Mutation in the mitochondrial tRNAIle gene causes progressive myoclonus epilepsy

PurposeThe group of the rare progressive myoclonic epilepsies (PME) include a wide spectrum of mitochondrial and metabolic diseases. In juvenile and adult ages, MERRF (myoclonic epilepsy with ragged red fibres) is the most common form. The underlying genetic defect in most patients with the syndrome of MERRF is a mutation in the tRNALys gene, but mutations were also detected in the tRNAPhe gene.MethodHere, we describe a 40 year old patient with prominent myoclonic seizures since 39 years of age without a mutation in the known genes who underwent intensive clinical, genetic and functional workup.ResultsThe patient had a slight mental retardation and a severe progressive hearing loss based on a defect of the inner ear on both sides. Ictal electroencephalography (EEG) showed bilateral occipital and generalized spikes and polyspikes induced and aggravated by photostimulation. A cranial magnetic resonance imaging (cMRI) detected a global cortical atrophy of the brain and mild periventricular white matter lesions. The electromyography (EMG) was normal but the muscle biopsy showed abundant ragged red fibres. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed a novel heteroplasmic mutation (m.4279A>G) in the tRNAIle gene which was functionally relevant as tested in single skeletal muscle fibre investigations.ConclusionMutations in tRNAIle were described in patients with chronic progressive external ophthalmoplegia (CPEO), prominent deafness or cardiomyopathy but, up to now, not in patients with myoclonic epilepsy. The degree of heteroplasmy of this novel mitochondrial DNA mutation was 70% in skeletal muscle but only 15% in blood, pointing to the diagnostic importance of a skeletal muscle biopsy also in patients with myoclonic epilepsy.     

The association between psychopathology of first-episode psychosis patients within the schizophrenia spectrum and previous offending

Patients with schizophrenia have been shown to have an increased risk of criminality. The aim was to describe possible psychopathological differences between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis. In a multi-centre study, 16 psychiatric treatment centres included and rated 477 patients with first-episode psychosis over a 2-year period on socio-demography, the Positive and Negative Syndrome Scale, OPerational CRITeria checklist, Global Assessment of Functioning, Premorbid Adjustment Scale and Self-report Insight Scale for psychosis. Data were linked with data concerning criminal and psychiatric history. No key characteristics were found to assist the early detection of criminal persons before first psychiatric hospital contact for a psychotic incident. However, when adjusted for sex, age, abuse, living conditions, marital status, employment status and education, a primarily positive symptomatology was associated with a prior criminal career. The premorbid level of functioning and several function parameters were also significantly associated with criminal history. There are significant differences in psychopathology between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis, and a better screening procedure in the judicial system could detect these individuals earlier and make adequate treatment possible.     

An exploratory study of health behaviors and the risks for triple H (hypertension,hyperlipidemia, and hyperglycemia) in young adults with disabilities between 20 and 39 years of age

Metabolic syndrome is highly prevalent and has important implications for the health care sector. However, information on the implications of metabolic syndrome for people with disabilities is limited. The purpose of this study was to explore the relationship between health behaviors and the risk for triple H (hypertension, hyperlipidemia, and hyperglycemia) in young adults with disabilities. The present study analyzed the annual health examination charts of 705 young adults with disabilities between ages 20 and 39 in Taiwan. Results found that the prevalence of hyperglycemia, hyperlipidemia, and hypertension in adults with disabilities was 5%, 15% and 17.7%, respectively. These prevalence figures were higher than those for the general population of the same age group in Taiwan. Multivariate logistic regression analyses revealed that almost none of the health behaviors were significantly correlated with the occurrence of triple H disorders among young adults with disabilities. Only one factor, BMI, independently predicted the occurrence of triple H disorders. We suggest that future studies should scrutinize the effects of health behaviors on triple-H disorders in people with disabilities to initiate personalize health promotion programs for this group.     

胰头切除治疗胰头部慢性胰腺炎不同术式疗效评价

 目的 探讨不同手术方式治疗胰头部慢性炎性反应的疗效。方法 回顾性分析长海医院、武警上海总队医院和上海市第七人民医院从2000-01至2015-01收治的145例胰头部慢性胰腺炎患者的临床资料和随访信息,比较各种手术方式的临床疗效。结果 术前伴有CA199升高、胰头肿块等怀疑恶变的患者多采用胰十二指肠切除术,术前伴有梗阻性黄疸、胰管结石等良性疾病的患者多采用保留十二指肠的胰头次全切除术,Beger术的总并发症率(P=0.040)和胆漏发生率(P=0.035),以及改良Beger术的总并发症率(P=0.035)和胆漏发生率(P=0.043)均高于改良Beger术联合胆肠吻合术式。结论 选择胰头部慢性胰腺炎患者的手术方式时应遵循个体化原则。改良Beger术联合胆肠吻合术式较Beger 术、改良Beger 术式更能减少胆漏的发生。     

广西壮族自治区2005-2021年新报告男男性行为人群HIV感染者晚发现及影响因素分析

目的分析广西壮族自治区(广西)防治艾滋病攻坚工程开展前后MSM HIV感染者(MSM感染者)的晚发现变化趋势及其影响因素, 从中寻找现阶段需要优先干预的人群。方法从中国疾病预防控制信息系统艾滋病防治基本信息系统中选取2005-2021年广西新报告的MSM感染者作为研究对象。采用Joinpoint 4.9.1.0软件对晚发现病例和非晚发现病例进行时间趋势检验, 运用logistic回归分析各阶段晚发现的影响因素。结果 2005-2021年广西新报告MSM感染者共5 764例, 晚发现比例为28.45%(1 640例)。以2015年为界, 晚发现比例呈先急速下降后趋于稳定的趋势, 平均年度变化百分比=-6.90%(P<0.001), 2010年后常住人口、职业为农民工和样本来源于就诊医疗等因素在攻坚工程开展前后对晚发现的影响效应变化较大, 现阶段晚发现的影响因素有年龄、常住人口、职业为农民工和学生。结论攻坚工程前后广西新报告MSM感染者的晚发现比例下降趋势明显, 但晚发现仍不容忽视, 需针对常住人口、农民工和学生人群开展精准防控。     

Cross sectional survey of Varicella-Zoster virus and measles seropositivity in people living with HIV in a Parisian suburb and a review of current immunization guidelines

According to evidence-based guidelines, vaccines against measles and varicella are generally recommended to susceptible HIV-positive patients, as long as they are not severely immunocompromised. However, routine screening to determine serologic status is not recommended. We conducted a seroprevalence study of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies in adults living with HIV (PLWHA) consulting at Avicenne University Hospital in a Parisian suburb. Sera were collected in years 2018–2020 and tested by commercial immunoassays in 268 patients. Most of the patients were born in Sub-Saharan Africa (55 %) and only 23 % in Europe. Measles and varicella seropositivity were present respectively in 91.4 % and 96.2 % of patients. One patient in ten was seronegative to at least one of tested diseases. In the univariate analysis, only younger age (p = 0.027) was associated with a higher risk of measles seronegativity, while shorter time since arrival in France (p < 0.001) and shorter time since HIV discovery (p = 0.007) were associated with a higher risk of VZV seronegativity. In multivariate analysis no association was found. This study highlights the absence of specific risk factors for VZV and measles seronegativity in PLWHA and supports the importance of routine screening, in order to increase immunization rates and reduce risk of complications.     

COVID-19 adenovirus vector vaccine induces higher interferon and pro-inflammatory responses than mRNA vaccines in human PBMCs,macrophages and moDCs

BackgroundDuring the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs).MethodsHuman PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells.ResultsAdenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells.ConclusionsAd-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.     

Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study

ObjectiveBiomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset.MethodsWe enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years.ResultsIn the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6–12 h), and 2,411 (12–24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL).ConclusionsThis study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.