1,721,249 research outputs found
Is mitochondrial oxidative metabolism the right therapy target in early Huntington disease?
No full textHuntington disease (HD) is a progressive and fatal autosomal dominant neurodegenerative disorder characterized by extrapyramidal motor signs often preceded by cognitive and behavioral disturbances, with a prevalence of 5-10 cases per 100,000 people worldwide 1; expanded CAG repeats within the coding sequence of the HTT gene on chromosome 4p 2 are the cause. The gene encodes huntingtin (HTT), a ubiquitously expressed protein associated with most intracellular organelles. CAG repeats of 40 or more are associated with nearly full penetrance by age 65 years with a mean age at onset of 40 years and death 15-20 years later. 3 Although the function of HTT remains incompletely understood, HD likely arises from gain of function caused by the abnormal conformation of the mutant protein.
Author response to the letter regarding the publication titled "Major cerebral vessels involvement in patients with MELAS syndrome: worth a scan? A systematic review"
No full textWe appreciate the interest in our systematic review, which revealed that dilatation or stenosis of major vessel caliber is present in 59% (27/46) of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) and underlined the importance of imaging intracranial vessels during prospective study protocols of patients with MELAS. We share the view that pathogenic mechanisms of (SLEs) are not fully understood and a variety of mechanisms has been proposed, including metabolically impaired mitochondrial energy production, as well as micro- and macrovascular angiopathy. A substantial degree of evidence has indicated that patients with MELAS have an inability to efficiently produce mitochondrial energy. In particular, a previous in vitro study of cybrid cell lines composed of cytoplasts from patients with MELAS bearing an A>G transition (nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome) fused with human cells lacking endogenous mitochondrial DNA (mtDNA) demonstrated impaired mitochondrial translation and protein synthesis. Consequently, the inability to efficiently produce mitochondrial energy is a biochemical feature of MELAS syndrome, which may periodically exacerbate during SLEs.
Furthermore, microangiopathy of small blood vessels can occur in patients with MELAS that may show abnormal staining of succinate dehydrogenase, a mitochondrial enzyme, as well as mitochondrial proliferation in smooth muscle and endothelial cells of small blood vessels.
Therefore, blood vessels’ impaired energy metabolism may intrinsically contribute to abnormal perfusion during SLEs. Notably, several studies have indicated increased perfusion in patients with MELAS using computed tomography (CT), magnetic resonance imaging (MRI) perfusion, and single photon emission computed tomography (SPECT) during SLEs.
As suggested, we reviewed the possible influence of mtDNA mutations and pharmacological treatment on the vessel caliber alterations.
It is well known that in patients harboring mtDNA mutations, both mutant and wild type mtDNA molecules may coexist within the same cell, defining a condition called heteroplasmy, which may vary widely among different tissues. Importantly, the skeletal muscle and blood heteroplasmy levels of the m.3243A>G mutation are correlated with disease severity in patients with MELAS.
Interestingly, a recent study of our group identified a common diffuse pattern of brain biochemical alterations detected in vivo by proton magnetic resonance spectroscopy, which correlated with mtDNA heteroplasmy in patients with MELAS. Unfortunately, in the reviewed studies, the percentage of mutated mtDNA was reported in only one third of them (n = 8/23, 35%). Heteroplasmy ranged from 22% to 76%, and was measured in different tissues such as skeletal muscle, fibroblasts, and blood cells
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Liquid Biopsy in Glioblastoma Management: From Current Research to Future Perspectives.
No full textGlioblastoma (GBM) is the most common primary tumor of the central nervous system. Arising from neuroepithelial glial cells, GBM is characterized by invasive behavior, extensive angiogenesis, and genetic heterogeneity that contributes to poor prognosis and treatment failure. Currently, there are several molecular biomarkers available to aid in diagnosis, prognosis, and predicting treatment outcomes; however, all require the biopsy of tumor tissue. Nevertheless, a tissue sample from a single location has its own limitations, including the risk related to the procedure and the difficulty of obtaining longitudinal samples to monitor treatment response and to fully capture the intratumoral heterogeneity of GBM. To date, there are no biomarkers in blood or cerebrospinal fluid for detection, follow-up, or prognostication of GBM. Liquid biopsy offers an attractive and minimally invasive solution to support different stages of GBM management, assess the molecular biology of the tumor, identify early recurrence and longitudinal genomic evolution, predict both prognosis and potential resistance to chemotherapy or radiotherapy, and allow patient selection for targeted therapies. The aim of this review is to describe the current knowledge regarding the application of liquid biopsy in glioblastoma, highlighting both benefits and obstacles to translation into clinical care. Implications for Practice To translate liquid biopsy into clinical practice, further prospective studies are required with larger cohorts to increase specificity and sensitivity. With the ever-growing interest in RNA nanotechnology, microRNAs may have a therapeutic role in brain tumors
Effects of light treatment on sleep, cognition, mood, and behavior in Alzheimer's disease: A systematic review
No full textBackground: Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer's disease (AD) patients. Recently, a handful of studies also focused on the effect on cognition and behavior. Conflicting findings are reported in the literature, and no definite conclusions have been drawn about its specific therapeutic effect. Summary: The aim of this review is to provide a critical evaluation of available evidence in this field, highlighting the specific characteristics of effective bright light treatment. Eligible studies were required to assess at least one of the following outcome measures: sleep, cognition, mood, and/or behavior (e.g., depression, agitation). A total of 32 articles were included in this systematic review and identified as research intervention studies about light treatment in AD. The quality of the papers was evaluated based on the US Preventive Service Task Force guidelines. Key Messages: Overall, the current literature suggests that the effects of light treatment in AD patients are mixed and may be influenced by several factors, but with a general trend toward a positive effect. Bright light seems to be a promising intervention treatment without significant adverse effects; therefore, further well-designed randomized controlled trials are needed taking into account the highlighted recommendations
Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery
No full text: Endoscopic endonasal surgery has gained a prominent role in the management of complex skull base tumors. It allows the resection of a large group of benign and malignant lesions through a natural anatomical extra-cranial pathway, represented by the nasal cavities, avoiding brain retraction and neurovascular manipulation. This is reflected by the patients' prompt clinical recovery and the low risk of permanent neurological sequelae, representing the main caveat of conventional skull base surgery. This surgery must be tailored to each specific case, considering its features and relationship with surrounding neural structures, mostly based on preoperative neuroimaging. Advanced MRI techniques, such as tractography, have been rarely adopted in skull base surgery due to technical issues: lengthy and complicated processes to generate reliable reconstructions for inclusion in the neuronavigation system. This paper aims to present the protocol implemented in the institution and highlights the synergistic collaboration and teamwork between neurosurgeons and the neuroimaging team (neurologists, neuroradiologists, neuropsychologists, physicists, and bioengineers) with the final goal of selecting the optimal treatment for each patient, improving the surgical results and pursuing the advancement of personalized medicine in this field
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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