Is traumatic and non-traumatic neck pain associated with brain alterations? : a systematic review

Background: Chronic neck pain affects 50% - 85% of people who have experienced an acute episode. This transition and the persistence of chronic complaints are believed to be mediated by brain alterations among different central mechanisms. Objectives: This study aimed to systematically review and critically appraise the current existing evidence regarding structural and functional brain alterations in patients with whiplash associated disorders (WAD) and idiopathic neck pain (INP). Additionally, associations between brain alterations and clinical symptoms reported in neck pain patients were evaluated. Study Design: Systematic review. Methods: The present systematic review was performed according to the PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were searched. First, the obtained articles were screened based on title and abstract. Secondly, the screening was based on the full text. Risk of bias in included studies was investigated. Results: Twelve studies met the inclusion criteria. Alterations in brain morphology and function, including perfusion, neurotransmission, and blood oxygenation level dependent-signal, were demonstrated in chronic neck pain patients. There is some to moderate evidence for both structural and functional brain alterations in patients with chronic neck pain. In contrast, no evidence for structural brain alterations in acute neck pain patients was found. Limitations: Only 12 articles were included, which allows only cautious conclusions to be drawn. Conclusion: Brain alterations were observed in both patients with chronic WAD and chronic INP. Furthermore, more evidence exists for brain alterations in chronic WAD, and different underlying mechanisms might be present in both pathologies. In addition, pain and disability were correlated with the observed brain alterations. Accordingly, morphological and functional brain alterations should be further investigated in patients with chronic WAD and chronic INP with newer and more sensitive techniques, and associative clinical measurements seem indispensable in future research

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Total Number of Alterations in Liquid Biopsies Is an Independent Predictor of Survival in Patients With Advanced Cancers.

PurposeStudies have demonstrated an association between quantity of circulating tumor DNA (ctDNA) and poorer survival. We investigated the relationship between percent ctDNA (%ctDNA), total number of ctDNA alterations, and overall survival (OS) in liquid biopsies.Materials and methodsOverall, 418 patients with blood-based next-generation sequencing (54 to 73 genes) were analyzed. Eligible patients included those who had advanced/metastatic solid tumor malignancies and never received immunotherapy treatment, which may alter the survival curve in patients with high mutational burden.ResultsPatients with a high (≥ 5%) %ctDNA had significantly shorter OS versus those with intermediate (≥ 0.4% to < 5%) or low (< 0.4%) values (median OS, 7.0 v 14.1 v not reached [NR] months, respectively; P < .0001). Patients with a high (≥ 5) total number of alterations had significantly shorter OS versus those with intermediate (≥ 1.46 to < 5), low (< 1.46), or no alterations (median OS, 4.6 v 11.7 v 21.3 v NR months, respectively; P < .0001). The total number of alterations correlated with %ctDNA (r = 0.85; 95% CI, 0.81 to 0.87; P < .0001). However, only an intermediate to high total number of alterations (≥ 1.46) was an independent predictor of worse OS (hazard ratio, 1.96; 95% CI, 1.30 to 2.96; P = .0014; multivariate analysis).ConclusionWe demonstrate that the total number of alterations and %ctDNA have prognostic value and correlate with one another, but only the total number of alterations was independently associated with survival outcomes. Our findings suggest that the total number of alterations in plasma may be an indicator of more aggressive tumor biology and therefore poorer survival

Telephonic alterations

This project explored the unique qualities of an artist’s hand (personal gesture) and was a study of mark making. Three compositions were created through automatic drawing. Completed drawings were presented to three groups: those who considered themselves non-artistic, advanced level art students and beginning level art students. The first individual from each group was asked to recreate an initial drawing. The first recreated drawing was then passed to the next participant for personal interpretation. The process was repeated for each subsequent member of a particular group. Results were similar to the outcome of the classic children’s game “Telephone” with noticeable variations associated with the artistic skill level of each group. Despite the differences it was observed that, in general, participants strove to preserve the essential form of the source sketch. Using the original drawing and the final interpretation of the same drawing, I then created paintings incorporating formal properties of line, composition and color.Department of ArtThesis (M.A.

Characterizing neuromorphologic alterations with additive shape functionals

The complexity of a neuronal cell shape is known to be related to its function. Specifically, among other indicators, a decreased complexity in the dendritic trees of cortical pyramidal neurons has been associated with mental retardation. In this paper we develop a procedure to address the characterization of morphological changes induced in cultured neurons by over-expressing a gene involved in mental retardation. Measures associated with the multiscale connectivity, an additive image functional, are found to give a reasonable separation criterion between two categories of cells. One category consists of a control group and two transfected groups of neurons, and the other, a class of cat ganglionary cells. The reported framework also identified a trend towards lower complexity in one of the transfected groups. Such results establish the suggested measures as an effective descriptors of cell shape

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

Charge structure in volcanic plumes: a comparison of plume properties predicted by an integral plume model to observations of volcanic lightning during the 2010 eruption of Eyjafjallajökull, Iceland

Cancer is a heterogeneous disease with different combinations of genetic alterations driving its development in different individuals. We introduce CoMEt, an algorithm to identify combinations of alterations that exhibit a pattern of mutual exclusivity across individuals, often observed for alterations in the same pathway. CoMEt includes an exact statistical test for mutual exclusivity and techniques to perform simultaneous analysis of multiple sets of mutually exclusive and subtype-specific alterations. We demonstrate that CoMEt outperforms existing approaches on simulated and real data. We apply CoMEt to five different cancer types, identifying both known cancer genes and pathways, and novel putative cancer genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0700-7) contains supplementary material, which is available to authorized users

Adenoid cystic carcinoma: emerging role of translocations and gene fusions.

Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized. Although the specific chromosomal translocations resulting in MYB-NFIB fusions provide insight into the ACC pathogenesis and represent attractive diagnostic and therapeutic targets, their clinical significance is unclear, and a substantial subset of ACCs do not harbor the MYB-NFIB translocation. Strategies based on detection of newly described genetic events (such as MYB activating super-enhancer translocations and alterations affecting another member of MYB transcription factor family-MYBL1) offer new hope for improved risk assessment, therapeutic intervention and tumor surveillance. However, the impact of these approaches is still limited by an incomplete understanding of the ACC biology, and the manner by which these alterations initiate and drive ACC remains to be delineated. This manuscript summarizes the current status of gene fusions and other driver genetic alterations in ACC pathogenesis and discusses new therapeutic strategies stemming from the current research