A Randomized Clinical Trial of Attempted Suicide Short Intervention Program versus Crisis Counseling in Preventing Repeat Suicide Attempts : A Two-Year Follow-Up Study

Introduction: The Attempted Suicide Short Intervention Program (ASSIP) is a brief psychotherapeutic intervention, and a pivotal study found it to be remarkably effective in reducing repeat suicide attempts. Objective: To compare the effectiveness of ASSIP to crisis counseling (CC) in a randomized clinical trial (ISRCTN13464512). Methods: Adult patients receiving treatment for a suicide attempt in a Helsinki City general hospital emergency room in 2016-2017 were eligible to participate. We excluded psychotic or likely non-adherent substance-abusing or substance-dependent patients. Eligible patients (n = 239) were randomly allocated to one of two interventions. (a) ASSIP comprised three visits, including a videotaped first visit, a case formulation, and an individualized safety plan, plus letters from the therapist every 3 months for 1 year, and then, every 6 months for the next year. (b) CC typically involved 2-5 (median 3) face-to-face individual sessions. In addition, all participants received their usual treatment. One and 2 years after baseline, information related to participants' suicidal thoughts and attempts, and psychiatric treatment received was collected via telephone and from medical and psychiatric records. Results: Among randomized patients, two-thirds initiated either ASSIP (n = 89) or CC (n = 72), with 73 (82%) completing ASSIP and 58 (81%) CC. The proportion of patients who attempted suicide during the 2-year follow-up did not differ significantly between ASSIP and CC (29.2% [26/89] vs. 35.2% [25/71], OR 0.755 [95% Cl 0.379-1.504]). Conclusions: We found no difference in the effectiveness of the two brief interventions to prevent repeat suicide attempts.Peer reviewe

Clinical and genetic spectrum of SCN2A-associated episodic ataxia

Background: Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability. Few reports have recently described SCN2A-associated episodic ataxia (EA). Our study identifies its broader clinical and genetic spectrum, and describes pharmacological approaches. Results: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases. The large majority of patients present with epileptic seizures (18/21, 86%), often starting within the first three months of life (12/18, 67%). In contrast, onset of episodic ataxia ranged from 10 months to 14 years of age. The frequency of EA episodes ranged from brief, daily events up to 1-2 episodes per year each lasting several weeks. Potential triggers include minor head traumas and sleep deprivation. Cognitive outcome is favorable in most patients with normal or mildly impaired cognitive development in 17/21 patients (81%). No clear genotype-phenotype correlations were identified in this cohort. However, two mutational hotspots were identified, i.e. 7/21 patients (33%) harbor the identical pathogenic variant p.A263V, whereas 5/21 (24%) carry pathogenic variants that affect the S4 segment and its cytoplasmic loop within the domain IV. In addition, we identified six novel pathogenic variants in SCN2A. While acetazolamide was previously reported as beneficial in SCN2A-associated EA in one case, our data show a conflicting response in 8 additional patients treated with acetazolamide: three of them profited from acetazolamide treatment, while 5/8 did not. Conclusions: Our study describes the heterogeneous clinical spectrum of SCN2A-associated EA, identifies two mutational hotspots and shows positive effects of acetazolamide in about 50%. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na+ current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.Peer reviewe

Pitfalls in genetic testing: the story of missed SCN1A mutations

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. METHODS: We sent out a survey to 16 genetic centers performing SCN1A testing. RESULTS: We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. CONCLUSION: We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

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The psychological development of children of epileptic parents. II. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors

After obtaining evidence that tetratogenic effects were operant in a sample of children born to epileptic mothers, we analyzed the effects of type of medication and further influential factors. Children with prenatal exposure to polytherapy had significantly lower scores than controls for a large number of psychological tests. In addition to polytherapy, there were even stronger effects of socioeconomic status and sex was found to be less influential than polytherapy. Among further epilepsy variables, only seizure frequency of the mother during pregnancy had a modest impact on the child's developmental outcome, whereas a score of obstetric abnormality was less effective in predicting developmental outcome, as measured and defined by various standardized psychological tests

Kinetic modeling of the simultaneous production of ethanol and fructose by Saccharomyces cerevisiae

Background: Ethanol and fructose are two important industrial products that enjoy many uses. In this contribution, their production via selective fermentation of date extract using Saccharomyces cerevisiae was studied. Scaling up the process for possible commercialization was investigated in three fermentors with working volume ratio of 1:40:400. Results: Higher ethanol concentration was obtained in the larger fermentor due to conversion of fructose. Fructose yields in the 0.5-L, 7.5-L and 80-L fermentors were 99, 92 and 90%, respectively. Good fitting was obtained with the modified Monod kinetics; however, a better fit of cell mass was obtained with the modified Ghose–Tyagi model which accounts for ethanol inhibition. Conclusions: The modified Gompertz model was expanded to facilitate prediction of products' formation and fructose fractions in all three fermentors. Such expansion will be beneficial in industrial applications.How to cite: Sulieman AK, Putra MD, Abasaeed AE, et al. Kinetic modeling of the simultaneous production of ethanol and fructose by Saccharomyces cerevisiae. Electron J Biotechnol 2018;34. https://doi.org/10.1016/j.ejbt.2018.04.006. Keywords: Bioreactor, Biosynthesis of ethanol, Ethanol, Fermenters, Fructose, Kinetic modeling, Kinetic models for ethanol biosynthesis, Kinetic models for fructose biosynthesis, Microbiological biosynthesis, Saccharomyces cerevisiae, Yeas