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Journal of Alternative and... Oct 2020The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus,... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus, scar thickening, and surface area. Systematic review and meta-analysis. Adults with any kind of scar tissue. Physical scar management versus control or no scar management. Pain, pigmentation, pliability, pruritus, surface area, scar thickness. The overall results revealed that physical scar management is beneficial compared with the control treatment regarding the management of pain ( = 0.012), pruritus ( < 0.001), pigmentation ( = 0.010), pliability ( < 0.001), surface area ( < 0.001), and thickness ( = 0.022) of scar tissue in adults. The observed risk of bias was high for blinding of participants and personnel (47%) and low for other bias (100%). Physical scar management demonstrates moderate-to-strong effects on improvement of scar issues as related to signs and symptoms. These results show the importance of specific physical management of scar tissue.
Topics: Cicatrix; Female; Humans; Male; Pigmentation Disorders; Postoperative Complications; Pruritus; Wound Healing
PubMed: 32589450
DOI: 10.1089/acm.2020.0109 -
Cell Apr 2018Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness...
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.
Topics: Carcinogenesis; Cell Dedifferentiation; DNA Methylation; Databases, Genetic; Epigenesis, Genetic; Humans; Machine Learning; MicroRNAs; Neoplasm Metastasis; Neoplasms; Stem Cells; Transcriptome; Tumor Microenvironment
PubMed: 29625051
DOI: 10.1016/j.cell.2018.03.034 -
Journal of Neurochemistry Sep 2019Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease-modifying therapies for Parkinson's disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson's disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non-invasive means is a pressing issue in the field. Since the discovery of α-synuclein (α-syn) as a protein linked to a familial form of Parkinson's disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson's disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson's disease biomarker discovery with a focus on α-synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α-synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. "This article is part of the Special Issue Synuclein."
Topics: Biomarkers; Blotting, Western; Body Fluids; Brain; Cross-Sectional Studies; Disease Progression; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Gonads; Humans; Longitudinal Studies; Mass Spectrometry; Mucous Membrane; Organ Specificity; Parkinson Disease; Phosphorylation; Positron-Emission Tomography; Protein Aggregates; Protein Processing, Post-Translational; Salivary Glands; Skin; alpha-Synuclein
PubMed: 31265130
DOI: 10.1111/jnc.14809 -
Cell Reports Apr 2018Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple...
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.
Topics: Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Humans; Molecular Targeted Therapy; Neoplasms; Oncogene Fusion; Oncogene Proteins, Fusion
PubMed: 29617662
DOI: 10.1016/j.celrep.2018.03.050 -
Cell Apr 2018We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens...
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.
Topics: Aneuploidy; Chromosomes; Cluster Analysis; CpG Islands; DNA Methylation; Databases, Factual; Humans; MicroRNAs; Mutation; Neoplasm Proteins; Neoplasms; RNA, Messenger
PubMed: 29625048
DOI: 10.1016/j.cell.2018.03.022 -
Cancer Cell Apr 2018Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas,...
Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy.
Topics: Aneuploidy; Carcinoma, Squamous Cell; Cell Cycle; Cell Proliferation; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human, Pair 3; Databases, Genetic; Genomics; Humans; Mutation Rate; Tumor Suppressor Protein p53
PubMed: 29622463
DOI: 10.1016/j.ccell.2018.03.007 -
International Journal of Sports... 2022Lifting something off the ground is an essential task and lifting is a documented risk factor for low back pain (LBP). The standard lifting techniques are stoop (lifting...
UNLABELLED
Lifting something off the ground is an essential task and lifting is a documented risk factor for low back pain (LBP). The standard lifting techniques are stoop (lifting with your back), squat (lifting with your legs), and semi-squat (midway between stoop and squat). Most clinicians believe the squat technique is optimal; however, training on squat lifting does not prevent LBP and utilizing greater lumbar flexion (i.e. stoop) when lifting is not a risk factor for LBP. The disconnect between what occurs in clinical practice and what the evidence suggests has resulted in ongoing debate. Clinicians must ask the right questions in order to apply the evidence appropriately. A proposed clinical framework of calm tissue down, build tissue up, improve work capacity can be used to determine which lifting technique is optimal for a patient at any given time. When applying this clinical framework, clinicians should consider metabolic, biomechanical, physical stress tolerance, and pain factors in order to address the movement system. For example, stoop lifting is more metabolically efficient and less challenging to the cardiopulmonary system. There may be few biomechanical differences in spinal postures and gross loads on the lumbar spine between stoop, squat, and semi-squat lifting; however, each lift has distinct kinematic patterns that affects muscle activation patterns, and ultimately the movement system. Clinicians must find the optimal dosage of physical stress to address all aspects of the movement system to minimize the risk of injury. There is no universal consensus on the optimal lifting technique which will satisfy every situation; however, there may be a lifting technique that optimizes movement to achieve a specific outcome. The calm tissue down, build tissue up, improve work capacity framework offers an approach to determine the best lifting technique for an individual patient at any give time.
LEVEL OF EVIDENCE
5.
PubMed: 35024210
DOI: 10.26603/001c.30023 -
Nature Biotechnology Jul 2023Oxytocin (OT), a peptide hormone and neuromodulator, is involved in diverse physiological and pathophysiological processes in the central nervous system and the...
Oxytocin (OT), a peptide hormone and neuromodulator, is involved in diverse physiological and pathophysiological processes in the central nervous system and the periphery. However, the regulation and functional sequences of spatial OT release in the brain remain poorly understood. We describe a genetically encoded G-protein-coupled receptor activation-based (GRAB) OT sensor called GRAB. In contrast to previous methods, GRAB enables imaging of OT release ex vivo and in vivo with suitable sensitivity, specificity and spatiotemporal resolution. Using this sensor, we visualize stimulation-induced OT release from specific neuronal compartments in mouse brain slices and discover that N-type calcium channels predominantly mediate axonal OT release, whereas L-type calcium channels mediate somatodendritic OT release. We identify differences in the fusion machinery of OT release for axon terminals versus somata and dendrites. Finally, we measure OT dynamics in various brain regions in mice during male courtship behavior. Thus, GRAB provides insights into the role of compartmental OT release in physiological and behavioral functions.
Topics: Male; Mice; Animals; Oxytocin; Neurons; Brain; Signal Transduction; Central Nervous System
PubMed: 36593404
DOI: 10.1038/s41587-022-01561-2 -
Frontiers in Bioengineering and... 2021Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher...
Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher loads in the lumbar spine. Even though recent biomechanical studies challenge these assumptions, conclusive evidence is still lacking. This study therefore aimed at comparing lumbar loads among different lifting styles using a comprehensive state-of-the-art motion capture-driven musculoskeletal modeling approach. Thirty healthy pain-free individuals were enrolled in this study and asked to repetitively lift a 15 kg-box by applying 1) a freestyle, 2) a squat and 3) a stoop lifting technique. Whole-body kinematics were recorded using a 16-camera optical motion capture system and used to drive a full-body musculoskeletal model including a detailed thoracolumbar spine. Continuous as well as peak compressive, anterior-posterior shear and total loads (resultant load vector of the compressive and shear load vectors) were calculated based on a static optimization approach and expressed as factor body weight (BW). In addition, lumbar lordosis angles and total lifting time were calculated. All parameters were compared among the lifting styles using a repeated measures design. For each lifting style, loads increased towards the caudal end of the lumbar spine. For all lumbar segments, stoop lifting showed significantly lower compressive and total loads (-0.3 to -1.0BW) when compared to freestyle and squat lifting. Stoop lifting produced higher shear loads (+0.1 to +0.8BW) in the segments T12/L1 to L4/L5, but lower loads in L5/S1 (-0.2 to -0.4BW). Peak compressive and total loads during squat lifting occurred approximately 30% earlier in the lifting cycle compared to stoop lifting. Stoop lifting showed larger lumbar lordosis range of motion (35.9 ± 10.1°) than freestyle (24.2 ± 7.3°) and squat (25.1 ± 8.2°) lifting. Lifting time differed significantly with freestyle being executed the fastest (4.6 ± 0.7 s), followed by squat (4.9 ± 0.7 s) and stoop (5.9 ± 1.1 s). Stoop lifting produced lower total and compressive lumbar loads than squat lifting. Shear loads were generally higher during stoop lifting, except for the L5/S1 segment, where anterior shear loads were higher during squat lifting. Lifting time was identified as another important factor, considering that slower speeds seem to result in lower loads.
PubMed: 34805121
DOI: 10.3389/fbioe.2021.769117