Pyruvate Dehydrogenase Activity Is Decreased in the Peripheral Blood Mononuclear Cells of Patients with Sepsis. A Prospective Observational Trial.

RATIONALE: Rodent studies have shown that pyruvate dehydrogenase (PDH) levels are low in sepsis. This may cause cells to shift to anaerobic metabolism, resulting in increased lactate production. Alterations in PDH during sepsis have never been studied in humans. OBJECTIVES: The objective of this pilot study was to measure PDH activity and quantity in patients with severe sepsis. METHODS: We conducted a pilot case-control study at a single urban tertiary care center. We compared PDH activity and quantity between patients with severe sepsis admitted to the intensive care unit and healthy control subjects. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We measured PDH activity and quantity in control subjects at baseline and in patients with sepsis at 0 (baseline), 24, 48, and 72 hours. MEASUREMENTS AND MAIN RESULTS: We enrolled 56 patients with sepsis and 20 control subjects with at least one blood sample being drawn from each patient. PDH activity and quantity in the sepsis group were significantly lower than the control group (P < 0.001). In multivariable linear regression adjusting for age, race, sex, and assay plate, the difference remained significant. Patients with sepsis who died had significantly lower PDH activity compared with those who survived (P = 0.03). CONCLUSIONS: PDH activity and quantity is decreased in peripheral blood mononuclear cells of humans with severe sepsis when compared with healthy control subjects, and may be associated with mortality. Whether decreased PDH activity plays a role in lactate metabolism or whether pharmacologic modification of PDH activity may improve outcomes remains unknown.

A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality.

The predictive utility of attitudes toward hookah tobacco smoking.

OBJECTIVE: To determine associations between positive and negative attitudes and hookah tobacco smoking (HTS) among college students. METHODS: Among a random sample of university students (N = 852), multivariable logistic regression models assessed associations between positive and negative attitudes toward HTS. RESULTS: Positive attitudes were associated with adjusted odds of 4.32 (95% CI = 3.20, 5.82) for current HTS, whereas negative attitudes were associated with lower adjusted odds for current smoking HTS (AOR = 0.64, 95% CI = 0.53, 0.76). Positive attitudes were also associated with adjusted odds of 9.31 (95% CI = 6.77, 12.80) for intention for future hookah use among non-HTS users. CONCLUSION: Positive attitudes toward HTS were more strongly associated with HTS compared to negative attitudes. It may be particularly valuable for future research and interventions to focus on decreasing positive attitudes toward HTS.

Associations between hookah tobacco smoking knowledge and hookah smoking behavior among US college students.

Hookah tobacco smoking is increasing among US college students, including those who would not otherwise use tobacco. Part of hookah's appeal is attributed to the perception that hookah is less harmful than cigarettes. The aims of this study were to assess knowledge of harmful exposures associated with hookah smoking relative to cigarette smoking and to determine associations between this knowledge and hookah smoking outcomes. Students (N = 852) at the University of Florida were randomly sampled via e-mail to obtain information on demographics, hookah smoking behavior and knowledge of five exposures (e.g. tar and nicotine). Multivariable logistic regression models assessed independent associations between knowledge and hookah smoking outcomes. Of the five factual knowledge items asked, 475 (55.8%) of the respondents answered none correctly. In multivariable models, correct responses to any knowledge items were not associated with lower odds of hookah smoking or susceptibility to hookah smoking in the future. Although college students are largely unaware of the toxicant exposures associated with hookah smoking, there is little association between knowledge and hookah smoking behavior.

Alcohol brand appearances in US popular music.

AIMS: The average US adolescent is exposed to 34 references to alcohol in popular music daily. Although brand recognition is an independent, potent risk factor for alcohol outcomes among adolescents, alcohol brand appearances in popular music have not been assessed systematically. We aimed to determine the prevalence of and contextual elements associated with alcohol brand appearances in US popular music. DESIGN: Qualitative content analysis. SETTING: We used Billboard Magazine to identify songs to which US adolescents were most exposed in 2005-07. For each of the 793 songs, two trained coders analyzed independently the lyrics of each song for references to alcohol and alcohol brand appearances. Subsequent in-depth assessments utilized Atlas.ti to determine contextual factors associated with each of the alcohol brand appearances. MEASUREMENTS: Our final code book contained 27 relevant codes representing six categories: alcohol types, consequences, emotional states, activities, status and objects. FINDINGS: Average inter-rater reliability was high (κ = 0.80), and all differences were easily adjudicated. Of the 793 songs in our sample, 169 (21.3%) referred explicitly to alcohol, and of those, 41 (24.3%) contained an alcohol brand appearance. Consequences associated with alcohol were more often positive than negative (41.5% versus 17.1%, P < 0.001). Alcohol brand appearances were associated commonly with wealth (63.4%), sex (58.5%), luxury objects (51.2%), partying (48.8%), other drugs (43.9%) and vehicles (39.0%). CONCLUSIONS: One in five songs sampled from US popular music had explicit references to alcohol, and one-quarter of these mentioned a specific alcohol brand. These alcohol brand appearances are associated commonly with a luxury life-style characterized by wealth, sex, partying and other drugs.