Objectively‐measured sleep and its association with adiposity and physical activity in a sample of Canadian children

Cross‐sectional associations between objectively‐measured sleep duration, sleep efficiency and sleep timing with adiposity and physical activity were examined in a cohort of 567 children from Ottawa, Canada. Five‐hundred and fifteen children (58.8% female; age: 10.0 ± 0.4 years) had valid sleep measurements and were included in the present analyses. Physical activity, sedentary time and sleep parameters were assessed over 7 days (actigraphy). Height, weight and waist circumference were measured according to standardized procedures. Percentage body fat was assessed using bioelectric impedance analysis. Light physical activity and sedentary time were greater in children with the shortest sleep durations (P < 0.0001), whereas children with the highest sleep efficiencies had lower light physical activity and more sedentary time across tertiles (P < 0.0001). In multivariable linear regression analyses, and after adjusting for a number of covariates, sleep efficiency was inversely related to all adiposity indices (P < 0.05). However, sleep duration and sleep timing were not associated with adiposity indices after controlling for covariates. Inverse associations were noted between sleep duration and light physical activity and sedentary time (P < 0.0001). Sleep efficiency (P < 0.0001), wake time and sleep timing midpoint (P < 0.05) were negatively associated with light physical activity, but positively associated with sedentary time. In conclusion, only sleep efficiency was independently correlated with adiposity in this sample of children. Participants with the shortest sleep durations or highest sleep efficiencies had greater sedentary time. More research is needed to develop better sleep recommendations in children that are based on objective measures of sleep duration, sleep efficiency and sleep timing alike.     

Hepatitis after intravenous buprenorphine misuse in heroin addicts

BACKGROUND: Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations. CASE REPORTS: We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin. CONCLUSIONS: Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.     

Variation in efficiency of DNA mismatch repair at different sites in the yeast genome

Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally that frameshift mutation rates in yeast microsatellites depend on the genomic context and that this variation primarily reflects the context-dependence of the efficiency of DNA mismatch repair. We measured the stability of a 16.5-repeat polyGT tract by using a reporter gene (URA3-GT) in which the microsatellite was inserted in-frame into the yeast URA3 gene. We constructed 10 isogenic yeast strains with the reporter gene at different locations in the genome. Rates of frameshift mutations that abolished the correct reading frame of this gene were determined by fluctuation analysis. A 16-fold difference was found among these strains. We made mismatch-repair-deficient (msh2) derivatives of six of the strains. Mutation rates were elevated for all of these strains, but the differences in rates among the strains were substantially reduced. The simplest interpretation of this result is that the efficiency of DNA mismatch repair varies in different regions of the genome, perhaps reflecting some aspect of chromosome structure.     

Impact of a multifaceted prevention program on ventilator-associated pneumonia including selective oropharyngeal decontamination

Purpose

We describe the impact of a multifaceted program for decreasing ventilator-associated pneumonia (VAP) after implementing nine preventive measures, including selective oropharyngeal decontamination (SOD).

Methods

We compared VAP rates during an 8-month pre-intervention period, a 12-month intervention period, and an 11-month post-intervention period in a cohort of patients who received mechanical ventilation (MV) for?>?48 h. The primary objective was to assess the effect on first VAP occurrence, using a Cox cause-specific proportional hazards model. Secondary objectives included the impact on emergence of antimicrobial resistance, antibiotic consumption, duration of MV, and ICU mortality.

Results

Pre-intervention, intervention and post-intervention VAP rates were 24.0, 11.0 and 3.9 VAP episodes per 1000 ventilation-days, respectively. VAP rates decreased by 56% [hazard ratio (HR) 0.44, 95% CI 0.29–0.65; P?<?0.001] in the intervention and by 85% (HR 0.15, 95% CI 0.08–0.27; P?<?0.001) in the post-intervention periods. During the intervention period, VAP rates decreased by 42% (HR 0.58, 95% CI 0.38–0.87; P?<?0.001) after implementation of eight preventive measures without SOD, and by 70% after adding SOD (HR 0.30, 95% CI 0.13–0.72; P?<?0.001) compared to the pre-intervention period. The incidence density of intrinsically resistant bacteria (to colistin or tobramycin) did not increase. We documented a significant reduction of days of therapy per 1000 patient-days of broad-spectrum antibiotic used to treat lower respiratory tract infection (P?<?0.028), median duration of MV (from 7.1 to 6.4 days; P?<?0.003) and ICU mortality (from 16.2 to 13.5%; P?<?0.049) for patients ventilated?>?48 h between the pre- and post-intervention periods.

Conclusions

Our preventive program produced a sustained decrease in VAP incidence. SOD provides an additive value.

     

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenstr?m's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.     

Taurocholate stimulates transcytotic vesicular pathways labeled by horseradish peroxidase in the isolated perfused rat liver

The effect of taurocholate on transcytotic vesicular pathways labeled with horseradish peroxidase was assessed in isolated perfused rat liver preparations. Forty-five minutes after a horseradish peroxidase load in a recirculating system, continuous infusion of taurocholate but not taurodehydrocholate significantly increased horseradish peroxidase excretion in bile by 50% compared with controls. When horseradish peroxidase (25 mg) was pulse loaded for 1 minute in control perfusions, it appeared in bile in early (4-6 minutes) and late (20-25 minutes) peaks, the latter accounting for 90% of total horseradish peroxidase output. Taurocholate infusion significantly increased horseradish peroxidase output in both early and late peaks, whereas only a small increase in the early peak was observed with taurodehydrocholate. Colchicine pretreatment increased the early peak in bile but abolished the second peak. Electron micrographs from control livers revealed the accumulation of horseradish peroxidase-containing vesicles in pericanalicular regions at early (2 minutes) as well as late (18 minutes) periods. When a morphometric analysis of electron micrographs was performed from pericanalicular regions 2 minutes after a 1-minute pulse of horseradish peroxidase (500 mg), taurocholate but not taurodehydrocholate increased both the density and percent area of horseradish peroxidase-containing vesicles compared with controls. In contrast, colchicine pretreatment had no effect on the density of the early-appearing vesicles, although their individual sizes were reduced. Taurocholate but not taurodehydrocholate also increased the percent of tubular structures in the pericanalicular region. These findings indicate that taurocholate stimulates both early and late transcytotic vesicle pathways and therefore probably microtubule-independent vesicle pathway is present in hepatocytes that must be distinguished from paracellular routes.     

Fusion of influenza virus membranes with liposomes at pH 7.5.

Influenza virus X-31 (H3N2) membranes fuse with liposomes containing ganglioside GD1a at pH 7.5. Fusion was demonstrated by electron microscopy and also can be measured by counting the labeled virus proteins incorporated into liposomes after bound virus has been removed. Liposomes composed of lipids that have no net charge behave as reported by other investigators and do not fuse with influenza X-31 membranes at neutral pH, but they do fuse at low pH. Therefore, the liposomal composition is a factor in whether liposomes fuse with influenza virus membranes at neutral pH, probably by determining whether binding occurs. The liposomal composition necessary for fusion at neutral pH needs to be individualized for each influenza subtype. To establish that a virus requires low pH for membrane fusion, it is first necessary to establish that fusion does not occur at neutral pH under conditions where adequate binding occurs.