The Impact of the Minimum Legal Drinking Age on Alcohol-Related Chronic Disease Mortality.

BACKGROUND: The minimum legal drinking age (MLDA) of 21 has been associated with a number of benefits compared to lower MLDAs, including long-term effects, such as reduced risk for alcoholism in adulthood. However, no studies have examined whether MLDA during young adulthood is associated with mortality later in life. We examined whether individuals exposed to permissive MLDA (<21) had higher risk of death from alcohol-related chronic disease compared to those exposed to the 21 MLDA. Because prior work suggests that MLDA affects college students differently, we also conducted conditional analyses based on ever having attended college. METHODS: Data from the 1990 through 2010 U.S. Multiple Cause-of-Death files were combined with data on the living population and analyzed. We included individuals who turned 18 during the years 1967 to 1990, the period during which MLDA varied across states. We examined records on death from several alcohol-related chronic diseases, employing a quasi-experimental approach to control for unobserved state characteristics and stable time trends. RESULTS: Individuals who reported any college attendance did not exhibit significant associations between MLDA and mortality for the causes of death we examined. However, permissive MLDA for those who never attended college was associated with 6% higher odds for death from alcoholic liver disease, 8% higher odds for other liver disease, and 7% higher odds for lip/oral/pharynx cancers (odds ratio [OR] = 1.06, 95% confidence interval [CI] [1.02, 1.10]; OR = 1.08, 95% CI [1.03, 1.13]; OR = 1.07, 95% CI [1.03, 1.12], respectively). CONCLUSIONS: The 21 MLDA likely protects against risk of death from alcohol-related chronic disease across the lifespan, at least for those who did not attend college. This is consistent with other work that shows that the long-term association between MLDA and alcohol-related outcomes is specific to those who did not attend college.

A reexamination of medical marijuana policies in relation to suicide risk.

OBJECTIVES: Previous research has suggested that medical marijuana policies lead to reductions in suicide rates. In this study, we further investigate the association between these policies and within-state changes in suicide risk. METHODS: Data on suicide deaths (n=662,993) from the National Vital Statistics System Multiple Cause of Death files were combined with living population data. Fixed-effects regression methods were employed to control for state differences in suicide rates and national and state secular trends. Analyses extended prior research that suggested a protective effect of medical marijuana policies by incorporating newer data and additional covariates. RESULTS: After adjustment for race/ethnicity, tobacco control policies, and other covariates, we found no association between medical marijuana policy and suicide risk in the population ages 15 and older (OR=1.000; 95% CI: 0.956, 1.045; p=0.98), among men overall (OR=0.996; 95% CI: 0.951, 1.043; p=0.87) or for any other age-by-sex groups. CONCLUSION: We find no statistically significant association between medical marijuana policy and suicide risk. These results contradict prior analyses which did not control for race/ethnicity and certain state characteristics such as tobacco control policies. Failure to control for these factors in future analyses would likely bias estimates of the associations between medical marijuana policy and health outcomes.

Prophylactic Subclavian Artery Intraaortic Balloon Counter-Pulsation is Safe in High-Risk Cardiac Surgery Patients.

The objective of this study was to determine the safety of prophylactic subclavian artery intraaortic balloon pumps (SCA-IABP) in high-risk cardiac surgery patients as a bridge to recovery (BTR). From November 2011 to January 2013, 11 consecutive patients at three institutions underwent prophylactic insertion of a SCA-IABP as a BTR. All patients (n = 11) had preoperative ejection fractions of 30% or less. Patients concurrently underwent one or a combination of the following procedures: coronary artery bypass grafting, mitral valve surgery, aortic valve replacement, left ventricular aneurysm resection, and ventricular/atrial septal defect closure. The primary outcome measure was a composite endpoint of device-related complications (including limb ischemia, stroke, device failure, bleeding requiring reoperation, brachial plexus injury, device-related infection, and vascular complications) and in-hospital mortality. Secondary outcome measures included interval to patient ambulation and postoperative length of stay. There were no device-related complications or in-hospital mortalities in this cohort of 11 consecutive patients. Mean time to ambulation, balloon pump support, and postoperative length of stay were 3.70 ± 2.50 days, 8.50 ± 7.00 days, and 15.9 ± 8.25 days, respectively. Prophylactic SCA-IABPs appear to be safe in high-risk cardiac surgery patients as a BTR.

Antagonist properties of Conus parius peptides on N-methyl-D-aspartate receptors and their effects on CREB signaling.

Three members of a family of small neurotoxic peptides from the venom of Conus parius, conantokins (Con) Pr1, Pr2, and Pr3, function as antagonists of N-methyl-D-aspartate receptors (NMDAR). We report structural characterizations of these synthetic peptides, and also demonstrate their antagonistic properties toward ion flow through NMDAR ion channels in primary neurons. ConPr1 and ConPr2 displayed moderate increases in α-helicity after addition of Mg(2+). Native apo-ConPr3 possessed an α-helical conformation, and the helicity increased only slightly on addition of Mg(2+). Additionally, these peptides diminished NMDA/Gly-mediated currents and intracellular Ca(2+) (iCa(2+)) influx in mature rat primary hippocampal neurons. Electrophysiological data showed that these peptides displayed slower antagonistic properties toward the NMDAR than conantokins from other species of cone snails, e.g., ConT and ConG. Furthermore, to demonstrate selectivity of the C. parius-derived conantokins towards specific NMDAR subunits, cortical neurons from GluN2A(-/-) and GluN2B(-/-) mice were utilized. Robust inhibition of NMDAR-mediated stimulation in GluN2A(-/-)-derived mouse neurons, as compared to those isolated from GluN2B(-/-)-mouse brains, was observed, suggesting a greater selectivity of these antagonists towards the GluN2B subunit. These C. parius conantokins mildly inhibited NMDAR-induced phosphorylation of CREB at Ser(133), suggesting that the peptides modulated iCa(2+) entry and, thereby, activation of CREB, a transcription factor that is required for maintaining long-term synaptic activity. Our data mechanistically show that while these peptides effectively antagonize NMDAR-directed current and iCa(2+) influx, receptor-coupled CREB signaling is maintained. The consequence of sustained CREB signaling is improved neuronal plasticity and survival during neuropathologies.