18 F-MK-6240 tau-PET in genetic frontotemporal dementia

Tau is one of several proteins associated with frontotemporal dementia. While knowing which protein is causing a patient\u27s disease is crucial, no biomarker currently exists for identifying tau in vivo in frontotemporal dementia. The objective of this study was to investigate the potential for the promising 18F-MK-6240 PET tracer to bind to tau in vivo in genetic frontotemporal dementia. We enrolled subjects with genetic frontotemporal dementia, who constitute an ideal population for testing because their pathology is already known based on their mutation. Ten participants (three with symptomatic P301L and R406W MAPT mutations expected to show tau binding, three with presymptomatic MAPT mutations and four with non-tau mutations who acted as disease controls) underwent clinical characterization, tau-PET scanning with 18F-MK-6240, amyloid-PET imaging with 18F-NAV-4694 to rule out confounding Alzheimer\u27s pathology, and high-resolution structural MRI. Tau-PET scans of all three symptomatic MAPT carriers demonstrated at least mild 18F-MK-6240 binding in expected regions, with particularly strong binding in a subject with an R406W MAPT mutation (known to be associated with Alzheimer\u27s like neurofibrillary tangles). Two asymptomatic MAPT carriers estimated to be 5 years from disease onset both showed modest 18F-MK-6240 binding, while one ∼30 years from disease onset did not exhibit any binding. Additionally, four individuals with symptomatic frontotemporal dementia caused by a non-tau mutation were scanned (two C9orf72; one GRN; one VCP): 18F-MK-6240 scans were negative for three subjects, while one advanced C9orf72 case showed minimal regionally non-specific binding. All 10 amyloid-PET scans were negative. Furthermore, a general linear model contrasting genetic frontotemporal dementia subjects to a set of 83 age-matched controls showed significant binding only in the MAPT carriers in selected frontal, temporal and subcortical regions. In summary, our findings demonstrate mild but significant binding of MK-6240 in amyloid-negative P301L and R406W MAPT mutation subjects, with higher standardized uptake value ratio in the R406W mutation associated with the presence of NFTs, and little non-specific binding. These results highlight that a positive 18F-MK-6240 tau-PET does not necessarily imply a diagnosis of Alzheimer\u27s disease and point towards a potential use for 18F-MK-6240 as a biomarker in certain tauopathies beyond Alzheimer\u27s, although further patient recruitment and autopsy studies will be necessary to determine clinical applicability

Penetrating spinal injury with wooden fragments causing cauda equina syndrome: case report and literature review

Study design: Case report Objective: To report an unusual case of cauda equina syndrome following penetrating injury to the lumbar spine by wooden fragments and to stress the importance of early magnetic resonance imaging (MRI) in similar cases. Summary of background data: A 22-year-old girl accidentally landed on wooden bannister and sustained a laceration to her back. She complained of back pain but had fully intact neurological function. The laceration in her back was explored and four large wooden pieces were removed. However 72 h later, she developed cauda equina syndrome. MRI demonstrated the presence of a foreign body between second and third lumbar spinal levels following which she underwent emergency decompressive laminectomy and the removal of the multiple wooden fragments that had penetrated the dura. Results: Post-operatively motor function in her lower limbs returned to normal but she continued to require a catheter for incontinence. At review 6 months later, she was mobilising independently but the incontinence remained unchanged. Conclusion: There are no reported cases in the literature of wooden fragments penetrating the dura from the back with or without the progression to cauda equina syndrome. The need for a high degree of suspicion and an early MRI scan to localise any embedded wooden fragments that may be separate from the site of laceration is emphasized even if initial neurology is intact

Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

The combined application of next-generation sequencing platforms has provided an economical approach to unlocking the potential of the turkey genome

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

On the shoulders of giants: a meta-review of strategic human resource management

Recent years have witnessed significant growth in the field of strategic HRM. This article summarizes the literature in this field by conducting a meta-review, a review of the reviews that have covered various topics of strategic HRM. In doing so, the authors highlight theoretical frameworks and empirical findings of studies in the field over the past three decades, identify methodological issues and challenges in the previous research, and discuss recent trends in the field of strategic HRM. The author concludes by suggesting some interesting and important directions for future work. Supplementary material attached below

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479Funder: Fonds de Recherche du Québec ‐ SantéFunder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024Funder: NIHR Rare Diseases Translational Research CollaborationFunder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers