance treatment efficacy and retention in CBT treatment protocols. PMID:19595295

  7. Cognitive and affective predictors of treatment outcome in Cognitive Processing Therapy and Prolonged Exposure for posttraumatic stress disorder.

    PubMed

    Rizvi, Shireen L; Vogt, Dawne S; Resick, Patricia A

    2009-09-01

    This study examined cognitive and affective predictors of treatment dropout and treatment efficacy in Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) for PTSD. Study participants were women with PTSD from a sexual assault who received at least one session of either treatment (n = 145) as part of a randomized clinical trial. Results revealed that younger age, lower intelligence, and less education were associated with higher treatment dropout, whereas higher depression and guilt at pretreatment were associated with greater improvement in PTSD symptomatology. Results by treatment condition indicated that women with higher anger at pretreatment were more likely to dropout of PE and that older women in PE and younger women in CPT had the best overall outcomes. These findings have implications for efforts to enhance treatment efficacy and retention in CBT treatment protocols. PMID:19595295

  8. Factors affecting the outcome of maternity care. 1. Relationship between staffing and perinatal deaths at the hospital of birth.

    PubMed Central

    Stilwell, J; Szczepura, A; Mugford, M

    1988-01-01

    This is the first of two papers describing a retrospective study of maternity hospitals in an English health region using data for the years 1977-83. The research was designed to investigate the relationship between resources (such as staff and equipment) and the outcomes of births at maternity units. Considerable variation in medical and nursing staffing levels in the units in the study was observed. Regression analysis suggests that, after taking account of differences in very low weight births at each unit, the level of paediatric staffing at a maternity unit is a significant factor in explaining differences in "in house" mortality. There was no identifiable relationship between staff categories other than paediatricians and the rate of perinatal death at the hospital of delivery. As selective referral and transfers between hospitals may affect the interpretation of these findings, a second paper follows presenting the results of a further analysis that adjusts both resources and outcomes to take account of neonatal transfers. PMID:3221166

  9. Examination of affective, cognitive, and behavioral factors and suicide-related outcomes in children and young adolescents.

    PubMed

    Nock, Matthew K; Kazdin, Alan E

    2002-03-01

    Examined the role of affective, cognitive, and behavioral factors in the occurrence of suicidal ideation, suicide attempts, and suicidal intent in child and young adolescent (N = 175, ages 6 to 13 years) psychiatric inpatients. The results indicated that (a) self-reported depressed mood, negative automatic thoughts, hopelessness about the future, and anhedonia were all significantly associated with suicide-related outcomes, and these relations remained statistically significant even after depressed mood was controlled; (b) suicidal participants (both ideators and attempters) were distinguished from nonsuicidal participants by higher scores on measures of depressed mood, negative automatic thoughts, and hopelessness; and (c) participants who reported making a suicide attempt were distinguished from those who did not by higher scores on a measure of anhedonia and a higher number of previous suicide attempts. The results demonstrate the importance of negative automatic thoughts and anhedonia, and provide support for the role of hopelessness and previous suicide attempts in the occurrence of different suicide-related outcomes in children and young adolescents. PMID:11845650

  10. An investigation of home advantage and other factors affecting outcomes in English one-day cricket matches.

    PubMed

    Morley, Bruce; Thomas, Dennis

    2005-03-01

    We examined the factors affecting the outcome of cricket matches played in the English one-day county cricket league. In particular, we focused on the home-field effect and the importance of winning the pre-match toss of a coin to determine a team's strategic decision to bat first or second. A home-field effect appeared to be confirmed in that home teams won 57% of all matches with a win/loss result. A logistical regression model was used, with the outcome variable defined in terms of a home team win/loss. We found that while winning the toss is an important aspect of a one-day cricket match, other factors tend to dominate in determining the result, especially team quality and match importance for the home and away teams in the overall league context. Our results also indicate, not surprisingly given the nature of cricket attendance and spectating, that the crowd effect is largely insignificant. The results of our study do not support any rule changes requiring the abandonment of the coin toss to determine batting order. PMID:15966344

  11. Genotypic Tannin Levels in Populus tremula Impact the Way Nitrogen Enrichment Affects Growth and Allocation Responses for Some Traits and Not for Others.

    PubMed

    Bandau, Franziska; Decker, Vicki Huizu Guo; Gundale, Michael J; Albrectsen, Benedicte Riber

    2015-01-01

    Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root:shoot ratios, and tissue lignin and N concentrations. A genotype's baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses, which suggests a

  12. Calcium-Vitamin D Co-supplementation Affects Metabolic Profiles, but not Pregnancy Outcomes, in Healthy Pregnant Women

    PubMed Central

    Asemi, Zatollah; Samimi, Mansooreh; Siavashani, Mehrnush Amiri; Mazloomi, Maryam; Tabassi, Zohreh; Karamali, Maryam; Jamilian, Mehri; Esmaillzadeh, Ahmad

    2016-01-01

    Background: Pregnancy is associated with unfavorable metabolic profile, which might in turn result in adverse pregnancy outcomes. The current study was designed to evaluate the effects of calcium plus Vitamin D administration on metabolic status and pregnancy outcomes in healthy pregnant women. Methods: This randomized double-blind placebo-controlled clinical trial was performed among 42 pregnant women aged 18–40 years who were at week 25 of gestation. Subjects were randomly allocated to consume either 500 mg calcium-200 IU cholecalciferol supplements (n = 21) or placebo (n = 21) for 9 weeks. Blood samples were obtained at the onset of the study and after 9-week trial to determine related markers. Post-delivery, the newborn's weight, length, and head circumference were measured during the first 24 h after birth. Results: Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein levels compared with placebo (−1856.8 ± 2657.7 vs. 707.1 ± 3139.4 μg/mL, P = 0.006). We also found a significant elevation of plasma total antioxidant capacity (89.3 ± 118.0 vs. −9.4 ± 164.9 mmol/L, P = 0.03), serum 25-hydroxyvitamin D (2.5 ± 3.5 vs. −1.7 ± 1.7 ng/mL, P < 0.0001), and calcium levels (0.6 ± 0.6 vs. −0.1 ± 0.4 mg/dL, P < 0.0001). The supplementation led to a significant decrease in diastolic blood pressure (−1.9 ± 8.3 vs. 3.1 ± 5.2 mmHg, P = 0.02) compared with placebo. No significant effect of calcium-Vitamin D co-supplements was seen on other metabolic profiles. We saw no significant change of the co-supplementation on pregnancy outcomes as well. Conclusions: Although calcium-Vitamin D co-supplementation for 9 weeks in pregnant women resulted in improved metabolic profiles, it did not affect pregnancy outcomes. PMID:27076887

  13. Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials

    PubMed Central

    Kelly, Michael P.; Anderson, Paul A.; Sasso, Rick C.; Riew, K. Daniel

    2015-01-01

    Object The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery. Methods A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single-level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-ltem Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/ hydrocodone), and opioid-naïve groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively. Results Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naïve. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong –52.3, weak –50.6, naïve –54.0, p = 0.244; neck: strong –52.7, weak –50.8, naïve –44.6, p = 0.355); NDI scores (strong –36.0, weak –33.3, naïve –32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naïve 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naïve 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point. Conclusions Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient

  14. An Analysis of Factors Affecting Genotyping Success from Museum Specimens Reveals an Increase of Genetic and Morphological Variation during a Historical Range Expansion of a European Spider

    PubMed Central

    Krehenwinkel, Henrik; Pekar, Stano

    2015-01-01

    Natural history collections house an enormous amount of plant and animal specimens, which constitute a promising source for molecular analyses. Storage conditions differ among taxa and can have a dramatic effect on the success of DNA work. Here, we analyze the feasibility of DNA extraction from ethanol preserved spiders (Araneae). We tested genotyping success using several hundred specimens of the wasp spider, Argiope bruennichi, deposited in two large German natural history collections. We tested the influence of different factors on the utility of specimens for genotyping. Our results show that not the specimen’s age, but the museum collection is a major predictor of genotyping success. These results indicate that long term storage conditions should be optimized in natural history museums to assure the utility of collections for DNA work. Using historical material, we also traced historical genetic and morphological variation in the course of a poleward range expansion of A. bruennichi by comparing contemporary and historical specimens from a native and an invasive population in Germany. We show that the invasion of A. bruennichi is tightly correlated with an historical increase of genetic and phenotypic variation in the invasive population. PMID:26309219

  15. An Analysis of Factors Affecting Genotyping Success from Museum Specimens Reveals an Increase of Genetic and Morphological Variation during a Historical Range Expansion of a European Spider.

    PubMed

    Krehenwinkel, Henrik; Pekar, Stano

    2015-01-01

    Natural history collections house an enormous amount of plant and animal specimens, which constitute a promising source for molecular analyses. Storage conditions differ among taxa and can have a dramatic effect on the success of DNA work. Here, we analyze the feasibility of DNA extraction from ethanol preserved spiders (Araneae). We tested genotyping success using several hundred specimens of the wasp spider, Argiope bruennichi, deposited in two large German natural history collections. We tested the influence of different factors on the utility of specimens for genotyping. Our results show that not the specimen's age, but the museum collection is a major predictor of genotyping success. These results indicate that long term storage conditions should be optimized in natural history museums to assure the utility of collections for DNA work. Using historical material, we also traced historical genetic and morphological variation in the course of a poleward range expansion of A. bruennichi by comparing contemporary and historical specimens from a native and an invasive population in Germany. We show that the invasion of A. bruennichi is tightly correlated with an historical increase of genetic and phenotypic variation in the invasive population. PMID:26309219

  16. Co-dependence of genotype and dietary protein intake to affect expression on amino acid/peptide transporters in porcine skeletal muscle.

    PubMed

    Liu, Y; Kong, X; Li, F; Tan, B; Li, Y; Duan, Y; Yin, Y; He, J; Hu, C; Blachier, F; Wu, Guoyao

    2016-01-01

    A total of 96 barrows (48 pure-bred Bama mini-pigs representing fatty genotype, and 48 Landrace pigs representing lean genotype) were randomly assigned to either a low- or adequate-protein treatment diet. The experimental period commenced at 5 weeks of age and extended to the finishing period. After euthanasia, blood and skeletal muscle samples were collected from pigs at the nursery, growing, and finishing phases. Our results indicate that the concentrations of free AAs in the plasma and muscle decreased as the age of the pigs increased. In addition, a strain × growth phase interaction (P < 0.05) was observed for the free AA pool in the plasma and muscle. The low-protein diet upregulated (P < 0.05) the mRNA levels for T1R1/T1R3 involved in glutamate binding, but downregulated (P < 0.05) the mRNA levels for PAT1, PAT2, and ASCT2, which transport neutral AAs into muscles. Bama mini-pigs had higher (P < 0.05) mRNA levels for LAT1, SNAT2, and EAAC1, but a lower (P < 0.05) mRNA level for PepT1, compared with Landrace pigs. Collectively, our findings indicate that adequate provision of dietary protein plays an important role in regulating profiles of free AA pools and expression of key AA/peptide transporters/transceptors in a genotype- and tissue-specific manner. PMID:26255284

  17. DNA Storage under High Temperature Conditions Does Not Affect Performance in Human Leukocyte Antigen Genotyping via Next-Generation Sequencing (DNA Integrity Maintained in Extreme Conditions)

    PubMed Central

    McDevitt, Shana L; Hogan, Michael E; Pappas, Derek J; Wong, Lily Y

    2014-01-01

    Background: Stable dry-state storage of DNA is desirable to minimize required storage space and to reduce electrical and shipping costs. DNA purified from various commercially available dry-state stabilization matrices has been used successfully in downstream molecular applications (e.g., quantitative polymerase chain reaction [qPCR], microarray, and sequence-based genotyping). However, standard DNA storage conditions still include freezing of DNA eluted in aqueous buffers or nuclease-free water. Broad implementation of dry-state, long-term DNA storage requires enhancement of such dry-state DNA stabilization products to control for temperature fluctuations at specimen collection, transit, and storage. This study tested the integrity of genomic DNA subjected to long-term storage on GenTegra™ DNA stabilization matrices (GenTegra LLC, Pleasanton, CA) at extreme conditions, as defined by a 4-year storage period at ambient temperature with an initial incubation for 7 months at 37°C, 56°C, or ambient temperature. Subsequently, purified DNA performance and integrity were measured by qPCR and next-generation sequencing (NGS)-based human leokocyte antigen (HLA) genotyping. Results: High molecular weight genomic DNA samples were recovered from the GenTegra product matrix and exhibited integrity comparable to a highly characterized commercial standard under assessment by qPCR. Samples were genotyped for classical HLA loci using next generation sequencing-based methodolgy on the Roche 454 GS Junior instrument. Amplification efficiency, sequence coverage, and sequence quality were all comparable with those produced from a cell line DNA sequenced as a control. No significant differences were observed in the mean, median, or mode quality scores between samples and controls (p≥0.4). Conclusions: Next generation HLA genotyping was chosen to test the integrity of GenTegra-treated genomic DNA due to the requirment for long sequence reads to genotype the highly polymorphic

  18. Diversity of killer cell immunoglobulin-like receptor (KIR) genotypes and KIR2DL2/3 variants in HCV treatment outcome.

    PubMed

    Vidal-Castiñeira, Jose Ramón; López-Vázquez, Antonio; Martínez-Borra, Jesús; Martínez-Camblor, Pablo; Prieto, Jesús; López-Rodríguez, Rosario; Sanz-Cameno, Paloma; de la Vega, Juan; Rodrigo, Luis; Pérez-López, Rosa; Pérez-Álvarez, Ramón; López-Larrea, Carlos

    2014-01-01

    The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism. PMID:24927414

  19. The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C

    PubMed Central

    Domagalski, Krzysztof; Pawłowska, Małgorzata; Kozielewicz, Dorota; Dybowska, Dorota; Tretyn, Andrzej; Halota, Waldemar

    2015-01-01

    The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer’s modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients. PMID:26115415

  20. Compressed Genotyping

    PubMed Central

    Erlich, Yaniv; Gordon, Assaf; Brand, Michael; Hannon, Gregory J.; Mitra, Partha P.

    2011-01-01

    Over the past three decades we have steadily increased our knowledge on the genetic basis of many severe disorders. Nevertheless, there are still great challenges in applying this knowledge routinely in the clinic, mainly due to the relatively tedious and expensive process of genotyping. Since the genetic variations that underlie the disorders are relatively rare in the population, they can be thought of as a sparse signal. Using methods and ideas from compressed sensing and group testing, we have developed a cost-effective genotyping protocol to detect carriers for severe genetic disorders. In particular, we have adapted our scheme to a recently developed class of high throughput DNA sequencing technologies. The mathematical framework presented here has some important distinctions from the ’traditional’ compressed sensing and group testing frameworks in order to address biological and technical constraints of our setting. PMID:21451737

  1. KIR2DL5B genotype predicts outcomes in CML patients treated with response-directed sequential imatinib/nilotinib strategy.

    PubMed

    Yeung, David T; Tang, Carine; Vidovic, Ljiljana; White, Deborah L; Branford, Susan; Hughes, Timothy P; Yong, Agnes S

    2015-12-17

    Killer immunoglobulin-like receptors (KIRs) on natural killer (NK) cells have been shown to predict for response in chronic phase-chronic myeloid leukemia (CP-CML) patients treated with tyrosine kinase inhibitors. We performed KIR genotyping in 148 newly diagnosed CP-CML patients treated with a novel sequential imatinib/nilotinib strategy aimed at achievement of optimal molecular responses at defined time points. We found the presence of KIR2DL5B to be associated with inferior transformation-free survival and event-free survival and an independent predictor of inferior major molecular response (BCR-ABL1 ≤0.1%) and molecular response 4.5 (BCR-ABL1 ≤0.0032%). This suggests a critical early role for NK cells in facilitating response to imatinib that cannot be overcome by subsequent intensification of therapy. KIR genotyping may add valuable prognostic information to future baseline predictive scoring systems in CP-CML patients and facilitate optimal frontline treatment selection. PMID:26500342

  2. SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours

    PubMed Central

    Khatri, A; Williams, B W; Fisher, J; Brundage, R C; Gurvich, V J; Lis, L G; Skubitz, K M; Dudek, A Z; Greeno, E W; Kratzke, R A; Lamba, J K; Kirstein, M N

    2014-01-01

    Background: Gemcitabine is used for the treatment of several solid tumours and exhibits high inter-individual pharmacokinetic variability. In this study, we explore possible predictive covariates on drug and metabolite disposition. Methods: Forty patients were enrolled. Gemcitabine and dFdU concentrations in the plasma and dFdCTP concentrations in peripheral blood mononuclear cell were measured to 72 h post infusion, and pharmacokinetic parameters were estimated by nonlinear mixed-effects modelling. Patient-specific covariates were tested in model development. Results: The pharmacokinetics of gemcitabine was best described by a two-compartment model with body surface area, age and NT5C2 genotype as significant covariates. The pharmacokinetics of dFdU and dFdCTP were adequately described by three-compartment models. Creatinine clearance and cytidine deaminase genotype were significant covariates for dFdU pharmacokinetics. Rate of infusion of <25 mg m−2 min−1 and the presence of homozygous major allele for SLC28A3 (CC genotype) were each associated with an almost two-fold increase in the formation clearance of dFdCTP. Conclusion: Prolonged dFdCTP systemic exposures (⩾72 h) were commonly observed. Infusion rate <25 mg m−2 min−1 and carriers for SLC28A3 variant were each associated with about two-fold higher dFdCTP formation clearance. The impacts of these covariates on treatment-related toxicity in more selected patient populations (that is, first-line treatment, single disease state and so on) are not yet clear. PMID:24300978

  3. Genotypic Tannin Levels in Populus tremula Impact the Way Nitrogen Enrichment Affects Growth and Allocation Responses for Some Traits and Not for Others

    PubMed Central

    Bandau, Franziska; Decker, Vicki Huizu Guo; Gundale, Michael J.; Albrectsen, Benedicte Riber

    2015-01-01

    Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root:shoot ratios, and tissue lignin and N concentrations. A genotype’s baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses, which suggests a

  4. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae).

    PubMed

    Silva-Brandão, Karina Lucas; Silva, Oscar Arnaldo Batista Neto E; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A H

    2015-06-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by geographic proximity between sampling localities. Overall genetic structure inferred by a nonhierarchical amova resulted in a significant ΦST value = 0.19109. Here, we demonstrate for the first time that SNPs gathered by genotyping-by-sequencing can be used to infer genetic structure of a pest insect in Brazil; moreover, our results indicate that those markers are very informative even over a restricted geographic scale. We also demonstrate that host plant association has little effect on genetic structure among Brazilian populations of G. molesta; on the other hand, reduced gene flow promoted by geographic isolation has a stronger impact on population differentiation. PMID:26029261

  5. Arsenic affects mineral nutrients in grains of various Indian rice (Oryza sativa L.) genotypes grown on arsenic-contaminated soils of West Bengal.

    PubMed

    Dwivedi, Sanjay; Tripathi, R D; Srivastava, Sudhakar; Singh, Ragini; Kumar, Amit; Tripathi, Preeti; Dave, Richa; Rai, U N; Chakrabarty, Debasis; Trivedi, P K; Tuli, R; Adhikari, B; Bag, M K

    2010-09-01

    The exposure of paddy fields to arsenic (As) through groundwater irrigation is a serious concern that may not only lead to As accumulation to unacceptable levels but also interfere with mineral nutrients in rice grains. In the present field study, profiling of the mineral nutrients (iron (Fe), phosphorous, zinc, and selenium (Se)) was done in various rice genotypes with respect to As accumulation. A significant genotypic variation was observed in elemental retention on root Fe plaque and their accumulation in various plant parts including grains, specific As uptake (29-167 mg kg(-1) dw), as well as As transfer factor (4-45%). Grains retained the least level of As (0.7-3%) with inorganic As species being the dominant forms, while organic As species, viz., dimethylarsinic acid and monomethylarsonic acid, were non-detectable. In all tested varieties, the level of Se was low (0.05-0.12 mg kg(-1) dw), whereas that of As was high (0.4-1.68 mg kg(-1) dw), considering their safe/recommended daily intake limits, which may not warrant their human consumption. Hence, their utilization may increase the risk of arsenicosis, when grown in As-contaminated areas. PMID:20490609

  6. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae)

    PubMed Central

    Silva-Brandão, Karina Lucas; Silva, Oscar Arnaldo Batista Neto e; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A H

    2015-01-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by geographic proximity between sampling localities. Overall genetic structure inferred by a nonhierarchical amova resulted in a significant ΦST value = 0.19109. Here, we demonstrate for the first time that SNPs gathered by genotyping-by-sequencing can be used to infer genetic structure of a pest insect in Brazil; moreover, our results indicate that those markers are very informative even over a restricted geographic scale. We also demonstrate that host plant association has little effect on genetic structure among Brazilian populations of G. molesta; on the other hand, reduced gene flow promoted by geographic isolation has a stronger impact on population differentiation. PMID:26029261

  7. Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

    PubMed Central

    Moulik, Nirmalya Roy; Kumar, Archana; Agrawal, Suraksha; Mahdi, Abbas Ali; Kumar, Ashutosh

    2016-01-01

    Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03) and longer duration of chemotherapy interruption (P = 0.009). Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03). All 3 deaths encountered were seen in folate deficient children. Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency. PMID:27168705

  8. CYP4F2 affects phenotypic outcome in adrenoleukodystrophy by modulating the clearance of very long-chain fatty acids.

    PubMed

    van Engen, Catherine E; Ofman, Rob; Dijkstra, Inge M E; van Goethem, Tessa Jacobs; Verheij, Eveline; Varin, Jennifer; Vidaud, Michel; Wanders, Ronald J A; Aubourg, Patrick; Kemp, Stephan; Barbier, Mathieu

    2016-10-01

    X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder caused by the accumulation of very long-chain fatty acids (VLCFA) due to mutations in the ABCD1 gene. The phenotypic spectrum ranges from a fatal cerebral demyelinating disease in childhood (cerebral ALD) to a progressive myelopathy without cerebral involvement in adulthood (adrenomyeloneuropathy). Because ABCD1 mutations have no predictive value with respect to clinical outcome a role for modifier genes was postulated. We report that the CYP4F2 polymorphism rs2108622 increases the risk of developing cerebral ALD in Caucasian patients. The rs2108622 polymorphism (c.1297G>A) results in an amino acid substitution valine for methionine at position 433 (p.V433M). Using cellular models of VLCFA accumulation, we show that p.V433M decreases the conversion of VLCFA into very long-chain dicarboxylic acids by ω-oxidation, a potential escape route for the deficient peroxisomal β-oxidation of VLCFA in ALD. Although p.V433M does not affect the catalytic activity of CYP4F2 it reduces CYP4F2 protein levels markedly. These findings open perspectives for therapeutic interventions in a disease with currently limited treatment options. PMID:27425035

  9. Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes

    PubMed Central

    Jin, Nana; Wu, Deng; Gong, Yonghui; Bi, Xiaoman; Jiang, Hong; Li, Kongning; Wang, Qianghu

    2014-01-01

    An increasing number of experiments have been designed to detect intracellular and intercellular molecular interactions. Based on these molecular interactions (especially protein interactions), molecular networks have been built for using in several typical applications, such as the discovery of new disease genes and the identification of drug targets and molecular complexes. Because the data are incomplete and a considerable number of false-positive interactions exist, protein interactions from different sources are commonly integrated in network analyses to build a stable molecular network. Although various types of integration strategies are being applied in current studies, the topological properties of the networks from these different integration strategies, especially typical applications based on these network integration strategies, have not been rigorously evaluated. In this paper, systematic analyses were performed to evaluate 11 frequently used methods using two types of integration strategies: empirical and machine learning methods. The topological properties of the networks of these different integration strategies were found to significantly differ. Moreover, these networks were found to dramatically affect the outcomes of typical applications, such as disease gene predictions, drug target detections, and molecular complex identifications. The analysis presented in this paper could provide an important basis for future network-based biological researches. PMID:25243127

  10. Factors affecting the outcome of fractures of the femoral neck in children and adolescents: a systematic review.

    PubMed

    Yeranosian, M; Horneff, J G; Baldwin, K; Hosalkar, H S

    2013-01-01

    Fractures of the femoral neck in children are rare, high-energy injuries with high complication rates. Their treatment has become more interventional but evidence of the efficacy of such measures is limited. We performed a systematic review of studies examining different types of treatment and their outcomes, including avascular necrosis (AVN), nonunion, coxa vara, premature physeal closure (PPC), and Ratliff's clinical criteria. A total of 30 studies were included, comprising 935 patients. Operative treatment and open reduction were associated with higher rates of AVN. Delbet types I and II fractures were most likely to undergo open reduction and internal fixation. Coxa vara was reduced in the operative group, whereas nonunion and PPC were not related to surgical intervention. Nonunion and coxa vara were unaffected by the method of reduction. Capsular decompression had no effect on AVN. Although surgery allows a more anatomical union, it is uncertain whether operative treatment or the type of reduction affects the rate of AVN, nonunion or PPC, because more severe fractures were operated upon more frequently. A delay in treatment beyond 24 hours was associated with a higher incidence of AVN. PMID:23307688

  11. The seed's protein and oil content, fatty acid composition, and growing cycle length of a single genotype of chia (Salvia hispanica L.) as affected by environmental factors.

    PubMed

    Ayerza, Ricardo

    2009-01-01

    As a botanical source, variability in chia seed composition could be expected between growing locations, and between years within a location, due to genotype and environment effects as well genetic x environment's interactions. The objective of the present study was to determine the location effect on the growing cycle length, and seed's protein content, lipid content, and fatty acid profiles, of a single chia genotype. Seeds of chia genotype Tzotzol grown on eight sites in five different ecosystems were tested. One site was in Argentina, in the Semi-Arid Chaco ecosystem (T(5)); one was in Bolivia, in the Sub-Humid Chaco ecosystem (T(4)); and six in Ecuador, one in the Coastal Desert (T(3)), two on the Tropical Rain Forest (T(2)), and three in the Inter-Andean Dry Valley ecosystem (T(1)). Seeds from plants grown in T(4) and in T(3) contained significantly (P <0.05) more protein percentage than did seeds from the other three ecosystems. No significant (P <0.05) differences in protein content were found between T(3) and T(4), and between T(1), T(2), and T(5). Seeds from T(1) and T(5) ecosystems, with 33.5 and 32.2%, respectively, were the numerically highest oil content producers, but their results were only significantly (P <0.05) higher when compared with the T(2) seeds. Significant (P <0.05) differences in palmitic, stearic, oleic, linoleic and alpha-linolenic fatty acids between oils from seeds grown in different ecosystems were detected, however. Oil of seeds grown in the T(3) ecosystem had the palmitic, stearic and oleic fatty acids' highest contents. Palmitic and oleic fatty acid levels were significantly (P <0.05) higher when were compared to that of seeds grown in the T(1) ecosystem, and stearic when was compared to that of seeds grown in the T(5) ecosystem; omega-6 linoleic fatty acid content was significantly (P <0.05) lower in oils of seeds produced in T(1), and T(2) than in those produced in T(3), T(4), and T(5) ecosystems; omega-3 alpha-linolenic fatty

  12. Amino acid substitutions in the hepatitis C virus core region of genotype 1b affect very early viral dynamics during treatment with telaprevir, peginterferon, and ribavirin.

    PubMed

    Akuta, Norio; Suzuki, Fumitaka; Hirakawa, Miharu; Kawamura, Yusuke; Yatsuji, Hiromi; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

    2010-04-01

    Substitution of amino acid (aa) 70 and 91 in the core region of hepatitis C virus (HCV) genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the rate of HCV RNA loss following 12-week triple therapy, and determine the effect of aa substitutions on very early (within 48 hr) viral dynamics. Sixty-seven patients infected with HCV genotype 1b (HCV-1b) and high viral load who received 12-week triple therapy were studied. RNA loss could be achieved in 2%, 34%, 80%, 92%, 95%, 94%, and 90% of the patients after 1, 2, 4, 6, 8, 10, and 12 weeks of triple therapy, respectively. After 24-hr treatment, the proportion of patients with Arg70 and Leu91 substitutions with > or = 3.0 log fall in HCV RNA was significantly higher than those with < 3.0 log fall (P = 0.008). However, the aa substitution patterns in the core region did not influence the fall in HCV RNA after 48-hr treatment. Multivariate analysis identified substitutions of aa 70 and 91 (P = 0.014) and level of viremia at baseline (> or = 7.0 log IU/ml; P = 0.085) as independent parameters that determined the > or = 3.0 log fall in HCV RNA level after 24-hr triple therapy. It is concluded that 12-week triple therapy achieved high rates of loss of HCV RNA in Japanese patients infected with HCV-1b and high viral load, and that the aa substitution pattern in the core region seems to influence very early viral dynamics. PMID:20166188

  13. Genotyping methods.

    PubMed

    Tümmler, Burkhard

    2014-01-01

    Genotyping allows for the identification of bacterial isolates to the strain level and provides basic information about the evolutionary biology, population biology, taxonomy, ecology, and genetics of bacteria. Depending on the underlying question and available resources, Pseudomonas aeruginosa strains may be typed by anonymous fingerprinting techniques or electronically portable sequence-based typing methods such as multiple locus variable number tandem repeat (VNTR) analysis (MLVA), multilocus sequence typing, or oligonucleotide microarray. Macrorestriction fragment pattern analysis is a genotyping method that is globally applicable to all bacteria and hence has been and still is the reference method for strain typing in bacteriology. Agarose-embedded chromosomal DNA is cleaved with a rare-cutting restriction endonuclease and the generated 20-70 fragments are then separated by pulsed-field gel electrophoresis. The chapter provides a detailed step-by-step manual for SpeI genome fingerprinting of Pseudomonas chromosomes that has been optimized for SpeI fragment pattern analysis of P. aeruginosa. PMID:24818895

  14. Genotypic and phenotypic comparison of Escherichia coli from uterine infections with different outcomes: clinical metritis in the cow and pyometra in the bitch.

    PubMed

    Henriques, Sofia; Silva, Elisabete; Lemsaddek, Abdelhak; Lopes-da-Costa, Luís; Mateus, Luisa

    2014-05-14

    Escherichia coli uterine infection originates different clinical outcomes in the canine and bovine species. Here, E. coli strains isolated from bovine clinical metritis and canine pyometra cases were analyzed by PFGE, screened for 33 virulence factor (VF) genes and for phylogenetic grouping. Bovine and canine E. coli isolates presented a low degree of genetic similarity. Canine E. coli strains belonged to phylogenetic group B2 and presented a high number of VF genes, whereas bovine E. coli strains belonged to phylogenetic groups B1 and A and had a low number of VF genes. In conclusion, E. coli strains isolated from cow clinical metritis had a low potential of virulence. In contrast, bitch pyometra E. coli isolates had a high virulence potential, which might be relevant in the pathogenesis of pyometra. These differences between canine and bovine E. coli isolates may partially explain the different outcomes of the uterine infection in the two species. PMID:24598134

  15. Treatment Outcome of Tuberculosis Patients under Directly Observed Treatment Short Course and Factors Affecting Outcome in Southern Ethiopia: A Five-Year Retrospective Study.

    PubMed

    Gebrezgabiher, Gebremedhin; Romha, Gebremedhin; Ejeta, Eyasu; Asebe, Getahun; Zemene, Endalew; Ameni, Gobena

    2016-01-01

    Tuberculosis (TB) is one of the major public health and socio-economic issues in the 21st century globally. Assessment of TB treatment outcomes, and monitoring and evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS) are among the major indicators of the performance of a national TB control program. Hence, this institution-based retrospective study was conducted to determine the treatment outcome of TB patients and investigate factors associated with unsuccessful outcome at Dilla University Referral Hospital, southern Ethiopia. Five years (2008 to 2013) TB record of TB clinic of the hospital was reviewed. A total 1537 registered TB patients with complete information were included. Of these, 942 (61.3%) were male, 1015 (66%) were from rural areas, 544 (35.4%) were smear positive pulmonary TB (PTB+), 816 (53.1%) were smear negative pulmonary TB (PTB-) and 177(11.5%) were extra pulmonary TB (EPTB) patients. Records of the 1537 TB patients showed that 181 (11.8%) were cured, 1129(73.5%) completed treatment, 171 (11.1%) defaulted, 52 (3.4%) died and 4 (0.3%) had treatment failure. The overall mean treatment success rate of the TB patients was 85.2%. The treatment success rate of the TB patients increased from 80.5% in September 2008-August 2009 to 84.8% in September 2012-May 2013. Tuberculosis type, age, residence and year of treatment were significantly associated with unsuccessful treatment outcome. The risk of unsuccessful outcome was significantly higher among TB patients from rural areas (AOR = 1.63, 95% CI: 1.21-2.20) compared to their urban counterparts. Unsuccessful treatment outcome was also observed in PTB- patients (AOR = 1.77, 95% CI: 1.26-2.50) and EPTB (AOR = 2.07, 95% CI: 1.28-3.37) compared to the PTB+ patients. In conclusion, it appears that DOTS have improved treatment success in the hospital during five years. Regular follow-up of patients with poor treatment outcome and provision of health information on TB treatment to

  16. Frame-of-Reference Training Effectiveness: Effects of Goal Orientation and Self-Efficacy on Affective, Cognitive, Skill-Based, and Transfer Outcomes

    ERIC Educational Resources Information Center

    Dierdorff, Erich C.; Surface, Eric A.; Brown, Kenneth G.

    2010-01-01

    Empirical evidence supporting frame-of-reference (FOR) training as an effective intervention for calibrating raters is convincing. Yet very little is known about who does better or worse in FOR training. We conducted a field study of how motivational factors influence affective, cognitive, and behavioral learning outcomes, as well as near transfer…

  17. The Development of an Indicator System for The Affective and Social Schooling Outcomes for Primary and Secondary Students in Hong Kong

    ERIC Educational Resources Information Center

    Moore, Phillip J.; Mo Ching Mok, Magdalena; Chan, Lorna K.S.; Yin Lai, Po

    2006-01-01

    This paper reports the development of performance indicators for measuring primary and secondary students? affective and social outcomes of schooling. Psychometric properties as well as norms for the selected performance indicators for Hong Kong students were developed. The performance indicator system developed in this study has been subsequently…

  18. Gene-Environment Interaction of ApoE Genotype and Combat Exposure on PTSD

    PubMed Central

    Lyons, Michael J.; Genderson, Margo; Grant, Michael D.; Logue, Mark; Zink, Tyler; McKenzie, Ruth; Franz, Carol E.; Panizzon, Matthew; Lohr, James B.; Jerskey, Beth; Kremen, William S.

    2015-01-01

    Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. PMID:24132908

  19. HCV NS3Ag: a reliable and clinically useful predictor of antiviral outcomes in genotype 1b hepatitis C virus-infected patients.

    PubMed

    Ren, S; Jin, Y; Huang, Y; Ma, L; Liu, Y; Meng, C; Guan, S; Xie, L; Chen, X

    2016-07-01

    Since hepatitis C virus (HCV) non-structural 3 (NS3) protease inhibitor (PI) combined with pegylated interferon/ribavirin (PR) has been approved for chronic HCV genotype (GT) 1b infection, a reliable and clinically useful predictor combining with serum HCV RNA to predict early virologic response, breakthrough, and relapse is important during HCV antiviral treatment. We evaluated the role of HCV NS3 antigen (HCV NS3Ag) on the prediction of virologic response in patients with HCV GT1b during PR or PR/simeprevir (triple) therapy. Three hundred patients were recruited, and HCV RNA and HCV NS3Ag were tested at baseline and weeks 2, 4, 12, 24, 48, and 72. NS3Ag and HCV RNA were significantly related (r(2) = 0.67) in the whole patient selection. The kinetic pattern of HCV RNA and HCV NS3Ag during triple treatment was similar. HCV NS3Ag levels in the triple group closely followed those of HCV RNA; the r(2) values were 0.756 (baseline), 0.837 (2 weeks), 0.989 (4 weeks), and 0.993 (12 weeks), respectively. For patients treated with PR, the positive and negative predictive values (PPVs and NPVs) for viral response were 96.31 % and 67.19 %, respectively, at week 4 by using the decrease of NS3Ag (dHCV NS3Ag) combined with HCV RNA. At week 12, the PPV was similar at 94.16 %, while the NPV reached 87.26 %. The PPV and NPV for the prediction of relapse and breakthrough were 90.6 % and 76.7 %, respectively. HCV NS3Ag is a valuable marker and could be a supplementary predictor of HCV RNA for the prediction of antiviral response, breakthrough, or relapse during HCV antiviral treatment. PMID:27173787

  20. Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.

    PubMed

    Pena, Loren D M; van Calcar, Sandra C; Hansen, Joyanna; Edick, Mathew J; Walsh Vockley, Cate; Leslie, Nancy; Cameron, Cynthia; Mohsen, Al-Walid; Berry, Susan A; Arnold, Georgianne L; Vockley, Jerry

    2016-08-01

    Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency can present at various ages from the neonatal period to adulthood, and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis, treatment, and surveillance can reduce mortality; hence, the disorder is included in the newborn Recommended Uniform Screening Panel (RUSP) in the United States. The Inborn Errors of Metabolism Information System (IBEM-IS) was established in 2007 to collect longitudinal information on individuals with inborn errors of metabolism included in newborn screening (NBS) programs, including VLCAD deficiency. We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1-18years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2/52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1-3years of age). Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified. PMID:27209629

  1. Comorbidity as a predictor and moderator of treatment outcome in youth with anxiety, affective, attention deficit/hyperactivity disorder, and oppositional/conduct disorders.

    PubMed

    Ollendick, Thomas H; Jarrett, Matthew A; Grills-Taquechel, Amie E; Hovey, Laura D; Wolff, Jennifer C

    2008-12-01

    In the present review, we examine one of the critical issues that have been raised about evidence-based treatments and their portability to real-world clinical settings: namely, the presence of comorbidity in the participants who have been treated in these studies and whether the presence of comorbidity predicts or moderates treatment outcomes. In doing so, we examine treatment outcomes for the four most commonly occurring childhood psychiatric disorders: Anxiety disorders, affective disorders, attention deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD)/conduct disorder (CD). For each of these disorders, we first review briefly the prevalence of comorbidity in epidemiological and clinical samples and then highlight the evidence-based treatments for these disorders. We next determine the effects of comorbidity on treatment outcomes for these disorders. For the most part, comorbidity in the treated samples is the rule, not the exception. However, the majority of studies have not explored whether comorbidity predicts or moderates treatment outcomes. For the not insignificant number of studies that have examined this issue, comorbidity has not been found to affect treatment outcomes. Notable exceptions are highlighted and recommendations for future research are presented. PMID:18973971

  2. Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms.

    PubMed

    Ghesquières, Hervé; Cartron, Guillaume; Seymour, John Francis; Delfau-Larue, Marie-Hélène; Offner, Fritz; Soubeyran, Pierre; Perrot, Aurore; Brice, Pauline; Bouabdallah, Réda; Sonet, Anne; Dupuis, Jehan; Casasnovas, Olivier; Catalano, John Vincent; Delmer, Alain; Jardin, Fabrice; Verney, Aurélie; Dartigues, Peggy; Salles, Gilles

    2012-09-27

    In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582. PMID:22885164

  3. IL36RN Mutations Affect Protein Expression and Function: A Basis for Genotype-Phenotype Correlation in Pustular Diseases.

    PubMed

    Tauber, Marie; Bal, Elodie; Pei, Xue-Yuan; Madrange, Marine; Khelil, Amel; Sahel, Houria; Zenati, Akila; Makrelouf, Mohamed; Boubridaa, Khaled; Chiali, Amel; Smahi, Naima; Otsmane, Farida; Bouajar, Bakar; Marrakchi, Slaheddine; Turki, Hamida; Bourrat, Emmanuelle; Viguier, Manuelle; Hamel, Yamina; Bachelez, Hervé; Smahi, Asma

    2016-09-01

    Homozygous or compound heterozygous IL36RN gene mutations underlie the pathogenesis of psoriasis-related pustular eruptions including generalized pustular psoriasis, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustular eruption. We identified two unreported IL36RN homozygous mutations (c.41C>A/p.Ser14X and c.420_426del/p.Gly141MetfsX29) in patients with familial generalized pustular psoriasis. We analyzed the impact of a spectrum of IL36RN mutations on IL-36 receptor antagonist protein by using site-directed mutagenesis and expression in HEK293T cells. This enabled us to differentiate null mutations with complete absence of IL-36 receptor antagonist (the two previously unreported mutations, c.80T>C/p.Leu27Pro, c.28C>T/p.Arg10X, c.280G>T/p.Glu94X, c.368C>G/p.Thr123Arg, c.368C>T/p.Thr123Met, and c.227C>T/p.Pro76Leu) from mutations with decreased (c.95A>G/p.His32Arg, c.142C>T/p.Arg48Trp, and c.308C>T/p.Ser113Leu) or unchanged (c.304C>T/p.Arg102Trp and c.104A>G/p.Lys35Arg) protein expression. Functional assays measuring the impact of mutations on the capacity to repress IL-36-dependent activation of the NF-κB pathway showed complete functional impairment for null mutations, whereas partial or no impairment was observed for other mutations considered as hypomorphic. Finally, null mutations were associated with severe clinical phenotypes (generalized pustular psoriasis, acute generalized exanthematous pustular eruption), whereas hypomorphic mutations were identified in both localized (palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) and generalized variants. These results provide a preliminary basis for genotype-phenotype correlation in patients with deficiency of the IL-36Ra (DITRA), and suggest the involvement of other factors in the modulation of clinical expression. PMID:27220475

  4. Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women

    PubMed Central

    Ma'som, Mahirah; Bhoo-Pathy, Nirmala; Nasir, Nazrila Hairizan; Bellinson, Jerome; Subramaniam, Shridevi; Ma, Yuntong; Yap, Siew-Hwei; Goh, Pik-Pin; Gravitt, Patti; Woo, Yin Ling

    2016-01-01

    Objective The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women. Method A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush (‘Just for Me’; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample. Results Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30–48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than

  5. Allocation of experimental resources to minimize the variance of genotype mean chip color and tuber composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeders select superior genotypes despite the environment affecting phenotypic variance. Minimal variance of genotype means facilitates the statistical identification of superior genotypes. The variance components calculated from three datasets describing tuber composition and fried chip color were...

  6. Long-term asymmetric hearing affects cochlear implantation outcomes differently in adults with pre- and postlingual hearing loss.

    PubMed

    Boisvert, Isabelle; McMahon, Catherine M; Dowell, Richard C; Lyxell, Björn

    2015-01-01

    In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears. PMID:26043227

  7. Long-Term Asymmetric Hearing Affects Cochlear Implantation Outcomes Differently in Adults with Pre- and Postlingual Hearing Loss

    PubMed Central

    Boisvert, Isabelle; McMahon, Catherine M.; Dowell, Richard C.; Lyxell, Björn

    2015-01-01

    In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears. PMID:26043227

  8. Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype

    PubMed Central

    Meyer, Benedicte; Nguyen, Chinh Bkrong Thuy; Moen, Aurora; Fagermoen, Even; Sulheim, Dag; Nilsen, Hilde; Wyller, Vegard Bruun; Gjerstad, Johannes

    2015-01-01

    Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12–18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS. PMID:26473596

  9. Serological Assay and Genotyping of Hepatitis C Virus in Infected Patients in Zanjan Province

    PubMed Central

    Esmaeilzadeh, Abdolreza; Erfanmanesh, Maryam; Ghasemi, Sousan; Mohammadi, Farzaneh

    2014-01-01

    Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Objectives: As distribution of HCV genotypes is different in various geographical regions and HCV genotyping of patients has not been investigated in Zanjan City, this study was designed for the first time, to determine HCV genotypes in the region and to promote the impact of the treatment. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment. PMID:25368655

  10. Prognostic significance of two sub-categorization methods for the treatment of binge eating disorder: negative affect and overvaluation predict, but do not moderate, specific outcomes.

    PubMed

    Masheb, R M; Grilo, C M

    2008-04-01

    Given the absence of known predictors and moderators for binge eating disorder (BED) treatment outcome and recent findings regarding meaningful sub-categorizations of BED patients, we tested the predictive validity of two subtyping methods. Seventy-five overweight patients with BED who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy (CBTgsh) and behavioral weight loss (BWLgsh)) were categorized in two ways. First, a cluster analytic approach yielded dietary-negative affect (29%) and pure dietary (71%) subtypes. Second, research conventions for categorizing patients based upon shape or weight self-evaluation yielded clinical overvaluation (51%) and subclinical overvaluation (49%) subtypes. At the end of treatment, participants subtyped as dietary-negative affect reported more frequent binge episodes compared to the pure dietary subtype, and those with clinical overvaluation reported greater eating disorder psychopathology compared to the subclinical overvaluation group. Neither method predicted binge remission, depressive symptoms, or weight loss. Neither sub-categorization moderated the effects of guided self-help CBT and BWL treatments on any BED outcomes, suggesting that these two specific treatments perform comparably across BED subtypes. In conclusion, dietary-negative affect subtyping and overvaluation subtyping each predicted, but did not moderate, specific and important dimensions of BED treatment outcome. PMID:18328464

  11. Gaze behavior and affect at 6 months: predicting clinical outcomes and language development in typically developing infants and infants at risk for autism.

    PubMed

    Young, Gregory S; Merin, Noah; Rogers, Sally J; Ozonoff, Sally

    2009-09-01

    This paper presents follow-up longitudinal data to research that previously suggested the possibility of abnormal gaze behavior marked by decreased eye contact in a subgroup of 6-month-old infants at risk for autism (Merin, Young, Ozonoff & Rogers, 2007). Using eye-tracking data and behavioral data recorded during a live mother-infant interaction involving the still-face procedure, the predictive utility of gaze behavior and affective behaviors at 6 months was examined using diagnostic outcome data obtained longitudinally over the following 18 months. Results revealed that none of the infants previously identified as showing lower rates of eye contact had any signs of autism at outcome. In contrast, three infants who were diagnosed with autism demonstrated consistent gaze to the eye region and typical affective responses at 6 months. Individual differences in face scanning and affective responsivity during the live interaction were not related to any continuous measures of symptom frequency or symptom severity. In contrast, results of growth curve models for language development revealed significant relationships between face scanning and expressive language. Greater amounts of fixation to the mother's mouth during live interaction predicted higher levels of expressive language at outcome and greater rates of growth. These findings suggest that although gaze behavior at 6 months may not provide early markers for autism as initially conceived, gaze to the mouth in particular may be useful in predicting individual differences in language development. PMID:19702771

  12. Does Combining School and Work Affect School and Post-School Outcomes? Longitudinal Surveys of Australian Youth

    ERIC Educational Resources Information Center

    Anlezark, Alison; Lim, Patrick

    2011-01-01

    In this report the authors seek to answer the question of whether combining school and work is detrimental or beneficial to a student's school educational performance and labour market outcomes. They find that young people who combine school and work are distributed right across the school population. Results show that individuals can combine…

  13. Cohorts and Relatedness: Self-Determination Theory as an Explanation of How Learning Communities Affect Educational Outcomes

    ERIC Educational Resources Information Center

    Beachboard, Martine Robinson; Beachboard, John C.; Li, Wenling; Adkison, Stephen R.

    2011-01-01

    This study examines whether feelings of relatedness constitute a substantial means by which learning communities (cohorts) improve learning outcomes in higher education. It applies Ryan and Deci's Self-Determination Theory to an analysis of the National Survey of Student Engagement. The SDT hypothesizes that environments that support perceptions…

  14. How does the context and design of participatory decision-making processes affect their outcomes? Evidence from sustainable land management in global drylands.

    NASA Astrophysics Data System (ADS)

    de Vente, Joris; Reed, Mark; Stringer, Lindsay; Valente, Sandra; Newig, Jens

    2014-05-01

    It is widely accepted that the design of participatory processes in environmental management needs to be adapted to local contexts. Yet, it is not clear which elements of process design are universal, making it difficult to design processes that deliver beneficial outcomes across different contexts. We used empirical evidence to analyse the extent to which context and process design can enable or impede stakeholder participation and facilitate beneficial environmental and social outcomes in a range of decision-making contexts where stakeholders are engaged in environmental management. To explore the role of national-scale context on the outcomes of participatory processes, we interviewed facilitators from a process that was replicated across 13 dryland study sites around the world, which focussed on selecting Sustainable Land Management (SLM) options in close collaboration with stakeholders. To explore the role of process design and local context, we interviewed participants and facilitators in 11 case studies in Spain and Portugal in which different process designs were used. Interview data were analysed using a combination of quantitative and qualitative approaches to characterise relationships between process design, context and process outcomes. The similarity of outcomes across the 13 international study sites suggested that the national socio-cultural context in which a participatory process is conducted has little impact on its outcomes. However, analysis of cases from Spain and Portugal showed that some aspects of local context may affect outcomes. Having said this, factors associated with process design and participant selection played a more significant role in influencing outcomes in both countries. Processes that led to more beneficial outcomes for the environment and/or participants were likely to include: the legitimate representation of stakeholders; professional facilitation including structured methods for eliciting and aggregating information and

  15. Insulin dependent diabetes mellitus epidemiology: HLA genotype study in 12 north eastern Italian families with two siblings affected by type I diabetes.

    PubMed

    Pinelli, L; Drei, F; Gonfiantini, E; Visentin, A; Roata, C; Ciaffoni, S; Maffeis, C

    1989-12-01

    The purpose of our study was to evaluate the relationship between the histocompatibility antigens and type I diabetes mellitus in families living in the north-eastern part of Italy. In each family two siblings were affected by diabetes. HLA-antigens were determined with the lymphocytotoxicity test, utilizing antisera of the series A-B-C-DR. The phenotypic frequencies were compared with those observed in controls. We showed that diabetes has a strong association with HLA DR 3 and/or DR 4 antigens. In particular we registered high frequency of compound heterozygous DR 3 - DR 4 subjects, and this fact supports the hypothesis of the existence of two different genes for diabetes associated with these HLA antigens. Moreover we observed a particular haplotype segregation with a very high percentage of HLA identity between patients belonging to the same family, confirming the association between HLA and genetic susceptibility to insulin dependent diabetes. These results confirm data in the literature and, completed by other data from other patients' families living in our area, will be useful in providing reliable genetic counselling. PMID:2606174

  16. Mentoring Programs to Affect Delinquency and Associated Outcomes of Youth At-Risk: A Comprehensive Meta-Analytic Reviewi

    PubMed Central

    Tolan, Patrick H.; Henry, David B.; Schoeny, Michael S.; Lovegrove, Peter; Nichols, Emily

    2013-01-01

    Objectives To conduct a meta-analytic review of selective and indicated mentoring interventions for effects for youth at risk on delinquency and key associated outcomes (aggression, drug use, academic functioning). We also undertook the first systematic evaluation of intervention implementation features and organization and tested for effects of theorized key processes of mentor program effects. Methods Campbell Collaboration review inclusion criteria and procedures were used to search and evaluate the literature. Criteria included a sample defined as at-risk for delinquency due to individual behavior such as aggression or conduct problems or environmental characteristics such as residence in high-crime community. Studies were required to be random assignment or strong quasi-experimental design. Of 163 identified studies published 1970 - 2011, 46 met criteria for inclusion. Results Mean effects sizes were significant and positive for each outcome category (ranging form d =.11 for Academic Achievement to d = .29 for Aggression). Heterogeneity in effect sizes was noted for all four outcomes. Stronger effects resulted when mentor motivation was professional development but not by other implementation features. Significant improvements in effects were found when advocacy and emotional support mentoring processes were emphasized. Conclusions This popular approach has significant impact on delinquency and associated outcomes for youth at-risk for delinquency. While evidencing some features may relate to effects, the body of literature is remarkably lacking in details about specific program features and procedures. This persistent state of limited reporting seriously impedes understanding about how mentoring is beneficial and ability to maximize its utility. PMID:25386111

  17. Defining Optimal Aerobic Exercise Parameters to Affect Complex Motor and Cognitive Outcomes after Stroke: A Systematic Review and Synthesis

    PubMed Central

    Hasan, S. M. Mahmudul; Rancourt, Samantha N.; Austin, Mark W.; Ploughman, Michelle

    2016-01-01

    Although poststroke aerobic exercise (AE) increases markers of neuroplasticity and protects perilesional tissue, the degree to which it enhances complex motor or cognitive outcomes is unknown. Previous research suggests that timing and dosage of exercise may be important. We synthesized data from clinical and animal studies in order to determine optimal AE training parameters and recovery outcomes for future research. Using predefined criteria, we included clinical trials of stroke of any type or duration and animal studies employing any established models of stroke. Of the 5,259 titles returned, 52 articles met our criteria, measuring the effects of AE on balance, lower extremity coordination, upper limb motor skills, learning, processing speed, memory, and executive function. We found that early-initiated low-to-moderate intensity AE improved locomotor coordination in rodents. In clinical trials, AE improved balance and lower limb coordination irrespective of intervention modality or parameter. In contrast, fine upper limb recovery was relatively resistant to AE. In terms of cognitive outcomes, poststroke AE in animals improved memory and learning, except when training was too intense. However, in clinical trials, combined training protocols more consistently improved cognition. We noted a paucity of studies examining the benefits of AE on recovery beyond cessation of the intervention. PMID:26881101

  18. Defining Optimal Aerobic Exercise Parameters to Affect Complex Motor and Cognitive Outcomes after Stroke: A Systematic Review and Synthesis.

    PubMed

    Hasan, S M Mahmudul; Rancourt, Samantha N; Austin, Mark W; Ploughman, Michelle

    2016-01-01

    Although poststroke aerobic exercise (AE) increases markers of neuroplasticity and protects perilesional tissue, the degree to which it enhances complex motor or cognitive outcomes is unknown. Previous research suggests that timing and dosage of exercise may be important. We synthesized data from clinical and animal studies in order to determine optimal AE training parameters and recovery outcomes for future research. Using predefined criteria, we included clinical trials of stroke of any type or duration and animal studies employing any established models of stroke. Of the 5,259 titles returned, 52 articles met our criteria, measuring the effects of AE on balance, lower extremity coordination, upper limb motor skills, learning, processing speed, memory, and executive function. We found that early-initiated low-to-moderate intensity AE improved locomotor coordination in rodents. In clinical trials, AE improved balance and lower limb coordination irrespective of intervention modality or parameter. In contrast, fine upper limb recovery was relatively resistant to AE. In terms of cognitive outcomes, poststroke AE in animals improved memory and learning, except when training was too intense. However, in clinical trials, combined training protocols more consistently improved cognition. We noted a paucity of studies examining the benefits of AE on recovery beyond cessation of the intervention. PMID:26881101

  19. Direct and indirect effects of caregiver social support on adolescent psychological outcomes in two South African AIDS-affected communities

    PubMed Central

    Casale, Marisa; Cluver, Lucie; Crankshaw, Tamaryn; Kuo, Caroline; Lachman, Jamie M.; Wild, Lauren G.

    2015-01-01

    Caregiver social support has been shown to be protective for caregiver mental health, parenting and child psychosocial outcomes. This is the first known analysis to quantitatively investigate the relationship between caregiver social support and adolescent psychosocial outcomes in HIV-endemic, resource-scarce Southern African communities. A cross-sectional household survey was conducted over 2009-2010 with 2477 South African adolescents aged 10-17 and their adult caregivers (18 years or older) in one urban and one rural community in South Africa’s KwaZulu-Natal province. Adolescent adjustment was assessed using adult caregiver reports of the Strengths and Difficulties questionnaire (SDQ), which measures peer problems, hyperactivity, conduct problems, emotional symptoms and child prosocial behavior. Hierarchical linear regressions and multiple mediation analyses, using bootstrapping procedures, were conducted to assess for: a) direct effects of more caregiver social support on better adolescent psychosocial wellbeing; and b) indirect effects mediated by better parenting and caregiver mental health. Direct associations (p<.001), and indirect associations mediated through better parenting, were found for all adolescent outcomes. Findings reinforce the importance of social support components within parenting interventions but also point to scope for positive intervention on adolescent psychosocial wellbeing through the broader family social network. PMID:25623784

  20. Direct and Indirect Effects of Caregiver Social Support on Adolescent Psychological Outcomes in Two South African AIDS-Affected Communities.

    PubMed

    Casale, Marisa; Cluver, Lucie; Crankshaw, Tamaryn; Kuo, Caroline; Lachman, Jamie M; Wild, Lauren G

    2015-06-01

    Caregiver social support has been shown to be protective for caregiver mental health, parenting and child psychosocial outcomes. This is the first known analysis to quantitatively investigate the relationship between caregiver social support and adolescent psychosocial outcomes in HIV-endemic, resource-scarce Southern African communities. A cross-sectional household survey was conducted over 2009-2010 with 2,477 South African adolescents aged 10-17 and their adult caregivers (18 years or older) in one urban and one rural community in South Africa's KwaZulu-Natal province. Adolescent adjustment was assessed using adult caregiver reports of the Strengths and Difficulties questionnaire (SDQ), which measures peer problems, hyperactivity, conduct problems, emotional symptoms and child prosocial behavior. Hierarchical linear regressions and multiple mediation analyses, using bootstrapping procedures, were conducted to assess for: (a) direct effects of more caregiver social support on better adolescent psychosocial wellbeing; and (b) indirect effects mediated by better parenting and caregiver mental health. Direct associations (p < .001), and indirect associations mediated through better parenting, were found for all adolescent outcomes. Findings reinforce the importance of social support components within parenting interventions but also point to scope for positive intervention on adolescent psychosocial wellbeing through the broader family social network. PMID:25623784

  1. Genotyping methodologies.

    PubMed

    Bevan, S; Houlston, R S

    2001-01-01

    With current advances in genetics it is now possible to routinely screen the entire genome of multiple affected individuals in the search for disease predisposition genes. Such a large-scale undertaking requires some careful management of both samples and data in order to make best use of all available information. Here we have detailed the two main approaches to a genome-wide search and the best ways we have found of storing, transforming, and analyzing the subsequently produced data, as well as some general considerations to enhance the chances of success. PMID:11280934

  2. Results of laparoscopic reoperation for failed antireflux surgery: does the indication for redo surgery affect the outcome?

    PubMed

    Safranek, P M; Gifford, C J; Booth, M I; Dehn, T C B

    2007-01-01

    Short and medium term outcomes from laparoscopic antireflux surgery are generally excellent. A small number of patients suffer recurrent reflux or intolerable side-effects and may require reoperation. In this paper we describe our experience of 35 laparoscopic reoperations from a single center. Data on patients undergoing antireflux surgery in our unit has been prospectively collected and includes more than 600 primary laparoscopic antireflux operations since 1993. Laparoscopic reoperations have been performed between 1996 and 2005 for patients suffering recurrent reflux, dysphagia or severe gas bloat symptomatic despite medical treatment. All patients underwent preoperative barium studies and endoscopy with selective manometry and pH studies. Symptomatic outcomes were evaluated at 6 weeks and 12 months with Visick scores. Anatomical results were assessed with barium studies at between 6 and 12 months. Thirty-five laparoscopic reoperations were performed in 20 women and 13 men (median age 56 years). Primary surgery had been performed in our unit in 27 (77%) and elsewhere in eight (23%). Median time from primary surgery was 28.5 months (5-360). Two patients underwent a second reoperation. Indication was recurrent reflux in 28 (80%), dysphagia in five (14%) and gas bloat in two (6%). Thirty-two of the 35 reoperations (91.4%) were completed laparoscopically, median operating time was 120.5 min (65-210) and median hospital stay 2 days. There was no mortality and there were only five minor complications. Twelve-month follow-up was available for 32 reoperations (91%). Overall good symptomatic outcomes were obtained in 26 (74%) Visick I or II at 6 weeks and 24 of 32 (75%) at 12 months. In reoperations for dysphagia/gas bloat there was a relative risk of 4.26 of a poor symptomatic outcome (Visick III or IV) at 12 months compared to those for recurrent reflux (P < 0.05, Fisher's exact test). Laparoscopic reoperation is feasible with low conversion rates and minimal

  3. Temperature and Plant Genotype Alter Alkaloid Concentrations in Ryegrass Infected with an Epichloë Endophyte and This Affects an Insect Herbivore.

    PubMed

    Hennessy, Louise M; Popay, Alison J; Finch, Sarah C; Clearwater, Michael J; Cave, Vanessa M

    2016-01-01

    Asexual Epichloë endophytes colonize agricultural forage grasses in a relationship which is mutually beneficial and provides the host plant with protection against herbivorous insects. The endophyte strain AR37 (Epichloë festucae var. lolii) produces epoxy-janthitrem alkaloids and is the only endophyte known to provide ryegrass with resistance against porina larvae (Wiseana cervinata (Walker)), a major pasture pest in cooler areas of New Zealand. This study examined the effect of temperature on concentrations of epoxy-janthitrems in AR37-infected ryegrass and determined how the resulting variations in concentration affected consumption, growth and survival of porina larvae. Twenty replicate pairs of perennial (Lolium perenne L.) and Italian ryegrass (L. multiflorum Lam.) plants with and without endophyte were prepared by cloning, with one of each pair grown at either high (20°C) or low (7°C) temperature. After 10 weeks, herbage on each plant was harvested, divided into leaf and pseudostem, then freeze dried and ground. Leaf and pseudostem material was then incorporated separately into semi-synthetic diets which were fed to porina larvae in a bioassay over 3 weeks. Epoxy-janthitrem concentrations within the plant materials and the semi-synthetic diets were analyzed by high performance liquid chromatography. AR37-infected ryegrass grown at high temperature contained high in planta concentrations of epoxy-janthitrem (30.6 μg/g in leaves and 83.9 μg/g in pseudostems) that had a strong anti-feedant effect on porina larvae when incorporated into their diets, reducing their survival by 25-42% on pseudostems. In comparison, in planta epoxy-janthitrem concentrations in AR37-infected ryegrass grown at low temperature were very low (0.67 μg/g in leaves and 7.4 μg/g in pseudostems) resulting in a small anti-feedant effect in perennial but not in Italian ryegrass. Although alkaloid concentrations were greatly reduced by low temperature this reduction did not occur until

  4. Temperature and Plant Genotype Alter Alkaloid Concentrations in Ryegrass Infected with an Epichloë Endophyte and This Affects an Insect Herbivore

    PubMed Central

    Hennessy, Louise M.; Popay, Alison J.; Finch, Sarah C.; Clearwater, Michael J.; Cave, Vanessa M.

    2016-01-01

    Asexual Epichloë endophytes colonize agricultural forage grasses in a relationship which is mutually beneficial and provides the host plant with protection against herbivorous insects. The endophyte strain AR37 (Epichloë festucae var. lolii) produces epoxy-janthitrem alkaloids and is the only endophyte known to provide ryegrass with resistance against porina larvae (Wiseana cervinata (Walker)), a major pasture pest in cooler areas of New Zealand. This study examined the effect of temperature on concentrations of epoxy-janthitrems in AR37-infected ryegrass and determined how the resulting variations in concentration affected consumption, growth and survival of porina larvae. Twenty replicate pairs of perennial (Lolium perenne L.) and Italian ryegrass (L. multiflorum Lam.) plants with and without endophyte were prepared by cloning, with one of each pair grown at either high (20°C) or low (7°C) temperature. After 10 weeks, herbage on each plant was harvested, divided into leaf and pseudostem, then freeze dried and ground. Leaf and pseudostem material was then incorporated separately into semi-synthetic diets which were fed to porina larvae in a bioassay over 3 weeks. Epoxy-janthitrem concentrations within the plant materials and the semi-synthetic diets were analyzed by high performance liquid chromatography. AR37-infected ryegrass grown at high temperature contained high in planta concentrations of epoxy-janthitrem (30.6 μg/g in leaves and 83.9 μg/g in pseudostems) that had a strong anti-feedant effect on porina larvae when incorporated into their diets, reducing their survival by 25–42% on pseudostems. In comparison, in planta epoxy-janthitrem concentrations in AR37-infected ryegrass grown at low temperature were very low (0.67 μg/g in leaves and 7.4 μg/g in pseudostems) resulting in a small anti-feedant effect in perennial but not in Italian ryegrass. Although alkaloid concentrations were greatly reduced by low temperature this reduction did not occur

  5. Simultaneous Genotyping and Quantification of Hepatitis B Virus for Genotypes B and C by Real-Time PCR Assay▿

    PubMed Central

    Zhao, Yao; Zhang, Xiu-Yu; Guo, Jin-Jun; Zeng, Ai-Zhong; Hu, Jie-Li; Huang, Wen-Xiang; Shan, You-Lan; Huang, Ai-Long

    2010-01-01

    Hepatitis B virus (HBV) is an important cause of human chronic liver diseases and is a major public health problem. Viral load and HBV genotype play critical roles in determining clinical outcomes and response to antiviral treatment in hepatitis B patients. Viral genotype detection and quantification assays are currently in use with different levels of effectiveness. In this study, the performance of a real-time genotyping and quantitative PCR (GQ-PCR)-based assay was evaluated. Through the use of genotype-specific primers and probes, this assay provides simultaneous identification and quantification of genotypes B and C in a single reaction. Our GQ-PCR correctly identified all predefined genotypes B and C, and no cross-reaction between genotypes B and C were observed. The GQ-PCR identified more cases of HBV infections with mixed genotypes B and C than direct sequencing did. Samples from 127 HBV-infected Chinese patients were genotyped with GQ-PCR, revealing 56.7% HBV as genotype B, 13.4% as genotype C, and 29.8% as mixed genotypes B and C. This assay provides a reliable, efficient, and cost-effective means for quantification of the B and C genotypes of HBV in single or mixed infections. This assay is suitable for sequential monitoring of viral load levels and for determining the relationship between the genotype viral load and stage of disease in Asians. PMID:20720032

  6. Relative reproductive success of co-infecting parasite genotypes under intensified within-host competition.

    PubMed

    Seppälä, Otto; Louhi, Katja-Riikka; Karvonen, Anssi; Rellstab, Christian; Jokela, Jukka

    2015-12-01

    In nature, host individuals are commonly simultaneously infected with more than one genotype of the same parasite species. These co-infecting parasites often interact, which can affect their fitness and shape host-parasite ecology and evolution. Many of such interactions take place through competition for limited host resources. Therefore, variation in ecological factors modifying the host resource level could be important in determining the intensity of competition and the outcome of co-infections. We tested this hypothesis by measuring the relative reproductive success of co-infecting genotypes of the trematode parasite Diplostomum pseudospathaceum in its snail host Lymnaea stagnalis while experimentally manipulating snail resource level using contrasting feeding treatments (ad libitum food supply, no food). We found that food deprivation constrained the overall parasite within-host reproduction as the release of parasite transmission stages (cercariae) was reduced. This indicates intensified competition among the parasite genotypes. The genotypic composition of the released cercariae, however, was not affected by the feeding treatments. This suggests that in this system, the relative reproductive success of co-infecting parasite genotypes, which is an important component determining their fitness, is robust to variation in ecological factors modifying the strength of resource competition. PMID:26296607

  7. Relative importance of various measures of HIV-related stigma in predicting psychological outcomes among children affected by HIV.

    PubMed

    Zhao, Guoxiang; Li, Xiaoming; Zhao, Junfeng; Zhang, Liying; Stanton, Bonita

    2012-06-01

    To assess the relative importance of four different measures of HIV-related stigma in predicting psychological problems among children affected by HIV in rural China. Cross-sectional data were collected from 755 orphans (i.e., children who lost one or both of their parents to HIV), 466 vulnerable children (children who were living with HIV-infected parents), and 404 comparison children who were from the same community and did not have HIV-related illness or death in their families. Four HIV-related stigma measures include perceived public stigma against people living with HIV/AIDS (PLWHA), perceived public stigma against children affected by HIV (orphans and vulnerable children), personal stigmatizing attitudes against PLWHA, and enacted stigma among children affected by HIV. Psychological problems included depression and adjustment problems. Various measures of HIV-related stigma independently and differentially contribute to children's psychological problems. Enacted stigma and children's perceived public stigma against PLWHA or children affected by HIV are generally stronger predictors of psychological problems than their own feelings or attitudes towards PLWHA. Various aspects of HIV-related stigma are important for us to understand the perception, attitudes, and experience of children affected by HIV, including both children experiencing HIV-related parental illness and death in their own family and children who were living in the communities hardly hit by HIV. Future health promotion and psychological care efforts for children affected by HIV need to consider the effect of various forms of HIV-related stigma on these children's psychosocial well-being and mobilize the community resources to mitigate the negative effect of HIV-related stigma on PLWHA and their children. PMID:21681458

  8. Frame-of-reference training effectiveness: effects of goal orientation and self-efficacy on affective, cognitive, skill-based, and transfer outcomes.

    PubMed

    Dierdorff, Erich C; Surface, Eric A; Brown, Kenneth G

    2010-11-01

    Empirical evidence supporting frame-of-reference (FOR) training as an effective intervention for calibrating raters is convincing. Yet very little is known about who does better or worse in FOR training. We conducted a field study of how motivational factors influence affective, cognitive, and behavioral learning outcomes, as well as near transfer indexed by achieving professional certification. Relying on goal orientation theory, we hypothesized effects for 3 goal orientations: learning, prove performance, and avoid performance. Results were generally supportive across learning outcomes and transfer. Findings further supported a hypothesized interaction between learning self-efficacy and avoid performance goal orientation, such that higher levels of learning self-efficacy mitigated the negative effects of higher performance avoid tendencies. PMID:20853944

  9. Do partial thickness, bursal side cuff tears affect outcome following arthroscopic subacromial decompression? A prospective comparative cohort study

    PubMed Central

    Al-Maiyah, Mohammed; Goodchild, Lorna; Fourie, J M Brendan; Finn, Paul; Rangan, Amar

    2014-01-01

    Background: The present study aimed to compare medium-term clinical outcomes of patients following arthroscopic subacromial decompression (ASAD): those with intact rotator cuff with two groups of increasing size of partial thickness bursal-side tears. Methods: Patients undergoing shoulder arthroscopy by a single surgeon had pre- and postoperative Constant scores prospectively recorded. Arthroscopic surgery included the assessment of any supraspinatus tears using the Ellman criteria, as well as ASAD and cuff debridement. Groups were created based on the status of rotator cuff and size of bursal tear. Outcome in these patient groups was then compared and analyzed Results: Seventy-four patients were suitable for inclusion in the study: 32 patients without a cuff tear; 21 patients with a cuff tear of 9 mm or less in length; and 21 patients with a cuff tear of 10 mm or more in length. Baseline characteristics of the three groups were similar. All three groups showed a significant improvement in their Constant scores following surgery. There was, however, no significant difference in Constant scores between the three groups. Conclusions: The results of the present study show that patients with varying sizes of bursal-side tears respond to ASAD as well as those with no rotator cuff tear.

  10. Perioperative blood transfusion affects hepatitis C virus (HCV)-specific immune responses and outcome following liver transplantation in HCV-infected patients

    PubMed Central

    Subramanian, Vijay; Bharat, Ankit; Vachharajani, Neeta; Crippin, Jeffrey; Shenoy, Surendra; Mohanakumar, Thalachallour; Chapman, William C

    2014-01-01

    Objectives:Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients. Methods:Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed. Results:Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1β and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival. Conclusions:Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes. PMID:23869514

  11. Differences in ovarian aging patterns between races are associated with ovarian genotypes and sub-genotypes of the FMR1 gene

    PubMed Central

    2012-01-01

    Background Ovarian aging patterns differ between races, and appear to affect fertility treatment outcomes. What causes these differences is, however, unknown. Variations in ovarian aging patterns have recently been associated with specific ovarian genotypes and sub-genotypes of the FMR1 gene. We, therefore, attempted to determine differences in how functional ovarian reserve (FOR) changes with advancing age between races, and whether changes are associated with differences in distribution of ovarian genotypes and sub-genotypes of the FMR1 gene. Methods We determined in association with in vitro fertilization (IVF) FOR in 62 young Caucasian, African and Asian oocyte donors and 536 older infertility patients of all three races, based on follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and oocyte yields, and investigated whether differences between races are associated with differences in distribution of FMR1 genotypes and sub-genotypes. Results Changes in distribution of mean FSH, AMH and oocyte yields between young donors and older infertility patients were significant (all P < 0.001). Donors did not demonstrate significant differences between races in AMH and FSH but demonstrated significant differences in oocyte yields [F(2,59) = 4.22, P = 0.019]: Specifically, African donors demonstrated larger oocyte yields than Caucasians (P = 0.008) and Asians (P = 0.022). In patients, AMH levels differed significantly between races [F (2,533) = 4.25, P = 0.015]. Holm-Sidak post-hoc comparisons demonstrated that Caucasians demonstrated lower AMH in comparison to Asians (P = 0.007). Percentages of FMR1 genotypes and sub-genotypes in patients varied significantly between races, with Asians demonstrating fewer het-norm/low sub-genotypes than Caucasians and Africans (P = 0.012). Conclusion FOR changes in different races at different rates, and appears to parallel ovarian FMR1 genotypes and sub-genotype distributions. Differences

  12. An Affective Dimension within Oppositional Defiant Disorder Symptoms among Boys: Personality and Psychopathology Outcomes into Early Adulthood

    ERIC Educational Resources Information Center

    Burke, Jeffrey D.

    2012-01-01

    Background: A dimension of negatively oriented affect within oppositional defiant disorder (ODD) symptoms, which has been described as irritability, has been shown to predict depression and anxiety. Related constructs have been linked to temperament and personality constructs. However, only a few studies have examined the prediction from…

  13. The factors affecting outcome after non-vascular bone grafting and internal fixation for nonunion of the scaphoid.

    PubMed

    Ramamurthy, C; Cutler, L; Nuttall, D; Simison, A J M; Trail, I A; Stanley, J K

    2007-05-01

    This study identified variables which influence the outcome of surgical management on 126 ununited scaphoid fractures managed by internal fixation and non-vascular bone grafting. The site of fracture was defined by a new method: the ratio of the length of the proximal fragment to the sum of the lengths of both fragments, calculated using specific views in the plain radiographs. Bone healing occurred in 71% (89) of cases. Only the site of nonunion (p = 1 x 10(-6)) and the delay to surgery (p = 0.001) remained significant on multivariate analysis. The effect of surgical delay on the probability of union increased as the fracture site moved proximally. A prediction model was produced by stepwise logistic regression analysis, enabling the surgeon to predict the success of surgery where the site of the nonunion and delay to surgery is known. PMID:17540748

  14. What is an “adverse” environment? Interactions of rearing experiences and MAOA genotype in rhesus monkeys

    PubMed Central

    Karere, Genesio M.; Kinnally, Erin L.; Sanchez, Jessica N.; Famula, Thomas R.; Lyons, Leslie A.; Capitanio, John P.

    2009-01-01

    Background Studies have been inconsistent in demonstrating that early adversity and specific genotype can be joint risk factors for poor behavioral outcomes. Using a rhesus monkey model, we examined how social context and different forms of early adversity influence whether a specific genotype (polymorphism in the promoter region of monoamine oxidase A) affects display of aggressive, fearful, and anxious behaviors. Methods Rhesus monkey infants (n=473) were exposed to brief social challenge at 3–4 months of age. Infants were reared a) with mothers and up to 150 other animals in large cages; b) with mothers in smaller social groups; c) with mother and access to, at most, one other mother-infant pair; and d) without mother, but with access to a same-aged peer in a nursery. Results No effects of genotype were found for infants reared by mothers in large social cages, although several genotype by rearing environment interactions were evident. Animals reared in smaller social groups were more likely to display aggression, which was especially true of animals possessing the low-activity MAOA genotype. In addition, animals with low-activity genotypes that had experienced restricted mother-rearing showed more anxious behavior (scratch, yawn). Conclusions Among mother-reared animals, broader contextual features, associated with the social environment and experience of the mother, can affect the extent to which genotype contributes to behavioral expression under conditions of challenge. Results also suggest that different forms of early adverse experience can affect the types of responses displayed by animals of different genotypes. PMID:19103441

  15. Timing of Maternal Immunization Affects Immunological and Behavioral Outcomes of Adult Offspring in Siberian Hamsters (Phodopus sungorus).

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2016-07-01

    Maternal influences are an important contributing factor to offspring survival, development, and behavior. Common environmental pathogens can induce maternal immune responses and affect subsequent development of offspring. There are likely sensitive periods during pregnancy when animals are particularly vulnerable to environmental disruption. Here we characterize the effects of maternal immunization across pregnancy and postpartum on offspring physiology and behavior in Siberian hamsters (Phodopus sungorus). Hamsters were injected with the antigen keyhole limpet hemocyanin (KLH) (1) prior to pairing with a male (premating), (2) at separation (postmating), (3) at midpregnancy, or (4) after birth (lactation). Maternal food intake, body mass, and immunity were monitored throughout gestation, and litters were measured weekly for growth until adulthood when social behavior, hormone concentrations, and immune responses were determined. We found that immunizations altered maternal immunity throughout pregnancy and lactation. The effects of maternal treatment differed between male and female offspring. Aggressive behavior was enhanced in offspring of both sexes born to mothers treated postmating and thus early in pregnancy relative to other stages. In contrast, maternal treatment and maternal stage differentially affected innate immunity in males and females. Offspring cortisol, however, was unaffected by maternal treatment. Collectively, these data demonstrate that maternal immunization affects offspring physiology and behavior in a time-dependent and sex-specific manner. More broadly, these findings contribute to our understanding of the effects of maternal immune activation, whether it be from environmental exposure or immunization, on immunological and behavioral responses of offspring. PMID:27320639

  16. Haunted by ghosts: prevalence, predictors and outcomes of spirit possession experiences among former child soldiers and war-affected civilians in Northern Uganda.

    PubMed

    Neuner, Frank; Pfeiffer, Anett; Schauer-Kaiser, Elisabeth; Odenwald, Michael; Elbert, Thomas; Ertl, Verena

    2012-08-01

    Phenomena of spirit possession have been documented in many cultures. Some authors have argued that spirit possession is a type of psychopathology, and should be included as a category in diagnostic manuals of mental disorders. However, there are hardly any quantitative studies that report the prevalence of spirit possession on a population level and that provide evidence for its validity as a psychopathological entity. In an epidemiological study that was carried out in 2007 and 2008 with N = 1113 youths and young adults aged between 12 and 25 years in war-affected regions of Northern Uganda we examined the prevalence, predictors and outcomes of cen, a local variant of spirit possession. Randomly selected participants were interviewed using a scale of cen, measures of psychopathology (PTSD and depression) as well as indicators of functional outcome on different levels, including suicide risk, daily activities, perceived discrimination, physical complaints and aggression. We found that cen was more common among former child soldiers then among subjects without a history of abduction. Cen was related to extreme levels of traumatic events and uniquely predicted functional outcome even when the effects of PTSD and depression were controlled for. Our findings show that a long-lasting war that is accompanied by the proliferation of spiritual and magical beliefs and propaganda can lead to high levels of harmful spirit possession. In addition, we provide evidence for the incremental validity of spirit possession as a trauma-related psychological disorder in this context. PMID:22580073

  17. Improving outcomes for caregivers through treatment of young people affected by war: a randomized controlled trial in Sierra Leone

    PubMed Central

    Salhi, Carmel; Hann, Katrina; Kellie, Jim; Kamara, Alimamy; Salomon, Joshua A; Kim, Jane J; Betancourt, Theresa S

    2015-01-01

    Abstract Objective To measure the benefits to household caregivers of a psychotherapeutic intervention for adolescents and young adults living in a war-affected area. Methods Between July 2012 and July 2013, we carried out a randomized controlled trial of the Youth Readiness Intervention – a cognitive–behavioural intervention for war-affected young people who exhibit depressive and anxiety symptoms and conduct problems – in Freetown, Sierra Leone. Overall, 436 participants aged 15–24 years were randomized to receive the intervention (n = 222) or care as usual (n = 214). Household caregivers for the participants in the intervention arm (n = 101) or control arm (n = 103) were interviewed during a baseline survey and again, if available (n = 155), 12 weeks later in a follow-up survey. We used a burden assessment scale to evaluate the burden of care placed on caregivers in terms of emotional distress and functional impairment. The caregivers’ mental health – i.e. internalizing, externalizing and prosocial behaviour – was evaluated using the Oxford Measure of Psychosocial Adjustment. Difference-in-differences multiple regression analyses were used, within an intention-to-treat framework, to estimate the treatment effects. Findings Compared with the caregivers of participants of the control group, the caregivers of participants of the intervention group reported greater reductions in emotional distress (scale difference: 0.252; 95% confidence interval, CI: 0.026–0.4782) and greater improvements in prosocial behaviour (scale difference: 0.249; 95% CI: 0.012–0.486) between the two surveys. Conclusion A psychotherapeutic intervention for war-affected young people can improve the mental health of their caregivers. PMID:26668435

  18. New ways of working: does flexibility in time and location of work change work behavior and affect business outcomes?

    PubMed

    Blok, Merle M; Groenesteijn, Liesbeth; Schelvis, Roos; Vink, Peter

    2012-01-01

    In the changing modern economy some new factors have been addressed that are of importance for productivity and economic growth, such as human skills, workplace organization, information and communication technologies (ICT) and knowledge sharing. An increasing number of companies and organizations are implementing measures to better address these factors, often referred to as 'the New Ways of Working (NWW)'. This consists of a large variety of measures that enable flexibility in the time and location of work. Expectations of these measures are often high, such as a reduction in operating costs and an increase of productivity. However, scientific proof is still lacking, and it is worth asking whether al these implementations actually cause a change in work behavior and effect business outcomes positively. This article describes a case study of three departments (total of 73 employees) that changed from a traditional way of working towards a new way of working. Questionnaires and a new developed objective measurement system called 'work@task' were used to measure changes in work behavior (i.e. increased variation in work location, work times and a change towards NWW management style) and the effect on business objectives such as knowledge sharing, employees satisfaction, and collaboration. PMID:22317507

  19. New Ways of Working: does flexibility in time and location of work change work behavior and affect business outcomes?

    PubMed

    Blok, Merle M; Groenesteijn, Liesbeth; Schelvis, Roos; Vink, Peter

    2012-01-01

    In the changing modern economy some new factors have been addressed that are of importance for productivity and economic growth, such as human skills, workplace organization, information and communication technologies (ICT) and knowledge sharing. An increasing number of companies and organizations are implementing measures to better address these factors, often referred to as 'the New Ways of Working (NWW)'. This consists of a large variety of measures that enable flexibility in the time and location of work. Expectations of these measures are often high, such as a reduction in operating costs and an increase of productivity. However, scientific proof is still lacking, and it is worth asking whether al these implementations actually cause a change in work behavior and effect business outcomes positively. This article describes a case study of three departments (total of 73 employees) that changed from a traditional way of working towards a new way of working. Questionnaires and a new developed objective measurement system called 'work@task' were used to measure changes in work behavior (i.e. increased variation in work location, work times and a change towards NWW management style) and the effect on business objectives such as knowledge sharing, employees satisfaction, and collaboration. PMID:22317114

  20. Early rehabilitation affects functional outcomes and activities of daily living after arthroscopic rotator cuff repair: a case report

    PubMed Central

    Shimo, Satoshi; Sakamoto, Yuta; Tokiyoshi, Akinari; Yamamoto, Yasuhiro

    2016-01-01

    [Purpose] The effect of early rehabilitation protocols after arthroscopic rotator cuff repair is currently unknown. We examined short-term effects of early rehabilitation on functional outcomes and activities of daily living after arthroscopic rotator cuff repair. [Subject and Methods] An 82-year-old male fell during a walk, resulting in a supraspinatus tear. Arthroscopic rotator cuff repair was performed using a single-row technique. He wore an abduction brace for 6 weeks after surgery. [Results] From day 1 after surgery, passive range of motion exercises, including forward flexion and internal and external rotation were performed twice per day. Starting at 6 weeks after surgery, active range of motion exercises and muscle strengthening exercises were introduced gradually. At 6 weeks after surgery, his active forward flexion was 150°, UCLA shoulder rating scale score was 34 points, and Quick Disabilities of the Arm, Shoulder, and Hand questionnaire disability/symptom score was 36 points. At 20 weeks after surgery, his active forward flexion was 120°, UCLA shoulder rating scale score was 34 points, and Quick Disabilities of the Arm, Shoulder, and Hand questionnaire disability/symptom score was 0 points. [Conclusion] These protocols are recommended to physical therapists during rehabilitation for arthroscopic rotator cuff repair to support rapid reintegration into activities of daily living. PMID:27064886

  1. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency.

    PubMed

    Schlotawa, Lars; Ennemann, Eva Charlotte; Radhakrishnan, Karthikeyan; Schmidt, Bernhard; Chakrapani, Anupam; Christen, Hans-Jürgen; Moser, Hugo; Steinmann, Beat; Dierks, Thomas; Gärtner, Jutta

    2011-03-01

    Multiple Sulfatase Deficiency (MSD) is caused by mutations in the sulfatase-modifying factor 1 gene encoding the formylglycine-generating enzyme (FGE). FGE post translationally activates all newly synthesized sulfatases by generating the catalytic residue formylglycine. Impaired FGE function leads to reduced sulfatase activities. Patients display combined clinical symptoms of single sulfatase deficiencies. For ten MSD patients, we determined the clinical phenotype, FGE expression, localization and stability, as well as residual FGE and sulfatase activities. A neonatal, very severe clinical phenotype resulted from a combination of two nonsense mutations leading to almost fully abrogated FGE activity, highly unstable FGE protein and nearly undetectable sulfatase activities. A late infantile mild phenotype resulted from FGE G263V leading to unstable protein but high residual FGE activity. Other missense mutations resulted in a late infantile severe phenotype because of unstable protein with low residual FGE activity. Patients with identical mutations displayed comparable clinical phenotypes. These data confirm the hypothesis that the phenotypic outcome in MSD depends on both residual FGE activity as well as protein stability. Predicting the clinical course in case of molecularly characterized mutations seems feasible, which will be helpful for genetic counseling and developing therapeutic strategies aiming at enhancement of FGE. PMID:21224894

  2. RISK FACTORS AFFECTING OUTCOME OF SECOND HLA-MATCHED SIBLING DONOR TRANSPLANTS FOR GRAFT FAILURE IN SEVERE ACQUIRED APLASTIC ANEMIA

    PubMed Central

    Horan, John T.; Carreras, Jeanette; Tarima, Sergey; Camitta, Bruce M.; Gale, Robert Peter; Hale, Gregory A.; Hinterberger, Wolfgang; Marsh, Judith; Passweg, Jakob R.; Walters, Mark C.; Eapen, Mary

    2009-01-01

    We examined transplant outcomes after second HLA-matched sibling transplants for primary (16%) and secondary (84%) graft failure in 166 patients with severe acquired aplastic anemia. Performance scores were < 90 in 67% of patients. Most (88%) transplantations used the same donor for both transplants and 84% of second transplants used bone marrow graft. We identified two prognostic factors: inter-transplant interval (surrogate for primary graft failure and early secondary graft failure) and performance status. Shorter inter-transplant interval (≤3 months) and poor performance score (<90) at second transplantation were associated with high mortality. The 8-year probabilities of overall survival when second transplantation was ≤ 3 and > 3 months from first transplant in patients with performance scores of 90–100% were 56% and 76%, respectively. Corresponding probabilities in patients with lower performance scores were 33% and 61%. The predominant cause of failure after second transplantation was non-engraftment (72 of 166 patients) and frequent in patients with primary or early secondary graft failure (51 of 72; 71%). Therefore, novel approaches including conditioning regimens with greater immunosuppression should be explored for these patients. PMID:19361755

  3. Early rehabilitation affects functional outcomes and activities of daily living after arthroscopic rotator cuff repair: a case report.

    PubMed

    Shimo, Satoshi; Sakamoto, Yuta; Tokiyoshi, Akinari; Yamamoto, Yasuhiro

    2016-01-01

    [Purpose] The effect of early rehabilitation protocols after arthroscopic rotator cuff repair is currently unknown. We examined short-term effects of early rehabilitation on functional outcomes and activities of daily living after arthroscopic rotator cuff repair. [Subject and Methods] An 82-year-old male fell during a walk, resulting in a supraspinatus tear. Arthroscopic rotator cuff repair was performed using a single-row technique. He wore an abduction brace for 6 weeks after surgery. [Results] From day 1 after surgery, passive range of motion exercises, including forward flexion and internal and external rotation were performed twice per day. Starting at 6 weeks after surgery, active range of motion exercises and muscle strengthening exercises were introduced gradually. At 6 weeks after surgery, his active forward flexion was 150°, UCLA shoulder rating scale score was 34 points, and Quick Disabilities of the Arm, Shoulder, and Hand questionnaire disability/symptom score was 36 points. At 20 weeks after surgery, his active forward flexion was 120°, UCLA shoulder rating scale score was 34 points, and Quick Disabilities of the Arm, Shoulder, and Hand questionnaire disability/symptom score was 0 points. [Conclusion] These protocols are recommended to physical therapists during rehabilitation for arthroscopic rotator cuff repair to support rapid reintegration into activities of daily living. PMID:27064886

  4. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

    PubMed Central

    Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

    2013-01-01

    Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

  5. Stereotypes as stumbling-blocks: how coping with stereotype threat affects life outcomes for people with physical disabilities.

    PubMed

    Silverman, Arielle M; Cohen, Geoffrey L

    2014-10-01

    Stereotype threat, the concern about being judged in light of negative stereotypes, causes underperformance in evaluative situations. However, less is known about how coping with stereotypes can aggravate underperformance over time. We propose a model in which ongoing stereotype threat experiences threaten a person's sense of self-integrity, which in turn prompts defensive avoidance of stereotype-relevant situations, impeding growth, achievement, and well-being. We test this model in an important but understudied population: the physically disabled. In Study 1, blind adults reporting higher levels of stereotype threat reported lower self-integrity and well-being and were more likely to be unemployed and to report avoiding stereotype-threatening situations. In Study 2's field experiment, blind students in a compensatory skill-training program made more progress if they had completed a values-affirmation, an exercise that bolsters self-integrity. The findings suggest that stereotype threat poses a chronic threat to self-integrity and undermines life outcomes for people with disabilities. PMID:25015337

  6. Factor V Leiden mutation does not affect coagulopathy or outcome in lethal H1N1 influenza.

    PubMed

    Schouten, M; van der Sluijs, K F; Roelofs, J J T H; Levi, M; Van't Veer, C; van der Poll, T

    2010-12-01

    Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined. Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study. Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection. In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A. PMID:20413539

  7. Association of caregiver quality of care with neurocognitive outcomes in HIV-affected children aged 2-5 years in Uganda.

    PubMed

    Bass, Judith K; Nakasujja, Noeline; Familiar-Lopez, Itziar; Sikorskii, Alla; Murray, Sarah M; Opoka, Robert; Augustinavicius, Jura; Boivin, Michael J

    2016-01-01

    Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver-child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver-child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected children

  8. Association of caregiver quality of care with neurocognitive outcomes in HIV-affected children aged 2–5 years in Uganda

    PubMed Central

    Bass, Judith K.; Nakasujja, Noeline; Familiar-Lopez, Itziar; Sikorskii, Alla; Murray, Sarah M.; Opoka, Robert; Augustinavicius, Jura; Boivin, Michael J.

    2016-01-01

    ABSTRACT Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver–child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver–child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected

  9. agr Dysfunction Affects Staphylococcal Cassette Chromosome mec Type-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia

    PubMed Central

    Kang, Chang Kyung; Cho, Jeong Eun; Choi, Yoon Jeong; Jung, Younghee; Kim, Nak-Hyun; Kim, Chung-Jong; Kim, Taek Soo; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Park, Wan Beom; Bang, Ji-Hwan; Kim, Eu Suk; Park, Kyoung Un; Park, Sang Won; Kim, Nam-Joong; Oh, Myoung-don

    2015-01-01

    Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea. PMID:25779574

  10. Preoperative Mild-to-Moderate Coronary Artery Disease Does Not Affect Long-Term Outcomes of Lung Transplantation

    PubMed Central

    Zanotti, Giorgio; Hartwig, Matthew G.; Castleberry, Anthony W.; Martin, Jeremiah T.; Shaw, Linda K.; Williams, Judson B.; Lin, Shu S.; Davis, Robert D.

    2015-01-01

    Background Coronary artery disease has a high prevalence among lung transplant recipients and has historically been a contraindication to transplant at many institutions. In patients with mild-to-moderate coronary artery disease (Mod-CAD) undergoing lung transplant, outcomes are not well defined. Methods All patients who underwent pulmonary transplantation from January 1996 through November 2010 with pretransplant coronary angiogram were included in our study. Recipients of multivisceral, redo, and lobar lung transplants and those who underwent pretransplant coronary revascularization were excluded. Patients were grouped into Mod-CAD or no-coronary artery disease group (No-CAD). Primary end point was overall survival. Secondary end points were 30-day events and the need for posttransplant coronary revascularization. Results Approximately 539 patients were included in the study: 362 in the No-CAD, 177 in the Mod-CAD group. Patients with Mod-CAD were predominantly male, older, and had a higher body mass index. No difference in either perioperative morbidity and mortality (Mod-CAD, 4.2% vs. No-CAD 3.3%, P=0.705) or late overall mortality was shown between groups. Mod-CAD patients had a shorter hospitalization (median: 12 days vs. 14 days, P=0.009) and required a higher rate of late coronary revascularization procedures (PCI: Mod-CAD vs. No-CAD, 0.3% vs. 4.0%, P=0.0035; CABG: Mod-CAD vs. No-CAD, 0.3% vs. 2.3%, P=0.0411). Conclusions Mod-CAD does not appear to be associated with increased perioperative morbidity or decreased survival after transplant. Coronary artery disease may worsen and require coronary revascularization in patients with risk factors for disease progression. In these patients, close follow-up and screening for progression of coronary artery disease may help prevent late cardiac morbidity. PMID:24646771

  11. Predictive Factors Affecting the Short Term and Long Term Exodrift in Patients with Intermittent Exotropia after Bilateral Rectus Muscle Recession and Its Effect on Surgical Outcome

    PubMed Central

    Yam, Jason C. S.; Chong, Gabriela S. L.; Wu, Patrick K. W.; Wong, Ursula S. F.; Chan, Clement W. N.; Ko, Simon T. C.

    2014-01-01

    Purpose. To determine the predictive factors that affect short term and long term postoperative drift in intermittent exotropia after bilateral lateral rectus recession and to evaluate its effect on surgical outcome. Methods. Retrospective review of 203 patients with diagnosis of intermittent exotropia, who had surgical corrections with more than 3 years of followup. Different preoperative parameters were obtained and evaluated using Pearson's correlation analysis. Results. The proportion of exodrift increased from 62% at 6 weeks to 84% at 3 years postoperatively. The postoperative drift was 4.3 ± 8.1 PD at 6 weeks, 5.8 ± 8.4 PD at 6 months, 7.2 ± 8.3 PD at 1 year, 7.4 ± 8.4 PD at 2 years, and 7.7 ± 8.5 PD at 3 years. Preoperative deviation and initial overcorrection were significant factors affecting the postoperative drift at 3 years (r = 0.177, P = 0.011, r = −0.349, and P < 0.001, resp.). Conclusions. Postoperative exodrift along three years occurs in a majority of patients after bilateral lateral rectus recession for intermittent exotropia. The long term surgical success is significantly affected by this postoperative exodrift. A larger preoperative deviation and a larger initial overcorrection are associated with a larger early and late postoperative exodrift. PMID:25093170

  12. Outcomes and moderators of a preventive school-based mental health intervention for children affected by war in Sri Lanka: a cluster randomized trial

    PubMed Central

    TOL, WIETSE A.; KOMPROE, IVAN H.; JORDANS, MARK J.D.; VALLIPURAM, ANAVARATHAN; SIPSMA, HEATHER; SIVAYOKAN, SAMBASIVAMOORTHY; MACY, ROBERT D.; DE JONG, JOOP T.

    2012-01-01

    We aimed to examine outcomes, moderators and mediators of a preventive school-based mental health intervention implemented by paraprofessionals in a war-affected setting in northern Sri Lanka. A cluster randomized trial was employed. Subsequent to screening 1,370 children in randomly selected schools, 399 children were assigned to an intervention (n=199) or waitlist control condition (n=200). The intervention consisted of 15 manualized sessions over 5 weeks of cognitive behavioral techniques and creative expressive elements. Assessments took place before, 1 week after, and 3 months after the intervention. Primary outcomes included post-traumatic stress disorder (PTSD), depressive, and anxiety symptoms. No main effects on primary outcomes were identified. A main effect in favor of intervention for conduct problems was observed. This effect was stronger for younger children. Furthermore, we found intervention benefits for specific subgroups. Stronger effects were found for boys with regard to PTSD and anxiety symptoms, and for younger children on pro-social behavior. Moreover, we found stronger intervention effects on PTSD, anxiety, and function impairment for children experiencing lower levels of current war-related stressors. Girls in the intervention condition showed smaller reductions on PTSD symptoms than waitlisted girls. We conclude that preventive school-based psychosocial interventions in volatile areas characterized by ongoing war-related stressors may effectively improve indicators of psychological wellbeing and posttraumatic stress-related symptoms in some children. However, they may undermine natural recovery for others. Further research is necessary to examine how gender, age and current war-related experiences contribute to differential intervention effects. PMID:22654944

  13. Caffeine Use Affects Pregnancy Outcome

    ERIC Educational Resources Information Center

    Diego, Miguel; Field, Tiffany; Hernandez-Reif, Maria; Vera, Yanexy; Gil, Karla; Gonzalez-Garcia, Adolfo

    2008-01-01

    A sample of 750 women were interviewed during pregnancy on their depression and anxiety symptoms, substance use and demographic variables. A subsample was seen again at the neonatal stage (n = 152), and their infants were observed for sleep-wake behavior. Symptoms of depression and anxiety were related to caffeine use. Mothers who consumed more…

  14. Animated pedagogical agents: How the presence and nonverbal communication of a virtual instructor affect perceptions and learning outcomes in a computer-based environment about basic physics concepts

    NASA Astrophysics Data System (ADS)

    Frechette, M. Casey

    One important but under-researched area of instructional technology concerns the effects of animated pedagogical agents (APAs), or lifelike characters designed to enhance learning in computer-based environments. This research sought to broaden what is currently known about APAs' instructional value by investigating the effects of agents' visual presence and nonverbal communication. A theoretical framework based on APA literature published in the past decade guided the design of the study. This framework sets forth that APAs impact learning through their presence and communication. The communication displayed by an APA involves two distinct kinds of nonverbal cues: cognitive (hand and arm gestures) and affective (facial expressions). It was predicted that the presence of an agent would enhance learning and that nonverbal communication would amplify these effects. The research utilized a between-subjects experimental design. Participants were randomly assigned to treatment conditions in a controlled lab setting, and group means were compared with a MANCOVA. Participants received (1) a non-animated agent, (2) an agent with hand and arm gestures, (3) an agent with facial expressions, or (4) a fully animated agent. The agent appeared in a virtual learning environment focused on Kepler's laws of planetary motion. A control group did not receive the visual presence of an agent. Two effects were studied: participants' perceptions and their learning outcomes. Perceptions were measured with an attitudinal survey with five subscales. Learning outcomes were measured with an open-ended recall test, a multiple choice comprehension test, and an open-ended transfer test. Learners presented with an agent with affective nonverbal communication comprehended less than learners exposed to a non-animated agent. No significant differences were observed when a group exposed to a fully animated agent was compared to a group with a non-animated agent. Adding both nonverbal communication

  15. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

    PubMed

    Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

    2014-09-01

    Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient. PMID:24760409

  16. Citrus tristeza virus: Evolution of Complex and Varied Genotypic Groups

    PubMed Central

    Harper, S. J.

    2013-01-01

    Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts. There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant. There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity. We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination. Additionally, genotype grouping has not been standardized. In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention. Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population. The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes. PMID:23630519

  17. Gonadotropin-releasing hormone agonist for oocyte triggering in endometrial preparation of letrozole stimulation protocols does not affect clinical outcome of frozen-thawed embryo transfer

    PubMed Central

    Huang, Pin-Xiu; Wei, Ji-Hong; Wei, Li-Hong

    2015-01-01

    Objective: This study aims to evaluate the effectiveness of GnRH agonist in comparison with hCG for triggering final oocyte maturation in endometrial preparation of letrozole stimulation protocols for frozen-thawed embryo transfer. Methods: The frozen-thawed embryo transfer cycles (FET) that use the letrozole stimulation protocols for endometrial preparation were divided into two groups according the different method of triggering final oocyte maturation. The serum LH and E2 levels, and the endometrial thickness on the day of triggering, the clinical pregnancy rates, the miscarriage rates and live birth rates were compared. Results: There were no significant differences in the age, the endometrial thickness, the number of embryos transferred between the two groups. The clinical pregnancy rate, abortion rate and live birth rates of the group A were similar compared with the group B, P<0.05. Conclusion: Using GnRH agonist for oocyte triggering in endometrial preparation of letrozole stimulation protocols for frozen-thawed embryo transfer does not affect the clinical outcome compared with hCG under the same luteal phase support. PMID:26770535

  18. HIV Genotypic Resistance Testing

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? HIV Antiretroviral Drug Resistance Testing, Genotypic Share this page: Was this page helpful? Also known as: Anti-retroviral Drug Resistance Testing; ARV Resistance Testing Formal name: ...

  19. HCV genotypes in Morocco.

    PubMed

    Benani, A; El-Turk, J; Benjelloun, S; Sekkat, S; Nadifi, S; Hda, N; Benslimane, A

    1997-08-01

    To determine the hepatitis C virus (HCV) genotypes circulating in Morocco, virus isolates from 105 chronically infected and 19 hemodialysis patients were examined using the line probe assay. Genotypes 1 and 2 only were found among Moroccan patients. Subtypes 1b (47.6%) and 2a/2c (37.1%) were the most common, whereas subtype 1a (2.8%) was less common. Among the hemodialysis patients, only genotype 1 was found with a prevalence of 68.4% for subtype 1b and 15.8% for the subtype 1a. It was also shown that the HCV genotypes distribution varies with age in both studied populations. Subtype 1b was most prevalent among older patients, whereas subtype 2a/2c was mainly found among younger ones. Although Morocco belongs to the African continent, the circulating HCV strains are similar to those observed in some American and European countries. PMID:9260687

  20. APOE Genotyping, Cardiovascular Disease

    MedlinePlus

    ... Risk Assessment ; HDL Cholesterol ; LDL Cholesterol ; Lipid Profile ; Triglycerides Were you looking instead for APOE genotyping ordered ... the skin called xanthomas, a high level of triglycerides in the blood, and atherosclerosis that develops at ...

  1. Sequence-based in silico analysis of well studied Hepatitis C Virus epitopes and their variants in other genotypes (particularly genotype 5a) against South African human leukocyte antigen backgrounds

    PubMed Central

    2012-01-01

    Background Host genetics influence the outcome of HCV disease. HCV is also highly mutable and escapes host immunity. HCV genotypes are geographically distributed and HCV subtypes have been shown to have distinct repertoires of HLA-restricted viral epitopes which explains the lack of cross protection across genotypes observed in some studies. Despite this, immune databases and putative epitope vaccines concentrate almost exclusively on HCV genotype 1 class I-epitopes restricted by the HLA-A*02 allele. While both genotype and allele predominate in developed countries, we hypothesise that HCV variation and population genetics will affect the efficacy of proposed epitope vaccines in South Africa. This in silico study investigates HCV viral variability within well-studied epitopes identified in genotype 1 and uses algorithms to predict the immunogenicity of their variants from other less studied genotypes and thus rate the most promising vaccine candidates for the South African population. Six class I- and seven class II- restricted epitope sequences within the core, NS3, NS4B and NS5B regions were compared across the six HCV genotypes using local genotype 5a sequence data together with global data. Common HLA alleles in the South African population are A30:01, A02:01, B58:02, B07:02; DRB1*13:01 and DRB1*03:01. Epitope binding to 13 class I- and 8 class –II alleles were described using web-based prediction servers, Immune Epitope Database, (IEDB) and Propred. Online population coverage tools were used to assess vaccine efficacy. Results Despite the homogeneity of genotype 1 and genotype 5 over the epitopes, there was limited promiscuity to local HLA-alleles.Host differences will make a putative vaccine less effective in South Africa. Of the 6 well-characterized class I- epitopes, only 2 class I- epitopes were promiscuous and 3 of the 7 class-II epitopes were better conserved and promiscuous. By fine tuning the putative vaccine using an optimal cocktail of genotype 1

  2. CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans.

    PubMed

    Wolf, Claudia; Mohr, Holger; Diekhof, Esther K; Vieker, Henning; Goya-Maldonado, Roberto; Trost, Sarah; Krämer, Bernd; Keil, Maria; Binder, Elisabeth B; Gruber, Oliver

    2016-07-01

    Cyclic AMP response element-binding protein (CREB) contributes to adaptation of mesocorticolimbic networks by modulating activity-regulated transcription and plasticity in neurons. Activity or expression changes of CREB in the nucleus accumbens (NAc) and orbital frontal cortex (OFC) interact with behavioral changes during reward-motivated learning. However, these findings from animal models have not been evaluated in humans. We tested whether CREB1 genotypes affect reward-motivated decisions and related brain activation, using BOLD fMRI in 224 young and healthy participants. More specifically, participants needed to adapt their decision to either pursue or resist immediate rewards to optimize the reward outcome. We found significant CREB1 genotype effects on choices to pursue increases of the reward outcome and on BOLD signal in the NAc, OFC, insula cortex, cingulate gyrus, hippocampus, amygdala, and precuneus during these decisions in comparison with those decisions avoiding total reward loss. Our results suggest that CREB1 genotype effects in these regions could contribute to individual differences in reward- and associative memory-based decision-making. PMID:26045569

  3. Impact of OAS1 Exon 7 rs10774671 Genetic Variation on Liver Fibrosis Progression in Egyptian HCV Genotype 4 Patients.

    PubMed

    Bader El Din, Noha G; Anany, Mohamed A; Dawood, Reham M; Ibrahim, Marwa K; El-Shenawy, Reem; El Abd, Yasmin S; El Awady, Mostafa K

    2015-11-01

    The aim of this study was to assess the impact of genetic variants of oligoadenylate synthetase 1 (OAS1) single-nucleotide polymorphism (SNP) rs10774671 at the exon 7 splice acceptor site on liver fibrosis progression and hepatitis C virus (HCV) outcome in Egyptian HCV genotype 4 patients. In this study, 195 subjects were enrolled; 60 controls and 135 chronic HCV genotype 4 patients with different fibrosis grades. All subjects were genotyped for OAS1 SNP rs10774671 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There was an increasing trend of liver fibrosis progression as 52.9% GG, 73.6% GA, and 83.3% AA genotypes were detected in late fibrosis patients (p = 0.025). The AA genotype was higher in the late fibrosis group than in the early fibrosis group (83.3% vs. 16.7%) (p = 0.001). The A allele was significantly affecting the liver fibrosis progression rate, more than the G allele (p = 0.001). The multivariate analysis showed that the OAS1 GA and AA genotypes were independent factors associated with liver progression (p = 0.009, odds ratio [OR] 3.467, 95% confidence interval [CI] 1.273-7.584). In addition, the A allele was associated with liver fibrosis progression (p = 0.014, OR 2.525, 95% CI 1.157-4.545). The polymorphism at OAS1 exon 7 rs3741981 might be a potential genetic marker and can be useful in the assessment of liver fibrosis progression and disease outcome in HCV-infected patients. PMID:26505957

  4. Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh

    PubMed Central

    Rume, Farzana Islam; Affuso, Alessia; Serrecchia, Luigina; Rondinone, Valeria; Manzulli, Viviana; Campese, Emanuele; Di Taranto, Pietro; Biswas, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Yasmin, Mahmuda; Fasanella, Antonio; Hugh-Jones, Martin

    2016-01-01

    In Bangladesh, anthrax, caused by the bacterium Bacillus anthracis, is considered an endemic disease affecting ruminants with sporadic zoonotic occurrences in humans. Due to the lack of knowledge about risks from an incorrect removal of infected carcasses, the disease is not properly monitored, and because of the socio-economic conditions, the situation is under-reported and under-diagnosed. For sensitive species, anthrax represents a fatal outcome with sudden death and sometimes bleeding from natural orifices. The most common source of infection for ruminants is ingestion of spores during grazing in contaminated pastures or through grass and water contaminated with anthrax spores. Domestic cattle, sheep and goats can also become infected through contaminated bone meal (used as feed) originating from anthrax-infected carcasses. The present investigation was conducted to isolate B. anthracis organisms from 169 samples (73 soil, 1 tissue, 4 bone and 91 bone meal samples) collected from 12 different districts of Bangladesh. The sampling was carried out from 2012 to 2015. Twelve samples resulted positive for B. anthracis. Biomolecular analyses were conducted starting from the Canonical Single Nucleotide Polymorphism (CanSNP) to analyze the phylogenetic origin of strains. The analysis of genotype, obtained through the Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) with the analysis of 15 Variable Number Tandem Repeats (VNTR), demonstrated four different genotypes: two of them were previously identified in the district of Sirajganj. The sub-genotyping, conducted with Single Nucleotide Repeats analysis, revealed the presence of eight subgenotypes. The data of the present study concluded that there was no observed correlation between imported cattle feed and anthrax occurrence in Bangladesh and that the remarkable genetic variations of B. anthracis were found in the soil of numerous outbreaks in this country. PMID:27082248

  5. Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh.

    PubMed

    Rume, Farzana Islam; Affuso, Alessia; Serrecchia, Luigina; Rondinone, Valeria; Manzulli, Viviana; Campese, Emanuele; Di Taranto, Pietro; Biswas, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Yasmin, Mahmuda; Fasanella, Antonio; Hugh-Jones, Martin

    2016-01-01

    In Bangladesh, anthrax, caused by the bacterium Bacillus anthracis, is considered an endemic disease affecting ruminants with sporadic zoonotic occurrences in humans. Due to the lack of knowledge about risks from an incorrect removal of infected carcasses, the disease is not properly monitored, and because of the socio-economic conditions, the situation is under-reported and under-diagnosed. For sensitive species, anthrax represents a fatal outcome with sudden death and sometimes bleeding from natural orifices. The most common source of infection for ruminants is ingestion of spores during grazing in contaminated pastures or through grass and water contaminated with anthrax spores. Domestic cattle, sheep and goats can also become infected through contaminated bone meal (used as feed) originating from anthrax-infected carcasses. The present investigation was conducted to isolate B. anthracis organisms from 169 samples (73 soil, 1 tissue, 4 bone and 91 bone meal samples) collected from 12 different districts of Bangladesh. The sampling was carried out from 2012 to 2015. Twelve samples resulted positive for B. anthracis. Biomolecular analyses were conducted starting from the Canonical Single Nucleotide Polymorphism (CanSNP) to analyze the phylogenetic origin of strains. The analysis of genotype, obtained through the Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) with the analysis of 15 Variable Number Tandem Repeats (VNTR), demonstrated four different genotypes: two of them were previously identified in the district of Sirajganj. The sub-genotyping, conducted with Single Nucleotide Repeats analysis, revealed the presence of eight subgenotypes. The data of the present study concluded that there was no observed correlation between imported cattle feed and anthrax occurrence in Bangladesh and that the remarkable genetic variations of B. anthracis were found in the soil of numerous outbreaks in this country. PMID:27082248

  6. Spartina alterniflora genotype influences facilitation and suppression of high marsh species colonizing an early successional salt marsh

    USGS Publications Warehouse

    Proffitt, C.E.; Chiasson, R.L.; Owens, A.B.; Edwards, K.R.; Travis, S.E.

    2005-01-01

    1. Genetically based phenotypic and ecotypic variation in a dominant plant species can influence ecological functions and patterns of recruitment by other species in plant communities. However, the nature and degree of importance of genotypic differences is poorly understood in most systems. 2. The dominant salt marsh species, Spartina alterniflora, is known to induce facultative and competitive effects in different plant species, and the outcomes of interactions can be affected by nutrients and flooding stress. Clonal genotypes, which maintained their different plant architecture phenotypes throughout 31 months of a field experiment, underwent considerable genet-specific senescence in their centres over the last 12 months. 3. Different clonal genotypes and different locations (robust edges vs. senescent centres) permitted significantly different levels of light penetration of the canopy (14.8-77.6%), thus establishing spatial heterogeneity for this important environmental factor. 4. S. alterniflora clonal genotype influenced the degree of suppression of the previously dominant Salicornia bigelovii as well as facilitation of recruitment and growth by other plant species. Aster subulatus and Atriplex, patula performed better in Spartina clone centres, and experienced reduced growth in Salicornia-dominated areas. 5. Four other high marsh species (Borrichia frutescens, Aster tenuifolius, Iva frutescens and Limonium carolinianum) colonized only into Spartina clones but not into the Salicornia-dominated area. 6. These results suggest that differences in clone size, centre senescence, stem density, height, total stem length and biomass in different genotypes of a dominant marsh plant species can influence recruitment and growth of other plant species. The spatial pattern of habitat heterogeneity is, at least in part, dependent on the genotypic diversity, and possibly the genetic diversity, of such foundation species. 7. We hypothesize that as genotypic diversity

  7. Evidence Based-Practice and Affect: The Impact of Physician Attitudes on Outcomes Associated with Clinical Reasoning and Decision-Making

    ERIC Educational Resources Information Center

    Dunphy, Bruce; Dunphy, Stacey; Cantwell, Robert; Bourke, Sid; Fleming, Mark

    2010-01-01

    The relationship between obstetrician attitudes and patient outcomes from intrapartum care was examined. Obstetrician attitudes were assessed utilizing a newly-designed pilot 35-item obstetrician attitude questionnaire (OAQ). Twelve obstetricians completed the OAQ, who provided intra-partum care to 4,149 women. Outcome measures included delivery…

  8. The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.

    PubMed

    Cannon, D M; Walshe, M; Dempster, E; Collier, D A; Marshall, N; Bramon, E; Murray, R M; McDonald, C

    2012-01-01

    We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAP(ICE) (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAP(ICE) haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders. PMID:23032943

  9. Host infection history modifies co-infection success of multiple parasite genotypes.

    PubMed

    Klemme, Ines; Louhi, Katja-Riikka; Karvonen, Anssi

    2016-03-01

    Co-infections by multiple parasite genotypes are common and have important implications for host-parasite ecology and evolution through within-host interactions. Typically, these infections take place sequentially, and therefore, the outcome of co-infection may be shaped by host immune responses triggered by previous infections. For example, in vertebrates, specific immune responses play a central role in protection against disease over the course of life, but co-infection research has mostly focused on previously uninfected individuals. Here, we investigated whether sequential exposure and activation of host resistance in rainbow trout Oncorhynchus mykiss affects infection success and interactions between co-infecting parasite genotypes of the trematode eye-fluke Diplostomum pseudospathaceum. In accordance with earlier results, we show that a simultaneous attack of two parasite genotypes facilitates parasite establishment in previously uninfected hosts. However, we find for the first time that this facilitation in co-infection is lost in hosts with prior infection. We conclude that vertebrate host infection history can affect the direction of within-host-parasite interactions. Our results may have significant implications for the evolution of co-infections and parasite transmission strategies. PMID:26589834

  10. Long-Term Clinical Impact of Adaptation of Initial Tacrolimus Dosing to CYP3A5 Genotype.

    PubMed

    Pallet, N; Etienne, I; Buchler, M; Bailly, E; Hurault de Ligny, B; Choukroun, G; Colosio, C; Thierry, A; Vigneau, C; Moulin, B; Le Meur, Y; Heng, A-E; Legendre, C; Beaune, P; Loriot, M A; Thervet, E

    2016-09-01

    Pretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: The transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/mL) at day 10. Our results indicate that the incidence of biopsy-proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Patients' death, cancer, cardiovascular events, and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes. PMID:26990694

  11. Genotypic richness predicts phenotypic variation in an endangered clonal plant.

    PubMed

    Evans, Suzanna M; Sinclair, Elizabeth A; Poore, Alistair G B; Bain, Keryn F; Vergés, Adriana

    2016-01-01

    Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species

  12. Genotypic richness predicts phenotypic variation in an endangered clonal plant

    PubMed Central

    Sinclair, Elizabeth A.; Poore, Alistair G.B.; Bain, Keryn F.; Vergés, Adriana

    2016-01-01

    Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species

  13. T-cell response relative to genotype and ethnicity during antiviral therapy for chronic hepatitis C.

    PubMed

    Kaplan, David E; Sugimoto, Kazushi; Ikeda, Fusao; Stadanlick, Jason; Valiga, Mary; Shetty, Kirti; Reddy, K Rajender; Chang, Kyong-Mi

    2005-06-01

    Viral genotype and host ethnicity are important predictors of viral clearance during antiviral therapy for chronic hepatitis C virus (HCV) infection. Based on the role of T cells in natural HCV clearance, we hypothesized that T cells may contribute to the genotypic and ethnic difference in treatment outcome. To test this hypothesis, T-cell response to HCV antigens (core, nonstructural NS3/4 and NS5) and control phytohemagglutinin (PHA) was monitored prospectively and was correlated with virological outcome in 41 patients chronically infected with HCV (27 genotype 1, 14 genotype 2 or 3; 19 black persons, 22 white persons) undergoing combined interferon alfa and ribavirin therapy. Interestingly, in patients with genotype 2 or 3 infection, enhanced virological response coincided with a greater T-cell response to HCV NS3/4 antigen at baseline (50% vs. 15%; P = .026) that augmented further during therapy (29% vs. 4%; P = .035) compared with genotype 1-infected patients. However, HCV-specific T-cell response remained weak in genotype 1-infected patients regardless of virological outcome or ethnicity. Furthermore, virological outcome was associated with a suppressed baseline proliferative response to phytohemagglutinin (P < .03) that increased during therapy (P < .003) independent of ethnicity or genotype. In conclusion, HCV-specific T-cell response was associated with HCV genotype but not with therapeutic clearance of HCV infection. The association between treatment outcome and phytohemagglutinin response suggests more global and antigen-nonspecific mechanisms for therapeutic HCV clearance. PMID:15915458

  14. Dysregulation Of Innate Immunity In HCV Genotype 1 IL28B Unfavorable Genotype Patients: Impaired Viral Kinetics And Therapeutic Response

    PubMed Central

    Naggie, Susanna; Osinusi, Anu; Katsounas, Antonios; Lempicki, Richard; Herrmann, Eva; Thompson, Alexander J; Clark, Paul J; Patel, Keyur; Muir, Andrew J; McHutchison, John G; Schlaak, Joerg F; Trippler, Martin; Shivakumar, Bhavana; Masur, Henry; Polis, Michael A.; Kottilil, Shyam

    2012-01-01

    Recent studies have shown that a single nucleotide polymorphism upstream of the interleukin (IL)-28B gene plays a major role in predicting therapeutic response in HCV-infected patients treated with pegylated interferon-alpha (IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics (VK), IFN pharmacokinetics (PK), IFN pharmacodynamics (PD), and gene expression profiles. Two prospective cohorts (HIV/HCV co-infected and HCV mono-infected) completing treatment with IFN/ribavirin were enrolled. Patients (N=88; 44 HIV/HCV and 44 HCV) were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort frequent serum sampling was completed for HCV RNA and IFN-levels. DNA microarray of PBMCs and individual expression of interferon stimulated genes (ISGs) were quantified on IFN-therapy. The IL28B favorable (CC) genotype was associated with improved therapeutic response compared to unfavorable (CT/TT) genotypes. Patients with favorable genotype had greater first and second phase VK (P=0.004 and P=0.036, respectively), IFN maximum anti-viral efficiency (P=0.007) and infected cell death loss (P=0.009) compared to unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of NK cells, from patients with unfavorable genotypes (P<0.004). Induction of innate immunity genes was also lower in unfavorable genotype. ISG expression at baseline and induction with IFN was independent of IL28B genotype. Conclusions Carriers of the IL28B favorable genotype were more likely to have superior innate immune response to IFN-therapy compared to unfavorable genotypes, this suggests the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of

  15. Chlamydia trachomatis genotypes in a cross-sectional study of urogenital samples from remote Northern and Central Australia

    PubMed Central

    Giffard, Philip M; Brenner, Nicole C; Tabrizi, Sepehr N; Garland, Suzanne M; Holt, Deborah C; Andersson, Patiyan; Lilliebridge, Rachael A; Tong, Steven Y C; Karimi, Mahdad; Boylan, Prudence; Ryder, Nathan; Johns, Tracy; Singh, Gurmeet

    2016-01-01

    Objectives The objective was to determine the frequency of trachoma genotypes of Chlamydia trachomatis-positive urogenital tract (UGT) specimens from remote areas of the Australian Northern Territory (NT). Setting The setting was analysis of remnants of C. trachomatis positive primarily UGT specimens obtained in the course of clinical practice. The specimens were obtained from two pathology service providers. Participants From 3356 C. trachomatis specimens collected during May 2012–April 2013, 439 were selected for genotyping, with a focus on specimens from postpubescent patients, in remote Aboriginal communities where ocular trachoma is potentially present. Primary and secondary outcome measures The primary outcome measure was the proportion of successfully genotyped UGT specimens that were trachoma genotypes. The secondary outcome measures were the distribution of genotypes, and the frequencies of different classes of specimens able to be genotyped. Results Zero of 217 successfully genotyped UGT specimens yielded trachoma genotypes (95% CI for frequency=0–0.017). For UGT specimens, the genotypes were E (41%), F (22%), D (21%) and K (7%), with J, H and G and mixed genotypes each at 1–4%. Four of the five genotyped eye swabs yielded trachoma genotype Ba, and the other genotype J. Two hundred twenty-two specimens (50.6%) were successfully genotyped. Urine specimens were less likely to be typable than vaginal swabs (p<0.0001). Conclusions Unlike in some other studies, in the remote NT, trachoma genotypes of C. trachomatis were not found circulating in UGT specimens from 2012 to 2013. Therefore, C. trachomatis genotypes in UGT specimens from young children can be informative as to whether the organism has been acquired through sexual contact. We suggest inclusion of C. trachomatis genotyping in guidelines examining the source of sexually transmitted infections in young children in areas where trachoma genotypes may continue to circulate, and continued

  16. The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning

    PubMed Central

    Levine, Andrew J.; Reynolds, Sandra; Cox, Christopher; Miller, Eric N.; Sinsheimer, Janet S.; Becker, James T.; Martin, Eileen; Sacktor, Ned

    2014-01-01

    Background Both HIV-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect ones risk for neurocognitive impairment. Both HIV and stimulant literature indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning was examined longitudinally over a 10 year period. Methods 952 Caucasian HIV+ and HIV− cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-HAART data was examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. Results No 4-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple 3-way interactions were found that involved genotype and HIV status. All immunologic-related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only CCL2 and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. Conclusion The findings support the role of immunologic-related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however their impact is minor. Consistent with findings from another cohort, DA-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV

  17. The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.

    PubMed

    Levine, Andrew J; Reynolds, Sandra; Cox, Christopher; Miller, Eric N; Sinsheimer, Janet S; Becker, James T; Martin, Eileen; Sacktor, Ned

    2014-06-01

    Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort

  18. Axiom turkey genotyping array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Axiom®Turkey Genotyping Array interrogates 643,845 probesets on the array, covering 643,845 SNPs. The array development was led by Dr. Julie Long of the USDA-ARS Beltsville Agricultural Research Center under a public-private partnership with Hendrix Genetics, Aviagen, and Affymetrix. The Turk...

  19. Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen

    PubMed Central

    BRUERA, GEMMA; CANNITA, KATIA; GIORDANO, ALDO VICTOR; VICENTINI, ROBERTO; FICORELLA, CORRADO; RICEVUTO, ENRICO

    2014-01-01

    First-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) can improve efficacy of metastatic colorectal cancer (MCRC), KRAS wild-type and mutant. Prognostic relevance of KRAS genotype was evaluated in patients unfit for FIr-B/FOx, treated with conventional medical treatments. Consecutive MCRC patients not eligible for FIr-B/FOx regimen due to age (≥75 years) and/or comorbidities were treated with tailored conventional first-line treatments. KRAS codon 12/13 mutations were screened by direct sequencing. Activity and efficacy were evaluated and compared according to medical treatments, age (non-elderly and elderly ≥65 years), comorbidity stage (Cumulative Illness Rating Scale), metastatic extension (liver-limited and other/multiple metastatic), and KRAS genotype, using log-rank. Selected first line treatments were medical in 37 patients (92.5%), and surgical in 3 patients (7.5%). Medical treatment regimens: triplet, 18 (45%); doublet, 15 (37.5%); mono-therapy, 4 (10%). At median follow-up of 8 months, objective response rate (ORR) was 37%, median progression-free survival (PFS) 7 months, liver metastasectomies 8% (liver-limited disease 37.5%), median overall survival (OS) 13 months. Triplet regimens failed to significantly affect clinical outcome, compared to doublet. According to KRAS genotype, ORR, PFS and OS were, respectively: wild-type 50%, 8 months, 13 months; mutant 25%, 6 months, 9 months. KRAS genotype wild-type compared to mutant significantly affected PFS, while not OS. KRAS c.35 G>A mutation (G12D) significantly affected worse PFS and OS compared to wild-type and/or other mutations. KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in MCRC patients unfit for intensive medical treatments. PMID:24715238

  20. Genomic Variants Revealed by Invariably Missing Genotypes in Nelore Cattle

    PubMed Central

    da Silva, Joaquim Manoel; Giachetto, Poliana Fernanda; da Silva, Luiz Otávio Campos; Cintra, Leandro Carrijo; Paiva, Samuel Rezende; Caetano, Alexandre Rodrigues; Yamagishi, Michel Eduardo Beleza

    2015-01-01

    High density genotyping panels have been used in a wide range of applications. From population genetics to genome-wide association studies, this technology still offers the lowest cost and the most consistent solution for generating SNP data. However, in spite of the application, part of the generated data is always discarded from final datasets based on quality control criteria used to remove unreliable markers. Some discarded data consists of markers that failed to generate genotypes, labeled as missing genotypes. A subset of missing genotypes that occur in the whole population under study may be caused by technical issues but can also be explained by the presence of genomic variations that are in the vicinity of the assayed SNP and that prevent genotyping probes from annealing. The latter case may contain relevant information because these missing genotypes might be used to identify population-specific genomic variants. In order to assess which case is more prevalent, we used Illumina HD Bovine chip genotypes from 1,709 Nelore (Bos indicus) samples. We found 3,200 missing genotypes among the whole population. NGS re-sequencing data from 8 sires were used to verify the presence of genomic variations within their flanking regions in 81.56% of these missing genotypes. Furthermore, we discovered 3,300 novel SNPs/Indels, 31% of which are located in genes that may affect traits of importance for the genetic improvement of cattle production. PMID:26305794

  1. Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003

    PubMed Central

    Lennard, Lynne; Cartwright, Cher S; Wade, Rachel; Vora, Ajay

    2015-01-01

    The influence of thiopurine methyltransferase (TPMT) genotype on treatment outcome was investigated in the United Kingdom childhood acute lymphoblastic leukaemia trial ALL2003, a trial in which treatment intensity was adjusted based on minimal residual disease (MRD). TPMT genotype was measured in 2387 patients (76% of trial entrants): 2190 were homozygous wild-type, 189 were heterozygous for low activity TPMT alleles (166 TPMT*1/*3A, 19 TPMT*1/*3C, 3 TPMT*1/*2 and 1 TPMT*1/*9) and 8 were TPMT deficient. In contrast to the preceding trial ALL97, there was no difference in event-free survival (EFS) between the TPMT genotypes. The 5-year EFS for heterozygous TPMT*1/*3A patients was the same in both trials (88%), but for the homozygous wild-type TPMT*1/*1 patients, EFS improved from 80% in ALL97% to 88% in ALL2003. Importantly, the unexplained worse outcome for heterozygous TPMT*1/*3C patients observed in ALL97 (5-year EFS 53%) was not seen in ALL2003 (5-year EFS 94%). In a multivariate Cox regression analysis the only significant factor affecting EFS was MRD status (hazard ratio for high-risk MRD patients 4·22, 95% confidence interval 2·97–5·99, P < 0·0001). In conclusion, refinements in risk stratification and treatment have reduced the influence of TPMT genotype on treatment outcome in a contemporary protocol. PMID:25940902

  2. Perinatal health care in a conflict-affected setting: evaluation of health-care services and newborn outcomes at a regional medical centre in Iraq.

    PubMed

    Ahamadani, F A B; Louis, H; Ugwi, P; Hines, R; Pomerleau, M; Ahn, R; Burke, T F; Nelson, B D

    2014-12-01

    A field-based assessment was conducted to assess maternal and newborn health-care services, perinatal and newborn outcomes and associated risk factors at Bint Al-Huda Maternal and Newborn Teaching Hospital, a large referral hospital in southern Iraq. The multi-method approach used interviews, discussions, observation and review of perinatal and newborn outcome data. There is limited assessment of maternal vital signs, labour pattern, fetal response, and complications during pregnancy and labour. Perinatal and neonatal mortality rates are 27.4/1000 births and 30.9/1000 live births respectively. Associated neonatal mortality factors were gestational age < 37 weeks, male sex, birth weight < 2.5 kg, maternal age > 35 years, rural maternal residence and vaginal delivery. Improving birth outcomes in southern Iraq requires evidence-based clinical guidelines, additional supplies and equipment, quality improvement initiatives and in-service training. PMID:25664517

  3. Mass genotyping by sequencing technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Large scale genotyping of a moderate number of loci is cost prohibitive with current chip-based technologies. We demonstrate the ability to use next generation sequencing technologies to genotype many DNA samples for a moderate number of loci – a mass genotyping by sequencing technology (MGST). Ou...

  4. Risk for family rejection and associated mental health outcomes among conflict-affected adult women living in rural eastern Democratic Republic of the Congo.

    PubMed

    Kohli, Anjalee; Perrin, Nancy A; Mpanano, Remy Mitima; Mullany, Luke C; Murhula, Clovis Mitima; Binkurhorhwa, Arsène Kajabika; Mirindi, Alfred Bacikengi; Banywesize, Jean Heri; Bufole, Nadine Mwinja; Ntwali, Eric Mpanano; Glass, Nancy

    2014-01-01

    Stigma due to sexual violence includes family rejection, a complex outcome including economic, behavioral, and physical components. We explored the relationship among conflict-related trauma, family rejection, and mental health in adult women living in rural eastern Democratic Republic of the Congo, who participate in a livestock-based microfinance program, Pigs for Peace. Exposure to multiple and different types of conflict-related trauma, including sexual assault, was associated with increased likelihood of family rejection, which in turn was associated with poorer mental health outcomes. Design of appropriate and effective interventions will require understanding family relationships and exposure to different types of trauma in postconflict environments. PMID:24660941

  5. Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART.

    PubMed

    Saracino, Annalisa; Gianotti, Nicola; Marangi, Marianna; Cibelli, Donatella C; Galli, Andrea; Punzi, Grazia; Monno, Laura; Lazzarin, Adriano; Angarano, Gioacchino

    2008-10-01

    The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 +/- 2.76) than in DNA (2.88 +/- 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had >or=1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. PMID:18712823

  6. Culture Matters. Community Report. Reporting on a Research Project To Explore Factors Affecting the Outcomes of Vocational Education and Training for Aboriginal and Torres Straits Islander People.

    ERIC Educational Resources Information Center

    Buchanan, Matthew; Egg, Mez

    The factors leading to positive outcomes in vocational education and training (VET) for Aboriginal and Torres Strait Islander people were examined through person-to-person and telephone interviews with indigenous Australian students and VET providers. The interviews focused on the following: the range of VET provision and the extent of its…

  7. Are Good Intentions Enough? An Investigation of How Mentor Experiences and Expertise Affect Mentor-Mentee Relationship Development and Targeted Youth Outcomes

    ERIC Educational Resources Information Center

    Silverstein, Lauren A.

    2012-01-01

    In the United States, youth mentoring programs are becoming an increasingly popular educational partnership between community adults and local children. Even though programs rely on mentors to help achieve the desired outcomes, very little is known about "what matters" in a mentor. Adhering to functionalist, human capital, teacher…

  8. In tribute to Bob Blanchard: Divergent behavioral phenotypes of 16p11.2 deletion mice reared in same-genotype versus mixed-genotype cages.

    PubMed

    Yang, Mu; Lewis, Freeman; Foley, Gillian; Crawley, Jacqueline N

    2015-07-01

    Mouse models offer indispensable heuristic tools for studying genetic and environmental causes of neuropsychiatric disorders, including autism. Development of useful animal models of complex human behaviors depends not only on extensive knowledge of the human disease, but also on a deep understanding of animal behavior and ethology. Robert and Caroline Blanchard pioneered a number of elegant social paradigms in rodents. Their early work led to systematic delineations of rodent naturalist defensive behaviors,which were proven to be highly useful models of human psychiatric disorders, including fear and anxiety. Their work using the Visible Burrow System to study social stress in rats represented an unprecedented approach to study biological mechanisms of depression. In recent years, their extensive knowledge of mouse behavior and ethology enabled them to quickly become leading figures in the field of behavioral genetics of autism. To commemorate Robert Blanchard's influences on animal models of human psychiatric disorders, here we describe a study conceptualized and led by Mu Yang who was trained as a graduate student in the Blanchard laboratory in the early 2000s. This investigation focuses on social housing in a genetic mouse model of 16p11.2 deletion syndrome. Heterozygous deletions and duplications of a segment containing about 29 genes on human chromosome 16 appear in approximately 0.5–1% of all cases of autism. 16p11.2 deletion syndrome is also associated with intellectual disabilities and speech impairments. Our previous studies showed that a mouse model of 16p11.2 deletion syndrome exhibited deficits in vocalizations and novel object recognition, as compared to wildtype littermate control cagemates. In the spirit of Bob Blanchard's careful attention to the role of social dominance in rodent behaviors, we became interested in the question of whether behavioral outcomes of a mutation differ when mutants are housed in mixed genotype cages, versus housing only

  9. Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study.

    PubMed

    Andrews, Shea; Das, Debjani; Anstey, Kaarin J; Easteal, Simon

    2015-01-01

    The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life. PMID:25672766

  10. COMT genotype, gambling activity, and cognition.

    PubMed

    Grant, Jon E; Leppink, Eric W; Redden, Sarah A; Odlaug, Brian L; Chamberlain, Samuel R

    2015-09-01

    Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes. PMID:26028545

  11. Clinical Impact of Mycobacterium tuberculosis W-Beijing Genotype Strain Infection on Aged Patients in Taiwan▿

    PubMed Central

    Feng, Jia-Yih; Su, Wei-Juin; Tsai, Cheng-Chien; Chang, Shi-Chuan

    2008-01-01

    The impact of W-Beijing genotype Mycobacterium tuberculosis on treatment outcome was evaluated in 249 newly diagnosed tuberculosis patients. No significant difference in the treatment outcome was found between the W-Beijing and non-W-Beijing groups. However, a poor outcome was more common in the elderly patients (≥65 years) infected with the W-Beijing strain. PMID:18596137

  12. Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?

    PubMed

    Ormeci, A; Emrence, Z; Baran, B; Soyer, O M; Gokturk, S; Evirgen, S; Akyuz, F; Karaca, C; Besisik, F; Kaymakoglu, S; Ustek, D; Demir, K

    2016-05-01

    Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis. PMID:27212172

  13. An Audit-Based, Infectious Disease Specialist-Guided Antimicrobial Stewardship Program Profoundly Reduced Antibiotic Use Without Negatively Affecting Patient Outcomes

    PubMed Central

    Nilholm, Hannah; Holmstrand, Linnea; Ahl, Jonas; Månsson, Fredrik; Odenholt, Inga; Tham, Johan; Melander, Eva; Resman, Fredrik

    2015-01-01

    Background. Antimicrobial stewardship programs are increasingly implemented in hospital care. They aim to simultaneously optimize outcomes for individual patients with infections and reduce financial and health-associated costs of overuse of antibiotics. Few studies have examined the effects of antimicrobial stewardship programs in settings with low proportions of antimicrobial resistance, such as in Sweden. Methods. An antimicrobial stewardship program was introduced during 5 months of 2013 in a department of internal medicine in southern Sweden. The intervention consisted of audits twice weekly on all patients given antibiotic treatment. The intervention period was compared with a historical control consisting of patients treated with antibiotics in the same wards in 2012. Studied outcome variables included 28-day mortality and readmission, length of hospital stay, and use of antibiotics. Results. A reduction of 27% in total antibiotic use (2387 days of any antibiotic) was observed in the intervention period compared with the control period. The reduction was due to fewer patients started on antibiotics as well as to significantly shorter durations of antibiotic courses (P < .001). An earlier switch to oral therapy and a specific reduction in use of third-generation cephalosporins and fluoroquinolones was also evident. Mortality, total readmissions, and lengths of stay in hospital were unchanged compared with the control period, whereas readmissions due to a nonresolved infection were fewer during the intervention of 2013. Conclusions. This study demonstrates that an infectious disease specialist-guided antimicrobial stewardship program can profoundly reduce antibiotic use in a low-resistance setting with no negative effect on patient outcome. PMID:26380341

  14. Premature Progesterone Elevation Does Not Affect Pregnancy Outcome in High-Responder Patients Undergoing Short-Interval Coasting in IVF Cycles.

    PubMed

    Acet, Mustafa; Aktün, Lebriz Hale; Başaranoğlu, Serdar; Yorgunlar, Betül; Acet, Tuba; Deregözü, Aysegul

    2015-01-01

    BACKGROUND We aimed to present the relationship between premature progesterone elevation (PPE) and clinical outcomes in high-responder patients who had a coasting period of <4 days in length due to their high risk of developing ovarian hyperstimulation syndrome (OHSS) and who were treated with a long-acting gonadotropin-releasing hormone agonist (GnRH-agonist) protocol in in vitro fertilization-embryo transfer (IVF-ET) cycles. MATERIAL AND METHODS This retrospective study was conducted at the University Hospital Assisted Reproductive Technology Center. The outcomes of 101 patients undergoing IVF- intracytoplasmic sperm injection (ICSI) cycles who showed a high response to COH (estradiol >4000 pg/ml and/or >20 follicles each ≥10 mm in diameter and at least 20% ≥15 mm) and who were coasted for <4 days were evaluated. Number of oocytes, 2 pronuclei (PN) embryos, implantation rate, and live birth rate were measured. RESULTS The incidence of PPE was 32.6%. Compared with those without PPE, patients with PPE had a higher number of oocytes retrieved. Total mature and fertilized oocytes and the mean number of embryos transferred were not significantly different between groups. Live birth rates (41.9% vs. 38.7%) and implantation rates (26.5% vs. 23%) were also not significantly divergent in the PPE and non-PPE groups, respectively. CONCLUSIONS P concentrations ≥1.3 ng/ml on the day of human chorionic gonadotropin (hCG) administration, designated in this study as PPE, does not appear to be related to adverse effects in terms of clinical outcomes in high-responder patients undergoing coasting <4 days due to their high risk of developing OHSS treated with a long-acting GnRH-a protocol in IVF-embryo transfer cycles. PMID:26634938

  15. Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping.

    PubMed

    Binkhorst, Lisette; Mathijssen, Ron H J; Jager, Agnes; van Gelder, Teun

    2015-03-01

    Clinical response to tamoxifen varies widely among women treated with this drug for hormone receptor-positive breast cancer. The principal active metabolite - endoxifen - is generated through hepatic metabolism of tamoxifen, with key roles for cytochrome P450 (CYP) CYP2D6 and CYP3A. By influencing endoxifen formation, genetic variants of CYP2D6 may affect response to tamoxifen. After a decade of research, examining the effects of CYP2D6 genetic variants on tamoxifen efficacy, there is still no agreement on the clinical utility of CYP2D6 genotype as biomarker for the prediction of breast cancer outcome, because studies revealed conflicting results. However, tamoxifen metabolism is complex and involves several other drug-metabolizing enzymes. Genetic variants of other CYP enzymes, including CYP3A4 and CYP2C9/19, as well as co-medication interfering with the metabolic activity of CYP2D6 and CYP3A4 have been shown to affect endoxifen concentrations and may also contribute to the variability in response to tamoxifen. Phenotyping strategies can predict endoxifen exposure more accurately than CYP2D6 genotype, but do not take into account all factors influencing endoxifen exposure. Therapeutic drug monitoring (TDM) is likely to be the optimal strategy for individualization of tamoxifen treatment. According to a growing amount of literature, endoxifen concentration seems to be a predictor of clinical outcome. The relationship between endoxifen levels and breast cancer outcomes has to be replicated and confirmed and the value of TDM should be evaluated in prospective clinical trials. Caution is advised regarding the concomitant use of medications which could interact with tamoxifen, including inhibitors and inducers of CYP enzymes. PMID:25618289

  16. Genotyping Sleep Disorders Patients

    PubMed Central

    Shadan, Farhad F.; Dawson, Arthur; Cronin, John W.; Jamil, Shazia M.; Grizas, Alexandra P.; Koziol, James A.; Kline, Lawrence E.

    2010-01-01

    Objective The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting. Methods To assess the validity of several candidate associations, we obtained saliva deoxyribonucleic acid (DNA) samples and clinical information from 360 consenting research participants who were undergoing clinical polysomnograms. Ten single nucleotide polymorphisms (SNPs) were genotyped. These were thought to be related to depression, circadian sleep disorders, sleep apnea, restless legs syndrome (RLS), excessive sleepiness, or to slow waves in sleep. Results With multivariate generalized linear models, the association of TEF rs738499 with depressive symptoms was confirmed. Equivocal statistical evidence of association of rs1801260 (the C3111T SNP in the CLOCK gene) with morningness/eveningness and an association of Apolipoprotein E (APOE) rs429358 with the Epworth Sleepiness Scale (ESS) were obtained, but these associations were not strong enough to be of clinical value by themselves. Predicted association of SNPs with sleep apnea, RLS, and slow wave sleep were not confirmed. Conclusion The SNPs tested would not, by themselves, be of use for clinical genotyping in a sleep clinic. PMID:20396431

  17. Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much?

    PubMed Central

    Olgan, Safak; Mumusoglu, Sezcan; Bozdag, Gurkan

    2016-01-01

    Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries. Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed. Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63–0.86, p = 0.001) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy. Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients. PMID:27123444

  18. Perceptions of Partners’ Problematic Alcohol Use Affect Relationship Outcomes Beyond Partner Self-Reported Drinking: Alcohol Use in Committed Romantic Relationships

    PubMed Central

    Rodriguez, Lindsey M.; Overup, Camilla S.; Neighbors, Clayton

    2013-01-01

    Alcohol use is prevalent among college students, including those who are in committed romantic relationships. Individuals’ perceptions of their partner’s alcohol use may have significant effects on how they view both their partner and their relationship. The current study examines the effect of one’s perception of one’s romantic partner’s drinking as problematic on one’s relationship satisfaction and commitment, and whether this varies as a function of one’s partner’s drinking. Both partners in romantic heterosexual relationships (N = 78 dyads) completed an online survey assessing alcohol use and problems, relationship satisfaction and commitment, and the perception that their partner’s drinking was problematic. Analyses using Actor-Partner Interdependence Models (APIMs) revealed a partner-moderated actor interaction, such that partner self-reported drinking significantly moderated the association between the actor’s perception of their partner’s drinking as problematic and actor relationship outcomes. Results indicated that when partners drank at higher levels, perceiving their drinking as problematic did not have an effect. These individuals were less satisfied regardless of their perceptions. However, when partners drank at lower levels, perceiving their drinking as problematic was negatively associated with relationship outcomes. Furthermore, for alcohol consumption, three-way interactions with gender emerged, indicating that this effect was stronger for males. Results extend the literature on drinking in relationships and on interpersonal perception. Implications and future directions are discussed. PMID:23438240

  19. Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much?

    PubMed

    Olgan, Safak; Mumusoglu, Sezcan; Bozdag, Gurkan

    2016-01-01

    Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries. Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed. Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63-0.86, p = 0.001) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy. Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients. PMID:27123444

  20. Realizing the potential of plasma genotyping in an age of genotype-directed therapies.

    PubMed

    Luke, Jason J; Oxnard, Geoffrey R; Paweletz, Cloud P; Camidge, D Ross; Heymach, John V; Solit, David B; Johnson, Bruce E

    2014-08-01

    The identification of oncogenic driver mutations in cancer has led to the rapid rise of genotype-directed treatments such as EGFR and BRAF kinase inhibitors. Standard tumor biopsy remains a cumbersome and morbid procedure for patients, leading to a growing interest in noninvasive plasma genotyping approaches. Circulating tumor cells are of interest; however, the processing of specimens is complicated and time consuming. By comparison, cell-free DNA (cfDNA) genotyping has the potential to be convenient and relatively simple to process in a short time period. Several technologies are under development for cfDNA analysis, such as allele-specific polymerase chain reaction (PCR), coamplification at Lower Denaturation temperatures (COLD) PCR, emulsion PCR, and massively parallel sequencing. Broad clinical validity will need to be established for different assays, and clinical utility will need to be evaluated within prospective trials to determine which assays will best predict the efficacy of therapy and patient outcomes. In addition, assay standardization will be critical prior to widespread use in routine clinical practice. The Cell Free DNA Working Group, under the sponsorship of Transgenomic, was convened to evaluate the molecular assays in development and provide recommendations for application and interpretation of these tests in the context of future clinical research. The consensus commentary of the Cell Free DNA Working Group for the use of cfDNA plasma genotyping assays is presented here, including future steps in the development of these technologies. PMID:25106647

  1. Too Much of a Good Thing? How Breadth of Extracurricular Participation Relates to School-Related Affect and Academic Outcomes during Adolescence

    ERIC Educational Resources Information Center

    Knifsend, Casey A.; Graham, Sandra

    2012-01-01

    Although adolescents often participate in multiple extracurricular activities, little research has examined how the breadth of activities in which an adolescent is involved relates to school-related affect and academic performance. Relying on a large, multi-ethnic sample (N = 864; 55.9% female), the current study investigated linear and non-linear…

  2. How Performance Information Affects Human-Capital Investment Decisions: The Impact of Test-Score Labels on Educational Outcomes. NBER Working Paper No. 17120

    ERIC Educational Resources Information Center

    Papay, John P.; Murnane, Richard J.; Willett, John B.

    2011-01-01

    Students receive abundant information about their educational performance, but how this information affects future educational-investment decisions is not well understood. Increasingly common sources of information are state-mandated standardized tests. On these tests, students receive a score and a label that summarizes their performance. Using a…

  3. Caregiving and Developmental Factors Differentiating Young At-Risk Urban Children Showing Resilient Versus Stress-Affected Outcomes: A Replication and Extension.

    ERIC Educational Resources Information Center

    Wyman, Peter A.; And Others

    1999-01-01

    Tested hypotheses from an organizational-developmental model for childhood resilience among 7- to 9-year olds. Found that caregiving factors and early development differentiated children with resilient and stress-affected adaptations. Variables reflecting emotionally responsive, competent parenting were direct, proximal predictors of resilience…

  4. A Process and Outcome Evaluation of an Affective In-Service Training Program for Junior High School Teachers: Second Year Results.

    ERIC Educational Resources Information Center

    Moskowitz, Joel M.; And Others

    Teachers were trained in either or both of two versions of Effective Classroom Management--Junior High (ECM). In the second year of the study, teachers were taught techniques in discipline, communication, and self-esteem enhancement. The goals of the in-service training were to make teachers more responsive to students' affective and cognitive…

  5. Patient Background Factors Affecting the Therapeutic Outcomes in Response to Eszopiclone in Adult Patients with Chronic Insomnia: A Post Hoc Analysis of a Double-Blind Phase III Study in Japan

    PubMed Central

    Inoue, Yuichi; Kamijo, Atsushi; Nagai, Reiko

    2015-01-01

    Study Objective: To identify whether baseline demographic factors or subjective sleep variables are associated with the outcomes following treatment with eszopiclone using data from a recent randomized controlled trial of 78 Japanese subjects with insomnia who were treated with 2 mg eszopiclone per day. Methods: We performed a post hoc analysis of factors including sleep latency (SL), wake time after sleep onset (WASO) (both assessed via sleep diaries), and several demographic variables. Subjects with a SL or WASO > 30 min at baseline and with evaluable SL/WASO data at Week 4 were included in SL and WASO remitter analyses, respectively; those with a SL or WASO ≤ 30 min at Week 4 were defined as SL or WASO remitters, respectively. Threshold baseline SL and WASO values for identification of remitters were determined. Results: No relationships between subjectively assessed therapeutic outcomes and demographic factors were identified. Patients with shorter SL and lower WASO values at baseline showed better outcomes following treatment with eszopiclone in terms of SL and WASO changes, respectively. Baseline SL of 75 min and baseline WASO of 80 min were selected as arbitrary cutoff values for determination of SL and WASO remitters/non-remitters, respectively. Conclusions: These findings may help clinicians to predict their patients' outcomes in response to standard doses of eszopiclone in clinical practice. Citation: Inoue Y, Kamijo A, Nagai R. Patient background factors affecting the therapeutic outcomes in response to eszopiclone in adult patients with chronic insomnia: a post hoc analysis of a double-blind phase III study in Japan. J Clin Sleep Med 2015;11(10):1171–1178. PMID:26094929

  6. The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia.

    PubMed

    Jovanovic-Cupic, Snezana; Glisic, Sanja; Stanojevic, Maja; Nozic, Darko; Petrovic, Nina; Mandusic, Vesna; Krajnovic, Milena

    2016-05-01

    The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p < 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p < 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p < 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b. PMID:26860912

  7. Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients

    PubMed Central

    Nakashima, Hiroaki; Tetreault, Lindsay A; Nagoshi, Narihito; Nouri, Aria; Kopjar, Branko; Arnold, Paul M; Bartels, Ronald; Defino, Helton; Kale, Shashank; Zhou, Qiang; Fehlings, Michael G

    2016-01-01

    Background In general, older patients with degenerative cervical myelopathy (DCM) are felt to have lower recovery potential following surgery due to increased degenerative pathology, comorbidities, reduced physiological reserves and age-related changes to the spinal cord. This study aims to determine whether age truly is an independent predictor of surgical outcome and to provide evidence to guide practice and decision-making. Methods A total of 479 patients with DCM were prospectively enrolled in the CSM-International study at 16 centres. Our sample was divided into a younger group (<65 years) and an elderly (≥65 years) group. A mixed model analytic approach was used to evaluate differences in the modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36) and Neck Disability Index (NDI) scores between groups. We first created an unadjusted model between age and surgical outcome and then developed two adjusted models that accounted for variations in (1) baseline characteristics and (2) both baseline and surgical factors. Results Of the 479 patients, 360 (75.16%) were <65 years and 119 (24.84%) were ≥65 years. Elderly patients had a worse preoperative health status (p<0.0001) and were functionally more severe (p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery, whereas the preferred approach in the elderly group was posterior (58.62%, p<0.0001). Elderly patients had a greater number of decompressed levels than younger patients (p<0.0001). At 24 months after surgery, younger patients achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score (p<0.0001) than elderly patients. After adjustments for patient and surgical characteristics, these differences in postoperative outcome scores decreased but remained significant. Conclusions Older age is an independent predictor of functional status in patients with DCM. However, patients over 65 with DCM still achieve functionally significant

  8. The sperm quality and clinical outcomes were not affected by sY152 deletion in Y chromosome for oligozoospermia or azoospermia men after ICSI treatment.

    PubMed

    Zhu, Yuanchang; Wu, Tonghua; Li, Guangui; Yin, Biao; Liu, Hongjie; Wan, Caiyun; Zhang, Hongzhan; Zeng, Yong

    2015-12-01

    Azoospermia factor (AZF) microdeletion plays a key role in the genetic etiology of male infertility. The relationship between sY152 deletion in the AZFc region and clinical outcomes is still unclear. This study was to determine the effects of sY152 deletion on the sperm parameters and clinical outcomes of non-obstructive azoospermia or oligozoospermia men after intracytoplasmic sperm injection (ICSI) treatment. A total of 61 infertile men with AZFc microdeletion of the Y chromosome from January 2008 to December 2012 were recruited in the present study. They were divided into two groups, the sY152 group (n=12) and the AZFc group (n=49), based upon whether they have deleted single sY152 marker or all AZFc markers. Fifty azoospermia or oligozoospermia patients without Y chromosome microdeletion were included as the control group. The sperm quality and clinical data were compared among the three groups. Retrospective cohort-control study was performed. The sperm concentration and motility in sY152 group were better than AZFc group (P<0.05), and were comparable to the control group (P>0.05); the morphology, seminal zinc, seminal fructose and seminal carnitine were similar among the three groups (P>0.05). Patients in both sY152 and AZFc groups had lower fertilization rates (68.40% and 70.63%, respectively) than those in the control group (74.91%), and the differences were statistically significant (P<0.05). No significant differences were found in terms of MII oocyte, high-grade embryo rate, 2PN zygote, number of available embryos and transferred embryos, clinical pregnancy rate, implantation rate, miscarriage rate, multiple pregnancy rate, delivery rate, preterm rate and the male/female ratio among the three groups (P>0.05). Single sY152 deletion might cause a lower fertilization rate, but no adverse effects on sperm quality and clinical outcomes were found. Our study may provide more information for consultation in these patients. PMID:26188156

  9. Vitamin D3 Deficiency Differentially Affects Functional and Disease Outcomes in the G93A Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Solomon, Jesse A.; Gianforcaro, Alexandro; Hamadeh, Mazen J.

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D3 supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS. Objective To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS. Methods At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D3 groups: 1) adequate (AI; 1 IU D3/g feed) and 2) deficient (DEF; 0.025 IU D3/g feed). At age 113 d, tibialis anterior (TA), quadriceps (quads) and brain were harvested from 42 mice (22 M and 20 F), whereas the remaining 60 mice (34 M and 26 F) were followed to endpoint. Results During disease progression, DEF mice had 25% (P = 0.022) lower paw grip endurance AUC and 19% (P = 0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P = 0.016) lower clinical score (CS) vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR = 0.57; 95% CI: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (AI: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (AI: r = 0.661, P = 0.001; DEF: r = 0.768; P<0.001) weights were strongly correlated with age at CS 2. Conclusion Vitamin D3 deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse. PMID:22216257

  10. Toward Innovative, Cost-Effective, and Systemic Solutions to Improve Outcomes and Well-Being of Military Families Affected by Autism Spectrum Disorder

    PubMed Central

    Klin, Ami; Wetherby, Amy M.; Woods, Juliann; Saulnier, Celine; Stapel-Wax, Jennifer; Klaiman, Cheryl; Jones, Warren; Rubin, Emily; Scahill, Lawrence; Call, Nathan; Bearss, Karen; Gunter, Chris; Courtemanche, Charles J.; Lemieux, Anthony; Cox, James C.; Mandell, David S.; Van Decar, James P.; Miller, Ronald A.; Shireman, Cherri L.

    2015-01-01

    The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit. PMID:25745376

  11. Toward innovative, cost-effective, and systemic solutions to improve outcomes and well-being of military families affected by autism spectrum disorder.

    PubMed

    Klin, Ami; Wetherby, Amy M; Woods, Juliann; Saulnier, Celine; Stapel-Wax, Jennifer; Klaiman, Cheryl; Jones, Warren; Rubin, Emily; Scahill, Lawrence; Call, Nathan; Bearss, Karen; Gunter, Chris; Courtemanche, Charles J; Lemieux, Anthony; Cox, James C; Mandell, David S; Van Decar, James P; Miller, Ronald A; Shireman, Cherri L

    2015-03-01

    The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit. PMID:25745376

  12. LaSota fusion (F) cleavage motif-mediated fusion activity is affected by other regions of the F protein from different genotype Newcastle disease virus in a chimeric virus: implication for virulence attenuation.

    PubMed

    Kim, Shin-Hee; Xiao, Sa; Collins, Peter L; Samal, Siba K

    2016-06-01

    The cleavage site sequence of the fusion (F) protein contributes to a wide range of virulence of Newcastle disease virus (NDV). In this study, we identified other important amino acid sequences of the F protein that affect cleavage and modulation of fusion. We generated chimeric Beaudette C (BC) viruses containing the cleavage site sequence of avirulent strain LaSota (Las-Fc) together with various regions of the F protein of another virulent strain AKO. We found that the F1 subunit is important for cleavage inhibition. Further dissection of the F1 subunit showed that replacement of four amino acids in the BC/Las-Fc protein with their AKO counterparts (T341S, M384I, T385A and I386L) resulted in an increase in fusion and replication in vitro. In contrast, the mutation N403D greatly reduced cleavage and viral replication, and affected protein conformation. These findings will be useful in developing improved live NDV vaccines and vaccine vectors. PMID:26932300

  13. Effects of plant genotype and insect dispersal rate on the population dynamics of a forest pest.

    PubMed

    Moran, Emily V; Bewick, Sharon; Cobbold, Christina A

    2013-12-01

    It has been shown that plant genotype can strongly affect not only individual herbivore performance, but also community composition and ecosystem function. Few studies, however, have addressed how plant genotype affects herbivore population dynamics. In this paper, we used a simulation modeling approach to ask how the genetic composition of a forest influences pest outbreak dynamics, using the example of aspen (Populus tremuloides) and forest tent caterpillars (FTC; Malacosoma disstria). Specifically, we examined how plant genotype, the relative size of genotypic patches, and the rate of insect dispersal between them, affect the frequency, amplitude, and duration of outbreaks. We found that coupling two different genotypes does not necessarily result in an averaging of insect dynamics. Instead, depending on the ratio of patch sizes, when dispersal rates are moderate, outbreaks in the two-genotype case may be more or less severe than in forests of either genotype alone. Thresholds for different dynamic behaviors were similar for all genotypic combinations. Thus, the qualitative behavior of a stand of two different genotypes can be predicted based on the response of the insect to each genotype, the relative sizes of the two patches, and the scale of insect dispersal. PMID:24597225

  14. Genotypic Variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe

    PubMed Central

    Crowder, Chris D.; Matthews, Heather E.; Schutzer, Steven; Rounds, Megan A.; Luft, Benjamin J.; Nolte, Oliver; Campbell, Scott R.; Phillipson, Curtis A.; Li, Feng; Sampath, Ranga; Ecker, David J.; Eshoo, Mark W.

    2010-01-01

    Background Lyme disease, caused by various species of Borrelia, is transmitted by Ixodes ticks in North America and Europe. Studies have shown the genotype of Borrelia burgdorferi sensu stricto (s.s.) or the species of B. burgdorferi sensu lato (s.l.) affects the ability of the bacteria to cause local or disseminated infection in humans. Methodology/Principal Findings We used a multilocus PCR electrospray mass spectrometry assay to determine the species and genotype Borrelia from ticks collected in New York, Connecticut, Indiana, Southern Germany, and California and characterized isolates from parts of the United States and Europe. These analyses identified 53 distinct genotypes of B. burgdorferi sensu stricto with higher resolution than ospC typing. Genotypes of other members of the B. burgdorferi sensu lato complex were also identified and genotyped including B. afzelii, B. garinii, B. lusitaniae, B. spielmanii, and B. valaisiana. While each site in North America had genotypes unique to that location, we found genotypes shared between individual regions and two genotypes found across the United States. Significant B. burgdorferi s.s. genotypic diversity was observed between North America and Europe: only 6.6% of US genotypes (3 of 45) were found in Europe and 27% of the European genotypes (3 of 11) were observed in the US. Interestingly, 39% of adult Ixodes scapularis ticks from North America were infected with more than one genotype of B. burgdorferi s.s. and 22.2% of Ixodes ricinus ticks from Germany were infected with more than one genotype of B. burgdorferi s.l. Conclusions/Significance The presence of multiple Borrelia genotypes in ticks increases the probability that a person will be infected with more than one genotype of B. burgdorferi, potentially increasing the risks of disseminated Lyme disease. Our study indicates that the genotypic diversity of Borrelia in ticks in both North America and Europe is higher then previously reported and can have

  15. HBV Genotypic Variability in Cuba

    PubMed Central

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  16. Migration, neighborhoods, and networks: approaches to understanding how urban environmental conditions affect syndemic adverse health outcomes among gay, bisexual and other men who have sex with men.

    PubMed

    Egan, James E; Frye, Victoria; Kurtz, Steven P; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A

    2011-04-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  17. Changes in rainfall amount and frequency do not affect the outcome of the interaction between the shrub Retama sphaerocarpa and its neighbouring grasses in two semiarid communities

    PubMed Central

    Soliveres, Santiago; García-Palacios, Pablo; Maestre, Fernando T.; Escudero, Adrián; Valladares, Fernando

    2015-01-01

    We evaluated the net outcome of the interaction between the shrub Retama sphaerocarpa, our target plant, and different herbaceous neighbours in response to changes in the magnitude and frequency of rainfall events during three years. The experiment was conducted in natural and anthropogenic grasslands dominated by a perennial stress-tolerator and ruderal annual species, respectively. In spite of the neutral or positive effects of neighbours on water availability, neighbouring plants reduced the performance of Retama juveniles, suggesting competition for resources other than water. The negative effects of grasses on the photochemical efficiency of Retama juveniles decreased with higher water availabilities or heavier irrigation pulses, depending on the grassland studied; however, these effects did not extent to the survival and growth of Retama juveniles. Our findings show the prevalence of competitive interactions among the studied plants, regardless of the water availability and its temporal pattern. These results suggest that positive interactions may not prevail under harsher conditions when shade-intolerant species are involved. This study could be used to further refine our predictions of how plant-plant interactions will respond to changes in rainfall, either natural or increased by the ongoing climatic change, in ecosystems where grass-shrubs interactions are prevalent. PMID:25914429

  18. The Role of Negative Affectivity and Negative Reactivity to Emotions in Predicting Outcomes in the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders

    PubMed Central

    Sauer-Zavala, Shannon; Boswell, James F.; Gallagher, Matthew W.; Bentley, Kate H.; Ametaj, Amantia; Barlow, David H.

    2012-01-01

    The present study aimed to understand the contributions of both the trait tendency to experience negative emotions and how one relates to such experience in predicting symptom change during participation in the Unified Protocol (UP), a transdiagnostic treatment for emotional disorders. Data were derived from a randomized controlled trial comparing the UP to a wait-list control / delayed-treatment condition. First, effect sizes of pre- to post-treatment change for frequency of negative emotions and several variables measuring reactivity to emotional experience (emotional awareness and acceptance, fear of emotions, and anxiety sensitivity) were examined. Second, the relative contributions of change in negative emotions and emotional reactivity in predicting symptom (clinician-rated anxiety, depression, and severity of principal diagnosis) reductions were investigated. Results suggested that decreases in the frequency of negative emotions and reactivity to emotions following participation in the UP were both large in magnitude. Further, two emotional reactivity variables (fear of emotions and anxiety sensitivity) remained significantly related to symptom outcomes when controlling for negative emotions, and accounted for significant incremental variance in their prediction. These findings lend support to the notion that psychological health depends less on the frequency of negative emotions and more on how one relates to these emotions when they occur. PMID:22738907

  19. Migration, Neighborhoods, and Networks: Approaches to Understanding How Urban Environmental Conditions Affect Syndemic Adverse Health Outcomes Among Gay, Bisexual and Other Men Who Have Sex with Men

    PubMed Central

    Egan, James E.; Kurtz, Steven P.; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A.

    2011-01-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  20. Special features of RAD Sequencing data: implications for genotyping

    PubMed Central

    Davey, John W; Cezard, Timothée; Fuentes-Utrilla, Pablo; Eland, Cathlene; Gharbi, Karim; Blaxter, Mark L

    2013-01-01

    Restriction site-associated DNA Sequencing (RAD-Seq) is an economical and efficient method for SNP discovery and genotyping. As with other sequencing-by-synthesis methods, RAD-Seq produces stochastic count data and requires sensitive analysis to develop or genotype markers accurately. We show that there are several sources of bias specific to RAD-Seq that are not explicitly addressed by current genotyping tools, namely restriction fragment bias, restriction site heterozygosity and PCR GC content bias. We explore the performance of existing analysis tools given these biases and discuss approaches to limiting or handling biases in RAD-Seq data. While these biases need to be taken seriously, we believe RAD loci affected by them can be excluded or processed with relative ease in most cases and that most RAD loci will be accurately genotyped by existing tools. PMID:23110438

  1. Special features of RAD Sequencing data: implications for genotyping.

    PubMed

    Davey, John W; Cezard, Timothée; Fuentes-Utrilla, Pablo; Eland, Cathlene; Gharbi, Karim; Blaxter, Mark L

    2013-06-01

    Restriction site-associated DNA Sequencing (RAD-Seq) is an economical and efficient method for SNP discovery and genotyping. As with other sequencing-by-synthesis methods, RAD-Seq produces stochastic count data and requires sensitive analysis to develop or genotype markers accurately. We show that there are several sources of bias specific to RAD-Seq that are not explicitly addressed by current genotyping tools, namely restriction fragment bias, restriction site heterozygosity and PCR GC content bias. We explore the performance of existing analysis tools given these biases and discuss approaches to limiting or handling biases in RAD-Seq data. While these biases need to be taken seriously, we believe RAD loci affected by them can be excluded or processed with relative ease in most cases and that most RAD loci will be accurately genotyped by existing tools. PMID:23110438

  2. IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

    PubMed Central

    Wang, Xiao-Wei; Ciccarino, Pietro; Rossetto, Marta; Marie, Yannick; Desestret, Virginie; Mokhtari, Karima; Sanson, Marc; Labussière, Marianne

    2014-01-01

    IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations. PMID:24877111

  3. Hepatitis B Virus Genotyping: Is the Time Ripe for Routine Clinical Use?

    PubMed Central

    Madan, Kaushal; Tyagi, Pankaj

    2012-01-01

    Hepatitis B is one of the major causes of end-stage liver disease and liver cancer worldwide. A number of host and viral factors influence the disease course and outcomes. One such viral factor is hepatitis B virus (HBV) genotypes. There are eight major HBV genotypes described from various geographic regions of the world. Although direct sequencing appears to be the gold standard for HBV genotyping, it is expensive and laborintensive and therefore cannot be applied for routine clinical use. The newer molecular methods including serotyping have made genotyping easier and simple to apply to large number of samples rapidly. The data collected mainly over the last decade have suggested that HBV genotypes may have a bearing over the natural course of the disease and its response to therapy. This review summarizes the available literature and highlights how genotyping could be incorporated into routine clinical practice in order to improve delivery of care to HBV-infected individuals. PMID:25755425

  4. Too much of a good thing? How breadth of extracurricular participation relates to school-related affect and academic outcomes during adolescence.

    PubMed

    Knifsend, Casey A; Graham, Sandra

    2012-03-01

    Although adolescents often participate in multiple extracurricular activities, little research has examined how the breadth of activities in which an adolescent is involved relates to school-related affect and academic performance. Relying on a large, multi-ethnic sample (N = 864; 55.9% female), the current study investigated linear and non-linear relationships of 11th grade activity participation in four activity domains (academic/leadership groups, arts activities, clubs, and sports) to adolescents' sense of belonging at school, academic engagement, and grade point average, contemporarily and in 12th grade. Results of multiple regression models revealed curvilinear relationships for sense of belonging at school in 11th and 12th grade, grade point average in 11th grade, and academic engagement in 12th grade. Adolescents who were moderately involved (i.e., in two domains) reported a greater sense of belonging at school in 11th and 12th grade, a higher grade point average in 11th grade, and greater academic engagement in 12th grade, relative to those who were more or less involved. Furthermore, adolescents' sense of belonging at school in 11th grade mediated the relationship of domain participation in 11th grade to academic engagement in 12th grade. This study suggests that involvement in a moderate number of activity domains promotes positive school-related affect and greater academic performance. School policy implications and recommendations are discussed. PMID:22160442

  5. AN EVALUATION OF CRYPTOSPORIDIUM PARVUM GENOTYPING

    EPA Science Inventory

    We evaluated the specificity and sensitivity of 11 previously described species differentiation and genotyping PCR protocols for detection of Cryptosporidium parasites. Genomic DNA from three species of Crytosporidium parasites (genotype 1 and genotype 2 of C. parvum, C. muris, a...

  6. Does the Type of Anesthetic Technique Affect In-Hospital and One-Year Outcomes after Off-Pump Coronary Arterial Bypass Surgery?

    PubMed Central

    Lee, Jong-Hwan; Hong, Kwan Young; Kim, Wook Sung; Lee, Young-Tak

    2016-01-01

    Despite numerous previous studies, there is little data on the effects of anesthetics on clinical outcome after off-pump coronary arterial bypass grafting (OPCAB). Therefore, we retrospectively compared the effects of anesthetic choice on in-hospital major adverse events (MAEs) and one-year major adverse cardiovascular and cerebral events (MACCEs) in patients undergoing OPCAB. Electronic medical records were reviewed in 192 patients who received propofol-remifenanil total intravenous anesthesia (TIVA) and propensity score-matched 662 patients who received isoflurane anesthesia. The primary endpoints were in-hospital MAEs and one-year MACCEs. The components of in-hospital MAEs were in-hospital death, myocardial infarction (MI), coronary revascularization, stroke, renal failure, prolonged mechanical ventilation longer than 72 h, and postoperative new cardiac arrhythmia requiring treatment. One-year MACCEs was defined as a composite of all-cause mortality, MI, coronary revascularization, and stroke. There was no significant difference in risk of in-hospital MAEs (OR = 1.29, 95% CI = 0.88–1.88, P = 0.20) or one-year MACCEs (OR = 0.81; 95% CI = 0.46–1.42, P = 0.46) between the groups. The risk of postoperative new arrhythmia including new atrial fibrillation significantly increased in the TIVA group compared to the isoflurane anesthesia group (OR = 1.72, 95% CI = 1.12–2.63, P = 0.01). In conclusion, the choice between propofol-remifentanil TIVA and isoflurane anesthesia did not show differences in incidence of in-hospital MAEs or one-year MACCEs in patients undergoing OPCAB. However, further studies on the effects of anesthetics on development of in-hospital new arrhythmia will be needed. PMID:27054364

  7. Testing how voluntary participation requirements in an environmental study affect the planned random sample design outcomes: implications for the predictions of values and their uncertainty.

    NASA Astrophysics Data System (ADS)

    Ander, Louise; Lark, Murray; Smedley, Pauline; Watts, Michael; Hamilton, Elliott; Fletcher, Tony; Crabbe, Helen; Close, Rebecca; Studden, Mike; Leonardi, Giovanni

    2015-04-01

    Random sampling design is optimal in order to be able to assess outcomes, such as the mean of a given variable across an area. However, this optimal sampling design may be compromised to an unknown extent by unavoidable real-world factors: the extent to which the study design can still be considered random, and the influence this may have on the choice of appropriate statistical data analysis is examined in this work. We take a study which relied on voluntary participation for the sampling of private water tap chemical composition in England, UK. This study was designed and implemented as a categorical, randomised study. The local geological classes were grouped into 10 types, which were considered to be most important in likely effects on groundwater chemistry (the source of all the tap waters sampled). Locations of the users of private water supplies were made available to the study group from the Local Authority in the area. These were then assigned, based on location, to geological groups 1 to 10 and randomised within each group. However, the permission to collect samples then required active, voluntary participation by householders and thus, unlike many environmental studies, could not always follow the initial sample design. Impediments to participation ranged from 'willing but not available' during the designated sampling period, to a lack of response to requests to sample (assumed to be wholly unwilling or unable to participate). Additionally, a small number of unplanned samples were collected via new participants making themselves known to the sampling teams, during the sampling period. Here we examine the impact this has on the 'random' nature of the resulting data distribution, by comparison with the non-participating known supplies. We consider the implications this has on choice of statistical analysis methods to predict values and uncertainty at un-sampled locations.

  8. Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner.

    PubMed

    Brummelte, Susanne; Lieblich, Stephanie E; Galea, Liisa A M

    2012-01-01

    Exposure to high levels of glucocorticoids in utero and during the postpartum period has a detrimental effect on brain development. We created an animal model of postpartum stress/depression based on administering high levels of corticosterone (CORT) to the dams during the postpartum period which caused behavioral changes and reduced hippocampal cell proliferation in the offspring. As the consequences of early exposure to glucocorticoids may depend on the dose and the developmental stage of the offspring, the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on the outcome of the offspring. Male and female offspring were weighed throughout the experiment, tested in a series of behavioral tests (forced swim test, open field, elevated plus maze) and basal and restraint stress CORT levels were examined in adolescence or young adulthood. Results show that maternal CORT exposure, regardless of when administered, significantly attenuated body weight gain until adulthood in the offspring. Offspring exposed to low maternal CORT, but not high maternal CORT, during the postpartum had higher basal levels of CORT as young adults. Further, male and female offspring of dams exposed to high maternal CORT in utero showed more depressive-like behavior in the forced swim test, while males of dams exposed to high maternal CORT postpartum exhibited more anxiety-like behavior in the elevated plus maze. Taken together, maternal glucocorticoid exposure have long lasting effects on male and female offspring's behavioral and neuroendocrine measures in adolescence and adulthood depending on the time of exposure to glucocorticoids. This article is part of a Special Issue entitled 'Anxiety and Depression'. PMID:21867716

  9. Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration?

    PubMed Central

    Fanari, Zaher; Hammami, Sumaya; Hammami, Muhammad Baraa; Hammami, Safa; Abdellatif, Abdul

    2015-01-01

    There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l) is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l) is considered deficiency. Levels below 50 nmol/l (20 ng/l) are linked independently to cardiovascular morbidity and mortality. PMID:26557744

  10. Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration?

    PubMed

    Fanari, Zaher; Hammami, Sumaya; Hammami, Muhammad Baraa; Hammami, Safa; Abdellatif, Abdul

    2015-10-01

    There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l) is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l) is considered deficiency. Levels below 50 nmol/l (20 ng/l) are linked independently to cardiovascular morbidity and mortality. PMID:26557744

  11. Genotype Specification Language.

    PubMed

    Wilson, Erin H; Sagawa, Shiori; Weis, James W; Schubert, Max G; Bissell, Michael; Hawthorne, Brian; Reeves, Christopher D; Dean, Jed; Platt, Darren

    2016-06-17

    We describe here the Genotype Specification Language (GSL), a language that facilitates the rapid design of large and complex DNA constructs used to engineer genomes. The GSL compiler implements a high-level language based on traditional genetic notation, as well as a set of low-level DNA manipulation primitives. The language allows facile incorporation of parts from a library of cloned DNA constructs and from the "natural" library of parts in fully sequenced and annotated genomes. GSL was designed to engage genetic engineers in their native language while providing a framework for higher level abstract tooling. To this end we define four language levels, Level 0 (literal DNA sequence) through Level 3, with increasing abstraction of part selection and construction paths. GSL targets an intermediate language based on DNA slices that translates efficiently into a wide range of final output formats, such as FASTA and GenBank, and includes formats that specify instructions and materials such as oligonucleotide primers to allow the physical construction of the GSL designs by individual strain engineers or an automated DNA assembly core facility. PMID:26886161

  12. Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing.

    PubMed

    Opmeer, Esther M; Kortekaas, Rudie; van Tol, Marie-José; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W J H; Veltman, Dick J; Aleman, André

    2014-05-01

    Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance. PMID:23482625

  13. Echinococcus granulosus genotypes in Iran

    PubMed Central

    Sharafi, Seyedeh Maryam; Rostami-Nejad, Mohammad; Moazeni, Mohammad; Yousefi, Morteza; Saneie, Behnam; Hosseini-Safa, Ahmad

    2014-01-01

    Hydatidosis, caused by Echinococcus granulosus is one of the most important zoonotic diseases, throughout most parts of the world. Hydatidosis is endemic in Iran and responsible for approximately 1% of admission to surgical wards. There are extensive genetic variations within E. granulosus and 10 different genotypes (G1–G10) within this parasite have been reported. Identification of strains is important for improvement of control and prevention of the disease. No new review article presented the situation of Echinococcus granulosus genotypes in Iran in the recent years; therefore in this paper we reviewed the different studies regarding Echinococcus granulosus genotypes in Iran. PMID:24834298

  14. Factors affecting outcomes in patients reaching end-stage kidney disease worldwide: differences in access to renal replacement therapy, modality use, and haemodialysis practices.

    PubMed

    Robinson, Bruce M; Akizawa, Tadao; Jager, Kitty J; Kerr, Peter G; Saran, Rajiv; Pisoni, Ronald L

    2016-07-16

    More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This Series paper provides an overview of incidence, modality use (in-centre haemodialysis, home dialysis, or transplantation), and mortality for patients with ESKD based on national registry data. We also present data from an international cohort study to highlight differences in haemodialysis practices that affect survival and the experience of patients who rely on this therapy, which is both life-sustaining and profoundly disruptive to their quality of life. Data illustrate disparities in access to renal replacement therapy of any kind and in the use of transplantation or home dialysis, both of which are widely considered preferable to in-centre haemodialysis for many patients with ESKD in settings where infrastructure permits. For most patients with ESKD worldwide who are treated with in-centre haemodialysis, overall survival is poor, but longer in some Asian countries than elsewhere in the world, and longer in Europe than in the USA, although this gap has reduced. Commendable haemodialysis practice includes exceptionally high use of surgical vascular access in Japan and in some European countries, and the use of longer or more frequent dialysis sessions in some countries, allowing for more effective volume management. Mortality is especially high soon after ESKD onset, and improved preparation for ESKD is needed including alignment of decision making with the wishes of patients and families. PMID:27226132

  15. Measuring fate and rate of single-molecule competition of amplification and restriction digestion, and its use for rapid genotyping tested with hepatitis C viral RNA.

    PubMed

    Sun, Bing; Rodriguez-Manzano, Jesus; Selck, David A; Khorosheva, Eugenia; Karymov, Mikhail A; Ismagilov, Rustem F

    2014-07-28

    We experimentally monitored, at the single-molecule level, the competition among reverse transcription, exponential amplification (RT-LAMP), and linear degradation (restriction enzymes) starting with hepatitis C viral RNA molecules. We found significant heterogeneity in the rate of single-molecule amplification; introduction of the restriction enzymes affected both the rate and the "fate" (the binary outcome) of single-molecule amplification. While end-point digital measurements were primarily sensitive to changes in fate, the bulk real-time kinetic measurements were dominated by the rate of amplification of the earliest molecules, and were not sensitive to fate of the rest of the molecules. We show how this competition of reactions can be used for rapid HCV genotyping with either digital or bulk readout. This work advances our understanding of single-molecule dynamics in reaction networks and may help bring genotyping capabilities out of clinical labs and into limited-resource settings. PMID:24889060

  16. Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation

    PubMed Central

    Rhainds, David; Brodeur, Mathieu; Feroz Zada, Yassamin; Fouodjio, René; Provost, Sylvie; Boulé, Marie; Alem, Sonia; Grégoire, Jean C.; L’Allier, Philippe L.; Ibrahim, Reda; Guertin, Marie-Claude; Mongrain, Ian; Olsson, Anders G.; Schwartz, Gregory G.; Rhéaume, Eric

    2016-01-01

    Background— Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation. Methods and Results— Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (P=0.0009) and 18.7% (P=0.00001) in participants with the GG and AG genotypes, respectively, but the change was −1.0% (P=0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (P=0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (P=0.005). There was a significant genetic effect for change in efflux for dalcetrapib (P=0.02), but not with placebo. Conclusions— Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309. Clinical Trials Registration— ClinicalTrials.gov; Unique Identifiers: NCT00658515 and NCT01059682. PMID:27418594

  17. Correlated genotypes in friendship networks

    PubMed Central

    Fowler, James H.; Settle, Jaime E.; Christakis, Nicholas A.

    2011-01-01

    It is well known that humans tend to associate with other humans who have similar characteristics, but it is unclear whether this tendency has consequences for the distribution of genotypes in a population. Although geneticists have shown that populations tend to stratify genetically, this process results from geographic sorting or assortative mating, and it is unknown whether genotypes may be correlated as a consequence of nonreproductive associations or other processes. Here, we study six available genotypes from the National Longitudinal Study of Adolescent Health to test for genetic similarity between friends. Maps of the friendship networks show clustering of genotypes and, after we apply strict controls for population stratification, the results show that one genotype is positively correlated (homophily) and one genotype is negatively correlated (heterophily). A replication study in an independent sample from the Framingham Heart Study verifies that DRD2 exhibits significant homophily and that CYP2A6 exhibits significant heterophily. These unique results show that homophily and heterophily obtain on a genetic (indeed, an allelic) level, which has implications for the study of population genetics and social behavior. In particular, the results suggest that association tests should include friends’ genes and that theories of evolution should take into account the fact that humans might, in some sense, be metagenomic with respect to the humans around them. PMID:21245293

  18. Early pregnancy vitamin D status and risk for adverse maternal and infant outcomes in a bi-ethnic cohort: the Behaviors Affecting Baby and You (B.A.B.Y.) Study.

    PubMed

    Nobles, Carrie J; Markenson, Glenn; Chasan-Taber, Lisa

    2015-12-28

    Vitamin D deficiency is common during pregnancy and higher in Hispanic as compared with non-Hispanic white women. However, the association between vitamin D deficiency and adverse pregnancy outcomes remains unclear and may vary across ethnic groups, in part because of genetic variation in the metabolism of vitamin D. Few studies have included Hispanic women. Therefore, we investigated this association among 237 participants in the Behaviors Affecting Baby and You Study, a randomised trial of an exercise intervention among ethnically diverse prenatal care patients in Massachusetts. Baseline serum 25-hydroxyvitamin D (25(OH)D) was measured at 15·2 (sd 4·7) weeks' gestation. Information on adverse pregnancy outcomes was abstracted from medical records. Mean 25(OH)D was 30·4 (sd 12·0) ng/ml; 53·2 % of participants had insufficient (<30 ng/ml) and 20·7 % had deficient (<20 ng/ml) 25(OH)D levels. After adjusting for month of blood draw, gestational age at blood draw, gestational age at delivery, age, BMI and Hispanic ethnicity, women with insufficient and deficient vitamin D had infants with birth weights 139·74 (se 69·16) g (P=0·045) and 175·52 (se 89·45) g (P=0·051) lower compared with women with sufficient vitamin D levels (≥30 ng/ml). Each 1 ng/ml increase in 25(OH)D was associated with an increased risk for gestational diabetes mellitus among Hispanic women only (relative risk 1·07; 95 % CI 1·03, 1·11) in multivariable analysis. We did not observe statistically significant associations between maternal vitamin D status and other pregnancy outcomes. Our findings provide further support for an adverse impact of vitamin D deficiency on birth weight in Hispanic women. PMID:26507186

  19. Genetic Variants in the Wnt Signaling Pathway Are Not Associated with Survival Outcome of Non-Small Cell Lung Cancer in a Korean Population

    PubMed Central

    2016-01-01

    Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I–IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population. PMID:26955250

  20. Genetic Variants in the Wnt Signaling Pathway Are Not Associated with Survival Outcome of Non-Small Cell Lung Cancer in a Korean Population.

    PubMed

    Yoo, Seung Soo; Hong, Mi Jeong; Choi, Jin Eun; Lee, Jang Hyuck; Baek, Sun Ah; Lee, Won Kee; Lee, So Yeon; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Cho, Sukki; Park, Jae Yong

    2016-03-01

    Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I-IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population. PMID:26955250

  1. Newcastle disease: genotypic variation and gross pathology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are currently 18 genotypes described for class II Newcastle disease viruses and one genotype for class I. While class I viruses are globally distributed in wild birds, the class II genotypes are found more selectively in different countries. For instance the NDV isolates in genotype V are mo...

  2. IL-10 and TNFα Genotypes in SLE

    PubMed Central

    López, Patricia; Gutiérrez, Carmen; Suárez, Ana

    2010-01-01

    The production of two regulators of the inflammatory response, interleukin 10 (IL-10) and tumor necrosis factor α (TNFα), has been found to be deeply deregulated in SLE patients, suggesting that these cytokines may be involved in the pathogenesis of the disease. Genetic polymorphisms at the promoter regions of IL-10 and TNFα genes have been associated with different constitutive and induced cytokine production. Given that individual steady-state levels of these molecules may deviate an initial immune response towards different forms of lymphocyte activation, functional genetic variants in their promoters could influence the development of SLE. The present review summarizes the information previously reported about the involvement of IL-10 and TNFα genetic variants on SLE appearance, clinical phenotype, and outcome. We show that, in spite of the heterogeneity of the populations studied, the existing knowledge points towards a relevant role of IL-10 and TNFα genotypes in SLE. PMID:20625422

  3. The p53 Codon 72 Pro/Pro Genotype Identifies Poor-Prognosis Neuroblastoma Patients: Correlation with Reduced Apoptosis and Enhanced Senescence by the p53-72P Isoform12

    PubMed Central

    Cattelani, Sara; Ferrari-Amorotti, Giovanna; Galavotti, Sara; Defferrari, Raffaella; Tanno, Barbara; Cialfi, Samantha; Vergalli, Jenny; Fragliasso, Valentina; Guerzoni, Clara; Manzotti, Gloria; Soliera, Angela Rachele; Menin, Chiara; Bertorelle, Roberta; McDowell, Heather P; Inserra, Alessandro; Belli, Maria Luisa; Varesio, Luigi; Tweddle, Deborah; Tonini, Gian Paolo; Altavista, Pierluigi; Dominici, Carlo; Raschellà, Giuseppe; Calabretta, Bruno

    2012-01-01

    The p53 gene is rarely mutated in neuroblastoma, but codon 72 polymorphism that modulates its proapoptotic activity might influence cancer risk and clinical outcome. We investigated whether this polymorphism affects neuroblastoma risk and disease outcome and assessed the biologic effects of the p53-72R and p53-72P isoforms in p53-null cells. Comparison of 288 healthy subjects and 286 neuroblastoma patients revealed that the p53-72 polymorphism had no significant impact on the risk of developing neuroblastoma; however, patients with the Pro/Pro genotype had a shorter survival than those with the Arg/Arg or the Arg/Pro genotypes even in the stage 3 and 4 subgroup without MYCN amplification. By Cox regression analysis, the p53 Pro/Pro genotype seems to be an independent marker of poor prognosis (hazard ratio = 2.74; 95% confidence interval = 1.14–6.55, P = .014) together with clinical stage, MYCN status, and age at diagnosis. In vitro, p53-72P was less effective than p53-72R in inducing apoptosis and inhibiting survival of p53-null LAN-1 cells treated with etoposide, topotecan, or ionizing radiation but not taxol. By contrast, p53-72P was more effective in promoting p21-dependent accelerated senescence, alone or in the presence of etoposide. Thus, the p53-72 Pro/Pro genotype might be a marker of poor outcome independent of MYCN amplification, possibly improving risk stratification. Moreover, the lower apoptosis and the enhanced accelerated senescence by the p53-72P isoform in response to DNA damage suggest that patients with neuroblastoma with the p53-72 Pro/Pro genotype may benefit from therapeutic protocols that do not rely only on cytotoxic drugs that function, in part, through p53 activation. PMID:22904680

  4. Predictive potential role of GSTs gene polymorphisms in the treatment outcome of advanced non-small cell lung cancer patients.

    PubMed

    Liu, Kaixiong; Lin, Qichang; Ding, Haibo; Jin, Yongxu; Chen, Gongping

    2015-01-01

    This study aimed to investigate the possible association between GSTP1, GSTM1, and GSTT1 polymorphisms and treatment outcome of advanced NSCLC. Between October 2009 and October 2011, a total of 308 patients of NSCLC on stage IIIA, IIIB or IV, treated with cisplatin-based chemotherapy were included. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the GSTP1 and GSTM1, and GSTT1 polymorphisms. We found that the IIe/Val and Val/Val genotypes of GSTP1 showed more CR+PR to chemotherapy in advanced NSCLC when compared with IIe/IIe genotype, and the Ors (95% CI) were 0.37 (0.18-0.71) and 0.15 (0.07-0.38). The IIe/Val and Val/Val genotypes of GSTP1 were associated with longer overall survival of advanced NSCLC when compared with the IIe/IIe genotype (For IIe/Val vs IIe/IIe, 37.63 ± 2.01 months vs 30.25 ± 2.06 months; for Val/Val vs IIe/IIe, 39.84 ± 3.36 months vs 30.25 ± 2.06 months). In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with advanced NSCLC, and the HRs (95% CIs) were 0.51 (0.28-0.94) and 0.35 (0.16-0.78), respectively. We found that the GSTP1 polymorphisms might affect the clinical outcome of patients with advanced NSCLC, and our results could help us to facilitate therapeutic decision for individualized therapy. PMID:26885019

  5. Magnitude of genotype x environment interactions affecting tomato fruit quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is a growing interest by consumers to purchase fresh tomato with improved quality traits including lycopene, total soluble solids (TSS), vitamin C and titratable acid (TA) content. Therefore, there are considerable efforts by tomato breeders to improve tomato for these traits. However, suitabl...

  6. Biochemical characterization of different genotypes of Paenibacillus larvae subsp. larvae, a honey bee bacterial pathogen.

    PubMed

    Neuendorf, Sandra; Hedtke, Kati; Tangen, Gerhard; Genersch, Elke

    2004-07-01

    Paenibacillus larvae subsp. larvae (P. l. larvae) is the aetiological agent of American foulbrood (AFB), the most virulent bacterial disease of honey bee brood worldwide. In many countries AFB is a notifiable disease since it is highly contagious, in most cases incurable and able to kill affected colonies. Genotyping of field isolates of P. l. larvae revealed at least four genotypes (AB, Ab, ab and alpha B) present in Germany which are genotypically different from the reference strain DSM 7030. Therefore, based on these data, five different genotypes of P. l. larvae are now identified with genotype AB standing out with a characteristic brown-orange and circled two-coloured colony morphology. Analysing the metabolic profiles of three German genotypes (AB, Ab and ab) as well as of the reference strain using the Biolog system, a characteristic biochemical fingerprint could be obtained for each strain. Cluster analysis showed that while genotypes Ab, ab and the reference strain DSM 7030 are rather similar, genotype AB is clearly different from the others. Analysis of all isolates for plasmid DNA revealed two different plasmids present only in isolates belonging to genotype AB. Therefore, genotype AB is remarkable in all aspects analysed so far. Future analysis will show whether or not these differences will expand to differences in virulence. PMID:15256579

  7. Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.

    PubMed

    Hwang, Young-Hwan; Conklin, John; Chan, Winnie; Roslin, Nicole M; Liu, Jannel; He, Ning; Wang, Kairong; Sundsbak, Jamie L; Heyer, Christina M; Haider, Masoom; Paterson, Andrew D; Harris, Peter C; Pei, York

    2016-06-01

    Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD. PMID:26453610

  8. How do COPD comorbidities affect ICU outcomes?

    PubMed Central

    Ongel, Esra Akkutuk; Karakurt, Zuhal; Salturk, Cuneyt; Takir, Huriye Berk; Burunsuzoglu, Bunyamin; Kargin, Feyza; Ekinci, Gulbanu H; Mocin, Ozlem; Gungor, Gokay; Adiguzel, Nalan; Yilmaz, Adnan

    2014-01-01

    Background and aim Chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) frequently require admission to the intensive care unit (ICU) for application of mechanical ventilation (MV). We aimed to determine whether comorbidities and clinical variables present at ICU admission are predictive of ICU mortality. Methods A retrospective, observational cohort study was performed in a tertiary teaching hospital’s respiratory ICU using data collected between January 2008 and December 2012. Previously diagnosed COPD patients who were admitted to the ICU with ARF were included. Patients’ demographics, comorbidities, body mass index (BMI), ICU admission data, application of noninvasive and invasive MV (NIV and IMV, respectively), cause of ARF, length of ICU and hospital stay, and mortality were recorded from their files. Patients were grouped according to mortality (survival versus non-survival), and all the variables were compared between the two groups. Results During the study period, a total of 1,013 COPD patients (749 male) with a mean age (standard deviation) of 70±10 years met the inclusion criteria. Comorbidities of the non-survival group (female/male, 40/131) were significantly higher compared with the survival group (female/male, 224/618): arrhythmia (24% vs 11%), hypertension (42% vs 34%), coronary artery disease (28% vs 11%), and depression (7% vs 3%) (P<0.001, P<0.035, P<0.001, and P<0.007, respectively). Logistic regression revealed the following mortality risk factors: need of IMV, BMI <20 kg/m2, pneumonia, coronary artery disease, arrhythmia, hypertension, chronic hypoxia, and higher acute physiology and chronic health evaluation II (APACHE II) scores. The respective odds ratios, confidence intervals, and P-values for each of these were as follows: 27.7, 15.7–49.0, P<0.001; 6.6, 3.5–412.7, P<0.001; 5.1, 2.9–8.8, P<0.001; 2.9, 1.5–5.6, P<0.001; 2.7, 1.4–5.2, P<0.003; 2.6, 1.5–4.4, P<0.001; 2.2, 1.2–3.9, P<0.008; and 1.1, 1.03–1.11, P<0.001. Conclusion Patients with severe COPD and cardiac comorbidities and cachexia should be closely monitored in ICU due to their high risk of ICU mortality. PMID:25378919

  9. Elevated carbon dioxide alters the relative fitness of Taraxacum officinale genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    I tested whether elevated carbon dioxide concentration differentially affected which genotypes of the apomictic species dandelion produced the largest number of viable seeds in two different field experiments, and identified morphological and physiological traits associated with fitness at elevated ...

  10. Catechol-O-methyltransferase val158met Polymorphism Interacts with Sex to Affect Face Recognition Ability

    PubMed Central

    Lamb, Yvette N.; McKay, Nicole S.; Singh, Shrimal S.; Waldie, Karen E.; Kirk, Ian J.

    2016-01-01

    The catechol-O-methyltransferase (COMT) val158met polymorphism affects the breakdown of synaptic dopamine. Consequently, this polymorphism has been associated with a variety of neurophysiological and behavioral outcomes. Some of the effects have been found to be sex-specific and it appears estrogen may act to down-regulate the activity of the COMT enzyme. The dopaminergic system has been implicated in face recognition, a form of cognition for which a female advantage has typically been reported. This study aimed to investigate potential joint effects of sex and COMT genotype on face recognition. A sample of 142 university students was genotyped and assessed using the Faces I subtest of the Wechsler Memory Scale – Third Edition (WMS-III). A significant two-way interaction between sex and COMT genotype on face recognition performance was found. Of the male participants, COMT val homozygotes and heterozygotes had significantly lower scores than met homozygotes. Scores did not differ between genotypes for female participants. While male val homozygotes had significantly lower scores than female val homozygotes, no sex differences were observed in the heterozygotes and met homozygotes. This study contributes to the accumulating literature documenting sex-specific effects of the COMT polymorphism by demonstrating a COMT-sex interaction for face recognition, and is consistent with a role for dopamine in face recognition. PMID:27445927

  11. Genotype imputation via matrix completion.

    PubMed

    Chi, Eric C; Zhou, Hua; Chen, Gary K; Del Vecchyo, Diego Ortega; Lange, Kenneth

    2013-03-01

    Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people. We describe an efficient genotype imputation method based on matrix completion. Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project. Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly. Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency. PMID:23233546

  12. [Determination of hepatitis C virus genotypes among hepatitis C patients in Eastern Black Sea Region, Turkey].

    PubMed

    Buruk, Celal Kurtuluş; Bayramoğlu, Gülçin; Reis, Ahu; Kaklıkkaya, Neşe; Tosun, Ilknur; Aydın, Faruk

    2013-10-01

    Hepatitis C virus (HCV), the major cause of transfusion-associated hepatitis, is an important public health problem in the world as well as in Turkey. HCV is grouped as six distinct genotypes and a large number of closely-related subtypes. Genotyping of HCV is an important tool for providing epidemiological data, prediction of prognosis, and optimization of antiviral therapy. This study was carried out to determine the distribution of HCV genotypes in hepatitis C patients residing in different provinces of the Eastern Black Sea Region, Turkey. A total of 304 HCV-RNA positive cases (151 male, 153 female; age range: 11-93 years, mean age: 55.2 ± 13.3 years) who were admitted to the Molecular Microbiology Unit of Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, between January 2009 to December 2012, were included in the study. HCV genotypes were detected in plasma samples of the patients by using commercial assays [INNO-LiPA HCV II (Innogenetics, Belgium) or Abbott RealTime HCV Genotype II (Abbott Molecular Inc, USA)]. Due to the ambiguous genotyping results in some samples with these methods, an in-house multiplex polymerase chain reaction (PCR) assay with genotype-specific primers was also used in the study. Similar to the previous reports from Turkey, our results showed that four HCV genotypes (1, 2, 3, and 4) prevailed in the Eastern Black Sea Region and the predominant genotype and subtype were genotype 1 (92.8%) and 1b (87.5%), respectively. Distribution of genotypes were observed to vary according to the province. Prevalences of subtype 1a, genotype 2, 3, and 4 were noted as 5.3%, 1.6%, 4.9%, and 0.7%, respectively. Furthermore, the samples from Giresun, Gumushane and Bayburt provinces, which are relatively less immigrated, had higher genotype 1, and the prevalence rates in the region was affected by the presence of non-citizen residents. This study is the first report on distribution of HCV genotypes in chronic hepatitis

  13. Transforming microbial genotyping: a robotic pipeline for genotyping bacterial strains.

    PubMed

    O'Farrell, Brian; Haase, Jana K; Velayudhan, Vimalkumar; Murphy, Ronan A; Achtman, Mark

    2012-01-01

    Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST) of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS) consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of < €25 per strain. Since developing this pipeline, >200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost. PMID:23144721

  14. Transforming Microbial Genotyping: A Robotic Pipeline for Genotyping Bacterial Strains

    PubMed Central

    Velayudhan, Vimalkumar; Murphy, Ronan A.; Achtman, Mark

    2012-01-01

    Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST) of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS) consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of < €25 per strain. Since developing this pipeline, >200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost. PMID:23144721

  15. Estimation of changes in C-reactive protein level and pregnancy outcome after nonsurgical supportive periodontal therapy in women affected with periodontitis in a rural set up of India

    PubMed Central

    Khairnar, Mayur S.; Pawar, Babita R.; Marawar, Pramod P.; Khairnar, Darshana M.

    2015-01-01

    Aims and Objectives: Estimation of changes in C-reactive protein (CRP) level and pregnancy outcome after nonsurgical supportive periodontal therapy in pregnant women affected with Periodontitis. Materials and Methods: A total of 100 pregnant females with periodontitis were assigned to treatment and control groups. All the details about previous and current pregnancies were obtained. Full-mouth periodontal examination was done at baseline, which included oral hygiene index simplified plaque index, gingival index, and clinical attachment loss. CRP level was also measured from collected blood sample initially at baseline and later after the delivery in both the group. Subjects in the treatment group received nonsurgical periodontal treatment during the second trimester of gestational period, and those in the control group did not receive any periodontal therapy during this period. Periodontal therapy included mechanical plaque control instructions and scaling and root planning. Outcome measures assessed were changes in CRP levels, gestational age, and birth weight of the infants. When delivery occurred at <37 weeks of gestation, it was considered as preterm birth (PTB), and low birth weight (LBW) was recorded when the infant weighed <2500 g. Results: In the treatment group, 32% of PTB and 68% of Normal term birth (NTB) delivery whereas in the control group 72% PTB and 28% of NTB were recorded. Infants measured with LBW were 36% in the treatment group and 52% in the control group. Mean birth weight was 2644.44 ± 450.53 g in the treatment group and 2447.82 ± 368.02 g in the control group (P < 0.05). Mean gestational age in the treatment group was 35.57 ± 2.40 weeks and 34.17 ± 2.92 weeks in the control group (P < 0.05). The treatment group showed statistically significant reduction in mean values of CRP level after delivery in comparison to baseline values (P < 0.05), whereas control group showed no significant reduction in values (P > 0.05). Conclusion: Nonsurgical

  16. Chemical Composition and Yield of Six Genotypes of Common Purslane (Portulaca oleracea L.): An Alternative Source of Omega-3 Fatty Acids.

    PubMed

    Petropoulos, Spyridon Α; Karkanis, Anestis; Fernandes, Ângela; Barros, Lillian; Ferreira, Isabel C F R; Ntatsi, Georgia; Petrotos, Konstantinos; Lykas, Christos; Khah, Ebrahim

    2015-12-01

    Common purslane (Portulaca oleracea L.) is an annual weed rich in omega-3 fatty acids which is consumed for its edible leaves and stems. In the present study six different genotypes of common purslane (A-F) were evaluated for their nutritional value and chemical composition. Nutritional value and chemical composition depended on genotype. Oxalic acid content was the lowest for genotype D, whereas genotypes E and F are more promising for commercial cultivation, since they have low oxalic acid content. Genotype E had a very good antioxidant profile and a balanced composition of omega-3 and omega-6 fatty acids. Regarding yield, genotype A had the highest yield comparing to the other genotypes, whereas commercial varieties (E and F) did not differ from genotypes B and C. This study provides new information regarding common purslane bioactive compounds as affected by genotype and could be further implemented in food industry for products of high quality and increased added value. PMID:26510561

  17. Effects of challenge with a virulent genotype II strain of porcine reproductive and respiratory syndrome virus on piglets vaccinated with an attenuated genotype I strain vaccine.

    PubMed

    Roca, M; Gimeno, M; Bruguera, S; Segalés, J; Díaz, I; Galindo-Cardiel, I J; Martínez, E; Darwich, L; Fang, Y; Maldonado, J; March, R; Mateu, E

    2012-07-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is endemic in most parts of Asia, where genotype I and II strains of diverse virulence may coexist. This study evaluated the outcome of infection with a highly virulent Asian genotype II PRRSV isolate in piglets vaccinated with a genotype I vaccine. Twenty-one 3-week-old piglets were divided in three groups: Pigs in group V (n=8) were vaccinated with an attenuated genotype I commercial PRRSV vaccine, while pigs in group U (n=8) and a control group (group C; n=5) were unvaccinated; 6 weeks later, pigs in groups V and U were challenged intranasally with a highly virulent strain of genotype II PRRSV (1×10(5) 50% tissue culture infectious doses/mL), while pigs in group C received a placebo. Over a period of 21 days after challenge, vaccinated pigs had significantly lower mortality (0/8 versus 2/8), fewer days of fever, a lower frequency of catarrhal bronchopneumonia, higher weight gains (13.4 versus 6.6 kg) and lower levels of viraemia compared to unvaccinated challenged pigs. Immunisation with a genotype I attenuated PRRSV vaccine provided partial protection against challenge with a highly virulent genotype II strain. PMID:22264642

  18. Genotype × genotype interactions between the toxic cyanobacterium Microcystis and its grazer, the waterflea Daphnia

    PubMed Central

    Lemaire, Veerle; Brusciotti, Silvia; van Gremberghe, Ineke; Vyverman, Wim; Vanoverbeke, Joost; De Meester, Luc

    2012-01-01

    Toxic algal blooms are an important problem worldwide. The literature on toxic cyanobacteria blooms in inland waters reports widely divergent results on whether zooplankton can control cyanobacteria blooms or cyanobacteria suppress zooplankton by their toxins. Here we test whether this may be due to genotype × genotype interactions, in which interactions between the large-bodied and efficient grazer Daphnia and the widespread cyanobacterium Microcystis are not only dependent on Microcystis strain or Daphnia genotype but are specific to genotype × genotype combinations. We show that genotype × genotype interactions are important in explaining mortality in short-time exposures of Daphnia to Microcystis. These genotype × genotype interactions may result in local coadaptation and a geographic mosaic of coevolution. Genotype × genotype interactions can explain why the literature on zooplankton–cyanobacteria interactions is seemingly inconsistent, and provide hope that zooplankton can contribute to the suppression of cyanobacteria blooms in restoration projects. PMID:25568039

  19. A Microfluidic Device for Multiplex Single-Nucleotide Polymorphism Genotyping

    PubMed Central

    Zhu, Jing; Qiu, Chunmei; Palla, Mirkó; Nguyen, ThaiHuu; Russo, James J.; Ju, Jingyue; Lin, Qiao

    2015-01-01

    Single-nucleotide polymorphisms (SNPs) are the most abundant type of genetic variations; they provide the genetic fingerprint of individuals and are essential for genetic biomarker discoveries. Accurate detection of SNPs is of great significance for disease prevention, diagnosis and prognosis, and for prediction of drug response and clinical outcomes in patients. Nevertheless, conventional SNP genotyping methods are still limited by insufficient accuracy or labor-, time-, and resource-intensive procedures. Microfluidics has been increasingly utilized to improve efficiency; however, the currently available microfluidic genotyping systems still have shortcomings in accuracy, sensitivity, throughput and multiplexing capability. To address these challenges, we developed a multi-step SNP genotyping microfluidic device, which performs single-base extension of SNP specific primers and solid-phase purification of the extension products on a temperature-controlled chip. The products are ready for immediate detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), providing identification of the alleles at the target loci. The integrated device enables efficient and automated operation, while maintaining the high accuracy and sensitivity provided by MS. The multiplex genotyping capability was validated by performing rapid, accurate and simultaneous detection of 4 loci on a synthetic template. The microfluidic device has the potential to perform automatic, accurate, quantitative and high-throughput assays covering a broad spectrum of applications in biological and clinical research, drug development and forensics. PMID:26594354

  20. Glutamine synthetase in Durum Wheat: Genotypic Variation and Relationship with Grain Protein Content

    PubMed Central

    Nigro, Domenica; Fortunato, Stefania; Giove, Stefania L.; Paradiso, Annalisa; Gu, Yong Q.; Blanco, Antonio; de Pinto, Maria C.; Gadaleta, Agata

    2016-01-01

    Grain protein content (GPC), is one of the most important trait in wheat and its characterized by a very complex genetic control. The identification of wheat varieties with high GPC (HGPC), as well as the characterization of central enzymes involved in these processes, are important for more sustainable agricultural practices. In this study, we focused on Glutamine synthetase (GS) as a candidate to study GPC in wheat. We analyzed GS expression and its enzymatic activity in different tissues and phenological stages in 10 durum wheat genotypes with different GPC. Although each genotype performed quite differently from the others, both because their genetic variability and their adaptability to specific environmental conditions, the highest GS activity and expression were found in genotypes with HGPC and vice versa the lowest ones in genotypes with low GPC (LGPC). Moreover, in genotypes contrasting in GPC bred at different nitrogen regimes (0, 60, 140 N Unit/ha) GS behaved differently in diverse organs. Nitrogen supplement increased GS expression and activity in roots of all genotypes, highlighting the key role of this enzyme in nitrogen assimilation and ammonium detoxification in roots. Otherwise, nitrogen treatments decreased GS expression and activity in the leaves of HGPC genotypes and did not affect GS in the leaves of LGPC genotypes. Finally, no changes in GS and soluble protein content occurred at the filling stage in the caryopses of all analyzed genotypes. PMID:27468287

  1. Glutamine synthetase in Durum Wheat: Genotypic Variation and Relationship with Grain Protein Content.

    PubMed

    Nigro, Domenica; Fortunato, Stefania; Giove, Stefania L; Paradiso, Annalisa; Gu, Yong Q; Blanco, Antonio; de Pinto, Maria C; Gadaleta, Agata

    2016-01-01

    Grain protein content (GPC), is one of the most important trait in wheat and its characterized by a very complex genetic control. The identification of wheat varieties with high GPC (HGPC), as well as the characterization of central enzymes involved in these processes, are important for more sustainable agricultural practices. In this study, we focused on Glutamine synthetase (GS) as a candidate to study GPC in wheat. We analyzed GS expression and its enzymatic activity in different tissues and phenological stages in 10 durum wheat genotypes with different GPC. Although each genotype performed quite differently from the others, both because their genetic variability and their adaptability to specific environmental conditions, the highest GS activity and expression were found in genotypes with HGPC and vice versa the lowest ones in genotypes with low GPC (LGPC). Moreover, in genotypes contrasting in GPC bred at different nitrogen regimes (0, 60, 140 N Unit/ha) GS behaved differently in diverse organs. Nitrogen supplement increased GS expression and activity in roots of all genotypes, highlighting the key role of this enzyme in nitrogen assimilation and ammonium detoxification in roots. Otherwise, nitrogen treatments decreased GS expression and activity in the leaves of HGPC genotypes and did not affect GS in the leaves of LGPC genotypes. Finally, no changes in GS and soluble protein content occurred at the filling stage in the caryopses of all analyzed genotypes. PMID:27468287

  2. Catechol-O-methyltransferase (COMT) genotype moderates the effects of childhood trauma on cognition and symptoms in schizophrenia.

    PubMed

    Green, Melissa J; Chia, T-Yunn; Cairns, Murray J; Wu, Jingqin; Tooney, Paul A; Scott, Rodney J; Carr, Vaughan J

    2014-02-01

    The interaction of genetic and environmental factors may affect the course and development of psychotic disorders. We examined whether the effects of childhood trauma on cognition and symptoms in schizophrenia were moderated by the Catechol-O-methyltransferase (COMT) Val(158)Met polymorphism, a common genetic variant known to affect cognition and prefrontal dopamine levels. Participants were 429 schizophrenia/schizoaffective cases from the Australian Schizophrenia Research Bank (ASRB). Cognitive performance was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Controlled Oral Word Association Test (COWAT), Letter Number Sequencing (LNS) test, and the Wechsler Test of Adult Reading (WTAR). Hierarchical regression was used to test the main effects and additive interaction effects of genotype and childhood trauma in the domains of physical abuse, emotional abuse, and emotional neglect, on cognition and symptom profiles of clinical cases. Consistent with previous findings, COMT Val homozygotes performed worse on cognitive measures in the absence of childhood adversity. In addition, a significant interaction between COMT genotype and physical abuse was associated with better executive function in Val homozygotes, relative to those of the same genotype with no history of abuse. Finally, the severity of positive symptoms was greater in Met carriers who had experienced physical abuse, and the severity of negative symptoms in Met carriers was greater in the presence of emotional neglect. These results suggest that the possible epigenetic modulation of the expression of the COMT Val(158)Met polymorphism and consequent effects on cognition and symptoms in schizophrenia, with worse outcomes associated with adverse childhood experiences in Met carriers. PMID:24252819

  3. Outcomes management in women's health.

    PubMed

    Houston, S; Fleschler, R

    1997-01-01

    Outcomes management uses a quality and research approach to reducing costs in health care. Populations may be targeted for high volumes or their potential for cost savings. Outcomes are identified and measured through data collection and analysis. System and care processes that drive these outcomes are analyzed. Tenets related to outcomes management include questioning practice, administrative and physician involvement; recognizing that change is necessary; accepting uncontrollable factors; and valuing the outcomes management process. Resources necessary for managing outcomes include the use of collaborative practice teams, outcomes assessment, information systems, and educational support services. The women's health population can benefit from an outcomes management effort by improving and standardizing care for mothers and infants across the continuum. There is the opportunity to affect the wellness of this population even before the pregnancy occurs. PMID:9170599

  4. Serum apolipoprotein B-100 concentration predicts the virological response to pegylated interferon plus ribavirin combination therapy in patients infected with chronic hepatitis C virus genotype 1b.

    PubMed

    Yoshizawa, Kai; Abe, Hiroshi; Aida, Yuta; Ishiguro, Haruya; Ika, Makiko; Shimada, Noritomo; Tsubota, Akihito; Aizawa, Yoshio

    2013-07-01

    Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity-determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg-IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b-infected patients to investigate whether the response to Peg-IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B-100 (apoB-100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB-100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046-2.456), alpha-fetoprotein (OR, 0.764; 95% CI, 0.610-0.958), non-wild-type ISDR (OR, 5.617; 95% CI, 1.274-24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225-114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3-log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB-100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB-100 concentrations could predict virological response to Peg-IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype. PMID:23918536

  5. The effects of female sex, viral genotype and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection

    PubMed Central

    Grebely, Jason; Page, Kimberly; Sacks-Davis, Rachel; van der Loeff, Maarten Schim; Rice, Thomas M.; Bruneau, Julie; Morris, Meghan D.; Hajarizadeh, Behzad; Amin, Janaki; Cox, Andrea L.; Kim, Arthur Y.; McGovern, Barbara H.; Schinkel, Janke; George, Jacob; Shoukry, Naglaa H.; Lauer, Georg M.; Maher, Lisa; Lloyd, Andrew R.; Hellard, Margaret; Dore, Gregory J.; Prins, Maria

    2014-01-01

    Although 20–40% of persons with acute HCV infection demonstrate spontaneous clearance, the time-course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes following acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had IL28B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV