Estimates of the Costs and Benefits of Expanding the Early Childhood Education Program in Kentucky

Excerpt from the executive summary: Kentucky officials are being encouraged to expand the availability of Kentucky’s state-funded preschool program. The current program restricts eligibility to three- and four-year-old students with disabilities and four-year-old students with family incomes up to 150 percent of the federal poverty level

LipidFinder: a computational workflow for discovery of lipids identifies eicosanoid-phosphoinositides in platelets

Accurate and high-quality curation of lipidomic datasets generated from plasma, cells, or tissues is becoming essential for cell biology investigations and biomarker discovery for personalized medicine. However, a major challenge lies in removing artifacts otherwise mistakenly interpreted as real lipids from large mass spectrometry files (>60 K features), while retaining genuine ions in the dataset. This requires powerful informatics tools; however, available workflows have not been tailored specifically for lipidomics, particularly discovery research. We designed LipidFinder, an open-source Python workflow. An algorithm is included that optimizes analysis based on users’ own data, and outputs are screened against online databases and categorized into LIPID MAPS classes. LipidFinder outperformed three widely used metabolomics packages using data from human platelets. We show a family of three 12-hydroxyeicosatetraenoic acid phosphoinositides (16:0/, 18:1/, 18:0/12-HETE-PI) generated by thrombin-activated platelets, indicating crosstalk between eicosanoid and phosphoinositide pathways in human cells. The software is available on GitHub (https://github.com/cjbrasher/LipidFinder), with full userguides

Efficacy of Intraoperative Dexmedetomidine Compared with Placebo for Postoperative Pain Management: A Meta-Analysis of Published Studies

INTRODUCTION: Dexmedetomidine (Dex) has sedative, analgesic, and anesthetic-sparing effects. This meta-analysis examines demonstrated intraoperative and postoperative effects of intraoperative Dex administration during pediatric surgery. METHODS: A search for randomized placebo-controlled trials was conducted to identify clinical trials examining intraoperative Dex use in children, infants, and neonates. Primary outcome was postoperative opioid consumption; secondary outcomes were: postoperative pain intensity and postoperative nausea and vomiting (PONV). RESULTS: Fourteen randomized controlled trials performed during painful procedures were analyzed. Intraoperative Dex administration was associated with significantly reduced postoperative opioid consumption in the postanesthesia care unit [PACU; risk ratio (RR) = 0.31 (0.17, 0.59), I (2) = 76%, p < 0.0001 and cumulative z score using trial sequential analysis], decreased pain intensity in PACU [standardized mean difference (SMD) = -1.18 (-1.88, -0.48), I (2) = 91%, p < 0.0001] but had no effect upon PONV incidence [RR = 0.67 (0.41, 1.08), I (2) = 0%, p = 0.48]. Subgroup analyses found administering Dex during adenotonsillectomy and using a bolus <0.5 µg/kg (irrespective to the use of a continuous administration) without effects on studies outcomes. Heterogeneity was high among results and a high suspicion of publication bias was present for all analyzed outcomes. CONCLUSIONS: This meta-analysis shows that intraoperative Dex administration in children reduces postoperative opioids consumption and postoperative pain in PACU. According to our results, optimal bolus dose was found to be ≥0.5 µg/kg. Future studies have to explore this particular point and the postoperative analgesic effects of Dex during longer periods

LipidFinder on LIPID MAPS: peak filtering, MS searching and statistical analysis for lipidomics

Summary We present LipidFinder online, hosted on the LIPID MAPS website, as a liquid chromatography/mass spectrometry (LC/MS) workflow comprising peak filtering, MS searching and statistical analysis components, highly customized for interrogating lipidomic data. The online interface of LipidFinder includes several innovations such as comprehensive parameter tuning, a MS search engine employing in-house customized, curated and computationally generated databases and multiple reporting/display options. A set of integrated statistical analysis tools which enable users to identify those features which are significantly-altered under the selected experimental conditions, thereby greatly reducing the complexity of the peaklist prior to MS searching is included. LipidFinder is presented as a highly flexible, extensible user-friendly online workflow which leverages the lipidomics knowledge base and resources of the LIPID MAPS website, long recognized as a leading global lipidomics portal

Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation

Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via β-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presente

Community coverage of an antimalarial combination of artesunate and amodiaquine in Makamba Province, Burundi, nine months after its introduction

BACKGROUND: In 2003, artesunate-amodiaquine (AS+AQ) was introduced as the new first-line treatment for uncomplicated malaria in Burundi. After confirmed diagnosis, treatment was delivered at subsidized prices in public health centres. Nine months after its implementation a study was carried out to assess whether children below five years of age with uncomplicated malaria were actually receiving AS+AQ. METHODS: A community-based study was conducted in Makamba province. Randomly selected households containing one or more children under five with reported fever onset within fourteen days before the study date were eligible. Case-management information was collected based on caregiver recall. A case definition of symptomatic malaria from observations of children presenting a confirmed malaria episode on the day of the survey was developed. Based on this definition, those children who had probable malaria among those with fever onset in the 14 days prior to the study were identified retrospectively. Treatment coverage with AS+AQ was then estimated among these probable malaria cases. RESULTS: Out of 195 children with fever on the day of the study, 92 were confirmed as true malaria cases and 103 tested negative. The combination of 'loss of appetite', 'sweating', 'shivering' and 'intermittent fever' yielded the highest possible positive predictive value, and was chosen as the case definition of malaria. Out of 526 children who had had fever 14 days prior to the survey, 165 (31.4%) were defined as probable malaria cases using this definition. Among them, 20 (14.1%) had been treated with AS+AQ, 10 with quinine (5%), 68 (41%) received non-malaria treatments, and 67 got traditional treatment or nothing (39.9%). Most people sought treatment from public health centres (23/99) followed by private clinics (15/99, 14.1%). The median price paid for AS+AQ was 0.5 US$. CONCLUSION: AS+AQ was the most common treatment for patients with probable malaria at public health centres, but coverage was low due to low health centre utilisation and apparently inappropriate prescribing. In addition, AS+AQ was given to patients at a price ten times higher than the subsidized price. The availability and proper use of ACTs should be monitored and maximized after their introduction in order to have a significant impact on the burden of malaria

Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7

French current practice for ambulatory anesthesia in children: a survey among the French-speaking Pediatric Anesthesiologists Association (ADARPEF)

International audienceBackground: This survey aims to describe current practice in ambulatory care among pediatric anesthesiologists in France. Methods: Members of the French-speaking Pediatric Anesthesiologists Association (ADARPEF) were sent a questionnaire examining the proportion of pediatric ambulatory anesthesia practiced by each responder, the level of adherence to pediatric ambulatory anesthesia guidelines, and responder consensus in decision making when faced with common case scenarios in pediatric ambulatory anesthesia. For the latter, consensus was defined as a >80 % opinion. Results: 145 pediatric anesthesiologists replied (43%). Ambulatory anesthesia appears underused in France. Recent French pediatric ambulatory anesthesia guidelines are being applied. Post operative pain is poorly managed. The choice of scheduling children for ambulatory anesthesia appears to be more heavily influenced by practitioners' subjective evaluation than evidence from the literature. Conclusion: Further studies are required to establish evidence-based guidelines that would allow one to select children safely for ambulatory surgery