33 research outputs found

    Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers

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    Externalizing psychopathology has been linked to prefrontal abnormalities. While clinically diagnosed subjects show altered frontal gray matter, it is unknown if similar deficits relate to externalizing traits in non-clinical populations. We used voxel-based morphometry (VBM) to retrospectively analyze the cerebral gray matter volume of 176 young adult social to heavy drinkers (mean age=24.0±2.9, male=83.5%) from studies of alcoholism risk. We hypothesized that prefrontal gray matter volume and externalizing traits would be correlated. Externalizing personality trait components-Boredom Susceptibility-Impulsivity (BS/IMP) and Empathy/Low Antisocial Behaviors (EMP/LASB)-were tested for correlations with gray matter partial volume estimates (gmPVE). Significantly large clusters (pFWE<0.05, family-wise whole-brain corrected) of gmPVE correlated with EMP/LASB in dorsolateral and medial prefrontal regions, and in occipital cortex. BS/IMP did not correlate with gmPVE, but one scale of impulsivity (Eysenck I7) correlated positively with bilateral inferior frontal/orbitofrontal, and anterior insula gmPVE. In this large sample of community-dwelling young adults, antisocial behavior/low empathy corresponded with reduced prefrontal and occipital gray matter, while impulsivity correlated with increased inferior frontal and anterior insula cortical volume. These findings add to a literature indicating that externalizing personality features involve altered frontal architecture

    Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

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    BACKGROUND: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. METHODS: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. RESULTS: HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. CONCLUSION: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells

    Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission

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    Background: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of,1%. Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86 % took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70 % displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three wome

    Diagnostic challenges and pockets of susceptibility identified during a measles outbreak, Luxembourg, 2019

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    Luxembourg was among the first countries in the World Health Organization (WHO) European Region documenting interruption of endemic measles transmission, but an increased incidence was registered in spring 2019. The outbreak started with an unvaccinated student who had been to a winter sports resort in a neighbouring country, where a measles outbreak was ongoing. Subsequently, 12 secondary and two tertiary cases were confirmed among students from the same school, relatives and healthcare workers, as well as six probably unrelated cases. Only 11 cases initially fulfilled the WHO definition for suspected measles cases. Fourteen of 20 cases with information on country of birth and the majority of unvaccinated cases (10/12) were born outside of Luxembourg. Measles IgM antibody results were available for 16 of the confirmed cases, and five of the eight IgM negative cases had been vaccinated at least once. All 21 cases were PCR positive, but for three previously vaccinated cases with multiple specimen types, at least one of these samples was negative. The outbreak highlighted diagnostic challenges from clinical and laboratory perspectives in a measles elimination setting and showed that people born abroad and commuters may represent important pockets of susceptible people in Luxembourg.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Performance of seven commercial automated assays for the detection of low levels of anti-Toxoplasma IgG in French immunocompromised patients

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    International audienceBackground: Immunocompromised patients are at high risk for the development of severe toxoplasmosis from tissue cyst reactivation, the most frequently, or from recently acquired acute infections. Knowledge of serologic status is therefore crucial. Screening for toxoplasmosis is sometimes performed while patients are already immunocompromised and have a low or even undetectable IgG titer by routine automated enzyme immunoassays. The aim of this study was to assess the sensitivity and specificity of seven reagents for the detection of low levels of IgG. Sera from 354 patients were collected and analysed. Results: ElecsysÂź offered the best analytic performances, superior to those of ArchitectÂź and PlateliaÂź, which were superior to those of Access IIÂź and TGS TAÂź. Vidas IIÂź and Liaison IIÂź reagents exhibited poor analytical performances in this cohort. For ElecsysÂź, PlateliaÂź and ArchitectÂź, new thresholds for the grey zone and positive zone have been defined to improve the sensitivity of these reagents while maintaining excellent specificity. Conclusions: Commercialized assays for toxoplasmosis screening are not suitable for IgG low-level detection in patients without adapting the supplier thresholds to avoid false negative results and risk generalized toxoplasmosis.Contexte : Les patients immunodĂ©primĂ©s courent un risque Ă©levĂ© de dĂ©velopper une toxoplasmose grave rĂ©sultant de la rĂ©activation de kystes tissulaires, le plus souvent, ou d’infections aiguĂ«s rĂ©cemment contractĂ©es. La connaissance du statut sĂ©rologique est donc cruciale. Le dĂ©pistage de la toxoplasmose est parfois effectuĂ© chez des patients dĂ©jĂ  immunodĂ©primĂ©s et dont le titre en IgG est faible, voire indĂ©tectable, par les immunoessais enzymatiques automatisĂ©s de routine. Le but de cette Ă©tude Ă©tait d’évaluer la sensibilitĂ© et la spĂ©cificitĂ© de sept rĂ©actifs pour la dĂ©tection de faibles taux d’IgG. Les sĂ©rums de 354 patients ont Ă©tĂ© recueillis et analysĂ©s. RĂ©sultats : ElecsysÂź offre les meilleures performances analytiques, supĂ©rieures Ă  celles d’ArchitectÂź et de PlateliaÂź, supĂ©rieures Ă  celles d’Access IIÂź et de TGS TAÂź. Les rĂ©actifs Vidas IIÂź et Liaison IIÂź ont prĂ©sentĂ© des performances analytiques mĂ©diocres dans cette cohorte. Pour ElecsysÂź, PlateliaÂź et ArchitectÂź, de nouveaux seuils pour la zone grise et la zone positive ont Ă©tĂ© dĂ©finis pour amĂ©liorer la sensibilitĂ© de ces rĂ©actifs tout en maintenant une excellente spĂ©cificitĂ©. Conclusions : Les tests commercialisĂ©s pour le dĂ©pistage de la toxoplasmose ne conviennent pas Ă  la dĂ©tection de faibles taux d’IgG chez les patients sans adaptation des seuils des fournisseurs pour Ă©viter les rĂ©sultats faux nĂ©gatifs et le risque de toxoplasmose gĂ©nĂ©ralisĂ©e
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