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2.
J Cardiothorac Surg ; 15(1): 91, 2020 May 12.
Article in English | MEDLINE | ID: mdl-32398105

ABSTRACT

BACKGROUND: Thoracic surgeons have been incorporating enhanced recovery after surgery (ERAS) protocols into their practices, not only to reduce narcotic usage but also to improve complication rates and decrease lengths of stay. Here, we describe the utility of a regional block technique that can be used for patients undergoing urgent or elective thoracic surgical procedures or suffering from rib fractures. METHODS: We report our initial one-year experience with these erector spinae plane (ESP) blocks. RESULTS: ESP blocks were placed in 42 patients. The procedure was performed by a trained team of anesthesiologists and certified nurse practitioners. It included placement of a catheter on the ipsilateral chest, followed by a 20 ml of 0.2% ropivacaine bolus and continuous infusion. Patients were then followed by the regional team, as long as the catheter was in place. While it had some technical challenges, the block was effective in 83.3% of patients with no reported mortality or major complications. However, given the confounding factors of the study (such as simultaneous implementation of ERAS protocol) and heterogeneity of the patient population, a control group was difficult to ascertain and meaningful opioid consumption analysis was difficult to perform. CONCLUSIONS: Regional blocks, such as the ESP block, complement fundamental ERAS principles and serve as an adjunct to the available armamentarium for non-narcotic ways to control pain in thoracic surgical and chest trauma patients. Continued collaboration between the thoracic surgeons and anesthesiologists is needed for its success.


Subject(s)
Anesthetics, Local , Musculoskeletal Pain/therapy , Nerve Block/methods , Pain Management/methods , Paraspinal Muscles , Ropivacaine , Adult , Aged , Aged, 80 and over , Enhanced Recovery After Surgery , Female , Humans , Male , Middle Aged , Musculoskeletal Pain/etiology , Rib Fractures/complications , Thoracic Surgical Procedures , Thorax
3.
Cell Stem Cell ; 27(1): 158-176.e10, 2020 07 02.
Article in English | MEDLINE | ID: mdl-32396864

ABSTRACT

The developmental trajectory of human skeletal myogenesis and the transition between progenitor and stem cell states are unclear. We used single-cell RNA sequencing to profile human skeletal muscle tissues from embryonic, fetal, and postnatal stages. In silico, we identified myogenic as well as other cell types and constructed a "roadmap" of human skeletal muscle ontogeny across development. In a similar fashion, we also profiled the heterogeneous cell cultures generated from multiple human pluripotent stem cell (hPSC) myogenic differentiation protocols and mapped hPSC-derived myogenic progenitors to an embryonic-to-fetal transition period. We found differentially enriched biological processes and discovered co-regulated gene networks and transcription factors present at distinct myogenic stages. This work serves as a resource for advancing our knowledge of human myogenesis. It also provides a tool for a better understanding of hPSC-derived myogenic progenitors for translational applications in skeletal muscle-based regenerative medicine.


Subject(s)
Muscle Development , Pluripotent Stem Cells , Cell Differentiation , Humans , Muscle, Skeletal , Transcription Factors
4.
Nat Cell Biol ; 20(1): 46-57, 2018 01.
Article in English | MEDLINE | ID: mdl-29255171

ABSTRACT

Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenicity of hPSC-SMPCs relative to human fetal or adult satellite cells remains unclear. We observed that hPSC-SMPCs derived by directed differentiation are less functional in vitro and in vivo compared to human satellite cells. Using RNA sequencing, we found that the cell surface receptors ERBB3 and NGFR demarcate myogenic populations, including PAX7 progenitors in human fetal development and hPSC-SMPCs. We demonstrated that hPSC skeletal muscle is immature, but inhibition of transforming growth factor-ß signalling during differentiation improved fusion efficiency, ultrastructural organization and the expression of adult myosins. This enrichment and maturation strategy restored dystrophin in hundreds of dystrophin-deficient myofibres after engraftment of CRISPR-Cas9-corrected Duchenne muscular dystrophy human induced pluripotent stem cell-SMPCs. The work provides an in-depth characterization of human myogenesis, and identifies candidates that improve the in vivo myogenic potential of hPSC-SMPCs to levels that are equal to directly isolated human fetal muscle cells.


Subject(s)
Muscle Development/genetics , Muscle Fibers, Skeletal/metabolism , Muscular Dystrophy, Duchenne/genetics , Myoblasts/metabolism , Nerve Tissue Proteins/genetics , Receptor, ErbB-3/genetics , Receptors, Nerve Growth Factor/genetics , Adult , Aged , CRISPR-Cas Systems , Cell Differentiation , Dystrophin/genetics , Dystrophin/metabolism , Female , Gene Editing , Gene Expression Regulation, Developmental , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Male , Middle Aged , Muscle Fibers, Skeletal/cytology , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/pathology , Muscular Dystrophy, Duchenne/therapy , Myoblasts/cytology , Myosins/genetics , Myosins/metabolism , Nerve Tissue Proteins/metabolism , PAX7 Transcription Factor/genetics , PAX7 Transcription Factor/metabolism , Receptor, ErbB-3/metabolism , Receptors, Nerve Growth Factor/metabolism , Signal Transduction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
5.
World J Gastroenterol ; 23(10): 1891-1898, 2017 Mar 14.
Article in English | MEDLINE | ID: mdl-28348496

ABSTRACT

AIM: To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS: From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS: The EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION: The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.


Subject(s)
Body Image/psychology , Colorectal Neoplasms/psychology , Psychometrics/methods , Quality of Life , Surgical Stomas/adverse effects , Adult , Aged , Asian People/psychology , China/epidemiology , Colorectal Neoplasms/complications , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Female , Humans , Karnofsky Performance Status , Male , Middle Aged , Reproducibility of Results , Surveys and Questionnaires
6.
Cell Rep ; 18(6): 1573-1585, 2017 02 07.
Article in English | MEDLINE | ID: mdl-28178531

ABSTRACT

Somites form during embryonic development and give rise to unique cell and tissue types, such as skeletal muscles and bones and cartilage of the vertebrae. Using somitogenesis-stage human embryos, we performed transcriptomic profiling of human presomitic mesoderm as well as nascent and developed somites. In addition to conserved pathways such as WNT-ß-catenin, we also identified BMP and transforming growth factor ß (TGF-ß) signaling as major regulators unique to human somitogenesis. This information enabled us to develop an efficient protocol to derive somite cells in vitro from human pluripotent stem cells (hPSCs). Importantly, the in-vitro-differentiating cells progressively expressed markers of the distinct developmental stages that are known to occur during in vivo somitogenesis. Furthermore, when subjected to lineage-specific differentiation conditions, the hPSC-derived somite cells were multipotent in generating somite derivatives, including skeletal myocytes, osteocytes, and chondrocytes. This work improves our understanding of human somitogenesis and may enhance our ability to treat diseases affecting somite derivatives.


Subject(s)
Embryonic Development/physiology , Morphogenesis/physiology , Pluripotent Stem Cells/physiology , Somites/physiology , Body Patterning/physiology , Cell Differentiation/physiology , Cells, Cultured , Gene Expression Regulation, Developmental/physiology , Humans , Mesoderm/metabolism , Mesoderm/physiology , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiology , Pluripotent Stem Cells/metabolism , Signal Transduction/physiology , Somites/metabolism , Transforming Growth Factor beta/metabolism , beta Catenin/metabolism
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