The cellular location of IRF2BPL was altered, and compared to control cells, the level of ubiquitinated proteins was significantly decreased in cells harbouring the mutation.
 
  In this study, we identified a truncating de novo variant of IRF2BPL as a causative gene in the neurodevelopmental disorder of a Chinese girl. Impairment of the ubiquitin-proteasome pathway caused by this IRF2BPL mutation may play an important role in this neurodevelopmental disorder.
 In this study, we identified a truncating de novo variant of IRF2BPL as a causative gene in the neurodevelopmental disorder of a Chinese girl. Impairment of the ubiquitin-proteasome pathway caused by this IRF2BPL mutation may play an important role in this neurodevelopmental disorder.
  This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE).
 
  Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed.
 
  Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI] 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants.
 
  This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology.
 This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology.This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3-21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.
  Methods for prognosis assessment and patient management in acute pulmonary embolism (PE) are much debated among physicians. We conducted an online survey to determine physician's attitudes and barriers towards the use of prognostic models when treating patients with acute PE.
 
  Physicians members of the French and the European scientific societies for emergency medicine or of a French thrombosis research network were reached by their respective scientific societies and invited to participate via email. The questionnaire was a mixture of close-ended with yes-no or multiple-choice options and a small number of open-ended questions.
 
  The survey included 461 respondents. The most commonly used prognostic tools were clinical judgment (36%) and prognostic models (29.5%). Prognostic models were used by 57% of respondents in more than half of all cases and prognostic indicators by 62% in addition to prognostic models. Affiliation group and type of hospital emerged as independent predictors for choosing prognostic models.  https://www.selleckchem.com/products/quinine-dihydrochloride.html  Many (52%) reported lack of familiarity with the models and reported clinical judgment (60%) or hospital checklists (73%) as being as good as or better than prognostic models. The highest acceptable 30-day mortality rate limit for early discharge or outpatient management was deemed to be 1%, but few patients are discharged early or completely managed on an outpatient basis.
 
  This survey provides new information for implementing knowledge translation strategies to improve prognostic risk assessment for acute PE patients, and highlights the need for considering the use of clinical judgment and hospital checklists in future clinical research.
 This survey provides new information for implementing knowledge translation strategies to improve prognostic risk assessment for acute PE patients, and highlights the need for considering the use of clinical judgment and hospital checklists in future clinical research.