Comment on "Information management in DNA replication modeled by directional, stochastic chains with memory" [J. Chem. Phys. 145, 185103 (2016)]

Arias-Gonzalez, JR.; Aleja, D. (2020). Comment on "Information management in DNA replication modeled by directional, stochastic chains with memory" [J. Chem. Phys. 145, 185103 (2016)]. The Journal of Chemical Physics. 152(4):1-2. https://doi.org/10.1063/1.5140055S121524Arias-Gonzalez, J. R. (2016). Information management in DNA replication modeled by directional, stochastic chains with memory. The Journal of Chemical Physics, 145(18), 185103. doi:10.1063/1.4967335The Journal of Chemical Physics14518185103201

BRIVA-LIFE–A multicenter retrospective study of the long-term use of brivaracetam in clinical practice

Objectives: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. Materials and Methods: This was a multicenter retrospective study. Patients aged =16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. Results: A total of 575 patients were included in analyses; most had been treated with =4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were =50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged =65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. Conclusions: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam

OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes

Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres. Most remarkably, we demonstrate that these patients all harboured multiple deletions of mitochondrial DNA (mtDNA) in their skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. The five OPA1 mutations associated with these DOA ‘plus’ phenotypes were all mis-sense point mutations affecting highly conserved amino acid positions and the nuclear genes previously known to induce mtDNA multiple deletions such as POLG1, PEO1 (Twinkle) and SLC25A4 (ANT1) were ruled out. Our results show that certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability

Accelerated forgetting in temporal lobe epilepsy:When does it occur?

Objective: the main goal of the study was to analyse differences in the forgetting rates of Temporal Lobe Epilepsy (TLE) patients at different intervals (30 sec, 10 min, 1 day and 1 week) compared with those of healthy controls. A secondary aim of this research was to provide an assessment of the relationship between clinical epilepsy-related variables and forgetting rates in TLE patients. Method: the sample was composed of 14 TLE patients and 14 healthy matched controls. All participants underwent a full standardised neuropsychological assessment including general intelligence, executive functioning, memory, language and other variables, such as depression, anxiety or everyday memory failures. Two specific memory tasks, consisting of cued recall of 4 short stories and 4 routes, were carried out at four different intervals. Results: there was a significant difference between groups at 10-min interval on the stories task, with the TLE group displaying greater forgetting than healthy controls. None of the other intervals on either task showed significant group differences. No differences were found when controlling for clinical epilepsy-related variables. Conclusion: forgetting of verbal information at 10 min was greater in patients with TLE compared with controls, but accelerated longer term forgetting was not found. This study suggests that a late consolidation process is not necessarily impaired in TLE patients.Israel Contador was supported by a post-doc fellowship (JC 2011-0012) from the Spanish Ministry of Education

Why Are There Six Degrees of Separation in a Social Network?

A wealth of evidence shows that real-world networks are endowed with the small-world property, i.e., that the maximal distance between any two of their nodes scales logarithmically rather than linearly with their size. In addition, most social networks are organized so that no individual is more than six connections apart from any other, an empirical regularity known as the six degrees of separation. Why social networks have this ultrasmall-world organization, whereby the graph’s diameter is independent of the network size over several orders of magnitude, is still unknown. We show that the “six degrees of separation” is the property featured by the equilibrium state of any network where individuals weigh between their aspiration to improve their centrality and the costs incurred in forming and maintaining connections. We show, moreover, that the emergence of such a regularity is compatible with all other features, such as clustering and scale-freeness, that normally characterize the structure of social networks. Thus, our results show how simple evolutionary rules of the kind traditionally associated with human cooperation and altruism can also account for the emergence of one of the most intriguing attributes of social networks

OPA 1 mutations induce mitochondrial DNA instability and optic atrophy "plus" phenotypes

Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres. Most remarkably, we demonstrate that these patients all harboured multiple deletions of mitochondrial DNA (mtDNA) in their skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. The five OPA1 mutations associated with these DOA 'plus' phenotypes were all mis-sense point mutations affecting highly conserved amino acid positions and the nuclear genes previously known to induce mtDNA multiple deletions such as POLG1, PEO1 (Twinkle) and SLC25A4 (ANT1) were ruled out. Our results show that certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability