Angiostrongylus cantonensis eosinophilic meningitis

AbstractIn the past 50 years, Angiostrongylus cantonensis, the most common cause of eosinophilic meningitis, has spread from Southeast Asia to the South Pacific, Africa, India, the Caribbean, and recently, to Australia and North America, mainly carried by cargo ship rats. Humans are accidental, “dead-end” hosts infected by eating larvae from snails, slugs, or contaminated, uncooked vegetables. These larvae migrate to the brain, spinal cord, and nerve roots, causing eosinophilia in both spinal fluid and peripheral blood. Infected patients present with severe headache, vomiting, paresthesias, weakness, and occasionally visual disturbances and extraocular muscular paralysis. Most patients have a full recovery; however, heavy infections can lead to chronic, disabling disease and even death. There is no proven treatment for this disease. In the authors' experience, corticosteroids have been helpful in severe cases to relieve intracranial pressure as well as neurologic symptoms due to inflammatory responses to migrating and eventually dying worms

Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb Repressive Complex 2 Components

Polycomb group (PcG) proteins are evolutionarily conserved in animals and plants, and play critical roles in the regulation of developmental gene expression. Here we show that the Arabidopsis Polycomb repressive complex 2 (PRC2) subunits CURLY LEAF (CLF), EMBRYONIC FLOWER 2 (EMF2) and FERTILIZATION INDEPENDENT ENDOSPERM (FIE) repress the expression of FLOWERING LOCUS C (FLC), a central repressor of the floral transition in Arabidopsis and FLC relatives. In addition, CLF directly interacts with and mediates the deposition of repressive histone H3 lysine 27 trimethylation (H3K27me3) into FLC and FLC relatives, which suppresses active histone H3 lysine 4 trimethylation (H3K4me3) in these loci. Furthermore, we show that during vegetative development CLF and FIE strongly repress the expression of FLOWERING LOCUS T (FT), a key flowering-time integrator, and that CLF also directly interacts with and mediates the deposition of H3K27me3 into FT chromatin. Our results suggest that PRC2-like complexes containing CLF, EMF2 and FIE, directly interact with and deposit into FT, FLC and FLC relatives repressive trimethyl H3K27 leading to the suppression of active H3K4me3 in these loci, and thus repress the expression of these flowering genes. Given the central roles of FLC and FT in flowering-time regulation in Arabidopsis, these findings suggest that the CLF-containing PRC2-like complexes play a significant role in control of flowering in Arabidopsis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Controlled Clinical Comparison of BacT/ALERT Standard Aerobic and Standard Anaerobic Blood Culture Bottles Inoculated Directly or after Transport in Sodium Polyanethol Sulfonate Tubes

To assess relative performances in the BacT/ALERT blood culture system, we compared results from the direct inoculation of standard media and inoculation after the transport of blood samples in Vacutainer tubes with sodium polyanethol sulfonate. No significant differences in yields or times to detection were found for 387 clinically important isolates from 4,306 blood culture sets

Predictors of sleep-disordered breathing in pregnancy

BACKGROUND:Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES:The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN:Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS:Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION:Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials

NuMoM2b Sleep-Disordered Breathing study: objectives and methods

OBJECTIVE: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. METHODS: nuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations, conducted across 8 sites, with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized Level 3 home sleep test was performed between 6(0)–15(0) weeks of pregnancy (Visit 1) and again between 22(0)–31(0) weeks of pregnancy (Visit 3). Scorings of tests were conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met “urgent referral” criteria based on threshold levels of apnea hypopnea indices, oxygen saturation levels or ECG abnormalities, but otherwise were not notified of test results. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes, fetal growth restriction, and preterm birth. RESULTS: Objective data were obtained at Visit 1 on 3261 women, 88.1% of studies attempted; and at Visit 3 on 2511 women, 87.6% of studies attempted. Basic characteristics of the substudy cohort are reported in this methods paper. CONCLUSION: The substudy is designed to address important questions regarding the relationship of sleep disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health

Association of Adverse Pregnancy Outcomes With Self-Reported Measures of Sleep Duration and Timing in Women Who Are Nulliparous.

Study objectivesTo examine the relationship of self-reported sleep during pregnancy with adverse pregnancy outcomes. A secondary objective was to describe the concordance between self-reported and objectively assessed sleep during pregnancy.MethodsIn this prospective cohort, women completed a survey of sleep patterns at 6 to 13 weeks' gestation (visit 1) and again at 22 to 29 weeks' gestation (visit 3). Additionally, at 16 to 21 weeks (visit 2), a subgroup completed a week-long sleep diary coincident with an actigraphy recording. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration &lt; 7 hours was defined as "short," and sleep midpoint after 5:00 AM was defined as "late." The relationship of these sleep abnormalities with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) was determined.ResultsOf the 10,038 women enrolled, sleep survey data were available for 7,524 women at visit 1 and 7,668 women at visit 3. A total of 752 women also provided ≥ 5 days of sleep diary data coincident with actigraphy at visit 2. We did not observe any consistent relationship between self-reported short sleep and HDP or GDM. There was an association between self-reported late sleep midpoint and GDM (visit 1 adjusted odds ratio 1.67, 95% confidence interval 1.17, 2.38; visit 2 adjusted odds ratio 1.73, 95% confidence interval 1.23, 2.43). At visit 2, 77.1% of participants had concordance between their diary and actigraphy for short sleep duration, whereas 94.3% were concordant for sleep midpoint.ConclusionsSelf-reported sleep midpoint, which is more accurate than self-reported sleep duration, is associated with the risk of GDM.Clinical trial registrationRegistry: ClinicalTrials.gov, Title: Pregnancy as a Window to Future Cardiovascular Health: Adverse Pregnancy Outcomes as Predictors of Increased Risk Factors for Cardiovascular Disease, Identifier: NCT02231398, URL: https://clinicaltrials.gov/ct2/show/NCT02231398

Association Between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus

ObjectiveTo estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM).MethodsIn this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models.ResultsThree thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM.ConclusionThere is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM