Role of elastin anisotropy in structural strain energy functions of arterial tissue

The vascular wall exhibits nonlinear anisotropic mechanical properties. The identification of a strain energy function (SEF) is the preferred method to describe its complex nonlinear elastic properties. Earlier constituent-based SEF models, where elastin is modeled as an isotropic material, failed in describing accurately the tissue response to inflation-extension loading. We hypothesized that these shortcomings are partly due to unaccounted anisotropic properties of elastin. We performed inflation-extension tests on common carotid of rabbits before and after enzymatic degradation of elastin and applied constituent-based SEFs, with both an isotropic and an anisotropic elastin part, on the experimental data. We used transmission electron microscopy (TEM) and serial block-face scanning electron microscopy (SBFSEM) to provide direct structural evidence of the assumed anisotropy. In intact arteries, the SEF including anisotropic elastin with one family of fibers in the circumferential direction fitted better the inflation-extension data than the isotropic SEF. This was supported by TEM and SBFSEM imaging, which showed interlamellar elastin fibers in the circumferential direction. In elastin-degraded arteries, both SEFs succeeded equally well in predicting anisotropic wall behavior. In elastase-treated arteries fitted with the anisotropic SEF for elastin, collagen engaged later than in intact arteries. We conclude that constituent-based models with an anisotropic elastin part characterize more accurately the mechanical properties of the arterial wall when compared to models with simply an isotropic elastin. Microstructural imaging based on electron microscopy techniques provided evidence for elastin anisotropy. Finally, the model suggests a later and less abrupt collagen engagement after elastase treatmen

Cerebellar Pathology in an Inducible Mouse Model of Friedreich Ataxia

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by deficiency of the mitochondrial protein frataxin. Lack of frataxin causes neuronal loss in various areas of the CNS and PNS. In particular, cerebellar neuropathology in FRDA patients includes loss of large principal neurons and synaptic terminals in the dentate nucleus (DN), and previous studies have demonstrated early synaptic deficits in the Knockin-Knockout mouse model of FRDA. However, the exact correlation of frataxin deficiency with cerebellar neuropathology remains unclear. Here we report that doxycycline-induced frataxin knockdown in a mouse model of FRDA (FRDAkd) leads to synaptic cerebellar degeneration that can be partially reversed by AAV8-mediated frataxin restoration. Loss of cerebellar Purkinje neurons and large DN principal neurons are observed in the FRDAkd mouse cerebellum. Levels of the climbing fiber-specific glutamatergic synaptic marker VGLUT2 decline starting at 4 weeks after dox induction, whereas levels of the parallel fiber-specific synaptic marker VGLUT1 are reduced by 18-weeks. These findings suggest initial selective degeneration of climbing fiber synapses followed by loss of parallel fiber synapses. The GABAergic synaptic marker GAD65 progressively declined during dox induction in FRDAkd mice, while GAD67 levels remained unaltered, suggesting specific roles for frataxin in maintaining cerebellar synaptic integrity and function during adulthood. Expression of frataxin following AAV8-mediated gene transfer partially restored VGLUT1/2 levels. Taken together, our findings show that frataxin knockdown leads to cerebellar degeneration in the FRDAkd mouse model, suggesting that frataxin helps maintain cerebellar structure and function

Visible charge exchange recombination spectroscopy on TFTR

Visible charge exchange recombination spectroscopy is routinely used to measure the time evolution of the ion temperature (T{sub i}) and toroidal rotation velocity (v{sub {phi}}) profiles on TFTR. These measurements are made with the CHERS diagnostic, a fiber-optically coupled spectrometer equipped with a two-dimensional photodiode array detector which provides both spectral and spatial resolution. The instrumentation, data analysis techniques, and examples of T{sub i} and v{sub {phi}} measurements are described. Recently, CHERS has been used to perform impurity transport experiments: radial profiles of diffusivities and convective velocities for helium and iron have been deduced from measurements of the time evolutions of He{sup 2+} and Fe{sup 24+} profiles following impurity injection. Examples of these measurements are given. 12 refs., 8 figs

Methodologies to assess blood flow in cerebral aneurysms: Current state of research and perspectives

With intracranial aneurysms disease bringing a weakened arterial wall segment to initiate, grow and potentially rupture an aneurysm, current understanding of vessel wall biology perceives the disease to follow the path of a dynamic evolution and increasingly recognizes blood flow as being one of the main stakeholders driving the process. Although currently mostly morphological information is used to decide on whether or not to treat a yet unruptured aneurysm, among other factors, knowledge of blood flow parameters may provide an advanced understanding of the mechanisms leading to further aneurismal growth and potential rupture. Flow patterns, velocities, pressure and their derived quantifications, such as shear and vorticity, are today accessible by direct measurements or can be calculated through computation. This paper reviews and puts into perspective current experimental methodologies and numerical approaches available for such purposes. In our view, the combination of current medical imaging standards, numerical simulation methods and endovascular treatment methods allow for thinking that flow conditions govern more than any other factor fate and treatment in cerebral aneurysms. Approaching aneurysms from this perspective improves understanding, and while requiring a personalized aneurysm management by flow assessment and flow correction, if indicated

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

Transport by intermittency in the boundary of the DIII-D tokamak

A271 TRANSPORT BY INTERMITTENCY IN THE BOUNDARY OF THE DIII-D TOKAMAK. Intermittent plasma objectives (IPOs) featuring higher pressure than the surrounding plasma, are responsible for {approx} 50% of the E x B{sub T} radial transport in the scrape off layer (SOL) of the DIII-D tokamak in L- and H-mode discharges. Conditional averaging reveals that the IPOs are positively charged and feature internal poloidal electric fields of up to 4000 V/m. The IPOs move radially with E x B{sub T}/B{sup 2} velocities of {approx} 2600 m/s near the last closed flux surface (LCFS), and {approx} 330 m/s near the wall. The IPOs slow down as they shrink in radial size from 4 cm at the LCFS to 0.5 cm near the wall. The skewness (i.e. asymmetry of fluctuations from the average) of probe and beam emission spectroscopy (BES) data indicate IPO formation at or near the LCFS and the existence of positive and negative IPOs which move in opposite directions. The particle content of the IPOs at the LCFS is linearly dependent on the local density and decays over {approx} 3 cm into the SOL while their temperature decays much faster ({approx} 1 cm)

Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients

This study aims at establishing relationships between genetic and non-genetic factors of variation of the pharmacokinetics of irinotecan and its metabolites; and also at establishing relationships between the pharmacokinetic or metabolic parameters and the efficacy and toxicity of irinotecan. We included 49 patients treated for metastatic colorectal cancer with a combination of 5-fluorouracil and irinotecan; a polymorphism in the UGT1A1 gene (TA repeat in the TATA box) and one in the CES2 gene promoter (830C>G) were studied as potential markers for SN-38 glucuronidation and irinotecan activation, respectively; and the potential activity of CYP3A4 was estimated from cortisol biotransformation into 6β-hydroxycortisol. No pharmacokinetic parameter was directly predictive of clinical outcome or toxicity. The AUCs of three important metabolites of irinotecan, SN-38, SN-38 glucuronide and APC, were tentatively correlated with patients' pretreatment biological parameters related to drug metabolism (plasma creatinine, bilirubin and liver enzymes, and blood leukocytes). SN-38 AUC was significantly correlated with blood leukocytes number and SN-38G AUC was significantly correlated with plasma creatinine, whereas APC AUC was significantly correlated with plasma liver enzymes. The relative extent of irinotecan activation was inversely correlated with SN-38 glucuronidation. The TATA box polymorphism of UGT1A1 was significantly associated with plasma bilirubin levels and behaved as a significant predictor for neutropoenia. The level of cortisol 6β-hydroxylation predicted for the occurrence of diarrhoea. All these observations may improve the routine use of irinotecan in colorectal cancer patients. UGT1A1 genotyping plus cortisol 6β-hydroxylation determination could help to determine the optimal dose of irinotecan

Experience of violence and adverse reproductive health outcomes, HIV risks among mobile female sex workers in India

<p>Abstract</p> <p>Background</p> <p>Female sex workers (FSWs) are a population sub-group most affected by the HIV epidemic in India and elsewhere. Despite research and programmatic attention to FSWs, little is known regarding sex workers' reproductive health and HIV risk in relation to their experiences of violence. This paper therefore aims to understand the linkages between violence and the reproductive health and HIV risks among a group of mobile FSWs in India.</p> <p>Methods</p> <p>Data are drawn from a cross-sectional behavioural survey conducted in 22 districts from four high HIV prevalence states (Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu) in India between September 2007 and July 2008. The survey sample included 5,498 FSWs who had moved to at least two different places for sex work in the past two years, and are classified as mobile FSWs in the current study. Analyses calculated the prevalence of past year experiences of violence; and adjusted logistic regression models examined the association between violence and reproductive health and HIV risks after controlling for background characteristics and program exposure.</p> <p>Results</p> <p>Approximately one-third of the total mobile FSWs (30.5%, n = 1,676) reported experiencing violence at least once in the past year; 11% reported experiencing physical violence, and 19.5% reported experiencing sexual violence. Results indicate that FSWs who had experienced any violence (physical or sexual) were significantly more likely to be vulnerable to both reproductive health and HIV risks. For example, FSWs who experienced violence were more likely than those who did not experience violence to have experienced a higher number of pregnancies (adjusted odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.0-1.6), ever experienced pregnancy loss (adjusted OR = 1.4, 95% CI = 1.2-1.6), ever experienced forced termination of pregnancy (adjusted OR = 2.4, 95% CI = 2.0-2.7), experienced multiple forced termination of pregnancies (adjusted OR = 2.2, 95% CI = 1.7-2.8), and practice inconsistent condom use currently (adjusted OR = 1.97, 95% CI: 1.4-2.0). Among FSWs who experienced violence, those who experienced sexual violence were more likely than those who had experienced physical violence to report inconsistent condom use (adjusted OR = 1.8, 95% CI: 1.4-2.3), and experience STI symptoms (adjusted OR = 1.3, 95% CI: 1.1-1.7).</p> <p>Conclusion</p> <p>The pervasiveness of violence and its association with reproductive health and HIV risk highlights that the abuse in general is an important determinant for reproductive health risks; and sexual violence is significantly associated with HIV risks among those who experienced violence. Existing community mobilization programs that have primarily focused on empowering FSWs should broaden their efforts to promote reproductive health in addition to the prevention of HIV among all FSWs, with particular emphasis on FSWs who experienced violence.</p