On the Effect of Thermodynamic Equilibrium on the Assembly Efficiency of Complex Multi-Layered Virus-Like Particles (VLP): the Case of Rotavirus VLP

Previous studies have reported the production of malformed virus-like-particles (VLP) in recombinant host systems. Here we computationally investigate the case of a large triple-layered rotavirus VLP (RLP). In vitro assembly, disassembly and reassembly data provides strong evidence of microscopic reversibility of RLP assembly. Light scattering experimental data also evidences a slow and reversible assembly untypical of kinetic traps, thus further strengthening the fidelity of a thermodynamically controlled assembly. In silico analysis further reveals that under favourable conditions particles distribution is dominated by structural subunits and completely built icosahedra, while other intermediates are present only at residual concentrations. Except for harshly unfavourable conditions, assembly yield is maximised when proteins are provided in the same VLP protein mass composition. The assembly yield decreases abruptly due to thermodynamic equilibrium when the VLP protein mass composition is not obeyed. The latter effect is more pronounced the higher the Gibbs free energy of subunit association is and the more complex the particle is. Overall this study shows that the correct formation of complex multi-layered VLPs is restricted to a narrow range of association energies and protein concentrations, thus the choice of the host system is critical for successful assembly. Likewise, the dynamic control of intracellular protein expression rates becomes very important to minimize wasted proteins

Mental health consultations in a prison population: a descriptive study

BACKGROUND: The psychiatric morbidity among prison inmates is substantially higher than in the general population. We do, however, have insufficient knowledge about the extent of psychiatric treatment provided in our prisons. The aim of the present study was to give a comprehensive description of all non-pharmacological interventions provided by the psychiatric health services to a stratified sample of prison inmates. METHODS: Six medium/large prisons (n = 928) representing 1/3 of the Norwegian prison population and with female and preventive detention inmates over-sampled, were investigated cross-sectionally. All non-pharmacological psychiatric interventions, excluding pure correctional programs, were recorded. Those receiving interventions were investigated further and compared to the remaining prison population. RESULTS: A total of 230 of the 928 inmates (25 %) had some form of psychiatric intervention: 184 (20 %) were in individual psychotherapy, in addition 40 (4 %) received ad hoc interventions during the registration week. Group therapy was infrequent (1 %). The psychotherapies were most often of a supportive (62 %) or behavioural-cognitive (26 %) nature. Dynamic, insight-oriented psychotherapies were infrequent (8 %). Concurrent psychopharmacological treatment was prevalent (52 %). Gender and age did not correlate with psychiatric interventions, whereas prisoner category (remanded, sentenced, or preventive detention) did (p < 0.001). Most inmates had a number of defined problem areas, with substance use, depression, anxiety, and personality disorders most prevalent. Three percent of all inmates were treated for a psychotic disorder. Remand prisoners averaged 14 sessions per week per 100 inmates, while sentenced inmates and those on preventive detention averaged 22 and 25 sessions per week per 100 inmates, respectively. Five out of six psychiatric health services estimated the inmates' psychiatric therapy needs as adequately met, both overall and in the majority of individual cases. CONCLUSION: Our results pertain only to prisons with adequate primary and mental health services and effective diversion from prison of individuals with serious mental disorders. Given these important limitations, we do propose that the service estimates found may serve as a rough guideline to the minimum number of sessions a prison's psychiatric health services should be able to fulfil in order to serve the inmates psychiatric needs. The results rely on the specialist services' own estimates only. Future studies should take other important informants, including the inmates themselves, into consideration

Risk factors predict post-traumatic stress disorder differently in men and women

<p>Abstract</p> <p>Background</p> <p>About twice as many women as men develop post-traumatic stress disorder (PTSD), even though men as a group are exposed to more traumatic events. Exposure to different trauma types does not sufficiently explain why women are more vulnerable.</p> <p>Methods</p> <p>The present work examines the effect of age, previous trauma, negative affectivity (NA), anxiety, depression, persistent dissociation, and social support on PTSD separately in men and women. Subjects were exposed to either a series of explosions in a firework factory near a residential area or to a high school stabbing incident.</p> <p>Results</p> <p>Some gender differences were found in the predictive power of well known risk factors for PTSD. Anxiety predicted PTSD in men, but not in women, whereas the opposite was found for depression. Dissociation was a better predictor for PTSD in women than in men in the explosion sample but not in the stabbing sample. Initially, NA predicted PTSD better in women than men in the explosion sample, but when compared only to other significant risk factors, it significantly predicted PTSD for both men and women in both studies. Previous traumatic events and age did not significantly predict PTSD in either gender.</p> <p>Conclusion</p> <p>Gender differences in the predictive value of social support on PTSD appear to be very complex, and no clear conclusions can be made based on the two studies included in this article.</p

Direct Binding of a Hepatitis C Virus Inhibitor to the Viral Capsid Protein

Over 130 million people are infected chronically with hepatitis C virus (HCV), which, together with HBV, is the leading cause of liver disease. Novel small molecule inhibitors of Hepatitis C virus (HCV) are needed to complement or replace current treatments based on pegylated interferon and ribavirin, which are only partially successful and plagued with side-effects. Assembly of the virion is initiated by the oligomerization of core, the capsid protein, followed by the interaction with NS5A and other HCV proteins. By screening for inhibitors of core dimerization, we previously discovered peptides and drug-like compounds that disrupt interactions between core and other HCV proteins, NS3 and NS5A, and block HCV production. Here we report that a biotinylated derivative of SL209, a prototype small molecule inhibitor of core dimerization (IC50 of 2.80 µM) that inhibits HCV production with an EC50 of 3.20 µM, is capable of penetrating HCV-infected cells and tracking with core. Interaction between the inhibitors, core and other viral proteins was demonstrated by SL209–mediated affinity-isolation of HCV proteins from lysates of infected cells, or of the corresponding recombinant HCV proteins. SL209-like inhibitors of HCV core may form the basis of novel treatments of Hepatitis C in combination with other target-specific HCV drugs such as inhibitors of the NS3 protease, the NS5B polymerase, or the NS5A regulatory protein. More generally, our work supports the hypothesis that inhibitors of viral capsid formation might constitute a new class of potent antiviral agents, as was recently also shown for HIV capsid inhibitors

Recovery from depressive symptoms, state anxiety and post-traumatic stress disorder in women exposed to physical and psychological, but not to psychological intimate partner violence alone: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>It is well established that intimate male partner violence (IPV) has a high impact on women's mental health. It is necessary to further investigate this impact longitudinally to assess the factors that contribute to its recovery or deterioration. The objective of this study was to assess the course of depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms and suicidal behavior over a three-year follow-up in female victims of IPV.</p> <p>Methods</p> <p>Women (n = 91) who participated in our previous cross-sectional study, and who had been either physically/psychologically (n = 33) or psychologically abused (n = 23) by their male partners, were evaluated three years later. A nonabused control group of women (n = 35) was included for comparison. Information about mental health status and lifestyle variables was obtained through face-to-face structured interviews.</p> <p>Results</p> <p>Results of the follow-up study indicated that while women exposed to physical/psychological IPV recovered their mental health status with a significant decrease in depressive, anxiety and PTSD symptoms, no recovery occurred in women exposed to psychological IPV alone. The evolution of IPV was also different: while it continued across both time points in 65.21% of psychologically abused women, it continued in only 12.12% of physically/psychologically abused women while it was reduced to psychological IPV in 51.5%. Hierarchical multiple regression analyses indicated that cessation of physical IPV and perceived social support contributed to mental health recovery, while a high perception of lifetime events predicted the continuation of PTSD symptoms.</p> <p>Conclusion</p> <p>This study shows that the pattern of mental health recovery depends on the type of IPV that the women had been exposed to. While those experiencing physical/psychological IPV have a higher likelihood of undergoing a cessation or reduction of IPV over time and, therefore, could recover, women exposed to psychological IPV alone have a high probability of continued exposure to the same type of IPV with a low possibility of recovery. Thus, women exposed to psychological IPV alone need more help to escape from IPV and to recuperate their mental health. Longitudinal studies are needed to improve knowledge of factors promoting or impeding health recovery to guide the formulation of policy at individual, social and criminal justice levels.</p

Trauma-related emotions and radical acceptance in dialectical behavior therapy for posttraumatic stress disorder after childhood sexual abuse

Background: Posttraumatic Stress Disorder (PTSD) related to childhood sexual abuse (CSA) is often associated with a wide range of trauma-related aversive emotions such as fear, disgust, sadness, shame, guilt, and anger. Intense experience of aversive emotions in particular has been linked to higher psychopathology in trauma survivors. Most established psychosocial treatments aim to reduce avoidance of trauma-related memories and associated emotions. Interventions based on Dialectical Behavior Therapy (DBT) also foster radical acceptance of the traumatic event. Methods: This study compares individual ratings of trauma-related emotions and radical acceptance between the start and the end of DBT for PTSD (DBT-PTSD) related to CSA. We expected a decrease in trauma-related emotions and an increase in acceptance. In addition, we tested whether therapy response according to the Clinician Administered PTSD-Scale (CAPS) for the DSM-IV was associated with changes in trauma-related emotions and acceptance. The data was collected within a randomized controlled trial testing the efficacy of DBT-PTSD, and a subsample of 23 women was included in this secondary data analysis. Results: In a multilevel model, shame, guilt, disgust, distress, and fear decreased significantly from the start to the end of the therapy whereas radical acceptance increased. Therapy response measured with the CAPS was associated with change in trauma-related emotions. Conclusions: Trauma-related emotions and radical acceptance showed significant changes from the start to the end of DBT-PTSD. Future studies with larger sample sizes and control group designs are needed to test whether these changes are due to the treatment. Trial registration: ClinicalTrials.gov, number NCT0048100

Working conditions, self-perceived stress, anxiety, depression and quality of life: A structural equation modelling approach

<p>Abstract</p> <p>Background</p> <p>The relationships between working conditions [job demand, job control and social support]; stress, anxiety, and depression; and perceived quality of life factors [physical health, psychological wellbeing, social relationships and environmental conditions] were assessed using a sample of 698 male automotive assembly workers in Malaysia.</p> <p>Methods</p> <p>The validated Malay version of the Job Content Questionnaire (JCQ), Depression Anxiety Stress Scales (DASS) and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) were used. A structural equation modelling (SEM) analysis was applied to test the structural relationships of the model using AMOS version 6.0, with the maximum likelihood ratio as the method of estimation.</p> <p>Results</p> <p>The results of the SEM supported the hypothesized structural model (<it>χ</it>²= 22.801, <it>df </it>= 19, <it>p </it>= 0.246). The final model shows that social support (JCQ) was directly related to all 4 factors of the WHOQOL-BREF and inversely related to depression and stress (DASS). Job demand (JCQ) was directly related to stress (DASS) and inversely related to the environmental conditions (WHOQOL-BREF). Job control (JCQ) was directly related to social relationships (WHOQOL-BREF). Stress (DASS) was directly related to anxiety and depression (DASS) and inversely related to physical health, environment conditions and social relationships (WHOQOL-BREF). Anxiety (DASS) was directly related to depression (DASS) and inversely related to physical health (WHOQOL-BREF). Depression (DASS) was inversely related to the psychological wellbeing (WHOQOL-BREF). Finally, stress, anxiety and depression (DASS) mediate the relationships between job demand and social support (JCQ) to the 4 factors of WHOQOL-BREF.</p> <p>Conclusion</p> <p>These findings suggest that higher social support increases the self-reported quality of life of these workers. Higher job control increases the social relationships, whilst higher job demand increases the self-perceived stress and decreases the self-perceived quality of life related to environmental factors. The mediating role of depression, anxiety and stress on the relationship between working conditions and perceived quality of life in automotive workers should be taken into account in managing stress amongst these workers.</p

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available

Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls

BACKGROUND: Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam. METHODS: We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models. RESULTS: Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively. CONCLUSION: When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD