Involvement of Cyclin K Posttranscriptional Regulation in the Formation of Artemia Diapause Cysts

Background: Artemia eggs tend to develop ovoviviparously to yield nauplius larvae in good rearing conditions; while under adverse situations, they tend to develop oviparously and encysted diapause embryos are formed instead. However, the intrinsic mechanisms regulating this process are not well understood. Principal Finding: This study has characterized the function of cyclin K, a regulatory subunit of the positive transcription elongation factor b (P-TEFb) in the two different developmental pathways of Artemia. In the diapause-destined embryo, Western blots showed that the cyclin K protein was down-regulated as the embryo entered dormancy and reverted to relatively high levels of expression once development resumed, consistent with the fluctuations in phosphorylation of position 2 serines (Ser2) in the C-terminal domain (CTD) of the largest subunit (Rpb1) of RNA polymerase II (RNAP II). Interestingly, the cyclin K transcript levels remained constant during this process. In vitro translation data indicated that the template activity of cyclin K mRNA stored in the postdiapause cyst was repressed. In addition, in vivo knockdown of cyclin K in developing embryos by RNA interference eliminated phosphorylation of the CTD Ser2 of RNAP II and induced apoptosis by inhibiting the extracellular signal-regulated kinase (ERK) survival signaling pathway. Conclusions/Significance: Taken together, these findings reveal a role for cyclin K in regulating RNAP II activity during diapause embryo development, which involves the post-transcriptional regulation of cyclin K. In addition, a further role wa

Mild hypoglycemia is strongly associated with increased intensive care unit length of stay

Background: Hypoglycemia is associated with increased mortality in critically ill patients. The impact of hypoglycemia on resource utilization has not been investigated. The objective of this investigation was to evaluate the association of hypoglycemia, defined as a blood glucose concentration (BG) <70 mg/dL, and intensive care unit (ICU) length of stay (LOS) in three different cohorts of critically ill patients. Methods: This is a retrospective investigation of prospectively collected data, including patients from two large observational cohorts: 3,263 patients admitted to Stamford Hospital (ST) and 2,063 patients admitted to three institutions in The Netherlands (NL) as well as 914 patients from the GLUCONTROL trial (GL), a multicenter prospective randomized controlled trial of intensive insulin therapy. Results: Patients with hypoglycemia were more likely to be diabetic, had higher APACHE II scores, and higher mortality than did patients without hypoglycemia. Patients with hypoglycemia had longer ICU LOS (median [interquartile range]) in ST (3.0 [1.4-7.1] vs. 1.2 [0.8-2.3] days, P <0.0001), NL (5.2 [2.6-10.3] vs. 2.0 [1.3-3.2] days, P <0.0001), and GL (9 [5-17] vs. 5 [3-9] days, P <0.0001). For the entire cohort of 6,240 patients ICU LOS was 1.8 (1.03.3) days for those without hypoglycemia and 3.0 (1.5-6.7) days for those with a single episode of hypoglycemia (P <0.0001). This was a consistent finding even when patients were stratified by severity of illness or survivor status. There was a strong positive correlation between the number of episodes of hypoglycemia and ICU LOS among all three cohorts. Conclusions: This multicenter international investigation demonstrated that hypoglycemia was consistently associated with significantly higher ICU LOS in heterogeneous cohorts of critically ill patients, independently of severity of illness and survivor status. More effective methods to prevent hypoglycemia in these patients may positively impact their cost of car

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay &gt;=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission

Implementing glucose control in intensive care: a multicenter trial using statistical process control

Glucose control (GC) with insulin decreases morbidity and mortality of critically ill patients. In this study we investigated GC performance over time during implementation of GC strategies within three intensive care units (ICUs) and in routine clinical practice. All adult critically ill patients who stayed for >24 h between 1999 and 2007 were included. Effects of implementing local GC guidelines and guideline revisions on effectiveness/efficiency-related indicators, safety-related indicators, and protocol-related indicators were measured. Data of 17,111 patient admissions were evaluated, with 714,141 available blood glucose levels (BGL) measurements. Mean BGL, time to reach target, hyperglycemia index, sampling frequency, percentage of hyperglycemia events, and in-range measurements statistically changed after introducing GC in all ICUs. The introduction of simple rules on GC had the largest effect. Subsequent changes in the protocol had a smaller effect than the introduction of the protocol itself. As soon as the protocol was introduced, in all ICUs the percentage of hypoglycemia events increased. Various revisions were implemented to reduce hypoglycemia events, but levels never returned to those from pre-implementation. More intensive implementation strategies including the use of a decision support system resulted in better control of the process. There are various strategies to achieve GC in routine clinical practice but with variable success. All of them were associated with an increase in hypoglycemia events, but GC was never stopped. Instead, these events have been accepted and managed. Statistical process control is a useful tool for monitoring phenomena over time and captures within-institution change

Relative fat oxidation is higher in children than adults

Background: Prepubescent children may oxidize fatty acids more readily than adults. Therefore, dietary fat needs would be higher for children compared with adults. The dietary fat recommendations are higher for children 4 to 18 yrs (i.e., 25 to 35% of energy) compared with adults (i.e., 20 to 35% of energy). Despite this, many parents and children restrict dietary fat for health reasons. Methods: This study assessed whether rates of fat oxidation are similar between prepubescent children and adults. Ten children (8.7 ± 1.4 yr, 33 ± 13 kg mean ± SD) in Tanner stage 1 and 10 adults (41.6 ± 8 yr, 74 ± 13 kg) were fed a weight maintenance diet for three days to maintain body weight and to establish a consistent background for metabolic rate measurements (all foods provided). Metabolic rate was measured on three separate occasions before and immediately after breakfast and for 9 hrs using a hood system (twice) or a room calorimeter (once) where continuous metabolic measurements were taken. Results: During all three sessions whole body fat oxidation was higher in children (lower RQ) compared to adults (mean RQ= 0.84 ± .016 for children and 0.87 ± .02, for adults, p < 0.02). Although, total grams of fat oxidized was similar in children (62.7 ± 20 g/24 hrs) compared to adults (51.4 ± 19 g/24 hrs), the grams of fat oxidized relative to calorie expenditure was higher in children (0.047 ± .01 g/kcal, compared to adults (0.032 ± .01 p < 0.02). Females oxidized more fat relative to calorie expenditure than males of a similar age. A two way ANOVA showed no interaction between gender and age in terms of fax oxidation. Conclusion: These data suggest that fat oxidation relative to total calorie expenditure is higher in prepubescent children than in adults. Consistent with current dietary guidelines, a moderate fat diet is appropriate for children within the context of a diet that meets their energy and nutrient needs. Originally published Nutrition Journal, Vol. 6, No. 19, Aug 200

Glucose variability measures and their effect on mortality: a systematic review

Objective: To systematically review the medical literature on the association between glucose variability measures and mortality in critically ill patients. Methods: Studies assessing the association between a measure of glucose variability and mortality that reported original data from a clinical trial or observational study on critically ill adult patients were searched in Ovid MEDLINE (R) and Ovid EMBASE (R). Data on patient populations, study designs, glucose regulations, statistical approaches, outcome measures, and glucose variability indicators (their definition and applicability) were extracted. Result: Twelve studies met the inclusion criteria; 13 different indicators were used to measure glucose variability. Standard deviation and the presence of both hypo-and hyperglycemia were the most common indicators. All studies reported a statistically significant association between mortality and at least one glucose variability indicator. In four studies both blood glucose levels and severity of illness were considered as confounders, but only one of them checked model assumptions to assert inference validity. Conclusions: Glucose variability has been quantified in many different ways, and in each study at least one of them appeared to be associated with mortality. Because of methodological limitations and the possibility of reporting bias, it is still unsettled whether and in which quantification this association is independent of other confounders. Future research will benefit from using an indicator reference subset for glucose variability, metrics that are linked more directly to negative physiological effects, more methodological rigor, and/or better reportin

Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality

<p>Abstract</p> <p>Background</p> <p>In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection.</p> <p>Methods</p> <p>We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis.</p> <p>Results</p> <p>Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052).</p> <p>Conclusions</p> <p>Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.</p

International recommendations for glucose control in adult non diabetic critically ill patients

The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishedPour la Société Française d'Anesthésie-Réanimation (SFAR); Société de Réanimation de langue Française (SRLF) and the Experts grou