Fusion of the Mycobacterium tuberculosis Antigen 85A to an Oligomerization Domain Enhances Its Immunogenicity in Both Mice and Non-Human Primates

To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4+ and CD8+ T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability

The Use of Continuous Ketamine for Analgesia and Sedation in Critically Ill Patients with Opioid Abuse: A Case Series

Managing pain and agitation in patients with opioid abuse is becoming more common in intensive care units. Tolerance to commonly used agents is often observed, leading to inadequate pain control and increased agitation. Ketamine’s unique mechanism of action and opioid-sparing effects make it an ideal agent for patients with suboptimal response to opioid therapy

Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs) may cause delirium and over-sedation. Phenobarbital (PBT) is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group) or BZDs with adjunctive PBT (PBT-adjunct group). The patients received at least one dose of PBT in addition to BZDs (variable doses) in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6%) in the PBT-adjunct group and 5 patients (23.8%) in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588). The median (IQR) duration of withdrawal symptoms was 44 (12-62) hours in the PBT-adjunct group compared to 53 (37-87) hours in the BZD only group, with no significant difference between the groups (P = 0.249). The median (IQR) cumulative BZD dose requirement (diazepam equivalent) in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226) vs. 326 (160-550) mg, P = 0.02). Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing

The effectiveness of an online intervention in preventing excessive gestational weight gain: the e-moms roc randomized controlled trial

Abstract Background Excessive gestational weight gain (GWG) is common and contributes to the development of obesity in women and their offspring. Electronic or e-health interventions have the potential to reach large groups of women and prevent excessive GWG, but their effectiveness has not been demonstrated. The purpose of this study was to evaluate, in a real-world setting, the effectiveness of a self-directed, integrated online and mobile phone behavioral intervention in preventing excessive GWG. Methods This effectiveness trial was a double-blind, three-arm trial with a parallel group design. Two arms received the same e-health intervention during pregnancy with the third arm serving as the placebo control. The intervention was based on a previously efficacious non-digital intervention that was adapted to electronic format. It included three behavior change tools: a weight gain tracker, and separate diet and physical activity goal-setting and self-monitoring tools. Both treatment conditions received access to informational tools, event reminders, and a blogging feature. Healthy pregnant women age 18-35 years with body mass indexes (BMI) ≥18.5 and < 35, at ≤20 weeks gestation, and an e-mail address were eligible. The proportion of women with excessive total GWG, as defined by the Institute of Medicine (IOM), was the primary outcome. 1689 randomized women were analyzed in the intent-to-treat (ITT) analysis. The study was designed to have 87% power to detect a 10 percentage point reduction from a control rate of 55% with a sample of 1641 (p = 0.0167, two-sided). Results In the ITT sample, 48.1% (SD = 2.0%) gained excessively in the intervention group as did 46.2% (SD = 2.4%) in the placebo control group. These proportions were not significantly different (RR 1.09; 95% CI 0.98, 1.20, p = 0.12). The results were not altered in several sensitivity analyses. Conclusion The addition of three behavior change tools to an informational placebo control did not result in a difference in the proportion of women with excessive total GWG compared to the placebo control in this effectiveness trial of an online, self-directed intervention. The similarity of intervention and control treatments and low usage of the behavior change tools in the intervention group are possible explanations. Trial registration NCT01331564, ClinicalTrials.gov

Pan genome of the phytoplankton Emiliania underpins its global distribution

Coccolithophores have influenced the global climate for over 200 million years1. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems2. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering themvisible fromspace3.Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean4. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate thatE. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions