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1.
Nucleic Acids Res ; 50(D1): D231-D235, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34893873

ABSTRACT

The MODOMICS database has been, since 2006, a manually curated and centralized resource, storing and distributing comprehensive information about modified ribonucleosides. Originally, it only contained data on the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. Over the years, prompted by the accumulation of new knowledge and new types of data, it has been updated with new information and functionalities. In this new release, we have created a catalog of RNA modifications linked to human diseases, e.g., due to mutations in genes encoding modification enzymes. MODOMICS has been linked extensively to RCSB Protein Data Bank, and sequences of experimentally determined RNA structures with modified residues have been added. This expansion was accompanied by including nucleotide 5'-monophosphate residues. We redesigned the web interface and upgraded the database backend. In addition, a search engine for chemically similar modified residues has been included that can be queried by SMILES codes or by drawing chemical molecules. Finally, previously available datasets of modified residues, biosynthetic pathways, and RNA-modifying enzymes have been updated. Overall, we provide users with a new, enhanced, and restyled tool for research on RNA modification. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.


Subject(s)
Databases, Nucleic Acid , Enzymes/genetics , RNA/genetics , Ribonucleosides/genetics , User-Computer Interface , Base Sequence , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Computer Graphics , Databases, Protein , Datasets as Topic , Enzymes/metabolism , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/metabolism , Gastrointestinal Diseases/pathology , Hematologic Diseases/genetics , Hematologic Diseases/metabolism , Hematologic Diseases/pathology , Humans , Internet , Mental Disorders/genetics , Mental Disorders/metabolism , Mental Disorders/pathology , Musculoskeletal Diseases/genetics , Musculoskeletal Diseases/metabolism , Musculoskeletal Diseases/pathology , Mutation , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , RNA/metabolism , RNA Processing, Post-Transcriptional , Ribonucleosides/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism
2.
Skeletal Radiol ; 52(3): 505-516, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36255472

ABSTRACT

Multidisciplinary communication and planning between the musculoskeletal radiologist and orthopedic oncologist are essential for proper biopsy planning when a primary musculoskeletal malignancy is suspected. Image-guided percutaneous biopsy allows for real-time visualization of the biopsy needle and surrounding structures, combining high diagnostic accuracy with safety and cost-effectiveness. However, determining a surgically optimal biopsy trajectory for a mass can be technically challenging due to critical surrounding anatomy or challenging needle approach angles. Inappropriately placed biopsies can have serious repercussions on patient function and oncological survival. The potential for needle tract seeding and local recurrence after biopsy of sarcoma has been central to the debate regarding the need for excision of the biopsy tract. This multidisciplinary review highlights current controversies in the field, including the issue of core needle biopsy tracts and their excision, technical considerations and advances in image-guidance in the setting of challenging biopsies, advances in histopathological diagnostics with implications for targeted therapy in sarcoma, as well as surgical and oncological outcomes after needle tract biopsy.


Subject(s)
Musculoskeletal Diseases , Humans , Biopsy, Large-Core Needle , Image-Guided Biopsy , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/surgery , Sarcoma/pathology , Sarcoma/surgery
3.
Skeletal Radiol ; 52(4): 705-714, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36202920

ABSTRACT

OBJECTIVE: To evaluate imaging features of soft tissue metastases, technical factors associated with diagnostic yield of image-guided biopsy, and clinical impact of biopsy results on patient outcomes. MATERIALS AND METHODS: A total of 1605 image-guided soft tissue biopsies were retrospectively identified from December 2010 to December 2020. Included lesions were histologically proven musculoskeletal soft tissue metastases. Lesions were excluded if intraabdominal, intrathoracic, retroperitoneal, associated with osseous lesions or surgical scar implants or arising from skin or lymph nodes. Image guidance modality, needle size, number of cores, and lesion location, size, and depth from skin were recorded. Patient demographics, malignancy history, biopsy-driven changes in management, and survival rate after biopsy were collected. RESULTS: Forty-six patients met the inclusion criteria with a biopsy diagnostic yield of 44/46 (95.7%). Metastases were most commonly located truncal (82.6%, p < 0.001) and intramuscular (78.3%, p < 0.001). A total of 37/46 (80.4%) biopsies were US-guided. And 9/46 (19.6%) were CT-guided. There was no significant difference in the number of cores or mean needle gauge between diagnostic and nondiagnostic biopsies. At time of review, 23 (50%) patients were deceased, with a mean survival of 13.5 months after biopsy. The majority (71.7%) of patients had a known primary malignancy at time of biopsy, most commonly lung (24.2%) and breast (24.2%). Overall survival showed no association with anatomic location (p > 0.83) or tissue type (p > 0.34). The most common biopsy-driven outcome was initiation of chemotherapy, immunotherapy, and/or radiotherapy (52.2%). CONCLUSION: Image-guided biopsy for soft tissue metastases has high diagnostic yield and commonly influences clinical management. Metastases were most commonly intramuscular in the trunk and are associated with poor prognosis.


Subject(s)
Musculoskeletal Diseases , Neoplasms, Second Primary , Sarcoma , Soft Tissue Neoplasms , Humans , Biopsy, Needle/methods , Retrospective Studies , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/pathology , Bone and Bones/pathology , Image-Guided Biopsy/methods , Musculoskeletal Diseases/pathology , Sarcoma/pathology , Cicatrix/pathology
4.
Hum Genet ; 140(6): 897-913, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33409574

ABSTRACT

Disease gene identification is a critical step towards uncovering the molecular mechanisms of diseases and systematically investigating complex disease phenotypes. Despite considerable efforts to develop powerful computing methods, candidate gene identification remains a severe challenge owing to the connectivity of an incomplete interactome network, which hampers the discovery of true novel candidate genes. We developed a network-based machine-learning framework to identify both functional modules and disease candidate genes. In this framework, we designed a semi-supervised non-negative matrix factorization model to obtain the functional modules related to the diseases and genes. Of note, we proposed a disease gene-prioritizing method called MapGene that integrates the correlations from both functional modules and network closeness. Our framework identified a set of functional modules with highly functional homogeneity and close gene interactions. Experiments on a large-scale benchmark dataset showed that MapGene performs significantly better than the state-of-the-art algorithms. Further analysis demonstrates MapGene can effectively relieve the impact of the incompleteness of interactome networks and obtain highly reliable rankings of candidate genes. In addition, disease cases on Parkinson's disease and diabetes mellitus confirmed the generalization of MapGene for novel candidate gene identification. This work proposed, for the first time, an integrated computing framework to predict both functional modules and disease candidate genes. The methodology and results support that our framework has the potential to help discover underlying functional modules and reliable candidate genes in human disease.


Subject(s)
Gene Regulatory Networks , Metabolic Networks and Pathways/genetics , Predictive Value of Tests , Supervised Machine Learning , Amino Acid Sequence , Computational Biology/methods , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/pathology , Humans , Immune System Diseases/diagnosis , Immune System Diseases/genetics , Immune System Diseases/pathology , Mental Disorders/diagnosis , Mental Disorders/genetics , Mental Disorders/pathology , Metabolic Diseases/diagnosis , Metabolic Diseases/genetics , Metabolic Diseases/pathology , Musculoskeletal Diseases/diagnosis , Musculoskeletal Diseases/genetics , Musculoskeletal Diseases/pathology , Neoplasms/diagnosis , Neoplasms/genetics , Neoplasms/pathology , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Protein Interaction Mapping , Terminology as Topic
5.
Hum Genet ; 140(8): 1253-1265, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34057592

ABSTRACT

OBJECTIVE: In the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations. METHODS: We leveraged available summary-based genetic data from genome-wide association studies on 1498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits. RESULTS: We identified 110 traits causally associated with obesity. Of those, 109 were causal outcomes of obesity, while only leg pain in calves was a causal determinant of obesity. Causal outcomes of obesity included 26 phenotypes associated with cardiovascular diseases, 22 anthropometric measurements, nine with the musculoskeletal system, nine with behavioural or lifestyle factors including loneliness or isolation, six with respiratory diseases, five with body bioelectric impedances, four with psychiatric phenotypes, four related to the nervous system, four with disabilities or long-standing illness, three with the gastrointestinal system, three with use of analgesics, two with metabolic diseases, one with inflammatory response and one with the neurodevelopmental disorder ADHD, among others. In particular, some causal outcomes of obesity included hypertension, stroke, ever having a period of extreme irritability, low forced vital capacity and forced expiratory volume, diseases of the musculoskeletal system, diabetes, carpal tunnel syndrome, loneliness or isolation, high leukocyte count, and ADHD. CONCLUSIONS: Our results indicate that obesity causally affects a wide range of traits and comorbid diseases, thus providing an overview of the metabolic, physiological, and neuropsychiatric impact of obesity on human health.


Subject(s)
Cardiovascular Diseases/genetics , Gastrointestinal Diseases/genetics , Lung Diseases/genetics , Mental Disorders/genetics , Metabolic Diseases/genetics , Musculoskeletal Diseases/genetics , Obesity/genetics , Body Mass Index , Cardiovascular Diseases/complications , Cardiovascular Diseases/pathology , Female , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/pathology , Genetic Association Studies , Genome-Wide Association Study , Genotype , Humans , Loneliness/psychology , Lung Diseases/complications , Lung Diseases/pathology , Male , Mental Disorders/complications , Mental Disorders/pathology , Metabolic Diseases/complications , Metabolic Diseases/pathology , Multifactorial Inheritance , Musculoskeletal Diseases/complications , Musculoskeletal Diseases/pathology , Obesity/complications , Obesity/pathology , Phenotype
6.
Rheumatology (Oxford) ; 60(3): 1410-1418, 2021 03 02.
Article in English | MEDLINE | ID: mdl-32984894

ABSTRACT

OBJECTIVES: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. METHODS: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. RESULTS: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). CONCLUSION: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.


Subject(s)
Microscopic Angioscopy , Musculoskeletal Diseases/pathology , Delphi Technique , Humans , Microscopic Angioscopy/methods , Microscopic Angioscopy/standards , Microscopic Angioscopy/statistics & numerical data , Musculoskeletal Diseases/diagnosis
7.
Pharmacol Res ; 165: 105427, 2021 03.
Article in English | MEDLINE | ID: mdl-33453372

ABSTRACT

Skeletal muscles and bone tissue form the musculoskeletal apparatus, a complex system essential for the voluntary movement. The loss of muscle mass and muscle strength is often associated with a loss of bone mass, in a "hazardous duet" which implies the co-existence of sarcopenia-osteoporosis and exposes patients to a deterioration in quality of life and increased mortality. From the mechanostat theory to the recent definition of the osteosarcopenia syndrome, many aspects of muscle-bone interaction have been investigated in recent decades. The mechanical interaction is now accepted, considering the close anatomical relationship between the two tissues, however, much remains to be discovered regarding the biochemical muscle-bone interaction. Skeletal muscle has been defined as an endocrine organ capable of exerting an action on other tissues. Myokines, bioactive polypeptides released by the muscle, could represent the encrypted message in the communication between muscle and bone. These two tissues have a reciprocal influence on their metabolisms and respond in a similar way to the multiple external factors. The aim of this review is to stimulate the understanding of the encrypted language between muscle and bone, highlighting the role of catabolic pathways and oxidative stress in the musculoskeletal apparatus to elucidate the shared mechanisms and the similarity of response to the same stimuli by different tissues. Our understanding of muscle-bone interactions it could be useful to identify and develop new strategies to treat musculoskeletal diseases, together with pharmacological, nutritional and exercise-based approaches, which are already in use for the treatment of these pathologies.


Subject(s)
Bone and Bones/metabolism , Muscle, Skeletal/metabolism , Musculoskeletal Diseases/metabolism , Animals , Bone and Bones/pathology , Humans , Muscle, Skeletal/pathology , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/therapy , Osteoporosis/metabolism , Osteoporosis/pathology , Osteoporosis/therapy , Sarcopenia/metabolism , Sarcopenia/pathology
8.
J Surg Oncol ; 123(1): 342-351, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33051865

ABSTRACT

BACKGROUND AND OBJECTIVES: Success rates for initial image-guided biopsy of musculoskeletal (MSK) lesions have been well documented; evidence regarding success rates for repeat biopsy following initially nondiagnostic (ND) image-guided biopsy of MSK lesions is more limited. This study evaluates the outcomes of repeat computerized tomography-guided MSK biopsies following ND biopsies using a multidisciplinary approach. MATERIALS AND METHODS: Electronic medical record search covering a 10-year period identified patients that received two or more biopsies for an MSK tumor or tumor-like process. The decision for initial and repeat image-guided biopsy of each lesion was made following multidisciplinary MSK tumor board review. Lesion location, histopathology results, size of biopsy needle when available, and change in technique between biopsy attempts was documented. RESULTS: Repeat biopsy rate was 1.6%. 23 patients with repeat MSK biopsy were identified. A total of 17 of 23 (74%) repeat biopsy attempts were diagnostic. A total of 22 of 23 (96%) repeat biopsy attempts were clinically useful. Diagnostic repeat biopsies were described as employing one or more of five technical differences compared to the first biopsy attempt, the most common being improved targeting of the lesion itself. CONCLUSIONS: A multidisciplinary approach may yield improved repeat-biopsy rates and clinical utility of repeat MSK biopsies compared to prior reports.


Subject(s)
Image-Guided Biopsy/methods , Interdisciplinary Communication , Musculoskeletal Diseases/pathology , Tomography, X-Ray Computed/methods , Follow-Up Studies , Humans , Musculoskeletal Diseases/diagnostic imaging , Prognosis , Retrospective Studies
9.
Int J Mol Sci ; 22(14)2021 Jul 07.
Article in English | MEDLINE | ID: mdl-34298917

ABSTRACT

Musculoskeletal conditions are known to involve biological, psychological, social and, often, lifestyle elements. However, these domains are generally considered in isolation from each other. This siloed approach is unlikely to be adequate to understand the complexity of these conditions and likely explains a major component of the disappointing effects of treatment. This paper presents a hypothesis that aims to provide a foundation to understand the interaction and integration between these domains. We propose a hypothesis that provides a plausible link between psychology and lifestyle factors with tissue level effects (such as connective tissue dysregulation/accumulation) in musculoskeletal conditions that is founded on understanding the molecular basis for interaction between systemic and local inflammation. The hypothesis provides plausible and testable links between mind and body, for which empirical evidence can be found for many aspects. We present this hypothesis from the perspective of connective tissue biology and pathology (fibrosis), the role of inflammation locally (tissue level), and how this inflammation is shaped by systemic inflammation through bidirectional pathways, and various psychological and lifestyle factors via their influence on systemic inflammation. This hypothesis provides a foundation for new consideration of the development and refinement of personalized multidimensional treatments for individuals with musculoskeletal conditions.


Subject(s)
Connective Tissue/pathology , Inflammation/pathology , Musculoskeletal Diseases/pathology , Animals , Fibrosis/pathology , Humans , Life Style
10.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807573

ABSTRACT

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, ß-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/ß-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.


Subject(s)
Liver Diseases/pathology , Musculoskeletal Diseases/pathology , Osteoporosis/pathology , Sarcopenia/pathology , Animals , Chronic Disease , Humans
11.
Int J Mol Sci ; 22(19)2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34638927

ABSTRACT

Recently published clinical trials involving the use of adipose-derived stem cells (ADSCs) indicated that approximately one-third of the studies were conducted on musculoskeletal disorders (MSD). MSD refers to a wide range of degenerative conditions of joints, bones, and muscles, and these conditions are the most common causes of chronic disability worldwide, being a major burden to the society. Conventional treatment modalities for MSD are not sufficient to correct the underlying structural abnormalities. Hence, ADSC-based cell therapies are being tested as a form of alternative, yet more effective, therapies in the management of MSDs. Therefore, in this review, MSDs subjected to the ADSC-based therapy were further categorized as arthritis, craniomaxillofacial defects, tendon/ligament related disorders, and spine disorders, and their brief characterization as well as the corresponding conventional therapeutic approaches with possible mechanisms with which ADSCs produce regenerative effects in disease-specific microenvironments were discussed to provide an overview of under which circumstances and on what bases the ADSC-based cell therapy was implemented. Providing an overview of the current status of ADSC-based cell therapy on MSDs can help to develop better and optimized strategies of ADSC-based therapeutics for MSDs as well as help to find novel clinical applications of ADSCs in the near future.


Subject(s)
Adipose Tissue/cytology , Cell- and Tissue-Based Therapy/methods , Mesenchymal Stem Cells/cytology , Musculoskeletal Diseases/therapy , Regenerative Medicine/methods , Stem Cell Transplantation/methods , Animals , Cell Differentiation , Clinical Trials as Topic/methods , Clinical Trials as Topic/statistics & numerical data , Humans , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/physiopathology
12.
J Zoo Wildl Med ; 52(1): 133-144, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33827170

ABSTRACT

The mountain chicken frog (Leptodactylus fallax) is the largest endemic amphibian species in the Western Hemisphere. Since 1998, this critically endangered species has been maintained as a European Endangered Species Programme, but low breeding success and a high mortality rate threaten the sustainability of the captive frog population. In the current study, we analyzed gross and histopathologic postmortem information from 212 mountain chicken frogs that died in European zoological collections from 1998 to 2018. Thin body condition was the most commonly reported finding across all submissions, observed in 125 frogs. The gastrointestinal and urinary systems were reported to have the highest prevalence of pathologic findings on gross and histopathologic examination. Inflammatory disease was the most frequent diagnosis after histopathologic examination of relevant tissues, with intestinal inflammatory disease (n = 76) followed by tubulointerstitial nephritis (n = 26) being the most commonly reported. Neoplasia was reported in 42 of 212 (19.8%) frogs, all of which were adults. A defined cause of death, or reason for euthanasia, was proposed for 164 of 212 (77.4%) frogs, with inflammatory diseases processes (74 of 212; 34.9%) most commonly implicated. Intestinal adenocarcinoma, seemingly restricted to the colon, caused the deaths of 31 adult frogs. Further investigations to determine factors contributing to the high incidence of inflammatory disease processes and neoplasia are advocated to improve the health and sustainability of the captive mountain chicken frog population.


Subject(s)
Anura , Endangered Species , Gastrointestinal Diseases/veterinary , Musculoskeletal Diseases/veterinary , Urologic Diseases/veterinary , Animals , Animals, Zoo , Digestive System Diseases/pathology , Digestive System Diseases/veterinary , Europe , Gastrointestinal Diseases/pathology , Musculoskeletal Diseases/pathology , Retrospective Studies , Urologic Diseases/pathology
13.
Med Care ; 58(12): 1082-1090, 2020 12.
Article in English | MEDLINE | ID: mdl-32925458

ABSTRACT

BACKGROUND: Military service confers an increased risk for musculoskeletal (MSK) injury among women and men Veterans. OBJECTIVE: The objective of this study was to determine the prevalence of MSK conditions at first visit to Veterans Affairs (VA), and the incidence rates of new MSK conditions in women and men Veterans with and without a baseline MSK condition. DESIGN: A cohort study including Veterans whose end of last deployment was between October 1, 2001 and October 1, 2015. SUBJECTS: A total of 765,465 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans. MAIN OUTCOME MEASURES: Prevalent and incident MSK conditions identified through the International Classification of Diseases, ninth Revision, Clinical Modification diagnostic codes. RESULTS: Twenty-six percent of women and 29% of men present to the VA with a MSK condition. In those without an MSK diagnosis at baseline, the unadjusted rate of developing at least 1 MSK condition was 168 and 180 per 1000 person-year [hazard ratio (HR)=0.94; 95% confidence interval (CI)=0.92-0.95] in women and men. Women were more likely to develop newly diagnosed MSK conditions of the hip (HR=1.9; 95% CI=1.83-1.98) or the ankle/foot (HR=1.17; 95% CI=1.15-1.20) and less likely to develop MSK conditions of the upper extremity (HR=0.75; 95% CI=0.73-0.78), knee (HR=0.87; 95% CI=0.86-0.89), and spine (HR=0.94; 95% CI=0.93-0.96). In those with prevalent MSK conditions at baseline, the rate of developing a second MSK condition was higher in women than men (151 and 133/1000 person-year; HR=1.13; 95% CI=1.11-1.15). CONCLUSIONS: A high proportion of Veterans present to the VA with MSK conditions. Women are less likely to develop conditions related to the upper extremities, spine or knee, and more likely to have conditions of the hip or ankle/foot.


Subject(s)
Afghan Campaign 2001- , Military Deployment/statistics & numerical data , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/pathology , Veterans/statistics & numerical data , Adult , Female , Humans , Male , Sex Factors , Socioeconomic Factors , United States , Young Adult
14.
Am J Med Genet A ; 182(4): 842-865, 2020 04.
Article in English | MEDLINE | ID: mdl-32091187

ABSTRACT

Osteogenesis imperfecta (OI) is a rare genetic disorder of the bones caused by a mutation in Type I collagen genes. As adults with OI are aging, medical concerns secondary to OI may arise. This integrative review sought to review, appraise, and synthesize the clinical manifestations faced by adults with OI. Four electronic bibliographic databases were searched. Published quantitative, qualitative, and mixed-methods studies, as well as case reports from 2000 to March 2019, addressing a clinical manifestation in adulthood, were reviewed. Eligible studies and case reports were subsequently appraised using the Mixed Methods Appraisal Tool and Case Report Checklist, respectively. Twenty quantitative studies and 88 case reports were included for review regardless of the varying methodological quality score. These studies collectively included 2,510 adults with different OI types. Several clinical manifestations were studied, and included: hearing loss, cardiac diseases, pregnancy complications, cerebrovascular manifestations, musculoskeletal manifestations, respiratory manifestations, vision impairment, and other clinical manifestations. Increased awareness may optimize prevention, treatment, and follow-up. Opportunities to enhance the methodological quality of research including better design and methodology, multisite collaborations, and larger and diverse sampling will optimize the generalizability and transferability of findings.


Subject(s)
Cerebrovascular Disorders/pathology , Hearing Loss/pathology , Heart Diseases/pathology , Musculoskeletal Diseases/pathology , Osteogenesis Imperfecta/complications , Respiratory Insufficiency/pathology , Vision Disorders/pathology , Adult , Cerebrovascular Disorders/etiology , Hearing Loss/etiology , Heart Diseases/etiology , Humans , Musculoskeletal Diseases/etiology , Prognosis , Respiratory Insufficiency/etiology , Vision Disorders/etiology
15.
J Pathol ; 247(1): 9-20, 2019 01.
Article in English | MEDLINE | ID: mdl-30246251

ABSTRACT

Bone morphogenetic proteins (BMPs) are secreted cytokines that were initially discovered on the basis of their ability to induce bone. Several decades of research have now established that these proteins function in a large variety of physiopathological processes. There are about 15 BMP family members, which signal via three transmembrane type II receptors and four transmembrane type I receptors. Mechanistically, BMP binding leads to phosphorylation of the type I receptor by the type II receptor. This activated heteromeric complex triggers intracellular signaling that is initiated by phosphorylation of receptor-regulated SMAD1, 5, and 8 (also termed R-SMADs). Activated R-SMADs form heteromeric complexes with SMAD4, which engage in specific transcriptional responses. There is convergence along the signaling pathway and, besides the canonical SMAD pathway, BMP-receptor activation can also induce non-SMAD signaling. Each step in the pathway is fine-tuned by positive and negative regulation and crosstalk with other signaling pathways. For example, ligand bioavailability for the receptor can be regulated by ligand-binding proteins that sequester the ligand from interacting with receptors. Accessory co-receptors, also known as BMP type III receptors, lack intrinsic enzymatic activity but enhance BMP signaling by presenting ligands to receptors. In this review, we discuss the role of BMP receptor signaling and how corruption of this pathway contributes to cardiovascular and musculoskeletal diseases and cancer. We describe pharmacological tools to interrogate the function of BMP receptor signaling in specific biological processes and focus on how these agents can be used as drugs to inhibit or activate the function of the receptor, thereby normalizing dysregulated BMP signaling. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Subject(s)
Bone Morphogenetic Protein Receptors/metabolism , Bone Morphogenetic Proteins/metabolism , Cardiovascular Diseases/metabolism , Musculoskeletal Diseases/metabolism , Neoplasms/metabolism , Signal Transduction , Animals , Bone Morphogenetic Protein Receptors/genetics , Bone Morphogenetic Proteins/genetics , Cardiovascular Diseases/genetics , Cardiovascular Diseases/pathology , Cardiovascular Diseases/physiopathology , Humans , Ligands , Musculoskeletal Diseases/genetics , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/physiopathology , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/physiopathology , Phosphorylation , Smad Proteins, Receptor-Regulated/metabolism
16.
BMC Endocr Disord ; 20(1): 124, 2020 Aug 14.
Article in English | MEDLINE | ID: mdl-32795274

ABSTRACT

BACKGROUND: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. METHODS: Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. RESULTS: The body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. CONCLUSION: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.


Subject(s)
Endothelium, Vascular/diagnostic imaging , Heart/diagnostic imaging , Liver/diagnostic imaging , Musculoskeletal System/diagnostic imaging , Obesity/diagnosis , Anatomy, Cross-Sectional , Animals , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Heart/physiopathology , Intercellular Adhesion Molecule-1/metabolism , Liver/physiopathology , Male , Musculoskeletal Diseases/diagnosis , Musculoskeletal Diseases/etiology , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/physiopathology , Musculoskeletal System/pathology , Musculoskeletal System/physiopathology , Myocardium/pathology , Obesity/complications , Obesity/physiopathology , Rats , Rats, Sprague-Dawley , Ultrasonography , Vascular Diseases/diagnosis , Vascular Diseases/etiology , Vascular Diseases/pathology , Vascular Diseases/physiopathology , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathology
17.
BMC Musculoskelet Disord ; 21(1): 57, 2020 Jan 30.
Article in English | MEDLINE | ID: mdl-32000751

ABSTRACT

BACKGROUND: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. METHODS: Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF; 2 h/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. RESULTS: 10-wk HRHF rats had higher serum levels of IL-1α, IL-1ß and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1ß and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. CONCLUSIONS: Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.


Subject(s)
Exercise Test/adverse effects , Forelimb/pathology , Inflammation Mediators/blood , Musculoskeletal Diseases/blood , Musculoskeletal Diseases/pathology , Running/physiology , Animals , Exercise Test/methods , Female , Forelimb/metabolism , Inflammation/blood , Inflammation/metabolism , Inflammation/pathology , Musculoskeletal Diseases/metabolism , Rats , Rats, Sprague-Dawley
18.
Skeletal Radiol ; 49(2): 257-262, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31327022

ABSTRACT

OBJECTIVE: The purpose of this study is first to determine the clinical utility of the postprocedure scan in detecting postinterventional complications after CT-guided musculoskeletal biopsies, and second to evaluate the contribution to the radiation dose of the postprocedural CT scan. MATERIALS AND METHODS: Retrospective analysis of 500 consecutive CT-guided musculoskeletal biopsies over an 18-month period from 29 March 2017 to 28 September 2018, where spiral postprocedure scans were obtained in every case. To assess the clinical utility of postinterventional CT scans, it was determined whether immediate post-procedural complications were detected on the postprocedural scans only or were also seen on the procedural images. To evaluate the relative radiation exposure of postprocedural scans, a ratio was obtained of the dose-length product (DLP) of the postprocedural scan compared with the total DLP of each case. RESULTS: A total of 397 bone biopsies and 103 soft-tissue biopsies were performed in 471 patients. The immediate postprocedural complication rate was 0.4% (2 out of 500) in all procedures. Both complications were minor (small hematomas) and detected only on postinterventional CT scans. The average total DLP for the procedures was 383.5 mGy*cm. The average DLP of the postprocedural scan was 64.0 mGy*cm. The average radiation dose contribution of the postprocedural CT scans toward the total DLP was 17.4%. CONCLUSION: Immediate postprocedural complications in CT-guided musculoskeletal interventions are rare. When complications do occur, they are usually minor. To substantially reduce radiation dose, postinterventional CT scans should not be performed routinely.


Subject(s)
Musculoskeletal Diseases/diagnostic imaging , Musculoskeletal Diseases/pathology , Radiography, Interventional/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Female , Humans , Image-Guided Biopsy , Male , Middle Aged , Muscles/diagnostic imaging , Muscles/pathology , Radiation Dosage , Retrospective Studies , Young Adult
19.
J Med Internet Res ; 22(4): e15822, 2020 04 24.
Article in English | MEDLINE | ID: mdl-32329746

ABSTRACT

BACKGROUND: Online support groups (OSGs) are one way for people with chronic diseases, their family or friends, and health professionals to communicate, gain information, and provide social support. As the number of peer-to-peer OSGs for chronic musculoskeletal conditions grows, it is important to gain insight into the different designs of groups available, who is accessing them, if and how they may be effective, and what strategies are being used to implement or increase consumer engagement. OBJECTIVE: The objectives of this systematic review of people with musculoskeletal conditions were to (1) describe the design features (functions, usage options, moderation, and expert input) of peer-to-peer OSGs, (2) describe the characteristics of the individuals using peer-to-peer OSGs, (3) synthesize the evidence on outcomes of participation, and (4) identify strategies used in the delivery and maintenance of OSGs. METHODS: A search comprising terms related to the population (people with musculoskeletal disorders) and the intervention (peer-to-peer OSGs) was conducted in 6 databases. Results were filtered from 1990 (internet inception) to February 2019. Studies identified in the search were screened according to predefined eligibility criteria using a 2-step process. Quantitative studies were appraised by 2 reviewers using the Risk Of Bias In Non-Randomized Studies of Interventions tool. Qualitative studies were appraised by 2 different reviewers using the Critical Appraisal Skills Programme checklist. Extracted data were synthesized narratively. RESULTS: We examined 21 studies with low to moderate risk of bias. Of these studies, 13 studies included OSGs hosted on public platforms, 11 studies examined OSGs that were conducted in English, and 6 studies used moderators or peer leaders to facilitate engagement. Studies either reported the number of OSG members (n=1985 across all studies) or the number of posts (range: 223-200,000). The majority of OSG members were females who were not full-time employees and with varied levels of education. There were no randomized controlled trials measuring the efficacy of OSGs. Qualitative and quantitative studies identified empowerment, social support, self-management behavior, and health literacy as primary constructs to measure OSG efficacy. Neutral or marginal improvement was reported in these constructs. Sharing experiences and a greater level of engagement appeared to have an important influence on OSGs efficacy. The extent to which members posted on the website influenced engagement. CONCLUSIONS: Across a diverse range of designs, languages, included features, and delivery platforms, peer-to-peer OSGs for chronic musculoskeletal conditions attract predominantly female participants of all ages and education levels. The level of participation of a member appears to be related to their perceived benefit, health literacy, and empowerment. Future studies are needed to identify which design and maintenance strategies have superior efficacy and whether there are concomitant improvements in health outcomes for people with chronic musculoskeletal conditions resulting from participation in OSGs. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42018090326; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018090326.


Subject(s)
Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/psychology , Musculoskeletal Diseases/therapy , Peer Group , Telemedicine/methods , Chronic Disease , Female , Humans , Male , Qualitative Research , Self-Help Groups , Treatment Outcome
20.
J Korean Med Sci ; 35(39): e348, 2020 Oct 12.
Article in English | MEDLINE | ID: mdl-33045771

ABSTRACT

BACKGROUND: This study aimed to describe the experience of providing older adult patients with transitional care from an acute care hospital to home in cooperation with a public health center, in order to present the barriers to that care and suggest better organizational methods. METHODS: This was a cross-sectional study to show the results of the Geriatric Screening for Care-10 (GSC-10) and outcomes of transitional care. Among 659 hospitalized patients aged 65 years or above who lived in an administrative district, forty-five subjects were enrolled between June 24, 2019 and January 23, 2020. Within 48 hours of admission, using the 10 areas of GSC-10, they were assessed for cognitive impairment, depression, polypharmacy (5 or more medications), functional mobility, dysphagia, malnutrition, pain, and incontinence, and were reassessed before discharge. The transitional care plan (containing the treatment summary, the results of the GSC-10 assessment, and the post-discharge plan) was forwarded to a representative of the public health center, who provided continued disease management and various health care services, such as chronic disease and frailty care, and physical rehabilitation. RESULTS: Of all the participants, 64.4% had more than 1 GSC-10 concern. The most prevalent concerns were functional immobility (35.6%) and polypharmacy (22.2%). About 15.6% of the participants were readmitted to a nursing home or hospital. A total of 38 participants received the transitional care intervention. They received an average of 2.7 administered interventions. However, the rate of rejection was high (30.1%) and patients were visited an average of 16.5 days after discharge. CONCLUSION: Through our experience of providing transitional care from an acute care hospital to home in cooperation with a public health center, we expect that the transitional care suitable for the Korean medical situation could be established and successful.


Subject(s)
Home Care Services , Patients/psychology , Transitional Care , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Gastrointestinal Diseases/pathology , Geriatric Assessment , Hospitals , Humans , Male , Musculoskeletal Diseases/pathology , Nurses/psychology , Nursing Homes , Patient Discharge , Polypharmacy
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