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Article ; Online: Use of Intravenous Immunoglobulins in Patients with Suspected Toxin-Mediated Shock Requiring Extracorporeal Membrane Oxygenation.

Peetermans, Marijke / Wan, Ruth Y Y / Camporota, Luigi / Barrett, Nicholas A / Retter, Andrew

2020 Volume 54, Issue 2, Page(s) 209–212

Abstract: Background: Toxin-producing, gram-positive bacteria can lead to severe and refractory septic shock with high attributable mortality. Adjunctive therapies such as intravenous immunoglobulins (IVIG) have been proposed for these patients. However, at ... ...

Abstract	Background: Toxin-producing, gram-positive bacteria can lead to severe and refractory septic shock with high attributable mortality. Adjunctive therapies such as intravenous immunoglobulins (IVIG) have been proposed for these patients. However, at presentation the presence of a toxin-producing organism is most often unknown. As IVIG is a potentially valuable but also limited resource, we investigated the use of IVIG in our critically ill patients requiring extracorporeal membrane oxygenation (ECMO). Materials and methods: Retrospective cohort study (April 2016 to March 2018) of adult patients with clinically suspected toxin-mediated shock requiring ECMO and who received IVIG in our regional severe respiratory failure (SRF)/ECMO center. Results: In 44% (15/34) of the patients, group A Streptococcus or Panton-Valentine Leukocidin producing S aureus was isolated. IVIG use in these patients was safe. The mortality was 30%, lower than the predicted mortality of >90% based on the SOFA scores. Conclusion: IVIG administration can be considered in a selected group of patients presenting with acute and very severe septic shock.
MeSH term(s)	Adult ; Extracorporeal Membrane Oxygenation ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Shock, Septic/drug therapy ; Shock, Septic/therapy
Chemical Substances	Immunoglobulins, Intravenous
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0000000000001519
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Zs.A 3985: Show issues

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Article ; Online: Sedation with alfentanil versus fentanyl in patients receiving extracorporeal membrane oxygenation: outcomes from a single-centre retrospective study.

Barker, Mike / Dixon, Alison A / Camporota, Luigi / Barrett, Nick A / Wan, Ruth Y Y

Perfusion

2019 Volume 35, Issue 2, Page(s) 104–109

Abstract: Introduction: In November 2016, our institution switched from alfentanil to fentanyl for analgesia and sedation in adult patients receiving extracorporeal membrane oxygenation. There is no published evidence comparing the use of alfentanil with fentanyl ...

Abstract	Introduction: In November 2016, our institution switched from alfentanil to fentanyl for analgesia and sedation in adult patients receiving extracorporeal membrane oxygenation. There is no published evidence comparing the use of alfentanil with fentanyl for sedation in extracorporeal membrane oxygenation patients. We conducted a retrospective observational study to explore any significant differences in patient outcomes or in the prescribing of adjunct sedatives before and after the switch. Methods: Patients were retrospectively identified from a prospectively recorded database of all patients who received extracorporeal membrane oxygenation at our institution between January 2016 and October 2017. Patients included those sedated with alfentanil or fentanyl. The total daily doses of intravenous opioids (alfentanil or fentanyl) were calculated for each patient, and the prescribing of adjunctive sedative or analgesic agents was recorded. Patient demographics, extracorporeal membrane oxygenation modality, clinical outcomes including mortality and length of intensive care and hospital stay were recorded. Results: A total of 174 patients were identified, 69 on alfentanil and 95 on fentanyl. There was no difference found between groups for mode of extracorporeal membrane oxygenation, age, Acute Physiology and Chronic Health Evaluation 2 score (APACHE II) and Charlson score, except for body mass index (p = 0.002). No differences in patient outcomes was observed between groups, although patients in the alfentanil group received a significantly higher median total daily dose of adjuvant sedatives (quetiapine (p = 0.016) and midazolam (p = 0.009)). Conclusions: No differences in patient outcomes were found between extracorporeal membrane oxygenation patients sedated with alfentanil compared with fentanyl. There was a statistically significant reduction in some adjunctive sedatives in patients managed with a fentanyl-based regimen. Prospective studies are required to confirm these results.
MeSH term(s)	Adult ; Alfentanil/pharmacology ; Alfentanil/therapeutic use ; Extracorporeal Membrane Oxygenation/methods ; Female ; Fentanyl/pharmacology ; Fentanyl/therapeutic use ; Humans ; Male ; Middle Aged ; Narcotics/pharmacology ; Narcotics/therapeutic use ; Prospective Studies ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Narcotics ; Alfentanil (1N74HM2BS7) ; Fentanyl (UF599785JZ)
Language	English
Publishing date	2019-07-12
Publishing country	England
Document type	Journal Article
ZDB-ID	645038-6
ISSN	1477-111X ; 0267-6591
ISSN (online)	1477-111X
ISSN	0267-6591
DOI	10.1177/0267659119858037
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Article ; Online: Dietary Intake of Anti-Oxidant Vitamins A, C, and E Is Inversely Associated with Adverse Cardiovascular Outcomes in Chinese-A 22-Years Population-Based Prospective Study.

Lee, Chi-Ho / Chan, Ruth S M / Wan, Helen Y L / Woo, Yu-Cho / Cheung, Chloe Y Y / Fong, Carol H Y / Cheung, Bernard M Y / Lam, Tai-Hing / Janus, Edward / Woo, Jean / Lam, Karen S L

Nutrients

2018 Volume 10, Issue 11

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adult ; Aged ; Antioxidants/administration & dosage ; Ascorbic Acid/administration & dosage ; Asian Continental Ancestry Group ; Blood Glucose/metabolism ; Body Mass Index ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Cardiovascular System/metabolism ; Cholesterol/blood ; Diet ; Dietary Fiber/administration & dosage ; Female ; Follow-Up Studies ; Hong Kong/epidemiology ; Humans ; Male ; Middle Aged ; Potassium/urine ; Prevalence ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Sodium/urine ; Triglycerides/blood ; Vitamin A/administration & dosage ; Vitamin E/administration & dosage ; Waist Circumference
Chemical Substances	Antioxidants ; Blood Glucose ; Dietary Fiber ; Triglycerides ; Vitamin A (11103-57-4) ; Vitamin E (1406-18-4) ; Cholesterol (97C5T2UQ7J) ; Sodium (9NEZ333N27) ; Ascorbic Acid (PQ6CK8PD0R) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2018-11-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu10111664
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Article ; Online: Risk factor management of atrial fibrillation using mHealth: The Atrial Fibrillation - Helping Address Care with Remote Technology (AF-HEART) Pilot Study.

Mitrani, Lindsey R / Goldenthal, Isaac / Leskowitz, Jamie / Wan, Elaine Y / Dizon, Jose / Saluja, Deepak / Creber, Ruth Masterson / Turchioe, Megan Reading / Sciacca, Robert R / Garan, Hasan / Hickey, Kathleen T / Korner, Judith / Biviano, Angelo B

Cardiovascular digital health journal

2021 Volume 3, Issue 1, Page(s) 14–20

Abstract: Background: Personalized treatment of atrial fibrillation (AF) risk factors using mHealth and telehealth may improve patient outcomes.: Objective: The purpose of this study was to assess the feasibility of the Atrial Fibrillation Helping Address Care ...

Abstract	Background: Personalized treatment of atrial fibrillation (AF) risk factors using mHealth and telehealth may improve patient outcomes. Objective: The purpose of this study was to assess the feasibility of the Atrial Fibrillation Helping Address Care with Remote Technology (AF-HEART) intervention on the following patient outcomes: (1) heart rhythm tracking; (2) weight, alcohol, blood pressure (BP), and sleep apnea reduction; (3) AF symptom reduction; and (4) quality-of-life (QOL) improvement. Methods: A total of 20 patients with AF undergoing antiarrhythmic therapy, cardioversion, and/or catheter ablation were enrolled and followed for 6 months. The AF-HEART intervention included remote heart rhythm, weight, and BP tracking; televisits with a dietician focusing on AF risk factors; and referrals for sleep apnea and hypertension treatment. Results: Patients transmitted a median of 181 rhythm recordings during the 6-month follow-up period. Patients lost an average of 3.5 kilograms at 6 months ( Conclusion: This study described the feasibility of the AF-HEART intervention for (1) consistent remote tracking of heart rhythm, weight, and BP; (2) achievement of weight loss; (3) reduction of symptoms; and (4) improvement in QOL. Expansion to a larger randomized study is planned.
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Journal Article
ISSN	2666-6936
ISSN (online)	2666-6936
DOI	10.1016/j.cvdhj.2021.11.003
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Article ; Online: Progressive retinal changes in pediatric multiple sclerosis.

Multiple sclerosis and related disorders

2022 Volume 61, Page(s) 103761

Abstract: Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS). Methods We acquired optical coherence tomography (OCT) data ( ... ...

Abstract	Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS). Methods We acquired optical coherence tomography (OCT) data (follow-up range: 2 weeks - 5 years, at variable intervals from presentation) in pediatric participants who had multiple sclerosis (MS), monophasic ADS, or were healthy. Multivariable mixed effects models were used to assess the association of the number of demyelinating episodes (either optic neuritis [ON], or non-ON relapses) with changes in retinal nerve fiber layer (RNFL) or ganglion cell layer-inner plexiform layer (GCIPL) thickness. Results 64 OCT sans from 23 MS, and 33 scans from 12 monophasic ADS participants were compared with 68 scans from 62 healthy participants. The first ON episode had the biggest impact on RNFL or GCIPL thickness in monophasic ADS (RNFL: -7.9 µm, CI=5.5, p = 0.0056; GCIPL: -8.4 µm, CI=4.4, p = 0.0002) and MS (RNFL: -16 µm, CI = 3.7, p < 10
MeSH term(s)	Adolescent ; Child ; Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging ; Nerve Fibers ; Optic Neuritis/complications ; Optic Neuritis/diagnostic imaging ; Recurrence ; Retina/diagnostic imaging ; Retinal Diseases ; Retinal Ganglion Cells ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2022-03-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.103761
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Article: Dietary Intake of Anti-Oxidant Vitamins A, C, and E Is Inversely Associated with Adverse Cardiovascular Outcomes in Chinese—A 22-Years Population-Based Prospective Study

Lee, Chi-Ho / Chan, Ruth S. M / Wan, Helen Y. L / Woo, Yu-Cho / Cheung, Chloe Y. Y / Fong, Carol H. Y / Cheung, Bernard M. Y / Lam, Tai-Hing / Janus, Edward / Woo, Jean / Lam, Karen S. L

Nutrients. 2018 Nov. 04, v. 10, no. 11

2018

Abstract: Background: Conflicting and population-dependent findings have been reported from epidemiological studies on the associations of dietary intake of anti-oxidant vitamins with cardiovascular events. We investigated the prospective relationship between ... ...

Abstract	Background: Conflicting and population-dependent findings have been reported from epidemiological studies on the associations of dietary intake of anti-oxidant vitamins with cardiovascular events. We investigated the prospective relationship between dietary intake of anti-oxidant vitamins and incident adverse cardiovascular outcomes amongst Hong Kong Chinese. Methods: In this prospective population-based study, baseline dietary intake of anti-oxidant vitamins (A, C, and E) were assessed using a food frequency questionnaire in 875 Chinese participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) in 1995–1996. The adjusted hazard ratio (HR) of incident adverse cardiovascular outcomes, defined as the first recorded diagnosis of cardiovascular deaths, non-fatal myocardial infarction or non-fatal stroke, and coronary or other arterial revascularizations, was calculated per unit intake of each vitamin using multivariable Cox regression. Results: Over a median follow-up of 22 years, 85 participants (9.7%) developed adverse cardiovascular outcomes. Dietary intakes of vitamin A, C, and E were independently and inversely associated with incident adverse cardiovascular outcomes (HR 0.68, 95%CI 0.53–0.88, p = 0.003 for vitamin A; HR 0.66, 95%CI 0.52–0.85, p = 0.001 for vitamin C; and HR 0.57, 95%CI 0.38–0.86, p = 0.017 for vitamin E) after adjustments for conventional cardiovascular risk factors at baseline. Conclusions: Dietary intakes of anti-oxidant vitamins A, C, and E reduced the risk of adverse cardiovascular outcomes in Hong Kong Chinese.
Keywords	antioxidants ; ascorbic acid ; food frequency questionnaires ; food intake ; myocardial infarction ; prospective studies ; regression analysis ; risk factors ; risk reduction ; stroke ; vitamin A ; vitamin E ; China
Language	English
Dates of publication	2018-1104
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu10111664
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.

Darst, Burcu F / Saunders, Ed / Dadaev, Tokhir / Sheng, Xin / Wan, Peggy / Pooler, Loreall / Xia, Lucy Y / Chanock, Stephen / Berndt, Sonja I / Wang, Ying / Patel, Alpa V / Albanes, Demetrius / Weinstein, Stephanie J / Gnanapragasam, Vincent / Huff, Chad / Couch, Fergus J / Wolk, Alicja / Giles, Graham G / Nguyen-Dumont, Tu /

Milne, Roger L / Pomerantz, Mark M / Schmidt, Julie A / Travis, Ruth C / Key, Timothy J / Stopsack, Konrad H / Mucci, Lorelei A / Catalona, William J / Marosy, Beth / Hetrick, Kurt N / Doheny, Kimberly F / MacInnis, Robert J / Southey, Melissa C / Eeles, Rosalind A / Wiklund, Fredrik / Conti, David V / Kote-Jarai, Zsofia / Haiman, Christopher A

JAMA oncology

2023 Volume 9, Issue 11, Page(s) 1514–1524

Abstract: Importance: Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, gene panels are also likely to be incomplete ... ...

Abstract	Importance: Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, gene panels are also likely to be incomplete and missing genes that influence PCa risk and aggressive disease. Objective: To identify genes associated with aggressive PCa. Design, setting, and participants: A 2-stage exome sequencing case-only genetic association study was conducted including men of European ancestry from 18 international studies. Data analysis was performed from January 2021 to March 2023. Participants were 9185 men with aggressive PCa (including 6033 who died of PCa and 2397 with confirmed metastasis) and 8361 men with nonaggressive PCa. Exposure: Sequencing data were evaluated exome-wide and in a focused investigation of 29 DNA repair pathway and cancer susceptibility genes, many of which are included on gene panels. Main outcomes and measures: The primary study outcomes were aggressive (category T4 or both T3 and Gleason score ≥8 tumors, metastatic PCa, or PCa death) vs nonaggressive PCa (category T1 or T2 and Gleason score ≤6 tumors without known recurrence), and metastatic vs nonaggressive PCa. Results: A total of 17 546 men of European ancestry were included in the analyses; mean (SD) age at diagnosis was 65.1 (9.2) years in patients with aggressive PCa and 63.7 (8.0) years in those with nonaggressive disease. The strongest evidence of association with aggressive or metastatic PCa was noted for rare deleterious variants in known PCa risk genes BRCA2 and ATM (P ≤ 1.9 × 10-6), followed by NBN (P = 1.7 × 10-4). This study found nominal evidence (P < .05) of association with rare deleterious variants in MSH2, XRCC2, and MRE11A. Five other genes had evidence of greater risk (OR≥2) but carrier frequency differences between aggressive and nonaggressive PCa were not statistically significant: TP53, RAD51D, BARD1, GEN1, and SLX4. Deleterious variants in these 11 candidate genes were carried by 2.3% of patients with nonaggressive, 5.6% with aggressive, and 7.0% with metastatic PCa. Conclusions and relevance: The findings of this study provide further support for DNA repair and cancer susceptibility genes to better inform disease management in men with PCa and for extending testing to men with nonaggressive disease, as men carrying deleterious alleles in these genes are likely to develop more advanced disease.
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; DNA Repair ; BRCA1 Protein/genetics ; Neoplasm Grading ; Germ Cells/pathology ; DNA-Binding Proteins/genetics
Chemical Substances	BRCA1 Protein ; XRCC2 protein, human ; DNA-Binding Proteins
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2023.3482
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Article ; Online: Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

Lam, W K Jacky / King, Ann D / Miller, Jacob A / Liu, Zhiwei / Yu, Kelly J / Chua, Melvin L K / Ma, Brigette B Y / Chen, Ming Yuan / Pinsky, Benjamin A / Lou, Pei-Jen / Woo, John K S / Hsu, Wan-Lun / Simon, Julia / Doolan, Denise L / Waterboer, Tim / Hui, Edwin P / Li, Hui / Tsang, Raymond K / Wong, Kenneth C W /

Goh, Julian P / Vlantis, Alexander C / Ai, Qi Yong / Wong, Lun M / Abdullah, Victor / Lin, Jin Ching / Chen, Chien-Jen / Pfeiffer, Ruth M / Le, Quynh-Thu / Lee, Anne W M / Ji, Mingfang / Cao, Sumei / Ma, Jun / Chan, Anthony T C / Chan, K C Allen / Hildesheim, Allan

Journal of the National Cancer Institute

2023 Volume 115, Issue 4, Page(s) 355–364

Abstract: A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of ... ...

Abstract	A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.
MeSH term(s)	Humans ; Nasopharyngeal Carcinoma/diagnosis ; Nasopharyngeal Neoplasms/diagnosis ; Herpesvirus 4, Human/genetics ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Carcinoma ; Early Detection of Cancer/methods ; DNA, Viral/genetics
Chemical Substances	DNA, Viral
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djad012
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Article: Deep evaluation of the evolutionary history of the Heat Shock Factor (HSF) gene family and its expansion pattern in seed plants.

Liao, Yiying / Liu, Zhiming / Gichira, Andrew W / Yang, Min / Mbichi, Ruth Wambui / Meng, Linping / Wan, Tao

PeerJ

2022 Volume 10, Page(s) e13603

Abstract: Heat shock factor (HSF) genes are essential in some of the basic developmental pathways in plants. Despite extensive studies on the structure, functional diversification, and evolution of HSF genes, their divergence history and gene duplication pattern ... ...

Abstract	Heat shock factor (HSF) genes are essential in some of the basic developmental pathways in plants. Despite extensive studies on the structure, functional diversification, and evolution of HSF genes, their divergence history and gene duplication pattern remain unknown. To further illustrate the probable divergence patterns in these subfamilies, we analyzed the evolutionary history of HSF genes using phylogenetic reconstruction and genomic syntenic analyses, taking advantage of the increased sampling of genomic data from pteridophytes, gymnosperms and basal angiosperms. We identified a novel clade that includes HSFA2, HSFA6, HSFA7, and HSFA9 with a complex relationship, which is very likely due to orthologous or paralogous genes retained after frequent gene duplication events. We hypothesized that HSFA9 derives from HSFA2 through gene duplication in eudicots at the ancestral state, and then expanded in a lineage-specific way. Our findings indicate that HSFB3 and HSFB5 emerged before the divergence of ancestral angiosperms, but were lost in the most recent common ancestors of monocots. We also presumed that HSFC2 derives from HSFC1 in ancestral monocots. This work proposes that during the radiation of flowering plants, an era during which there was a differentiation of angiosperms, the size of the HSF gene family was also being adjusted with considerable sub- or neo-functionalization. The independent evolution of HSFs in eudicots and monocots, including lineage-specific gene duplication, gave rise to a new gene in ancestral eudicots and monocots, and lineage-specific gene loss in ancestral monocots. Our analyses provide essential insights for studying the evolutionary history of this multigene family.
Language	English
Publishing date	2022-08-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.13603
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Article ; Online: Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration.

Ransom, Ryan C / Carter, Ava C / Salhotra, Ankit / Leavitt, Tripp / Marecic, Owen / Murphy, Matthew P / Lopez, Michael L / Wei, Yuning / Marshall, Clement D / Shen, Ethan Z / Jones, Ruth Ellen / Sharir, Amnon / Klein, Ophir D / Chan, Charles K F / Wan, Derrick C / Chang, Howard Y / Longaker, Michael T

Nature

2018 Volume 563, Issue 7732, Page(s) 514–521

Abstract: During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton ... ...

Abstract	During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis-which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.
MeSH term(s)	Animals ; Bone Regeneration ; Chromatin/genetics ; Chromatin/metabolism ; Disease Models, Animal ; Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Gene Expression Regulation ; Male ; Mandible/cytology ; Mandible/physiology ; Mandible/surgery ; Mice ; Mice, Inbred C57BL ; Neural Crest/cytology ; Osteogenesis, Distraction ; Retroelements/genetics ; Signal Transduction ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription, Genetic
Chemical Substances	Chromatin ; Retroelements ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2)
Language	English
Publishing date	2018-10-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-018-0650-9
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