Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

On measurement of top polarization as a probe of ttˉt \bar t production mechanisms at the LHC

In this note we demonstrate the use of top polarization in the study of $t \bar t$ resonances at the LHC, in the possible case where the dynamics implies a non-zero top polarization. As a probe of top polarization we construct an asymmetry in the decay-lepton azimuthal angle distribution (corresponding to the sign of $\cos\phi_\ell$) in the laboratory. The asymmetry is non-vanishing even for a symmetric collider like the LHC, where a positive $z$ axis is not uniquely defined. The angular distribution of the leptons has the advantage of being a faithful top-spin analyzer, unaffected by possible anomalous $tbW$ couplings, to linear order. We study, for purposes of demonstration, the case of a $Z'$ as might exist in the little Higgs models. We identify kinematic cuts which ensure that our asymmetry reflects the polarization in sign and magnitude. We investigate possibilities at the LHC with two energy options: $\sqrt{s} = 14$ TeV and $\sqrt{s} = 7$ TeV, as well as at the Tevatron. At the LHC the model predicts net top quark polarization of the order of a few per cent for $M_{Z'} \simeq 1200$ GeV, being as high as $10$ for a smaller mass of the $Z'$ of $700$ GeV and for the largest allowed coupling in the model, the values being higher for the $7$ TeV option. These polarizations translate to a deviation from the standard-model value of azimuthal asymmetry of up to about $4$ ($7$) for $14$ ($7$) TeV LHC, whereas for the Tevatron, values as high as $12$ are attained. For the $14$ TeV LHC with an integrated luminosity of 10 fb$^{-1}$, these numbers translate into a $3 \sigma$ sensitivity over a large part of the range $500 \lesssim M_{Z'} \lesssim 1500$ GeV.Comment: 28 page, LaTeX, requires JHEP style file, 12 figures. Typos corrected and references adde

T-duality and closed string non-commutative (doubled) geometry

We provide some evidence that closed string coordinates will become non-commutative turning on H-field flux background in closed string compactifications. This is in analogy to open string non-commutativity on the world volume of D-branes with B- and F-field background. The class of 3-dimensional backgrounds we are studying are twisted tori (fibrations of a 2-torus over a circle) and the their T-dual H-field, 3-form flux backgrounds (T-folds). The spatial non-commutativity arises due to the non-trivial monodromies of the toroidal Kahler resp. complex structure moduli fields, when going around the closed string along the circle direction. In addition we study closed string non-commutativity in the context of doubled geometry, where we argue that in general a non-commutative closed string background is T-dual to a commutative closed string background and vice versa. Finally, in analogy to open string boundary conditions, we also argue that closed string momentum and winding modes define in some sense D-branes in closed string doubled geometry.Comment: 31 pages, references added, extended version contains new sections 3.3., 3.4 and

The Effect of Oxidant and the Non-Oxidant Alteration of Cellular Thiol Concentration on the Formation of Protein Mixed-Disulfides in HEK 293 Cells

Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with vicinal thiols, was used to determine the possible role of vicinal thiols in the amount of glutathionylation. Our data shows phenylarsine oxide did not change glutathione concentrations, but it did enhance the amount of glutathionylation in oxidant-treated cells

Exploring mediating factors in the association between parental psychological distress and psychosocial maladjustment in adolescence

Abstract: Parental psychopathology is associated with increased psychosocial maladjustment in adolescents. We examined, from a psychosocial perspective, the association between parental psychological distress and psychosocial maladjustment in adolescents and assessed the mediating role of psychosocial covariates. This is a cross-sectional survey and the setting include representative sample of Quebec adolescents in 1999. The participants of the study include 13- and 16-year-old children (N = 2,346) in the Social and Health Survey of Quebec Children and Adolescents. The main outcome measures are internalizing disorders, externalizing disorders, substance use, and alcohol consumption. For statistical analysis, we used structural equation modeling to test for mediation. Internalizing and externalizing disorders were significantly associated with parental psychological distress, but not substance use or alcohol consumption. The higher the parental distress, the higher the risk of adolescent mental health disorders. The association between parental psychological distress and internalizing disorders was mediated by adolescent self-esteem, parental emotional support and extrafamilial social support. As for externalizing disorders, these variables only had an independent effect. In conclusion, A family’s well being is a necessary condition for psychosocial adjustment in adolescence. Beyond the psychiatric approach, psychosocial considerations need to be taken into consideration to prevent negative mental health outcomes in children living in homes with distressed parents

When Do Objects Become Landmarks? A VR Study of the Effect of Task Relevance on Spatial Memory

We investigated how objects come to serve as landmarks in spatial memory, and more specifically how they form part of an allocentric cognitive map. Participants performing a virtual driving task incidentally learned the layout of a virtual town and locations of objects in that town. They were subsequently tested on their spatial and recognition memory for the objects. To assess whether the objects were encoded allocentrically we examined pointing consistency across tested viewpoints. In three experiments, we found that spatial memory for objects at navigationally relevant locations was more consistent across tested viewpoints, particularly when participants had more limited experience of the environment. When participants’ attention was focused on the appearance of objects, the navigational relevance effect was eliminated, whereas when their attention was focused on objects’ locations, this effect was enhanced, supporting the hypothesis that when objects are processed in the service of navigation, rather than merely being viewed as objects, they engage qualitatively distinct attentional systems and are incorporated into an allocentric spatial representation. The results are consistent with evidence from the neuroimaging literature that when objects are relevant to navigation, they not only engage the ventral “object processing stream”, but also the dorsal stream and medial temporal lobe memory system classically associated with allocentric spatial memory

Clinical training alone is not sufficient for reducing barriers to IUD provision among private providers in Pakistan

<p>Abstract</p> <p>Background</p> <p>IUD uptake remains low in Pakistan, in spite of three major efforts to introduce the IUD since the 1960s, the most recent of these being through the private sector. This study examines barriers to IUD recommendation and provision among private providers in Pakistan.</p> <p>Methods</p> <p>A facility-based survey was conducted among randomly selected private providers who were members of the Greenstar network and among similar providers located within 2 Kilometers. In total, 566 providers were interviewed in 54 districts of Pakistan.</p> <p>Logistic regression analysis was conducted to determine whether correct knowledge regarding the IUD, self-confidence in being able to insert the IUD, attitudes towards suitability of candidates for the IUD and medical safety concerns were influenced by provider type (physician vs. Lady Health Visitor), whether the provider had received clinical training in IUD insertion in the last three years, membership of the Greenstar network and experience in IUD insertion. OLS regression was used to identify predictors of provider productivity (measured by IUD insertions conducted in the month before the survey).</p> <p>Results</p> <p>Private providers consider women with children and in their peak reproductive years to be ideal candidates for the IUD. Women below age 19, above age 40 and nulliparous women are not considered suitable IUD candidates. Provider concerns about medical safety, side-effects and client satisfaction associated with the IUD are substantial. Providers' experience in terms of the number of IUDs inserted in their careers, appears to improve knowledge, self-confidence in the ability provide the IUD and to lower age-related attitudinal barriers towards IUD recommendation. Physicians have greater medical safety concerns about the IUD than Lady Health Visitors. Clinical training does not have a consistent positive effect on lowering barriers to IUD recommendation. Membership of the Greenstar network also has little effect on lowering these barriers. Providers' barriers to IUD recommendation significantly lower their monthly IUD insertions.</p> <p>Conclusions</p> <p>Technical training interventions do not reduce providers' attitudinal barriers towards IUD provision. Formative research is needed to better understand reasons for the high levels of provider barriers to IUD provision. "Non-training" interventions should be designed to lower these barriers.</p

Asymmetry of Early Endosome Distribution in C. elegans Embryos

development, we examined the distribution and dynamics of early endosomes (EEs) in embryos.EEs are primarily found at the cell periphery with an initially uniform distribution after fertilization. Strikingly, we find that during the first cell cycle, EEA-1 positive EEs become enriched at the anterior cortex. In contrast, the Golgi compartment shows no asymmetry in distribution. Asymmetric enrichment of EEs depends on acto-myosin contractility and embryonic PAR polarity. In addition to their localization at the cortex, EEs are also found around the centrosome. These EEs move rapidly (1.3um/s) from the cortex directly to the centrosome, a speed comparable to that of the minus end directed motor dynein.We speculate that the asymmetry of early endosomes might play a role in cell asymmetries or fate decisions

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse