The impact of methamphetamine use on subjective well-being in an Internet survey: preliminary findings

Methamphetamine is one of the most widely used stimulants worldwide. Common reasons for use of the drug include efforts to improve or enhance one's life and to uplift one's mood. Nevertheless, acute effects of the drug lead to temporary improvements in mood followed by negative affect. The purpose of the present study was to expand on the current literature and examine other aspects of mood and satisfaction with life in methamphetamine users. Over 6000 adults completed an Internet survey and reported on depression, apathy, satisfaction with life, happiness, and subjective well-being, in addition to measures of methamphetamine use. We compared those who had used methamphetamine at least once within the past year (N = 610) to those who had never used (N = 6063). Methamphetamine use accounted for significant variance in depression, apathy, satisfaction with life, happiness, and subjective well-being even when alcohol and other drugs served as covariates. Methamphetamine use may decrease one's subjective well-being instead of enhancing it, which is contradictory to the perceptions of many users. Increasing awareness about methamphetamine's negative impact on mood and life satisfaction might help decrease prevalence of the drug's use and associated troubles.     

Impact of time to treatment on myocardial reperfusion and infarct size with primary percutaneous coronary intervention for acute myocardial infarction (from the EMERALD Trial)

The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p=0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.     

Self-Report and Linguistic Indicators of Emotional Expression in Narratives as Predictors of Adjustment to Cancer

Emotional expression and cognitive efforts to adapt to cancer have been linked to better psychological adjustment. However, little is known about the relationship between linguistic indicators of emotional and cognitive coping efforts and corresponding self-report measures of related constructs. In this study, we sought to evaluate the interrelationships between self-reports of emotional suppression and linguistic indicators of emotional and cognitive coping efforts in those living with cancer. Seventy-one individuals attending a community cancer support group completed measures of emotional suppression and mood disturbance and provided a written narrative describing their cancer experience. Self-reports of emotional suppression were associated with more rather than less distress. Although linguistic indicators of both emotional expression and cognitive processing were generally uncorrelated with self-report measures of emotional suppression and mood disturbance, a significant interaction was observed between emotional suppression and use of cognitive words on mood disturbance. Among those using higher levels of emotional suppression, increasing use of cognitive words was associated with greater levels of mood disturbance. These findings have implications for a) the therapeutic use of emotion in psychosocial interventions and b) the use of computer-assisted technologies to conduct content analysis.     

Risk estimation with epidemiologic data when response attenuates at high-exposure levels

Background

In occupational studies, which are commonly used for risk assessment for environmental settings, estimated exposure–response relationships often attenuate at high exposures. Relative risk (RR) models with transformed (e.g., log- or square root–transformed) exposures can provide a good fit to such data, but resulting exposure–response curves that are supralinear in the low-dose region may overestimate low-dose risks. Conversely, a model of untransformed (linear) exposure may underestimate risks attributable to exposures in the low-dose region.

Methods

We examined several models, seeking simple parametric models that fit attenuating exposure–response data well. We have illustrated the use of both log-linear and linear RR models using cohort study data on breast cancer and exposure to ethylene oxide.

Results

Linear RR models fit the data better than do corresponding log-linear models. Among linear RR models, linear (untransformed), log-transformed, square root–transformed, linear-exponential, and two-piece linear exposure models all fit the data reasonably well. However, the slopes of the predicted exposure–response relations were very different in the low-exposure range, which resulted in different estimates of the exposure concentration associated with a 1% lifetime excess risk (0.0400, 0.00005, 0.0016, 0.0113, and 0.0100 ppm, respectively). The linear (in exposure) model underestimated the categorical exposure–response in the low-dose region, whereas log-transformed and square root–transformed exposure models overestimated it.

Conclusion

Although a number of models may fit attenuating data well, models that assume linear or nearly linear exposure–response relations in the low-dose region of interest may be preferred by risk assessors, because they do not depend on the choice of a point of departure for linear low-dose extrapolation and are relatively easy to interpret.     

Resistance to the Translation Initiation Inhibitor Silvestrol is Mediated by ABCB1/P-Glycoprotein Overexpression in Acute Lymphoblastic Leukemia Cells

Protein synthesis is a powerful therapeutic target in leukemias and other cancers, but few pharmacologically viable agents are available that affect this process directly. The plant-derived agent silvestrol specifically inhibits translation initiation by interfering with eIF4A/mRNA assembly with eIF4F. Silvestrol has potent in vitro and in vivo activity in multiple cancer models including acute lymphoblastic leukemia (ALL) and is under pre-clinical development by the US National Cancer Institute, but no information is available about potential mechanisms of resistance. In a separate report, we showed that intraperitoneal silvestrol is approximately 100% bioavailable systemically, although oral doses were only 1% bioavailable despite an apparent lack of metabolism. To explore mechanisms of silvestrol resistance and the possible role of efflux transporters in silvestrol disposition, we characterized multi-drug resistance transporter expression and function in a silvestrol-resistant ALL cell line generated via culture of the 697 ALL cell line in gradually increasing silvestrol concentrations. This resistant cell line, 697-R, shows significant upregulation of ABCB1 mRNA and P-glycoprotein (Pgp) as well as cross-resistance to known Pgp substrates vincristine and romidepsin. Furthermore, 697-R cells readily efflux the fluorescent Pgp substrate rhodamine 123. This effect is prevented by Pgp inhibitors verapamil and cyclosporin A, as well as siRNA to ABCB1, with concomitant re-sensitization to silvestrol. Together, these data indicate that silvestrol is a substrate of Pgp, a potential obstacle that must be considered in the development of silvestrol for oral delivery or targeting to tumors protected by Pgp overexpression.     

Occlusive and reperfused myocardial infarcts: differentiation with Mn- DPDP--enhanced MR imaging

To assess whether the administration of manganese N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (DPDP) permits differentiation between occlusive and reperfused infarcts, the authors subjected rats to either 6 hours of left coronary artery occlusion (n = 13) or 2 hours of occlusion followed by 4 hours of reperfusion (n = 10) before magnetic resonance (MR) imaging. Electrocardiographic-gated T1-weighted images were obtained before and for 1 hour after injection of 400 mumol/kg of Mn-DPDP. On T1-weighted images obtained before injection of Mn-DPDP. no significant differences in signal intensity were observed between normal and infarcted regions. Use of Mn-DPDP permitted delineation of the area of infarction. The pattern of enhancement in the injured zone was different for occlusive and reperfused myocardial infarcts. In rats with occlusive infarcts, In rats with occlusive infarcts, three well-defined zones were seen. Epicardium and endocardium were enhanced, while the midmyocardial zone was hypointense. The midmyocardial signal intensity gradually increased during the 60 minutes after injection. In rats with reperfused infarcts, the injured area was uniformly and intensely enhanced. Histologic examination confirmed the presence and location of myocardial infarct. Mn-DPDP may improve the detection and delineation of acute myocardial infarcts, demonstrate perfusion of the infarct, and permit discrimination between reperfused and occlusive infarcts.     

A new method of cannabis ingestion: The dangers of dabs?

A new method for administering cannabinoids, called butane hash oil (“dabs”), is gaining popularity among marijuana users. Despite press reports that suggest that “dabbing” is riskier than smoking flower cannabis, no data address whether dabs users experience more problems from use than those who prefer flower cannabis.