Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy

The impact of SARS-CoV-2 vaccination in Dravet Syndrome: A UK survey

Background: The COVID-19 pandemic led to the urgent need for accelerated vaccine development. Approved vaccines have proved to be safe and well tolerated across millions of people in the general population. Dravet Syndrome (DS) is a severe, early onset, developmental and epileptic encephalopathy. Vaccination is a precipitating factor for seizures. Whilst there is no evidence that vaccine-precipitated seizures lead to adverse outcomes in people with DS, fear surrounding vaccination can remain for caregivers of people with DS, in some cases resulting in rejection of recommended vaccinations, leaving individuals more vulnerable to the relevant infections. A greater understanding of the safety profile of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in this vulnerable group will help provide guidance for caregivers and clinicians when considering vaccination. / Methods: A cross‐sectional survey regarding COVID-19 and SARS-CoV-2 vaccine, in people with DS, was conducted by Dravet Syndrome UK (DSUK). Concomitantly, a review of individuals with DS who had recently received the SARS-CoV-2 vaccine, and who are resident at the Chalfont Centre for Epilepsy (CCE), or attend epilepsy clinics at the National Hospital for Neurology and Neurosurgery (NHNN), was undertaken. / Results: 38 people completed the DSUK survey. 37% of caregivers reported being concerned about someone with DS receiving the SARS-CoV-2 vaccine; with some reporting that they would decline a vaccine when offered. 77% had not received any advice from a health care professional about the SARS-CoV-2 vaccination. 18/38 were eligible for SARS-CoV-2 vaccination, of whom nine had received their first vaccine dose. Combining the results of the DSUK survey and the review of individuals monitored at CCE or NHNN, fifteen people with DS had received their first dose of the SARS-CoV-2 vaccine. 11/15 (73%) reported at least one side effect, the most common being fatigue (6/15; 40%) and fever (6/15; 40%). Three individuals (20%) reported an increase in seizure frequency after the first vaccine dose. No increase in seizure frequency or duration was reported after the second dose. / Conclusion: Overall, these results suggest that SARS-CoV-2 vaccines are safe and well tolerated in individuals with DS, as they are in most people without DS. In most people with DS, SARS-CoV-2 vaccine does not appear to be associated with an increase in the frequency or duration of seizures, even in those who develop fever post-vaccination. Many caregivers are concerned about a person with DS receiving a SARS-CoV-2 vaccine, with some reporting that they would decline a SARS-CoV-2 vaccine when offered. It is crucial that healthcare professionals are proactive in providing accurate information regarding the risks and benefits of vaccination in this population, given the potential for serious outcomes from infection

Tubular aggregates caused by serine active site containing 1 (SERAC1) mutations in a patient with a mitochondrial encephalopathy.

Tubular aggregates (TAs) are cytoplasmic aggregates of membranous tubules derived from the sarcoplasmic reticulum and usually 50–70 nm in diameter [1]. They may be seen in a range of genetic myopathies, including gyrate atrophy caused by ornithine aminotransferase deficiency, periodic paralysis and two disorders of glycosylation caused by mutations in the GFPT1 and DPAGT1 genes [2,3]. In addition, they may occur as a minor or inconsistent feature in a wide range of myopathies or be the predominant feature in idiopathic or congenital myopathies [4]. However, the mechanisms underlying TA formation remain poorly understood. We now report the development of TAs in a patient with a lipid remodelling disorder, providing new insight into the formation of TAs

Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice

<p>Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice</p

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (&lt;i&gt;Xiphophorus helleri&lt;/i&gt;) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Massively Parallel Sequencing Reveals the Complex Structure of an Irradiated Human Chromosome on a Mouse Background in the Tc1 Model of Down Syndrome

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439