Gibbonsbrandstrup0098

Their circulating cholesterol concentrations were unchanged. In mice, there were no significant differences in serum cholesterol or corticosterone at 1-day or 1-week post-treatment compared to both pre-treatment baseline levels and control group levels. We conclude that acute dysregulation of the production of certain glucocorticoid precursor molecules was observed after a single treatment with a lipophilic statin drug. This may be of clinical relevance for individuals with underlying or subclinical adrenal insufficiency. © Georg Thieme Verlag KG Stuttgart · New York.Background Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT). Objective To determine the safety and efficacy of Triplex. Design First-in-patient, phase 2 trial. (ClinicalTrials.gov NCT02506933). Setting 3 U.S. HCT centers. Participants 102 CMV-seropositive HCT recipients at high risk for CMV reactivation. Intervention Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens. Xevinapant nmr Measurements The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injecd CMV viremia. Primary Funding Source National Cancer Institute and Helocyte.Background Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART). Objective To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis. Design Randomized controlled trial. (ClinicalTrials.gov NCT01348308). Setting Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20). Participants 416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE). Intervention C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks. Measurements The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher. Results 409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]). Limitations Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification. Conclusion Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection. Primary Funding Source INSERM-ANRS (French National Agency for Research on AIDS).Perennial ryegrass is an important feed base for the dairy and livestock industries around the world. It is often infected with mutualistic fungal endophytes that confer protection to the plant against biotic and abiotic stresses. link2 Bioassays that test their antibiotic effect on invertebrates are varied and range from excised leaves to whole plants. The aim of this study was to design and validate a "high-throughput" in-planta bioassay using 7-day-old seedlings confined in small cups, allowing for rapid assessments of aphid life history to be made while maintaining high replication and treatment numbers. Antibiosis was evaluated on the foliar and the root aphid species; Diuraphis noxia (Mordvilko) and Aploneura lentisci (Passerini) feeding on a range of perennial ryegrass-Epichloë festucae var. Lolii endophyte symbiota. As expected, both D. noxia and A. lentisci reared on endophyte-infected plants showed negatively affected life history traits by comparison to non-infected plants. Both species exhibited the highest mortality at the nymphal stage with an average total mortality across all endophyte treatments of 91% and 89% for D. noxia and A. lentisci respectively. Fecundity decreased significantly on all endophyte treatments with an average total reduction of 18% and 16% for D. noxia and A. lentisci respectively by comparison to non-infected plants. Overall, the bioassay proved to be a rapid method of evaluating the insecticidal activity of perennial ryegrass-endophyte symbiota on aphids (nymph mortality could be assessed in as little as 24 and 48 hours for D. noxia and A. lentisci respectively). This rapid and simple approach can be used to benchmark novel grass-endophyte symbiota on a range of aphid species that feed on leaves of plants, however we would caution that it may not be suitable for the assessment of root-feeding aphids, as this species exhibited relatively high mortality on the control as well.OBJECTIVE To analyze the effect of adjuvant oral application of honey for treating postoperative pain after tonsillectomy. DESIGN Single centre prospective cohort study. SETTING Two cohorts of patients after tonsillectomy. PARTICIPANTS 56 patients treated with honey 8 times per day (honey group), 18 patients treated without honey (control group); baseline analgesia were non-steroidal anti-inflammatory drugs (NSAID) or coxibs; opioids were used as pro re nata (PRN) medication; mean age 34.4 ± 13.4 years; 36% women. MAIN OUTCOME MEASURES On first to fifth postoperative day, patients rated their pain using the validated questionnaire of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including a numeric rating scale (NRS, 0-10) for determination of patient's pain. QUIPS allows standardized assessment of patients' characteristics andpain-associated patient-reported outcomes (PROs). The influence of preoperative and postoperative parameters on patients' postoperative pain were efifth postoperative day a higher risk of increased minimal pain (OR = -2.424, CI = -4.075 --0.385). Gender was an independent factor for compliance of honey consumption on the second postoperative day (p = 0.037). Men had a lower probability for compliance of honey consumption (OR = -0.288, CI = -2.863 --0.090). CONCLUSION There was a trend of reduced postoperative pain after oral honey application. Honey also seems to reduce pain-related impairments. The need for additional opioids on the first day could be reduced. A larger controlled trial is now needed to varify the effect of honey on pain after tonsillectomy. CLINICAL TRIAL REGISTRATION NUMBER German Clinical Trials Register DRKS00006153. The authors confirm that all ongoing and related trials for this drug/intervention are registered.The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions via actions at two G protein-coupled receptors MT1 and MT2. Circadian release of high nighttime levels of melatonin from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing physiology and behavior to the light-dark cycle1-4. The two receptors are established drug targets for aligning circadian phase in disorders of sleep5,6 and depression7,1-4,8,9. Despite their importance, few if any in vivo active MT1 selective ligands have been reported2,8,10-12, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked over 150 million virtual molecules against an MT1 crystal structure, prioritizing structural fit and chemical novelty. Thirty-eight high-ranking molecules were synthesized and tested, revealing ligands in the 470 pM to 6 μM range. Structure-based optimization led to two selective MT1 inverse agonists, topologically unrelated to previously explored chemotypes, that were tested in mouse models of circadian behavior. Unexpectedly, the MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3-1.5 hrs when given at subjective dusk, an agonist-like effect eliminated in MT1- but not in MT2-knockout mice. This study illustrates opportunities for modulating melatonin receptor biology via MT1-selective ligands, and for the discovery of new, in vivo-active chemotypes from structure-based screens of diverse, ultra-large libraries.AIM To validate the prognostic role of a panel of genes previously uncovered by our group to be specific targets of miRNAs differentially expressed in lung carcinoids with aggressive pathological features. METHODS Four genes, namely CREBP1, ACVR2B, LHX2 and KFL12, were identified in a previous study by our group using in silico analysis to be regulated by three miRNAs (miR-409-3p, miR-409-5p and miR-431-5p) which were shown to be down-regulated in aggressive lung carcinoids. These genes were analyzed using real-time PCR in a cohort of 102 lung carcinoids. Fifty high grade lung carcinomas served as control group. Their expression was correlated with the expression of miR-409-3p, miR-409-5p and miR-431-5p and with clinical pathological parameters and disease-free survival. RESULTS The expression of all but CREBP1 gene was significantly different between lung carcinoids and high grade neuroendocrine carcinomas. ACVR2B and LHX2 were significantly inversely correlated with miR-409-3p and miR-409-5p. High levels of ACVR2B and LHX2 were significantly associated with atypical histotype, high tumor grade and higher proliferation Ki-67 index (all p less then 0.05). Low levels of KLF12 were significantly associated with the presence of necrosis and positive nodal status (all p less then 0.05). Finally, low KLF12 expression was associated with shorter disease-free survival in lung carcinoids as a whole and in atypical carcinoids, only (all p less then 0.001). link3 CONCLUSIONS ACVR2B, LHX2 and KFL12 are novel potential biomarkers associated with aggressive features in lung carcinoids. © 2020 S. Karger AG, Basel.OBJECTIVE To investigate the prognostic values of the preoperative modified Glasgow Prognostic Score (mGPS) and carcinoembryonic antigen (CEA) alone and combined in elderly patients with colorectal cancer (CRC) planning to receive curative surgery. METHODS We retrospectively analyzed 130 elderly patients (aged ≥80 years) with CRC who received curative surgery between 2008 and 2016. The preoperative mGPS and CEA levels were calculated. RESULTS Elevated preoperative mGPS or CEA level was significantly associated with shorter relapse-free survival (p = 0.005, both) and cancer-specific survival (p = 0.011 and p less then 0.001, respectively). Combined use of these two factors improved the predictive accuracy for tumor recurrence relative to that of either factor. CONCLUSION Both mGPS and CEA were independent prognostic factors of CRC in elderly patients receiving curative surgery, but their combination was more accurate. © 2020 S. Karger AG, Basel.