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Dystrophic calcification and heterotopic ossification in fibrocartilaginous tissues of the spine in diffuse idiopathic skeletal hyperostosis(DISH)

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Bone Research 2020年第2期8卷 209-218页

作者： Dale E.Fournier Patti K.Kiser ryan j.Beach S.j.ffrey Dixon Cheryle A.Séguin Health and Rehabilitation Sciences(Physical Therapy) Faculty of Health SciencesThe University of Western OntarioLondonON N6A 5B9Canada Bone and j.int Institute The University of Western OntarioLondonON N6G 2V4Canada Department of Laboratory Medicine and Pathology Schulich School of Medicine&DentistryThe University of Western OntarioLondonON N6A 5C1Canada Department of Physiology and Pharmacology Schulich School of Medicine&DentistryThe University of Western OntarioLondonON N6A 5C1Canada

Diffuse idiopathic skeletal hyperostosis(DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our obj.ctive was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors(one female and five males;median age 82 years)meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Overall,the histological features of ectopic mineralization at individual motion segments were heterogeneous, including regions of heterotopic ossification and dystrophic calcification. Heterotopic ossifications were characterized by woven and lamellar bone,multifocal areas of metaplastic cartilage, and bony bridges along the anterior aspect of the intervertebral disc space. Dystrophic calcifications were characterized by an amorphous appearance, a high content of calcium and phosphorus, an X-ray diffraction pattern matching that of hydroxyapatite, and radiodensities exceeding that of cortical bone. Dystrophic calcifications were found within the anterior longitudinal ligament and annulus fibrosus in motion segments both meeting and not meeting the radiographic criteria for DISH. In summary, our findings indicate that in DISH, ectopic mineral forms along the anterior aspect of the spine by both heterotopic ossification and dystrophic calcification of fibrocartilaginous tissues. Although both types of ectopic mineralization are captured by current radiographic criteria for DISH, dystrophic calcification may reflect a distinct disease process or an early stage in the pathogenesis of DISH.

关键词： DISH ossification calcification

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Identification of anticancer drugs to radiosensitise BRAF-wild-type and mutant colorectal cancer

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Cancer Biology & Medicine 2019年第2期16卷 234-246页

作者： Rebecca Carter Azadeh Cheraghchi-Bashi Adam Westhorpe Sheng Yu Yasmin Shanneik Elena Seraia Dj.mila Ouaret Yasuhiro Inoue Catherine Koch j.nny Wilding Daniel Ebner Anderson j. ryan Francesca M. Buffa Ricky A. Sharma NIHR University College London Hospitals Biomedical Research Centre/ UCL Cancer Institute University College London London WC1E 6DD UK NIHR Oxford Biomedical Research Centre Department of Oncology University of Oxford Oxford 0X1 2JD UK Computational Biology and Integrative Genomics University of Oxford Oxford 0X1 2JD UK NDM Research Building Nuffield Department of Medicine University of Oxford Oxford 0X1 2JD UK Weatherall Institute of Molecular Medicine John Radcliffe Hospital University of Oxford Oxford 0X1 2JD UK Mie University Graduate School of Medicine Department of Gastrointestinal and Pediatric Surgery Division of Reparative Medicine Institute of Life Sciences Edobashi 2-174 Tsu Japan Departme nt of Biology Massachusetts In stitute of Tech no logy Cambridge Massachusetts 02142 USA Target Discovery Institute National Phenotypic Screening Centre Nuffield Department of Medicine University of OxfordOxford 0X1 2JD UK CRUK & MRC Oxford Institute for Radiation Oncology University of Oxford Oxford 0X1 2JD UK

Obj.ctive: Patients with BRAF-mutant colorectal cancer(CRC) have a poor prognosis. Molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF ***: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in ***: Most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1(BRAF-wildtype) cells and 1.8 in RKO(BRAF V600 E) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth(P ≤ 0.01).Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds.

关键词： Radiosensitizer colorectal cancer PARP inhibitor radiotherapy

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Molecular regulation of sucrose catabolism and sugar transport for development~ defence and phloem function

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j.urnal of Integrative Plant Biology 2017年第5期59卷 322-335页

作者： j.n Li Limin Wu ryan Foster Yong-Ling Ruan Australia-China Research Centre for Crop Improvement and School of Environmental and Life Sciences The University of NewcastleNSW 2308 Australia CSIRO Agriculture Canberra ACT 26oi Australia

Sucrose （Suc） is the maj.r end product of photosynthesis in mesophyll cells of most vascular plants. It is loaded into phloem of mature leaves for long-distance translocation to non-photosynthetic organs where it is unloaded for diverse uses. Clearly, Suc transport and metabolism is central to plant growth and development and the functionality of the entire vascular system. Despite vast information in the literature about the physiological roles of individual sugar metabolic enzymes and transporters, there is a lack of systematic evaluation about their molecular regulation from transcriptional to post-translational levels. Knowledge on this topic is essential for understanding and improving plant development, optimizing resource distri- bution and increasing crop productivity. We therefore focused our analyses on molecular control of key players in Suc metabolism and transport, including：（i） the identifica- tion of promoter elements responsive to sugars and hormones or targeted by transcription factors and micro- RNAs degrading transcripts of target genes; and （ii） modulation of enzyme and transporter activities through protein-protein interactions and other post-translational modifications. We have highlighted maj.r remaining questions and discussed opportunities to exploit current understanding to gain new insights into molecular control of carbon partitioning for improving plant performance.

关键词： William j. Lucas University of California Davis USA

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Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rej.ction risk

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World j.urnal of Transplantation 2023年第4期13卷 138-146页

作者： Wai-Kit Lo ryan Flanagan Nirmal Sharma Hilary j.Goldberg Walter W Chan Division of Gastroenterology Hepatology and EndoscopyBrigham and Women's HospitalHarvard Medical SchoolBostonMA Division of Pulmonary and Critical Care Medicine Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States

BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic *** is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are *** To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with *** This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung *** with pretransplant anti-reflux surgery were *** characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were *** testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH ***-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic *** primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation *** analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards *** After applying inclusion and exclusion criteria,a total of 60 patients were included in the *** all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant *** evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subj.cts,representing 58%of the tested *** patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical

关键词： Cystic fibrosis Gastroesophageal reflux Lung transplantation pH monitoring

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Macrophages are the primary effector cells in IL-7-induced arthritis

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Cellular & Molecular Immunology 2020年第7期17卷 728-740页

作者： Seung-j.e Kim Huan j.Chang michael VVolin Sadiq Umar Katrien Van Raemdonck Aimee Chevalier Karol Palasiewicz j.hn W.Christman Suncica Volkov Shiva Arami Mehrdad Maz Anj.li Mehta ryan K.Zomorrodi David A.Fox Nadera Sweiss Shiva Shahrara Division of Rheumatology Jesse Brown VAMedical CenterChicagoIL 60612USA Department of Medicine Division of RheumatologyUniversity of Illinois at ChicagoChicagoIL 60612USA Department of Microbiology and Immunology Chicago College of Osteopathic MedicineMidwestern UniversityDowners GroveIL 60515USA Pulmonary Critical Care and Sleep MedicineOhio State University Wexner Medical CenterDavis Heart and Lung Research InstituteColumbusOH 43210USA Division of Allergy Clinical Immunology and RheumatologyThe University of Kansas Medical CenterKansas CityKS 66160USA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMI 481096USA

Synovial macrophages are crucial in the development of j.int inflammation and bone damage;however, the pathways that controlmacrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined thatelevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highlyresponsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), andtumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine *** local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480^(+)iNOS^(+) cells rather than CD3^(+)T cells. Ectopic LPS inj.ction stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ ***, in RAG−/− mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lackof IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in theunique F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) subset, with no impact on the F480^(+)Arginase^(+) cell or CD3^(+) T cell frequency. Consistent with thepreclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealedthat IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) cell function, which activates TH-1 cells to amplify myeloid IL-7Rexpression and disease severity.

关键词： myeloid elevated inflammation

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Subarachnoid and Peripheral Nerve Block in a Patient with Charcot-Marie-Tooth Disease

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Open j.urnal of Anesthesiology 2013年第1期3卷 44-47页

作者： Stinson T. Ritter ryan j. j.nse j.anna M. Davies Department of Anesthesiology and Pain Medicine University of Washington Seattle USA

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy characterized by progressive distal muscle weakness and wasting. If conservative treatment fails, or is not appropriately initiated, deformity, immobility and chronic pain may result. In severe cases, surgical intervention may be required. With the exception of case reports and case series, limited safety and efficacy data exists regarding the use of neuraxial and regional anesthesia for patients with CMT. This paper describes an anesthetic case report of a patient with CMT, and also provides a review of general and regional anesthetic considerations for this cohort. The purpose of this report is to highlight the potential benefits of neuraxial and regional anesthesia in patients with neuromuscular disorders, especially in settings where intra- and post-operative resources may be limited.

关键词： Charcot-Marie-Tooth Disease CMT Regional Anesthesia Neuraxial Anesthesia

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Expiratory Upper Airway Obstruction Caused by the Soft Palate during Bag-Mask Ventilation

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Open j.urnal of Anesthesiology 2012年第2期2卷 38-43页

作者： Charles W. Buffington Cynthia M. Q. Wells ryan j. Soose Departments of Anesthesiology and Otolaryngology University of Pittsburgh Pittsburgh USA Departments of Anesthesiology and Otolaryngology University of Pittsburgh Pittsburgh USA.

Introduction: Expiratory upper airway obstruction during bag-mask ventilation is not well characterized. Methods: An audit was done to assess expiratory obstruction in 90 adult surgical patients undergoing bag-mask ventilation during the induction of general anaesthesia. Results: Clinicians experienced difficulty delivering gas to the lungs when the head was neutral in 52 of 90 patients (58%;inspiratory obstruction) but this problem was corrected by head tilt and chin lift in all but 2 patients. Clinicians experienced difficulty recovering gas from the lungs when the mouth was held closed under the mask in 30 of the remaining 88 patients (34%;expiratory obstruction). This problem persisted despite head tilt and chin lift in all but one patient but was uniformly corrected by opening the mouth. Inspection of the soft palate revealed that it was lying on the posterior pharyngeal wall in 27 of 30 patients with expiratory obstruction and that the retropalatal space was patent in 55 of 58 patients without expiratory obstruction (χ2, P < 0.001). The clinical predictors of expiratory upper airway obstruction included advanced age, large tongue, and large uvula. Conclusion: Expiratory airway obstruction should be suspected in all cases of difficult mask ventilation that cannot be corrected by head tilt and chin lift. Simply allowing the mouth to open between positive pressure breaths will permit gas to exit the lungs.

关键词： Expiration Soft Palate Mask Ventilation

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A creative method to tune Fe–O interaction in ferrites

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先进陶瓷(英文) 2023年第8期12卷 1612-1624页

作者： Farshad Farshidfar Arash Fattahi Ralf Brüning Dominic H.ryan Khashayar Ghandi Department of Chemistry University of GuelphGuelph N1G 2W1Canada Physics Department Mount Allison UniversitySackville E4L 1E6Canada Physics Department McGill UniversityMontreal H3A 2T8Canada

To be able to regulate the anionic oxygen position in ferrites,an original compositing method is developed by introducing a porous p-type phase in the n-type matrix of ferrite spinel semiconductors.A result of this method is the synergetic effect of the enhanced mass and charge transport that impacted the morphology and anionic oxygen position within the MgFe_(2)O_(4) *** hypothesis is that fine tuning of the anionic oxygen position in ferrites allows us to regulate their physicochemical properties significantly,with the implications for diverse *** electron exchange interaction(j.between O-centered and octahedral-occupying iron(Fe)-centered orbitals affected both the electrical and magnetic properties of the matrix significantly,supporting our *** three-dimensional variable range electron hopping is one such effect.

关键词： Fe_(2)O_(4) spinel structural distortion electron hopping

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Coronary Perfusion Pressure Response to High-Dose Intraosseous versus Standard-Dose Intravenous Epinephrine Administration after Prolonged Cardiac Arrest

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Open j.urnal of Emergency Medicine 2014年第1期2卷 1-7页

作者： Timothy j. Mader ryan A. Coute Adam R. Kellogg j.shua L. Harris Department of Emergency Medicine at Baystate Medical Center Tufts University School of Medicine Springfield MA USA

Background: This study was done to compare coronary perfusion pressure (CPP) prior to the first rescue shock (RS) among a group of animals that received intraosseous (IO) epinephrine 0.1 mg/ kg (high-dose epinephrine [HDE]) with a group that received intravenous (IV) epinephrine 0.01 mg/kg (standard-dose epinephrine [SDE]) during cardiac arrest resuscitation using a swine model of prolonged out-of-hospital ventricular fibrillation (VF) cardiac arrest. Methods: This was a secondary analysis of prospectively collected data from two IACUC approved protocols. Seventy-nine Yorkshire swine (25 - 35 kg) were surgically instrumented under anesthesia and VF was electrically induced. After 10 minutes of untreated VF in the IO study (n = 26) and 12 minutes of untreated VF in the IV study (n = 53), resuscitation commenced with closed chest compressions (CCC). A single dose of epinephrine (HDE IO or SDE IV, respectively) was given and flushed with saline. The CCC and RS attempts were standardized for all animals. The CPP was defined as aortic diastolic pressure minus right atrial diastolic pressure measured 2.5 minutes after medication delivery. Descriptive statistics were used to analyze the data. Results: Baseline group characteristics were mathematically the same. j.st prior to the first RS, HDE IO resulted in a mean CPP of 33.2 mmHg (95%CI: 26.6, 39.9), while SDE IV resulted in a mean CPP of 25.0 mmHg (95%CI: 20.5, 29.4). Conclusion: This observation study reaffirms the assertion that HDE IO may be required to generate CPP values similar to SDE IV during resuscitation of prolonged VF.

关键词： Cardiac Arrest Resuscitation Coronary Perfusion Pressure Intraosseous Epinephrine

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Assessing Social Vulnerability to Flood Hazards in the Dutch Province of Zeeland

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International j.urnal of Disaster Risk Science 2019年第2期10卷 233-243页

作者： ryan H.Kirby Margaret A.Reams Nina S.N.Lam Lei Zou Gerben G.j.Dekker D.Q.P.Fundter Department of Environmental Sciences Louisiana StateUniversityBaton RougeLA70803USA Climate Studies Wageningen University&ResearchWageningen6708PBGelderlandThe Netherlands Delta Management University of Applied SciencesVlissingen4382NWZeelandThe Netherlands

The 2007 European Union Floods Directive encouraged member nations to pursue a more integrated view of flood risks and management strategies, taking into account social vulnerabilities of residents. To date, most flood-risk analyses conducted by the Dutch government have focused on physical risk. This study utilizes fine-scale data to construct a social vulnerability index for 147 districts of the Dutch province of Zeeland, located in the Southwestern Delta and the scene of widespread devastation following the 1953 North Sea Flood. Factor analysis of 25 indicators of social vulnerability selected from related research in Europe and the United States results in seven factors explaining roughly 66% of the total variance. These factors of social vulnerability in Zeeland are urban density,low-income households, recent population change, female gender, train access, and self-employed and service-sector employment. The index was constructed using the toploading variable in each of these factors, with weights determined by the variance explained by each *** range from a low of 0.20 in Schore, municipality of Kapelle, to the highest score of 0.64 in Oudelandse Hoeve of Terneuzen. The most vulnerable districts are located in South Zeeland, with eight of the 10 found in *** maj.rity of less vulnerable districts are located in Zeeland’s central region.

关键词： Factor analysis Flood hazards Netherlands Social vulnerability index Southwest Delta Zeeland

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