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Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

World j.urnal of Gastroenterology 2018年第11期24卷 1269-1277页

作者： Mazen Noureddin Micaela M Wong Tsuyoshi Todo Shelly C Lu Arun j.Sanyal edward A Mena Fatty Liver Program Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States California Liver Research Institute PasadenaCA 91105United States Comprehensive Transplant Center Department of SurgeryCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineSchool of MedicineVirginia Commonwealth UniversityRichmondVA 23298United States

AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting *** Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study *** stiffness/fibrosis was measured before and 47 wk after treatment *** with genotype 3 and patients with cirrhosis were *** One hundred and one patients were included in the ***-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced *** with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < ***,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients *** patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced *** term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

关键词： Nonalcoholic fatty liver disease Hepatitis C Fibrosis Steatosis Sustained virological response Direct-acting antivirals

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Remote monitoring of implantable defibrillators is associated with fewer inappropriate shocks and reduced time to medical assessment in a remote and rural area

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World j.urnal of Cardiology 2021年第3期13卷 46-54页

作者： Kara Callum Claudia Graune Elizabeth Bowman edward Molden Stephen j.Leslie Department of Cardiology NHS HighlandInverness IV23UJUnited Kingdom

BACKGROUND Implantable cardioverter defibrillators(ICDs)and cardiac resynchronisation therapy with defibrillators(CRT-D)reduce mortality in certain cardiac patient ***,inappropriate shocks pose a problem,having both adverse physical and psychological effects on the *** advances in device technology now allow remote monitoring(RM)of devices to replace clinic follow up *** allows real time data to be analysed and actioned and this may improve patient *** To determine if RM in patients with an ICD is associated with fewer inappropriate shocks and reduced time to medical *** This was a single centre,retrospective observational study,involving 156 patients implanted with an ICD or CRT-D,followed up for 2 years post *** appropriate and inappropriate shocks were recorded along with cause for inappropriate shocks and time to medical *** RM was associated with fewer inappropriate shocks(13.6%clinic vs 3.9%RM;P=0.030)and a reduced time to medical assessment(15.1±6.8 vs 1.0±0.0 d;P<0.001).CONCLUSION RM in patients with an ICD is associated with improved patient outcomes.

关键词： Implantable cardioverter defibrillator Inappropriate shocks Remote monitoring Cardiac patients Heart failure Arrythmia

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Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice

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Bone Research 2017年第2期5卷 95-108页

作者： Eric E Beier Tzong-j.n Sheu Emily A Resseguie Masahiko Takahata Hani A Awad Deborah A Cory-Slechta j.edward Puzas Department of Environmental Medicine University of Rochester School of Medicine and Dentistry Rochester NY USA Department of Environmental and Occupational Medicine Rutgers University Piscataway NJ USA and Center for Musculoskeletal Research University of Rochester School of Medicine and Dentistry Rochester NY USA

Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress(PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead(Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subj.cted to PS on gestational days 16 and 17, lifetime Pb exposure(100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously(controlled-release pellet, 5 mg·kg^(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in ***, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone.

关键词： Sclerostin prenatal negative

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MicroRNA in TLR signaling and endotoxin tolerance

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Cellular & Molecular Immunology 2011年第5期8卷 388-403页

作者： Md A Nahid Minoru Satoh edward KL Chan Department of Oral Biology University of FloridaGainesvilleFLUSA Division of Rheumatology and Clinical Immunology Department of Medicineand PathologyImmunologyand Laboratory MedicineUniversity of FloridaGainesvilleFLUSA

Toll-like receptors(TLRs)in innate immune cells are the prime cellular sensors for microbial *** activation leads to the production of proinflammatory mediators and thus TLR signaling must be properly regulated by various mechanisms to maintain ***4-ligand lipopolysaccharide(LPS)-induced tolerance or cross-tolerance is one such mechanism,and it plays an important role in innate *** is established and sustained by the activity of the microRNA miR-146a,which is known to target key elements of the myeloid differentiation factor 88(MyD88)signaling pathway,including IL-1 receptor-associated kinase(IRAK1),IRAK2 and tumor-necrosis factor(TNF)receptor-associated factor 6(TRAF6).In this review,we comprehensively examine the TLR signaling involved in innate immunity,with special focus on LPS-induced *** function of TLR ligand-induced microRNAs,including miR-146a,miR-155 and miR-132,in regulating inflammatory mediators,and their impact on the immune system and human diseases,are *** of these microRNAs may affect TLR pathway activation and help to develop therapeutics against inflammatory diseases.

关键词： innate immunity lipopolysaccharide LPS tolerance microRNA Toll-like receptor

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Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy

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Bone Research 2024年第1期12卷 95-106页

作者： Tian Nie Varun S.Venkatesh Suzanne Golub Kathryn S.Stok Haniyeh Hemmatian Reena Desai David j.Handelsman j.ffrey D.Zaj.c Mathis Grossmann Rachel A.Davey Department of Medicine Austin HealthUniversity of MelbourneHeidelbergVIC 3084Australia Department of Biomedical Engineering University of MelbourneParkvilleVIC 3010Australia ANZAC Research Institute University of Sydney and AndrologyConcord Repatriation General HospitalConcordNSW 2137Australia

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are *** address this knowledge gap,we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol *** was suppressed by orchidectomy in male mice at 5 weeks of *** 3 weeks post-surgery,male-to-female mice were treated with a high dose of estradiol(~0.85 mg)by intraperitoneal silastic implantation for 12 *** included intact and orchidectomized males at 3 weeks post-surgery,vehicle-treated intact males,intact females and orchidectomized males at 12 weeks *** to male controls,orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to *** treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis,while the periosteal circumference increased to a level that was intermediate between intact male and female controls,resulting in increased maximal force and *** trabecular bone,estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate,consistent with the anabolic action of estradiol on osteoblast *** data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of *** study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.

关键词： treatment treatment strength

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The bisulfite genomic sequencing protocol

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Advances in Lung Cancer 2013年第1期2卷 21-25页

作者： j.ne j. Pappas André Toulouse Walter edward Clarke Bradley Department of Anatomy and Neuroscience University College Cork Cork Ireland Department of Pharmacology and Therapeutics McGill University Montreal Canada

The bisulfite genomic sequencing (BGS) protocol has gained worldwide popularity as the method of choice for analyzing DNA methylation. It is this popular because it is a powerful protocol and it may be coupled with many other applications. However, users often run into a slew ofproblems, including incomplete conversion,overly degraded DNA, sub-optimal PCR amplifications, false positives, uninformative results, or altogether failed experiments. We pinpoint the reasons why these problems arise and carefully explain the critical steps toward accomplishing a successful experiment step-by-step. This protocol has worked successfully (>99.9% conversion) on as little as 100 ng of DNA derived from nearly 10-year-old DNA samples extracted from whole blood stored at -80°C and resulted in enough converted DNA for more than 50 PCRreactions. The aim of this article is to makelearning and usage of BGS easier, more efficient and standardized for all users.

关键词： Bisulfite Genomic Sequencing DNA Methylation Epigenetics Cancer

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Enhancing work hardening and ductility in additively manufacturedβTi:roles played by grain orientation,morphology and substructure

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j.urnal of Materials Science & Technology 2022年第10期105卷 131-141页

作者： Ahmad Zafari edward Wen Chiek Lui Mogeng Li Kenong Xia Department of Mechanical Engineering The University of MelbourneVictoria 3010Australia Centre for Additive Manufacturing School of EngineeringRMIT UniversityMelbourneVIC 3000Australia Physics of Fluids Group Max Planck Center for Complex Fluid DynamicsJ.M.Burgers Center for Fluid Dynamics and MESA+Research InstituteDepartment of Science and TechnologyUniversity of Twente7500AE Enschedethe Netherlands

A metastableβTi alloy was additively manufactured by laser powder bed fusion(LPBF).Tensile testing along the build direction of the as-LPBF material(LPBF-0°)revealed signifcant work softening immediately following yielding with no uniform *** contrast,substantial work hardening and uniform elongation well over 10%were achieved perpendicular to the build direction(LPBF-90°).Similar effects were obtained in the build direction after super transus heat treatment(LPBF-0°+HT)although the strength was slightly *** addition,the yield drop phenomenon observed in both orientations of the as-LPBF materials disappeared after *** enhanced work hardening ability,and thus ductility,can be attributed to increased interactions of slip bands/slip bands owing to additional{112}slip systems becoming operative in LPBF-0°+HT and LPBF-90°while LPBF-0°was dominated by{110}*** other variations after HT may be related to the coarsening of grain structure and removal of specifc substructures in the as-LPBF microstructure.

关键词： βtitanium Work hardening Anisotropy Equiaxed microstructure Slip band Laser powder bed fusion

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Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation

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Bone Research 2015年第3期3卷 173-181页

作者： edward Maharam Miguel Yaport Nathaniel L Villanueva Takintope Akinyibi Damien Laudier Zhiyong He Daniel j.Leong Hui B Sun Leni and Peter W.May Department of Orthopedics Icahn School of Medicine at Mount Sinai Departments of Orthopedic Surgery Albert Einstein College of Medicine Radiation Oncology Albert Einstein College of Medicine

Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

关键词： MSCs Figure Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation

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Earth::An Introduction to Physical Geology/ 7th ed.

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2002年

作者： edward j. Tarbuck Frederick K. Lutgens.

Includes index.

ISBN: (数字)0130920258

ISBN: (纸本)0130920258

Includes index.

关键词： Physical geology.

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The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water

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j.urnal of Environmental Sciences 2017年第8期29卷 173-182页

作者： Clara H.j.ong edward j.Machek Morteza Shakeri Stephen E.Duirk Thomas A.Ternes Susan D.Richardson Elizabeth D.Wagner Michael j.Plewa Molecular and Environmental Toxicology Center School of Medicine and Public Health University of Wisconsin-Madison Madison WI USA Department of Civil Engineering University of Akron Akron OH USA Department of Water Chemistry Federal Institute of Hydrology Koblenz Germany Department of Chemistry and Biochemistry University of South Carolina Columbia SC USA Department of Crop Sciences and the Safe Global Water Institute University of Illinois at Urbana-Champaign Urbana IL USA

The presence of iodinated X-ray contrast media（ICM） in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products（DBPs）. The obj.ctive of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron,OH were treated with five different ICMs, including iopamidol, iopromide, iohexol,diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs（iopromide, iohexol, diatrizoate, and iomeprol） expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water.

关键词： Disinfection by-products Iodo-DBPs Iodinated X-ray contrast media

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