Cano-de-la-Cuerda R, Rev Neurol. 2016 Jul 16;63(2):79-84.
[Article in Spanish]
Neurorehabilitation is understood as the process intended to reduce the deficiency, limitation of activity and restriction of participation experienced by people as a result of a neurological diseases, and where the professionals involved in this field will aim to reduce the functional involvement degree of the patient.
Tuesday, July 19, 2016
Sunday, July 17, 2016
Cerebellar Dysfunction and Ataxia in Patients with Epilepsy: Coincidence, Consequence, or Cause?
Filip P, Bareš M, Brázdil M.; Tremor Other Hyperkinet Mov. 2016; 6. doi: 10.7916/D8KH0NBT
Open-access (article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License.)
Other spinocerebellar ataxias might also be accompanied by epilepsy, although this is probably a coincidence. There was a case report of mesiotemporal epilepsy in an SCA13 patient and one of nocturnal frontal lobe epilepsy in an SCA17 patient. There was also a description of epilepsy in patients with Friedreich ataxia. A list of all possible conditions exceeds the scope of this article.
Open-access (article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License.)
Other spinocerebellar ataxias might also be accompanied by epilepsy, although this is probably a coincidence. There was a case report of mesiotemporal epilepsy in an SCA13 patient and one of nocturnal frontal lobe epilepsy in an SCA17 patient. There was also a description of epilepsy in patients with Friedreich ataxia. A list of all possible conditions exceeds the scope of this article.
Saturday, July 16, 2016
Stalled DNA Replication Forks at the Endogenous GAA Repeats Drive Repeat Expansion in Friedreich’s Ataxia Cells
Jeannine Gerhardt, Angela D. Bhalla, Jill Sergesketter Butler, James W. Puckett, Peter B. Dervan, Zev Rosenwaks, Marek Napierala, Cell Reports, Available online 14 July 2016, ISSN 2211-1247, doi:10.1016/j.celrep.2016.06.075.
Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3′-5′ progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases.
Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3′-5′ progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases.
Thursday, July 14, 2016
Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy
Nishimura Yuhei, Sasagawa Shota, Okabe Shiko, Murakami Soichiro, Ashikawa Yoshifumi, Yuge Mizuki, Kawaguchi Koki, Kawase Reiko, Okamoto Ryuji, Ito Masaaki, TANAKA TOSHIO; Front. Pharmacol., 14 June 2016, doi:10.3389/fphar.2016.00162
Open-access (article distributed under the terms of the Creative Commons Attribution License).
HCM has multiple etiologies, including mutation in sarcomeric genes such as myosin heavy chain 7 (MYH7) and tropomyosin 1 (TPM1) and in non-sarcomeric genes such as PLN and FXN.Haploinsufficiency of FXN is a major cause of FA. FA is associated with progressive HCM, and this is a common cause of death in FA patients. FXN is an iron-binding protein targeted to the mitochondrial matrix, and consistent with this, mitochondrial function is impaired in FA. Comparative transcriptomics could represent a new frontier in the search for novel biomarkers and/or therapeutic targets in diseases with multiple etiologies because it facilitates the identification of dysregulated genes common to all disease etiologie. We identified five genes dysregulated in all five HCM transcriptome datasets, among which glutathione S-transferase kappa 1 (Gstk1) was the only gene downregulated. We demonstrate here that knockout of gstk1 in zebrafish increased the expression of HCM marker genes and decreased the cardiac EDV and, to a lesser extent, the ESV, suggesting that downregulation of GSTK1 may be a common mechanism underlying HCM of various etiologies.
Open-access (article distributed under the terms of the Creative Commons Attribution License).
HCM has multiple etiologies, including mutation in sarcomeric genes such as myosin heavy chain 7 (MYH7) and tropomyosin 1 (TPM1) and in non-sarcomeric genes such as PLN and FXN.Haploinsufficiency of FXN is a major cause of FA. FA is associated with progressive HCM, and this is a common cause of death in FA patients. FXN is an iron-binding protein targeted to the mitochondrial matrix, and consistent with this, mitochondrial function is impaired in FA. Comparative transcriptomics could represent a new frontier in the search for novel biomarkers and/or therapeutic targets in diseases with multiple etiologies because it facilitates the identification of dysregulated genes common to all disease etiologie. We identified five genes dysregulated in all five HCM transcriptome datasets, among which glutathione S-transferase kappa 1 (Gstk1) was the only gene downregulated. We demonstrate here that knockout of gstk1 in zebrafish increased the expression of HCM marker genes and decreased the cardiac EDV and, to a lesser extent, the ESV, suggesting that downregulation of GSTK1 may be a common mechanism underlying HCM of various etiologies.
Wednesday, July 13, 2016
Big Data in medical research and EU data protection law: challenges to the consent or anonymise approach
Mostert M, Bredenoord AL, Biesaart MC, van Delden JJ., European Journal of Human Genetics (2016) 24, 956–960; doi:10.1038/ejhg.2015.239; published online 11 November 2015
In recent years, both medical research and the legal landscape have been changing as a result of the rapid developments in information technology (IT). Medical researchers are collecting, re-using and linking health-related and genomic data on an unprecedented scale, based on the presupposition that this research will significantly improve human health. Developments in IT have however led to an increasing concern about the effectiveness of existing data protection law, and the need for a more consistent and comprehensive protection of personal data was recognised in the European Union (EU).
In recent years, both medical research and the legal landscape have been changing as a result of the rapid developments in information technology (IT). Medical researchers are collecting, re-using and linking health-related and genomic data on an unprecedented scale, based on the presupposition that this research will significantly improve human health. Developments in IT have however led to an increasing concern about the effectiveness of existing data protection law, and the need for a more consistent and comprehensive protection of personal data was recognised in the European Union (EU).
Tuesday, July 12, 2016
The role of R-loops in the pathology of trinucleotide expansion diseases
Matthias Groh, Natalia Gromak (Supervisor), Thesis, ORA Oxford University Research Archive
Friedreich ataxia and fragile X syndrome are among 40 human diseases associated with expansion of repeated DNA sequences. In both disorders repeat expansion leads to gene silencing, the molecular mechanism of which is not well understood.
Friedreich ataxia and fragile X syndrome are among 40 human diseases associated with expansion of repeated DNA sequences. In both disorders repeat expansion leads to gene silencing, the molecular mechanism of which is not well understood.
Monday, July 11, 2016
Vestibulo-ocular reflex dynamics with head-impulses discriminates spinocerebellar ataxias types 1, 2 and 3 and Friedreich ataxia
Luis, L., Costa, J., Muñoz, E., de Carvalho, M., Carmona, S., Schneider, E., Gordon, C.R., Valls-Solé, J.; Journal of Vestibular Research, vol. 26, no. 3, pp. 327-334, 2016, DOI: 10.3233/VES-160579
Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity.
Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity.
Sunday, July 10, 2016
Friedreich’s ataxia and Advanced Heart Failure: An Ethical Conundrum in Decision Making
Peter Ivak, Alena Zumrová, Ivan Netuka, The Journal of Heart and Lung Transplantation, Available online 7 July 2016, ISSN 1053-2498, doi:10.1016/j.healun.2016.06.021
The postoperative course was uneventful and allograft function remained without rejection with preserved function through the follow-up at 100 months. Notably, her neurological status improved and at 8 years stabilized with favorable scores compared to pre-transplant baseline.
Heart transplant; dilated cardiomyopathy
The postoperative course was uneventful and allograft function remained without rejection with preserved function through the follow-up at 100 months. Notably, her neurological status improved and at 8 years stabilized with favorable scores compared to pre-transplant baseline.
Heart transplant; dilated cardiomyopathy
Friday, July 8, 2016
Deuterium switcheroo breathes life into old drugs
Bethany Halford, Chemical & Engineering News, Volume 94 Issue 27 pp. 32-36 Issue Date: July 4, 2016
Drugmakers juggle isotopes in hopes of achieving novelty, stability, and success. Heavier than hydrogen by a single neutron, deuterium might not seem to have much chemical heft. But the small matter of that subatomic particle makes a massive difference in the reactivity of hydrogen versus its isotope deuterium.
Currently in Friedreich ataxia's Research Pipeline: RT001 (RETROTOPE).
The strategy here is to stabilize the PUFAs and protect the cells from this oxidative damage. One approach to stabilizing the PUFAs is to create mimetics (very similar chemical substitutes) of PUFAs. Retrotope filed their IND with FDA in 2015 and announced enrollment of a 28-day, first-in-human, randomized, double-blind, controlled, ascending dose study of orally dosed RT001 to evaluate the safety, tolerability, pharmacokinetics (PK), disease state, and exploratory endpoints in patients with Friedreich’s ataxia (FA) in August 2015. This study is taking place at University of South Florida and University of California Los Angeles.
Drugmakers juggle isotopes in hopes of achieving novelty, stability, and success. Heavier than hydrogen by a single neutron, deuterium might not seem to have much chemical heft. But the small matter of that subatomic particle makes a massive difference in the reactivity of hydrogen versus its isotope deuterium.
Currently in Friedreich ataxia's Research Pipeline: RT001 (RETROTOPE).
The strategy here is to stabilize the PUFAs and protect the cells from this oxidative damage. One approach to stabilizing the PUFAs is to create mimetics (very similar chemical substitutes) of PUFAs. Retrotope filed their IND with FDA in 2015 and announced enrollment of a 28-day, first-in-human, randomized, double-blind, controlled, ascending dose study of orally dosed RT001 to evaluate the safety, tolerability, pharmacokinetics (PK), disease state, and exploratory endpoints in patients with Friedreich’s ataxia (FA) in August 2015. This study is taking place at University of South Florida and University of California Los Angeles.
Thursday, July 7, 2016
Genetic testing in neurology
Henrietta Lefroy, Victoria Harrison, Andrea H. Németh, Medicine, Available online 25 June 2016, ISSN 1357-3039, doi:10.1016/j.mpmed.2016.05.006.
Keywords: Carrier testing; confidentiality; consent; diagnostic testing; genetic testing; neurogenetics; neurology; next-generation sequencing; pre-symptomatic testing
Keywords: Carrier testing; confidentiality; consent; diagnostic testing; genetic testing; neurogenetics; neurology; next-generation sequencing; pre-symptomatic testing
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