416 research outputs found

    Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

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    SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

    Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia

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    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs.</p> <p>Methods</p> <p>Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426), Colombia (n = 5,782) and the United States (USA; n = 8,228). The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO) users across these surveyed populations.</p> <p>Results</p> <p>The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004) and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001).</p> <p>Conclusions</p> <p>This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that might make cannabis-related social and legal problems more frequent in Colombia than in the USA.</p

    Crisis Visits and Psychiatric Hospitalizations Among Patients Attending a Community Clinic in Rural Southern California

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    Ethnic minorities from disadvantaged socioeconomic backgrounds report increased utilization of mental health emergency services; however findings have been inconsistent across ethnic/racial groups. In this study we describe patients who present to a rural crisis unit in Southern California, examine rates of psychiatric hospitalizations across ethnic/racial groups, and investigate factors that are associated with increased psychiatric hospitalizations in this sample. This is a retrospective study of 451 racially and ethnically diverse patients attending a crisis unit in Imperial County, California. Chart review and data abstraction methods were used to characterize the sample and identify factors associated with psychiatric crises and subsequent hospitalizations. The sample was predominantly Latino/Hispanic (58.5%). Based on chart review, common psychosocial stressors which prompted a crisis center visit were: (a) financial problems; (b) homelessness; (c) partner or family conflict; (d) physical and health problems; (e) problems at school/work; (f) medication compliance; (g) aggressive behavior; (h) delusional behavior; (i) addiction and (j) anxiety/depression. Bivariate analyses revealed that Hispanics had a disproportionately lower rate of psychiatric hospitalizations while African Americans had a higher rate. Multivariate analyses which included demographic, clinical and psychosocial stressor variables revealed that being African American, having a psychotic disorder, and presenting as gravely disabled were associated with a higher likelihood of hospitalization while partner/family conflict was associated with a lesser likelihood in this rural community. These data elucidate the need for longitudinal studies to understand the interactions between psychosocial stressors, ethnicity and social support as determinants of psychiatric hospitalizations

    The optimal number of lymph nodes examined in stage II colorectal cancer and its impact of on outcomes

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    Background: Lymph node status is the most important prognostic factor for colorectal cancer. The number of lymph nodes that should be histologically examined has been controversial. The aims of this study were to assess the impact of the number of lymph nodes examined on survival of patients with stage II colorectal cancer and to determine the optimal number of lymph nodes that should be examined.Methods: The study included 664 patients who underwent resection for stage II colorectal cancer. The clinical and histopathologic data of the patients were prospectively collected and analyzed.Results: The median number of lymph nodes examined was 12 (range: 1 to 58). The 5-year disease free survival rate was significantly higher for patients with 12 or more lymph nodes examined compared to those with less than 12 lymph nodes examined. The significant difference in 5-year disease free survival persisted if the dividing number increased progressively from 12 to 23. However, the difference in survival was most significant (lowest p value and highest hazard ratio) for the number 21. The 5-year disease free survival of patients with 21 or more lymph nodes examined was 80% whereas that of patients with less than 21 lymph nodes examined was 60% (p = 0.001, hazard ratio 2.08). Multivariate analysis showed that 21 or more lymph nodes examined was a factor that independently influenced survival. The 5-year disease free survival also increased progressively with the number of lymph node examined up to the number 21. After the number 21, the survival rate did not increase further. It was likely that 21 was the optimal number, at and above which the chance of lymph node metastasis was minimal.Conclusions: The number of lymph nodes examined in colorectal cancer specimen significantly influences survival. It is recommended that at least 21 lymph nodes should be examined for accurate diagnosis of stage II colorectal cancer. © 2010 Choi et al; licensee BioMed Central Ltd.published_or_final_versio

    Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

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    <p>Abstract</p> <p>Objective</p> <p>To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.</p> <p>Methods</p> <p>Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described.</p> <p>Results</p> <p>CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance.</p> <p>Conclusions</p> <p>CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00052078.</p

    Psychiatric Context of Acute/Early HIV Infection. The NIMH Multisite Acute HIV Infection Study: IV

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    Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected

    A cross-sectional study of patients with and without substance use disorders in Community Mental Health Centres

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    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies have consistently established high comorbidity between psychiatric disorders and substance use disorders (SUD). This comorbidity is even more prominent when psychiatric populations are studied. Previous studies have focused on inpatient populations dominated by psychotic disorders, whereas this paper presents findings on patients in Community Mental Health Centres (CMHCs) where affective and anxiety disorders are most prominent. The purpose of this study is to compare patients in CMHCs with and without SUD in regard to differences in socio-demographic characteristics, level of morbidity, prevalence of different diagnostic categories, health services provided and the level of improvement in psychiatric symptoms.</p> <p>Methods</p> <p>As part of the evaluation of the National Plan for Mental Health, all patients seen in eight CMHCs during a 4-week period in 2007 were studied (n = 2154). The CMHCs were located in rural and urban areas of Norway. The patients were diagnosed according to the ICD-10 diagnoses and assessed with the Health of the Nation Outcome Scales, the Alcohol Use Scale and the Drug Use Scale.</p> <p>Results</p> <p>Patients with SUD in CMHCs are more frequently male, single and living alone, have more severe morbidity, less anxiety and mood disorders, less outpatient treatment and less improvement in regard to recovery from psychological symptoms compared to patients with no SUD.</p> <p>Conclusion</p> <p>CMHCs need to implement systematic screening and diagnostic procedures in order to detect the special needs of these patients and improve their treatment.</p

    Brain Circuitries Involved in Semantic Interference by Demands of Emotional and Non-Emotional Distractors

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    BACKGROUND: Previous studies have indicated that the processes leading to the resolution of emotional and non-emotional interference conflicts are unrelated, involving separate networks. It is also known that conflict resolution itself suggests a considerable overlap of the networks. Our study is an attempt to examine how these findings may be related. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging (fMRI) to study neural responses of 24 healthy subjects to emotional and non-emotional conflict paradigms involving the presentation of congruent and incongruent word-face pairs based on semantic incompatibility between targets and distractors. In the emotional task, the behavioral interference conflict was greater (compared to the non-emotional task) and was paralleled by involvement of the extrastriate visual and posterodorsal medial frontal cortices. In both tasks, we also observed a common network including the dorsal anterior cingulate, the supplemental motor area, the anterior insula and the inferior prefrontal cortex, indicating that these brain structures are markers of experienced conflict. However, the emotional task involved conflict-triggered networks to a considerably higher degree. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that responses to emotional and non-emotional distractors involve the same systems, which are capable of flexible adjustments based on conflict demands. The function of systems related to conflict resolution is likely to be adjusted on the basis of an evaluation process that primarily involves the extrastriate visual cortex, with target playing a significant role
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