De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females

Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity.     

Epidemiology and natural history of hepatitis C virus infection among children and young people

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J波与J波综合征

J波是指心电图上QRS波与ST段之间的圆顶状或驼峰状电位变化。新近临床研究表明，在早期复极综合征、Brugada综合征和特发性心室颤动等心电图中，均存在J波形态、时限和幅度的显著改变，上述与J波密切相关的一系列临床综合征统称为J波综合征。本文详尽阐述了J波的细胞电生理和离子流机制，分析了早期复极综合征、Brugada综合征、心电图下壁导联高大J波相关的心脏性猝死的临床特点及内在机制。     

The effect of diaries written by relatives for intensive care patients on posttraumatic stress (DRIP study): protocol for a randomized controlled trial and mixed methods study

Background

Critically ill patients and their relatives have complex needs for support during their stay in the intensive care unit (ICU) and the post-ICU rehabilitation period. Diaries written by nurses have proven beneficial for patients and relatives, preventing post-traumatic stress, anxiety and depression and helping patients and families find meaning. Actively involving relatives in writing a diary for critically ill patients is a new approach to helping relatives and patients cope; however, research is limited.The aim of this study is to test the hypothesis that a diary written by a close relative of a critically ill patient will reduce the risk of developing symptoms of post-traumatic stress disorder (PTSD) in the patient and relatives at 3 months post-ICU. Furthermore, the aim is to explore the perceptions and use of the diary and describe the diary content and structure.

Method

The intervention consists of a hard-cover notebook that will be given to a close relative to write a diary for the critically ill patient while in the ICU. Guidance will be offered by ICU nurses on how to author the diary. The effect of the intervention will be tested in a two-arm, single-blind, randomized controlled trial, which aims to include 100 patient/relative pairs in each group. The primary outcome studied is symptoms of post-traumatic stress (PTSS-14). Secondary outcomes are scores on anxiety and depression (HADS) and the Medical Outcomes Study Questionnaire Short Form 36 (SF-36). The narrative structure and content of the diary as well as its use will be explored in two qualitative studies.

Discussion

The results of this study will inform ICU nurses about the effects, strengths and limitations of prompting relatives to author a diary for the patient. This will allow the diary intervention to be tailored to the individual needs of patients and relatives.

Trial registration

NCT02357680. Registered September 3, 2015.

     

Screening for risk of violence using service users’ self‐perceptions: A prospective study from an acute mental health unit

Service users’ self‐perception of risk has rarely been emphasized in violence risk assessments. A recent review pointed to the importance of a multidisciplinary approach, because different perspectives may provide a deeper and improved understanding of risk assessment. The aim of this study was to investigate service users’ perceptions of their own risk of committing violence, using a self‐report risk scale, to determine the feasibility and efficacy of this potential violence risk marker during acute mental health hospitalization. All service users admitted to a psychiatric emergency hospital in Norway during one calendar year were included (N = 512). Nearly 80% self‐reported no risk or low risk; only seven (1.4%) reported moderate risk or high risk. Service users who reported moderate risk, high risk, don't know, or won't answer were more likely to be violent (OR = 4.65, 95% CI = 2.79–7.74) compared with those who reported no risk or low risk. There was a significant gender interaction with higher OR for women on both univariate and multivariate analyses. Although the OR was higher for women, women's violence rate (11.0%) was almost half that of men (21.8%). For women, sensitivity and specificity were 0.55 and 0.88, respectively; corresponding values for men were 0.40 and 0.80. Inclusion of self‐perception of violence risk is the first step towards service users’ collaborative involvement in violence prediction; these results indicate that self‐perception can contribute to violence risk assessments in acute mental health settings. Findings also indicate that there are gender differences in these assessments.