Risk taking and the triarchic model of psychopathy

Introduction: High risk behaviors, such as aggression, criminality, sexual promiscuity, drug use, and gambling, are often associated with psychopathic traits. Such behaviors might arise due to a lack of fear of the consequences (boldness) or due to impulsive actions (disinhibition). We examined risk taking behavior in the laboratory setting using the Balloon Analogue Risk Task (BART), where an individual can inflate a balloon to earn a reward, but will lose this accumulated reward if the balloon bursts. The task reflects the willingness to take risks under conditions where the risk-taking behavior is understood and is made clear to the individual. Method: BART performance was measured in a mixed community and offender sample, and psychopathy was characterized via the triarchic conceptualization of psychopathy, which proposes that psychopathy is a combination of boldness, meanness, and disinhibition. Results: Total psychopathy score was correlated with greater risk taking on the BART, and this effect was mainly due to the Boldness scale rather than the Meanness or Disinhibition scales. These relationships were not moderated by the nature of the sample (offender vs. community) or by gender. Conclusions: Individuals with high psychopathy scores appear more willing to take risks on this simple laboratory task, and this behavior appears due to boldness rather than being related to an impulsive disposition.     

Calcium lability of cytoplasmic microtubules and its modulation by microtubule-associated proteins

Detergent-extracted BSC-1 monkey cells have been used as a model system to study the Ca²⁺ sensitivity of in vivo polymerized microtubules under in vitro conditions. The effects of various experimental treatments were observed by immunofluorescence microscopy. Whereas microtubules are completely stable at Ca²⁺ concentrations below 1 μM, Ca²⁺ at greater than 1-4 μM induces microtubule disassembly that begins in the cell periphery and proceeds towards the cell center. At concentrations of up to 500 μM, both the pattern and time course of disassembly are not markedly altered, suggesting that, within this concentration range, Ca²⁺ effects are catalytic rather than stoichiometric. Higher (millimolar) Ca²⁺ concentration results in rapid destruction of microtubules. Of other divalent cations, only Sr²⁺ has a slight depolymerizing effect, whereas millimolar Ba²⁺, Mg²⁺, or Mn²⁺ is ineffective. Disassembly induced by micromolar Ca²⁺ is inhibited by pharmacological agents known to bind to calmodulin and inhibit its function, suggesting that calmodulin mediates Ca²⁺ effects. Both the addition of exogenous brain microtubule-associated proteins (MAPs) after lysis and the retention of endogenous cellular MAPs normally extracted during the lysis step stabilize microtubules against the depolymerizing effect of micromolar Ca²⁺. The results indicate that, in this model system, microtubules are sensitive to physiological Ca²⁺ concentrations and that this sensitivity may be conferred by calmodulin associated with the microtubules. MAPs appear to have a modulating effect on microtubular Ca²⁺ sensitivity and thus may function as a discriminating factor in cellular functions performed by calmodulin. It is hypothesized that Ca²⁺-stimulated microtubule disassembly depends on the relative amount of MAPs.     

Effects of mutations and glycosylations on STS activity: a site-directed mutagenesis study

Steroid sulphatase (STS) catalyses the formation of active steroids from inactive steroid sulphates. High levels of intra-tumoural STS mRNA are associated with a poor prognosis in post-menopausal patients with oestrogen receptor positive breast cancer. In this study, analysis of the mutated STS protein showed that N- and C-terminal truncated STS constructs are inactive. Histidine 136, located inside the active site, is crucial for STS activity whereas proline 212, which allows the protein turn into the membrane, is not. Mutations in glycosylation sites asparagine 47 and 259 decreased STS activity while asparagine 333 and 459 mutations did not affect it. However, immunoblot studies revealed that all four N-linked sites are glycosylated to some extent. In addition, a polyclonal antibody raised in rabbits against human STS was developed and characterised. These data increase our knowledge of the STS enzyme structure and may help design new STS inhibitors.     

High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study

Background

As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described.

Methods

Medication adherence was measured in 60 HCV, genotype-1, treatment-naïve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report.

Results

Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report.

Conclusions

Adherence to short courses of DAA therapy with 1–3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.