Kjerreimer0644

Purpose To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. Methods We recruited 10,245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. Results A total of 222,180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1. We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0201 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. Conclusions Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.Objectives Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal and other infections. We investigated the correlation between adenovirus viral load in clinical respiratory samples and the respiratory disease severity in pediatric patients. Methods Medical records of patients hospitalized in the Sheba Medical Center (SMC) with confirmed adenovirus infection were retrospectively analyzed. The possible correlation between disease severity score and Real time PCR 'cycle threshold' (Ct), a proxy of viral load, was assessed in patients aged 9 years and under. In addition, Ct values of hospitalized versus community-care patient samples, positive for various respiratory viruses including adenovirus, were compared. Results Adenovirus load in respiratory samples, as measured by Ct values, was found to be negatively correlated with respiratory disease severity in hospitalized pediatric patients aged under 9 years. Moreover, hospitalized patients presented with significantly higher Ct levels for various respiratory viruses as compared to community-care patients. Conclusion In this study we found a correlation between Ct values obtained from adenovirus q-PCR analysis of respiratory clinical samples and disease severity in patients aged 9 years and under. Such finding may serve as a predictor of respiratory disease course in pediatric patients and will be beneficial for the differential diagnosis and treatment of pediatric patients.Background To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). Methods Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. Results 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. Bezafibrate mouse 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR=1.5-5). Conclusions One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established.Background Facial emotion perception (FEP) is pivotal for discriminating salient emotional information. Accumulating data indicate that FEP responses, particularly to sad emotional stimuli, are impaired in depression. This study tests whether sleep disturbance and inflammation, two risk factors for depression, contribute to impaired FEP to sad emotional stimuli. Methods In older adults (n = 40, 71.7 ± 6.8y, 56.4% female), disturbance of sleep maintenance (i.e., wake time after sleep onset [WASO]) was evaluated by polysomnography. In the morning, plasma concentrations of two markers of systemic inflammation were evaluated (i.e., interleukin [IL]-6, tumor necrosis factor [TNF]-α), followed by two FEP tasks, which assessed delays in emotion recognition (ER) and ratings of perceived emotion intensity (EI) in response to sad facial emotional stimuli, with exploration of FEP responses to happiness and anger. Linear regression models tested whether WASO, IL-6, and TNF-α would be associated with impaired FEP to sad ehat sleep disturbance and inflammation converge and contribute to impaired FEP with implications for risk for late-life depression.Impaired extinction of pain-related fear memories can lead to persistent or resurging fear of pain, contributing to the development and maintenance of chronic pain conditions. The mechanisms underlying maladaptive pain-related learning and memory processes remain incompletely understood, particularly in the context of interoceptive, visceral pain. Inflammation is known to interfere with learning and memory, but its effects on the extinction of pain-related fear memories have never been tested. In a randomized, double-blind, placebo-controlled study, we assessed the impact of experimental acute inflammation on the extinction and reinstatement of conditioned visceral pain-related fear. Forty healthy male volunteers underwent differential fear conditioning with visceral pain as clinically relevant unconditioned stimulus (US). Participants then received an intravenous injection of either 0.8 ng/kg lipopolysaccharide (LPS) as inflammatory stimulus or physiological saline as placebo, and extinction training was conducted at the peak of the inflammatory response.