Predictors of severe hyperbiliruniaemia in HIV-infected patients treated with atazanavir (ATV)

Methods HIV-infected subjects on ATV/ritonavir containing stable HAART regimen were included. ATV plasma concentrations were measured 24 hours after the last dose by HPLC with UV detector. Polymorphism at the uridin-glocoronosyl-transferase 1A1 (UGT1A1) was examined in DNA extracted from blood mononuclear cells, to identify subjects with Gilbert's syndrome. The correlation between bilirubin plasma levels, ATV concentration and polymorphism of UGT1A1 (defined as the presence than at least one TA7 allele) were evaluated by multivariate linear regression (other covariates included: gender, age, CD4 count, months of ATV exposure). Predictors of severe hyperbilirubinemia (>2.5 μmol/l; grade 3) were evaluated by multivariate logistic regression (polymorphism at UGT1A1, Cmin, BMI, age included as covariates)

Construction and validation of a dimensional scale exploring mood disorders: MAThyS (Multidimensional Assessment of Thymic States)

<p>Abstract</p> <p>Background</p> <p>The boundaries between mood states in bipolar disorders are not clear when they are associated with mixed characteristics. This leads to some confusion to define appropriate therapeutic strategies. A dimensional approach might help to better define bipolar moods states and more specifically those with mixed features.</p> <p>Therefore, we proposed a new tool based on a dimensional approach, built with a priori five sub-scales and focus on emotional reactivity rather than exclusively on mood tonality. This study was designed to validate this MAThyS Scale (Multidimensional Assessment of Thymic States).</p> <p>Methods</p> <p>One hundred and ninety six subjects were included: 44 controls and 152 bipolar patients in various states: euthymic, manic or depressed. The MAThyS is a visual analogic scale consisting of 20 items. These items corresponded to five quantitative dimensions ranging from inhibition to excitation: emotional reactivity, thought processes, psychomotor function, motivation and sensory perception. They were selected as they represent clinically relevant quantitative traits.</p> <p>Results</p> <p>Confirmatory analyses demonstrated a good validity for this scale, and a good internal consistency (Cronbach's alpha coefficient = 0.95). The MathyS scale is moderately correlated of both the MADRS scale (depressive score; r = -0.45) and the MAS scale (manic score; r = 0.56).</p> <p>When considering the Kaiser-Guttman rule and the scree plot, our model of 5 factors seems to be valid. The four first factors have an eigenvalue greater than 1.0 and the eigenvalue of the factor five is 0.97. In the scree plot, the "elbow", or the point at which the curve bends, indicates 5 factors to extract. This 5 factors structure explains 68 per cent of variance.</p> <p>Conclusion</p> <p>The characterisation of bipolar mood states based on a global score assessing inhibition/activation process (total score of the MATHyS) associated with descriptive analysis on sub-scores such as emotional reactivity (rather than the classical opposition euphoria/sadness) can be useful to better understand the broad spectrum of mixed states.</p

Molecular targets for therapy in systemic sclerosis

Despite significant advances have been made in the recent years regarding organ-specific therapies, there is no approved 'disease-modifying' antifibrotic drug for systemic sclerosis (SSc) available to date. Although non-selective immunosuppressive agents are routinely used to treat patients with SSc, large well-controlled studies are lacking for almost all immunosuppressive agents and further evidence is required for long-term beneficial effects of these drugs. Considering these facts about immunosuppressive agents in SSc and also considering the high mortality of SSc, other therapeutic strategies are urgently needed. Recently an important role of the 5-hydroxytryptamine (5-HT: serotonin) pathway in fibrosis was reported. In this review, we discuss the role of 5-HT in fibrosis and therapeutic potential of this molecule. Besides 5-HT, there are a number of promising targets that have been extensively characterized in recent years. For many of these molecular targets, modifiers are readily available for clinical studies, and often these modifiers are used already in clinical use for other diseases. Results from these studies will show, in how far the promising preclinical results for novel antifibrotic strategies can be translated to clinical practice

Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

<p>Abstract</p> <p>Objectives </p> <p>We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of <it>TEL-AML1 </it>fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD).</p> <p>Methods</p> <p>All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of <it>TEL-AML1 </it>fusion represented by disease course and survival.</p> <p>Results</p> <p><it>TEL-AML1 </it>fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between <it>TEL-AML1 </it>fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of <it>TEL-AML1 </it>fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006). Also, the persistence at <it>TEL-AML1 </it>fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of <it>TEL-AML1 </it>fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS.</p> <p>Conclusion</p> <p>For most patients, the presence of <it>TEL-AML1 </it>fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of <it>TEL-AML1 </it>fusion as MRD has no additive prognostic value.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Resin tapping in Pinus pinaster: effects on growth and response function to climate

Dendrocronología sobre Pinus pinaster, como la recolección de resina y los factores climáticos han afectado a su crecimiento

Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion

Background Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Methods Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Results Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04). Conclusion This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively

Diversity, dynamics, direction, and magnitude of high-altitude migrating insects in the Sahel

This is the final version. Available from Nature Research via the DOI in this record. Long-distance migration of insects impacts food security, public health, and conservation–issues that are especially significant in Africa. Windborne migration is a key strategy enabling exploitation of ephemeral havens such as the Sahel, however, its knowledge remains sparse. In this first cross-season investigation (3 years) of the aerial fauna over Africa, we sampled insects flying 40–290 m above ground in Mali, using nets mounted on tethered helium-filled balloons. Nearly half a million insects were caught, representing at least 100 families from thirteen orders. Control nets confirmed that the insects were captured at altitude. Thirteen ecologically and phylogenetically diverse species were studied in detail. Migration of all species peaked during the wet season every year across localities, suggesting regular migrations. Species differed in flight altitude, seasonality, and associated weather conditions. All taxa exhibited frequent flights on southerly winds, accounting for the recolonization of the Sahel from southern source populations. “Return” southward movement occurred in most taxa. Estimates of the seasonal number of migrants per species crossing Mali at latitude 14°N were in the trillions, and the nightly distances traversed reached hundreds of kilometers. The magnitude and diversity of windborne insect migration highlight its importance and impacts on Sahelian and neighboring ecosystems.Biotechnology and Biological Sciences Research Council (BBSRC)National Institutes of Health (NIH)U.S. Armylorida Department of Agriculture and Consumer Services-Division of Plant Industr

Long-Term Effects of Autologous Bone Marrow Stem Cell Treatment in Acute Myocardial Infarction: Factors That May Influence Outcomes

AIMS: To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. METHODS AND RESULTS: MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction. CONCLUSIONS: Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials