1,033 research outputs found
Viral dynamics during structured treatment interruptions of chronic human immunodeficiency virus type 1 infection
Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses
Facial emotion processing in schizophrenia : a non-specific neuropsychological deficit?
Original article can be found at : http://journals.cambridge.org/ Copyright Cambridge University PressBackground: Identification of facial emotions has been found to be impaired in schizophrenia but there are uncertainties about the neuropsychological specificity of the finding. Method: Twenty-two patients with schizophrenia and 20 healthy controls were given tests requiring identification of facial emotion, judgement of the intensity of emotional expressions without identification, familiar face recognition and the Benton Facial Recognition Test (BFRT). The schizophrenia patients were selected to be relatively intellectually preserved. Results: The patients with schizophrenia showed no deficit in identifying facial emotion, although they were slower than the controls. They were, however, impaired on judging the intensity of emotional expression without identification. They showed impairment in recognizing familiar faces but not on the BFRT. Conclusions: When steps are taken to reduce the effects of general intellectual impairment, there is no deficit in identifying facial emotions in schizophrenia. There may, however, be a deficit in judging emotional intensity. The impairment found in naming familiar faces is consistent with other evidence of semantic memory impairment in the disorder.Peer reviewe
Manifestacions glaciaires quaternaires dans le haut bassin du Llobregat (Prépyrénées Catalanes)
Dans une zone prépyrénéenne en roches sedimentaires avant tout calcaires et marnoargileuses, et avec des altitudes maximales comprises entre 1.700 et 2.500 m, nous avons observé des formations superiicielles pour lesquelles nous proposons une origine glaciaire, du fait de leur granulométrie et structure, des caracteres morphométriques de ses galets, et des formes associées aux dépots. Des criteres de datation relative, surtout géomorphologiques, nous amenent ?t proposer trois différents périodes d'englacement, qui ne puissent pas correspondre a de simples stades d'une meme période glaciaire, mais a de vraies glaciations
Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1
Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naïve patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change ≤0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further
Brain functional abnormality in schizo-affective disorder: an fMRI study.
Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction
Conditional Mutual Information Maps as Descriptors of Net Connectivity Levels in the Brain
There is a growing interest in finding ways to summarize the local connectivity properties of the brain through single brain maps. Here we propose a method based on the conditional mutual information (CMI) in the frequency domain. CMI maps quantify the amount of non-redundant covariability between each site and all others in the rest of the brain, partialling out the joint variability due to gross physiological noise. Average maps from a sample of 45 healthy individuals scanned in the resting state show a clear and symmetric pattern of connectivity maxima in several regions of cortex, including prefrontal, orbitofrontal, lateral–parietal, and midline default mode network components; and in subcortical nuclei, including the amygdala, thalamus, and basal ganglia. Such cortical and subcortical hotspots of functional connectivity were more clearly evident at lower frequencies (0.02–0.1 Hz) than at higher frequencies (0.1–0.2 Hz) of endogenous oscillation. CMI mapping can also be easily applied to perform group analyses. This is exemplified by exploring effects of normal aging on CMI in a sample of healthy controls and by investigating correlations between CMI and positive psychotic symptom scores in a sample of 40 schizophrenic patients. Both the normative aging and schizophrenia studies reveal functional connectivity trends that converge with reported findings from other studies, thus giving further support to the validity of the proposed method
Herb-drug interaction between Echinacea purpurea and darunavir/ritonavir in HIV-infected patients
Circumcision and penile human papillomavirus prevalence in human immunodeficiency virus-infected men: heterosexual and men who have sex with men
AbstractMale circumcision is associated with a lower risk of penile human papillomavirus (HPV) infection in human immunodeficiency virus (HIV) uninfected men. Few studies have evaluated the role of male circumcision in penile HPV infection in HIV-infected men. The aim of this cross-sectional study was to examine the association between male circumcision and the prevalence of penile HPV infection among HIV-infected men—both men who have sex with men (MSM) and heterosexual men. Samples from 706 consecutive men included in the CARH-MEN cohort (overall 24% circumcised: 26% of MSM, 18% of heterosexual men) were examined by Multiplex-PCR. In the overall group (all HIV-infected men included), the prevalence of any penile HPV infection was 22% in circumcised men and 27% in uncircumcised men (OR = 1.0, 95% CI 0.6–1.6, adjusted analysis). In the circumcised group the overall prevalence of HPV infection was 22% in MSM and 24% in the heterosexual men, whereas in the uncircumcised group the prevalence was 26% and 28%, respectively. The prevalence of high-risk HPV types tended to be lower in the circumcised MSM (14% vs 21%, OR = 0.6, 95% CI 0.3–1.1, p 0.088), but it was similar in the heterosexual men (18% in circumcised vs 20% in uncircumcised). These results suggest that male circumcision may be associated with a lower prevalence of oncogenic high-risk penile HPV infection in HIV-infected MSM
Monotherapy with boosted protease inhibitors as antiretroviral treatment simplification strategy in the clinical setting
Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV-1-infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow-up visit in our clinic. When two consecutive PI-monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV-1 VL <50 c/mL) through follow-up. Virological failure was defined as at least two consecutive HIV-1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis) either as “on treatment” or as “treatment switch equals failure”. Five hundred and seventy-three PI-monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR) follow-up were 50 (26.3–107.6) and 85.6 (36.9–179.1) weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001). Overall, 67 (11.7%) subjects experienced virological failure, 23 (8.7%) were on darunavir/ritonavir and 42 (13.5%) were on lopinavir/ritonavir (p=0.796). Two hundred and three (77.5%) patients on darunavir/ritonavir and 154 (49.5%) on lopinavir/ritonavir maintained virological suppression in the “treatment switch equals failure” (p=0.002). Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation were more frequent in patients on lopinavir/ritonavir (10.6% and 10.3%, respectively) than in patients on darunavir/ritonavir (3.1% and 0.8%, respectively). Monotherapy with darunavir/ritonavir or lopinavir/ritonavir as simplification strategy appears to be effective and safe in subjects with virological suppression in clinical practice. Virological efficacy seems to be similar between regimens. However, rates of discontinuation due to toxicities were higher in subjects on lopinavir/ritonavir than darunavir/ritonavir
Spherical deconvolution of multichannel diffusion MRI data with non-Gaussian noise models and spatial regularization
Spherical deconvolution (SD) methods are widely used to estimate the
intra-voxel white-matter fiber orientations from diffusion MRI data. However,
while some of these methods assume a zero-mean Gaussian distribution for the
underlying noise, its real distribution is known to be non-Gaussian and to
depend on the methodology used to combine multichannel signals. Indeed, the two
prevailing methods for multichannel signal combination lead to Rician and
noncentral Chi noise distributions. Here we develop a Robust and Unbiased
Model-BAsed Spherical Deconvolution (RUMBA-SD) technique, intended to deal with
realistic MRI noise, based on a Richardson-Lucy (RL) algorithm adapted to
Rician and noncentral Chi likelihood models. To quantify the benefits of using
proper noise models, RUMBA-SD was compared with dRL-SD, a well-established
method based on the RL algorithm for Gaussian noise. Another aim of the study
was to quantify the impact of including a total variation (TV) spatial
regularization term in the estimation framework. To do this, we developed TV
spatially-regularized versions of both RUMBA-SD and dRL-SD algorithms. The
evaluation was performed by comparing various quality metrics on 132
three-dimensional synthetic phantoms involving different inter-fiber angles and
volume fractions, which were contaminated with noise mimicking patterns
generated by data processing in multichannel scanners. The results demonstrate
that the inclusion of proper likelihood models leads to an increased ability to
resolve fiber crossings with smaller inter-fiber angles and to better detect
non-dominant fibers. The inclusion of TV regularization dramatically improved
the resolution power of both techniques. The above findings were also verified
in brain data
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