Interventions Delivered in Clinical Settings are Effective in Reducing Risk of HIV Transmission Among People Living with HIV: Results from the Health Resources and Services Administration (HRSA)’s Special Projects of National Significance Initiative

To support expanded prevention services for people living with HIV, the US Health Resources and Services Administration (HRSA) sponsored a 5-year initiative to test whether interventions delivered in clinical settings were effective in reducing HIV transmission risk among HIV-infected patients. Across 13 demonstration sites, patients were randomized to one of four conditions. All interventions were associated with reduced unprotected vaginal and/or anal intercourse with persons of HIV-uninfected or unknown status among the 3,556 participating patients. Compared to the standard of care, patients assigned to receive interventions from medical care providers reported a significant decrease in risk after 12 months of participation. Patients receiving prevention services from health educators, social workers or paraprofessional HIV-infected peers reported significant reduction in risk at 6 months, but not at 12 months. While clinics have a choice of effective models for implementing prevention programs for their HIV-infected patients, medical provider-delivered methods are comparatively robust

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up

<p>Abstract</p> <p>Background</p> <p>The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function.</p> <p>Methods</p> <p>In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure.</p> <p>Results</p> <p>The presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; <it>P </it>= .027/<it>P </it>= .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, <it>P </it>= .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, <it>P </it>= .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, <it>P </it><.002).</p> <p>Conclusions</p> <p>Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.</p

Deconstructing the Late Phase of Vimentin Assembly by Total Internal Reflection Fluorescence Microscopy (TIRFM)

Quantitative imaging of intermediate filaments (IF) during the advanced phase of the assembly process is technically difficult, since the structures are several µm long and therefore they exceed the field of view of many electron (EM) or atomic force microscopy (AFM) techniques. Thereby quantitative studies become extremely laborious and time-consuming. To overcome these difficulties, we prepared fluorescently labeled vimentin for visualization by total internal reflection fluorescence microscopy (TIRFM). In order to investigate if the labeling influences the assembly properties of the protein, we first determined the association state of unlabeled vimentin mixed with increasing amounts of labeled vimentin under low ionic conditions by analytical ultracentrifugation. We found that bona fide tetrameric complexes were formed even when half of the vimentin was labeled. Moreover, we demonstrate by quantitative atomic force microscopy and electron microscopy that the morphology and the assembly properties of filaments were not affected when the fraction of labeled vimentin was below 10%. Using fast frame rates we observed the rapid deposition of fluorescently labeled IFs on glass supports by TIRFM in real time. By tracing their contours, we have calculated the persistence length of long immobilized vimentin IFs to 1 µm, a value that is identical to those determined for shorter unlabeled vimentin. These results indicate that the structural properties of the filaments were not affected significantly by the dye. Furthermore, in order to analyze the late elongation phase, we mixed long filaments containing either Alexa 488- or Alexa 647-labeled vimentin. The ‘patchy’ structure of the filaments obtained unambiguously showed the elongation of long IFs through direct end-to-end annealing of individual filaments

MRP3 is a sex determining gene in the diatom Pseudo-nitzschia multistriata

A broad diversity of sex-determining systems has evolved in eukaryotes. However, information on the mechanisms of sex determination for unicellular microalgae is limited, including for diatoms, key-players of ocean food webs. Here we report the identification of a mating type (MT) determining gene for the diatom Pseudo-nitzschia multistriata. By comparing the expression profile of the two MTs, we find five MT-biased genes, of which one, MRP3, is expressed exclusively in MT+ strains in a monoallelic manner. A short tandem repeat of specific length in the region upstream of MRP3 is consistently present in MT+ and absent in MT- strains. MRP3 overexpression in an MT- strain induces sex reversal: the transgenic MT- can mate with another MT- strain and displays altered regulation of the other MT-biased genes, indicating that they lie downstream. Our data show that a relatively simple genetic program is involved in defining the MT in P. multistriata

Impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on prescription dug spending for children and adolescents: increasing relevance of health economic evidence

<p>Abstract</p> <p>Background</p> <p>During the last decade, pharmaceutical spending for patients with attention-deficit-hyperactivity disorder (ADHD) has been escalating internationally.</p> <p>Objectives</p> <p>First, to estimate future trends of ADHD-related drug expenditures from the perspectives of the statutory health insurance (SHI; Gesetzliche Krankenversicherung, GKV) in Germany and the National Health Service (NHS) in England, respectively, for children and adolescents age 6 to 18 years. Second, to evaluate the budgetary impact on individual prescribers (child and adolescent psychiatrists and pediatricians treating patients with ADHD) in Germany.</p> <p>Methods</p> <p>A model was developed to predict plausible scenarios of future pharmaceutical expenditures for treatment of ADHD. Model inputs were derived from demographic and epidemiological data, a literature review of past spending trends, and an analysis of new pharmaceutical products in development for ADHD. Only products in clinical development phase III or later were considered. Uncertainty was addressed by way of scenario analysis. For each jurisdiction, five scenarios used different assumptions of future diagnosis prevalence, treatment prevalence, rates of adoption and unit costs of novel drugs, and treatment intensity.</p> <p>Results</p> <p>Annual ADHD pharmacotherapy expenditures for children and adolescents will further increase and may exceed €310 m (D; E: ₤78 m) in 2012 (2002: ~€21.8 m; ~₤7.0 m). During this period, overall drug spending by individual physicians may increase 2.3- to 9.5-fold, resulting from the multiplicative effects of four variables: increased number of diagnosed cases, growing acceptance and intensity of pharmacotherapy, and higher unit costs of novel medications.</p> <p>Discussion</p> <p>Even for an extreme low case scenario, a more than six-fold increase of pharmaceutical spending for children and adolescents is predicted over the decade from 2002 to 2012, from the perspectives of both the NHS in England and the GKV in Germany. This budgetary impact projection represents a partial analysis only because other expenditures are likely to rise as well, for instance those associated with physician services, including diagnosis and psychosocial treatment. Further to this, by definition budgetary impact analyses have little to nothing to say about clinical appropriateness and about value of money.</p> <p>Conclusion</p> <p>Providers of care for children and adolescents with ADHD should anticipate serious challenges related to the cost-effectiveness of interventions.</p

Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

<p>Abstract</p> <p>Background</p> <p>Extracts of <it>Hypericum perforatum </it>(St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration.</p> <p>Methods</p> <p>CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.</p> <p>Results</p> <p>The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.</p> <p>Conclusion</p> <p>These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.</p

Synapse Clusters Are Preferentially Formed by Synapses with Large Recycling Pool Sizes

Synapses are distributed heterogeneously in neural networks. The relationship between the spatial arrangement of synapses and an individual synapse's structural and functional features remains to be elucidated. Here, we examined the influence of the number of adjacent synapses on individual synaptic recycling pool sizes. When measuring the discharge of the styryl dye FM1–43 from electrically stimulated synapses in rat hippocampal tissue cultures, a strong positive correlation between the number of neighbouring synapses and recycling vesicle pool sizes was observed. Accordingly, vesicle-rich synapses were found to preferentially reside next to neighbours with large recycling pool sizes. Although these synapses with large recycling pool sizes were rare, they were densely arranged and thus exhibited a high amount of release per volume. To consolidate these findings, functional terminals were marked by live-cell antibody staining with anti-synaptotagmin-1-cypHer or overexpression of synaptopHluorin. Analysis of synapse distributions in these systems confirmed the results obtained with FM 1–43. Our findings support the idea that clustering of synapses with large recycling pool sizes is a distinct developmental feature of newly formed neural networks and may contribute to functional plasticity

Modelling Vesicular Release at Hippocampal Synapses

We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure