Association between intraoperative electroencephalographic suppression and postoperative mortality

BACKGROUND Low bispectral index values frequently reflect EEG suppression and have been associated with postoperative mortality. This study investigated whether intraoperative EEG suppression was an independent predictor of 90 day postoperative mortality and explored risk factors for EEG suppression. METHODS This observational study included 2662 adults enrolled in the B-Unaware or BAG-RECALL trials. A cohort was defined with >5 cumulative minutes of EEG suppression, and 1:2 propensity-matched to a non-suppressed cohort (≤5 min suppression). We evaluated the association between EEG suppression and mortality using multivariable logistic regression, and examined risk factors for EEG suppression using zero-inflated mixed effects analysis. RESULTS Ninety day postoperative mortality was 3.9% overall, 6.3% in the suppressed cohort, and 3.0% in the non-suppressed cohort {odds ratio (OR) [95% confidence interval (CI)]=2.19 (1.48-3.26)}. After matching and multivariable adjustment, EEG suppression was not associated with mortality [OR (95% CI)=0.83 (0.55-1.25)]; however, the interaction between EEG suppression and mean arterial pressure (MAP) <55 mm Hg was [OR (95% CI)=2.96 (1.34-6.52)]. Risk factors for EEG suppression were older age, number of comorbidities, chronic obstructive pulmonary disease, and higher intraoperative doses of benzodiazepines, opioids, or volatile anaesthetics. EEG suppression was less likely in patients with cancer, preoperative alcohol, opioid or benzodiazepine consumption, and intraoperative nitrous oxide exposure. CONCLUSIONS Although EEG suppression was associated with increasing anaesthetic administration and comorbidities, the hypothesis that intraoperative EEG suppression is a predictor of postoperative mortality was only supported if it was coincident with low MAP. CLINICAL TRIAL REGISTRATION NCT00281489 and NCT00682825.

Seltene Krankheiten - eine Herausforderung für das schweizerische Gesundheitsrecht

Der Beitrag widmet sich dem durch technologische Entwicklungen herausgeforderten schweizerischen Gesundheitsrecht. Am Beispiel der seltenen Krankheiten wird aufgezeigt, dass das geltende Recht der medizinisch-technischen Realität hinterher hinkt und den Bedürfnissen von Menschen mit seltenen Krankheiten nur unzureichend gerecht wird. Es gilt abzuwarten, ob die demnächst vom BAG vorzulegende nationale Strategie für seltene Krankheiten den Betroffenen zu einem rechtsgleichen und transparenten Zugang zum Gesundheitswesen verhilft.

Real-time analysis of δ13C- and δD-CH4 in ambient air with laser spectroscopy: method development and first intercomparison results

In situ and simultaneous measurement of the three most abundant isotopologues of methane using mid-infrared laser absorption spectroscopy is demonstrated. A field-deployable, autonomous platform is realized by coupling a compact quantum cascade laser absorption spectrometer (QCLAS) to a preconcentration unit, called trace gas extractor (TREX). This unit enhances CH4 mole fractions by a factor of up to 500 above ambient levels and quantitatively separates interfering trace gases such as N2O and CO2. The analytical precision of the QCLAS isotope measurement on the preconcentrated (750 ppm, parts-per-million, µmole mole−1) methane is 0.1 and 0.5 ‰ for δ13C- and δD-CH4 at 10 min averaging time. Based on repeated measurements of compressed air during a 2-week intercomparison campaign, the repeatability of the TREX–QCLAS was determined to be 0.19 and 1.9 ‰ for δ13C and δD-CH4, respectively. In this intercomparison campaign the new in situ technique is compared to isotope-ratio mass spectrometry (IRMS) based on glass flask and bag sampling and real time CH4 isotope analysis by two commercially available laser spectrometers. Both laser-based analyzers were limited to methane mole fraction and δ13C-CH4 analysis, and only one of them, a cavity ring down spectrometer, was capable to deliver meaningful data for the isotopic composition. After correcting for scale offsets, the average difference between TREX–QCLAS data and bag/flask sampling–IRMS values are within the extended WMO compatibility goals of 0.2 and 5 ‰ for δ13C- and δD-CH4, respectively. This also displays the potential to improve the interlaboratory compatibility based on the analysis of a reference air sample with accurately determined isotopic composition.

Eine national-jüdische Hochschule

Ben Bag

The eukaryotic cellular stress response: Biochemical and genetic analyses in Saccharomyces cerevisiae

All cells must have the ability to deal with a variety of environmental stresses. Failure to correctly adapt to and/or protect against adverse stress conditions can lead to cell death. In humans, stress response defects have been linked to a number of neurodegenerative diseases and cancer, underscoring the importance of developing a fundamental understanding of the eukaryotic stress response.^ In an effort to characterize cellular response to high temperature stress, I identified and described one member of a novel gene family— RTR1. I show that the RTR1 gene and its protein product genetically and biochemically interact with core subunits of the RNA polymerase II enzyme. Appropriately, loss of RTR1 results in defective transcription from multiple promoters. These data provide evidence that Rtr1, which is essential under stress conditions, acts as a key regulator of transcription.^ In addition to transcriptional regulation, cells deal with many stressors by inducing molecular chaperones. Molecular chaperones are ubiquitous in all living cells and bind unfolded or damaged proteins and catalyze refolding or degradation. Hsp90 is a unique chaperone because it targets specific clients—typically signaling proteins—for maturation. While it has been shown that Sse1, the yeast Hsp110, is a critical regulator of the Hsp90 chaperone cycle, this work describes the molecular basis for that regulation. I show that Sse1 modulates Hsp90 function through regulation of Hsp70 nucleotide exchange. Further, Hsp110-type nucleotide exchange factors (NEFs) appear to have a specific role in modulating Hsp90 function in this manner. Finally, in addition to Hsp110, the eukaryotic cytosol contains two other types of Hsp70 NEF: Snl1 (BAG-domain protein) and Fes1 (HspBP1-like protein). I investigated the cellular roles of these NEFs to better understand the reason that eukaryotic cells contain three distinct protein families that perform the same biochemical function. I show that while cytsolic Hsp70 NEFs have some degree of functional overlap, they also exhibit striking divergence. Taken together, the work presented in this dissertation provides a more detailed understanding of the eukaryotic stress response. ^

Effect of parental weight status on the food packed in preschool children's lunches

Problem. Recent statistics show that over a fifth of children aged 2-5 years in 2006-2008 were overweight, with 7% above the 97 th percentile of the BMI-for-age growth charts (extreme obesity). Because poor diet is an important environmental determinant of obesity and the preschool years are crucial developmentally, examination of factors related to diet in the pre-school years is important for obesity prevention efforts. ^ Objective. The goals of this study were to determine the association between BMI of the parents and the number of servings of fruits, vegetables, and whole grains (FVWG) packed; the nutrient content of preschool children’s lunches; and norms and expectations about FVWG intake.^ Methods. This study was a cross sectional analysis of parents enrolled in the Lunch is in the Bag program at baseline. The independent measure was weight status of the parents/caregivers, which was determined using body mass index (BMI) calculated from self-reported height and weight. BMI was classified as healthy weight (BMI <25) or overweight/obese (BMI ≥25). Outcomes for the study included the number of servings of fruits, vegetables and whole grains (FVWG) in sack lunches, as well as the nutrient content of the lunches, and psychosocial constructs related to FVWG consumption. Linear regression analysis was conducted and adjusted for confounders to examine the associations of these outcomes with parental weight status, the main predictor. ^ Results. A total of 132 parent/child dyads were enrolled in the study; 59.09% (n=78) of the parents/caregivers were healthy weight and 39.01% (n=54) of the parents/caregivers were overweight/obese. Parents/caregivers in the study were predominantly white (68%, n=87) and had at least some college education (98%, n=128). No significant associations were found between the weight status of the parents and the servings of fruits, vegetables and whole grain packed in preschool children’s lunchboxes. The results were similar for the association of parental weight status and the nutrient contents of the packed lunches. Both healthy weight and overweight/obese parents packed less than the recommended amounts of vegetables (mean servings = 0.49 and 0.534, respectively) and whole grains (mean servings = 0.58 and 0.511, respectively). However, the intentions of the obese/overweight parents were higher compare to the healthy for vegetables and whole grains.^ Conclusion. Results from this study indicate that there are few differences in the servings of fruits, vegetables and whole grains packed by healthy weight parents/caregivers compared to overweight/obese parents/caregivers in a high income, well-educated population, although neither group met the recommended number of servings of vegetables or whole grains. Thus, results indicate the need for behaviorally-based health promotion programs for parents, regardless of their weight status; however, this study should be replicated with larger and more diverse populations to determine if these results are similar with less homogenous populations.^

BIOCHEMICAL CHARACTERIZATION OF BINDING PARTNERS OF TWO HSP70 CO-CHAPERONES IN SACCHAROMYCES CEREVISIAE

Cells are exposed to a variety of environmental and physiological changes including temperature, pH and nutrient availability. These changes cause stress to cells, which results in protein misfolding and altered cellular protein homeostasis. How proteins fold into their three-dimensional functional structure is a fundamental biological process with important relevance to human health. Misfolded and aggregated proteins are linked to multiple neurodegenerative diseases, cardiovascular disease and cystic fibrosis. To combat proteotoxic stress, cells deploy an array of molecular chaperones that assist in the repair or removal of misfolded proteins. Hsp70, an evolutionarily conserved molecular chaperone, promotes protein folding and helps maintain them in a functional state. Requisite co-chaperones, including nucleotide exchange factors (NEFs) strictly regulate and serve to recruit Hsp70 to distinct cellular processes or locations. In yeast and human cells, three structurally non-related cytosolic NEFs are present: Sse1 (Hsp110), Fes1 (HspBP1) and Snl1 (Bag-1). Snl1 is unique among the cytosolic NEFs as it is localized at the ER membrane with its Hsp70 binding (BAG) domain exposed to the cytosol. I discovered that Snl1 distinctly interacts with assembled ribosomes and several lines of evidence indicate that this interaction is both independent of and concurrent with binding to Hsp70 and is not dependent on membrane localization. The ribosome-binding site is identified as a short lysine-rich motif within the amino terminus of the Snl1 BAG domain distinct from the Hsp70 interaction region. In addition, I demonstrate ribosome association with the Snl1 homolog in the pathogenic fungus, Candida albicans and localize this putative NEF to a perinuclear/ER membrane, suggesting functional conservation in fungal BAG domain-containing proteins. As a first step in determining specific domain architecture in fungal BAG proteins, I present the preliminary steps of protein purification and analysis of the minimal Hsp70 binding region in in both S.cerevisiae and C. albicans Snl1. Contrary to previous in vitro evidence which showed the Fes1 NEF to interact with both cytosolic Hsp70s, Ssa and Ssb, Fes1 is shown to interact specifically with Ssa when expressed under normal cellular conditions in S. cerevisiae. This is the first reported evidence of Hsp70 binding selectivity for a cytosolic NEF, and suggests a possible mechanism to achieve specificity in Hsp70-dependent functions. Taken together, the work presented in this dissertation highlights the striking divergence among Hsp70 co-chaperones in selecting binding partners, which may correlate with their specific roles in the cell.

Evaluation of Bt and Non-Bt Corn with and without Soil Insecticides for Control of Corn Rootworm

The purpose of this study was to evaluate the effectiveness of Bt corn and soil insecticides, either alone or in combination, for the control of corn rootworm. Evaluation of Bt hybrids included SmartStax, SmartStax with refuge in a bag, and Herculex XTRA. Soil insecticides evaluated were SmartChoice-SB, Counter-SB, Aztec, and Force.

Evaluation of a Blended Refuge for Corn Rootworm

The purpose of this study was to evaluate the effectiveness of the blended refuge concept against corn rootworms. The treatments evaluated include a pure stand of Herculex XTRA (HXX), a pure stand of Roundup Ready 2 (RR2), a pure stand of RR2 with Force 3G applied overtop, and two treatments with the refuge in a bag concept–one with 95 percent HXX and a 5 percent RR2 blended refuge and the other with 90 percent HXX and a 10 percent RR2 blended refuge.

Evaluation of Bt and Non-Bt Corn with and without Soil Insecticides for Control of Corn Rootworm

The purpose of this study was to evaluate the effectiveness of Bt corn and soil insecticides, either alone or in combination, for the control of corn rootworm. Evaluation of Bt hybrids included SmartStax, SmartStax with a blended refuge (refuge in the bag), and Herculex XTRA. Soil insecticides evaluated were SmartChoice-SB, Counter-SB, Aztec, and Force.