A longitudinal and cross-sectional study of plasma neurofilament light chain concentration in Charcot-Marie-Tooth disease

Advances in genetic technology and small molecule drug development have paved the way for clinical trials in Charcot-Marie-Tooth disease (CMT); however, the current FDA-approved clinical trial outcome measures are insensitive to detect a meaningful clinical response. There is, therefore, a need to identify sensitive outcome measures or clinically relevant biomarkers. The aim of this study was to further evaluate plasma neurofilament light chain (NFL) as a disease biomarker in CMT. Plasma NFL was measured using SIMOA technology in both a cross-sectional study of a US cohort of CMT patients and longitudinally over 6 years in a UK CMT cohort. In addition, plasma NFL was measured longitudinally in two mouse models of CMT2D. Plasma concentrations of NFL were increased in a US cohort of patients with CMT1B, CMT1X and CMT2A but not CMT2E compared with controls. In a separate UK cohort, over a 6-year interval, there was no significant change in plasma NFL concentration in CMT1A or HSN1, but a small but significant reduction in patients with CMT1X. Plasma NFL was increased in wild type compared to GARSC201R mice. There was no significant difference in plasma NFL in GARSP278KY compared to wild type mice. In patients with CMT1A, the small difference in cross-sectional NFL concentration vs healthy controls and the lack of change over time suggests that plasma NFL may lack sufficient sensitivity to detect a clinically meaningful treatment response in adulthood

Testing for sexually transmitted infections and blood borne viruses on admission to Western Australian prisons

<p>Abstract</p> <p>Background</p> <p>Prison populations are known to be at high risk of sexually transmitted infections (STIs) and blood borne viruses (BBVs). In accordance with State health guidelines, the Western Australian Department of Correctional Services' policy is to offer testing for STIs and BBVs to all new prison entrants. This audit was undertaken to assess the completeness and timeliness of STI and BBV testing among recent prison entrants in Western Australia, and estimate the prevalence of STIs and BBVs on admission to prison.</p> <p>Methods</p> <p>A retrospective audit of prison medical records was conducted among 946 individuals admitted to prison in Western Australia after the 1^stJanuary 2005, and discharged between the 1^stJanuary and 31^stDecember 2007 inclusive. Quota sampling was used to ensure adequate sampling of females, juveniles, and individuals from regional prisons. Main outcomes of interest were the proportion of prisoners undergoing STI and BBV testing, and the prevalence of STIs and BBVs.</p> <p>Results</p> <p>Approximately half the sample underwent testing for the STIs chlamydia and gonorrhoea, and almost 40% underwent testing for at least one BBV. Completeness of chlamydia and gonorrhoea testing was significantly higher among juveniles (84.1%) compared with adults (39.8%; p < 0.001), and Aboriginal prisoners (58.3%) compared with non-Aboriginal prisoners (40.4%; p < 0.001). Completeness of BBV testing was significantly higher among adults (46.5%) compared with juveniles (15.8%; p < 0.001) and males (43.3%) compared with females (33.1%; p = 0.001). Among prisoners who underwent testing, 7.3% had a positive chlamydia test result and 24.8% had a positive hepatitis C test result.</p> <p>Conclusion</p> <p>The documented coverage of STI and BBV testing among prisoners in Western Australia is not comprehensive, and varies significantly by age, gender and Aboriginality. Given the high prevalence of STIs and BBVs among prisoners, increased test coverage is required to ensure optimal use of the opportunity that prison admission presents for the treatment and control of STIs and BBVs among this high risk group.</p

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

<p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p

Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review

Contains fulltext : 110141.pdf (publisher's version ) (Open Access)BACKGROUND: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. METHODS: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. RESULTS: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. CONCLUSIONS: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed

When public action undermines public health: A critical examination of antifluoridationist literature

Background: The addition of the chemical fluorine to the water supply, called water fluoridation, reduces dental caries by making teeth more resistant to demineralisation and more likely to remineralise when initially decayed. This process has been implemented in more than 30 countries around the world, is cost-effective and has been shown to be efficacious in preventing decay across a person's lifespan. However, attempts to expand this major public health achievement in line with Australia's National Oral Health Plan 2004–2013 are almost universally met with considerable resistance from opponents of water fluoridation, who engage in coordinated campaigns to portray water fluoridation as ineffective and highly dangerous. Discussion: Water fluoridation opponents employ multiple techniques to try and undermine the scientifically established effectiveness of water fluoridation. The materials they use are often based on Internet resources or published books that present a highly misleading picture of water fluoridation. These materials are used to sway public and political opinion to the detriment of public health. Despite an extensive body of literature, both studies and results within studies are often selectively reported, giving a biased portrayal of water fluoridation effectiveness. Positive findings are downplayed or trivialised and the population implications of these findings misinterpreted. Ecological comparisons are sometimes used to support spurious conclusions. Opponents of water fluoridation frequently repeat that water fluoridation is associated with adverse health effects and studies are selectively picked from the extensive literature to convey only claimed adverse findings related to water fluoridation. Techniques such as "the big lie" and innuendo are used to associate water fluoridation with health and environmental disasters, without factual support. Half-truths are presented, fallacious statements reiterated, and attempts are made to bamboozle the public with a large list of claims and quotes often with little scientific basis. Ultimately, attempts are made to discredit and slander scientists and various health organisations that support water fluoridation. Summary: Water fluoridation is an important public health initiative that has been found to be safe and effective. Nonetheless, the implementation of water fluoridation is still regularly interrupted by a relatively small group of individuals who use misinformation and rhetoric to induce doubts in the minds of the public and government officials. It is important that public health officials are aware of these tactics so that they can better counter their negative effectJason M Armfiel