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Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions

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World journal of Gastroenterology 2017年第9期23卷 1618-1626页

作者： jacob A Langness Matthew Nguyen Amanda Wieland Gregory T Everson jennifer j kiser Hepatology and Transplant Clinic University of Colorado Hospital Department of Pharmacy University of Colorado Hospital University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Department of Gastroenterology School of MedicineUniversity of Colorado

To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this *** standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and july 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive *** hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients

关键词： Clinical pharmacist Drug-drug interaction Hepatitis C virus treatment

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Phase 3 trial of first generation protease inhibitor therapy for hepatitis C virus/human immunodeficiency virus coinfection

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World journal of Hepatology 2017年第4期9卷 217-223页

作者： Kenneth E Sherman Minhee Kang Richard Sterling Triin Umbleja Kristen Marks jennifer j kiser Beverly Alston-Smith Wayne Greaves Adeel A Butt 无 Division of Digestive Diseases University of Cincinnati College of Medicine harvard T.h. Chan School of Public health Department of Gastroenterology Virginia Commonwealth University Division of Infectious Disease Weill Cornell Medical School University of Colorado School of Pharmacy NIAID-Division of AIDS Merck and Co Inc. University of Pittsburgh School of Medicine hamad healthcare Quality Institute the ACTG 5294 BIRTH Study Team

AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR). RESULTSA total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09). CONCLUSIONThe trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.

关键词： Human immunodeficiency virus Hepatitis C virus Boceprevir Pegylated interferon alfa Ribavirin

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna jennifer Aguilar Emily Lee William j.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Data-driven analysis of process,structure,and properties of additively manufactured Inconel 718 thin walls

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npj Computational Materials 2022年第1期8卷 1168-1182页

作者： Lichao Fang Lin Cheng jennifer A.Glerum jennifer Bennett jian Cao Gregory j.Wagner Department of Mechanical Engineering Northwestern UniversityEvanstonIL60208USA Department of Materials Science and Engineering Northwestern UniversityEvanstonIL60208USA DMG MORI Hoffman EstatesIL60192USA Department of Mechanical and Materials Engineering Worcester Polytechnic InstituteWorcesterMA01609USA Department of Civil and Mechanical Engineering US Military Acadeemy at West PointWest PointNY10996USA

In additive manufacturing of metal parts,the ability to accurately predict the extremely variable temperature field in detail,and relate it quantitatively to structure and properties,is a key step in predicting part performance and optimizing process *** this work,a finite element simulation of the directed energy deposition(DED)process is used to predict the space-and time-dependent temperature field during the multi-layer build process for Inconel 718 *** thermal model results show good agreement with dynamic infrared images captured in situ during the DED *** relationship between predicted cooling rate,microstructural features,and mechanical properties is examined,and cooling rate alone is found to be insufficient in giving quantitative property *** machine learning offers an efficient way to identify important features from series data,we apply a 1D convolutional neural network data-driven framework to automatically extract the dominant predictive features from simulated temperature *** good predictions of material properties,especially ultimate tensile strength,are obtained using simulated thermal history *** further interpret the convolutional neural network predictions,we visualize the extracted features produced on each convolutional layer and compare the convolutional neural network detected features of thermal histories for high and low ultimate tensile strength cases.A key result is the determination that thermal histories in both high and moderate temperature regimes affect material properties.

关键词： Inconel process additive

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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.jeffrey Dixon Cheryle A.Séguin Health and Rehabilitation Sciences(Physical Therapy) Faculty of Health SciencesThe University of Western OntarioLondonON N6A 5B9Canada Bone and joint 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 objective 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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Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda’s human African trypanosomiasis elimination programme

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Infectious Diseases of Poverty 2018年第1期7卷 844-859页

作者： Shona j.Lee jennifer j.Palmer Centre of African Studies University of EdinburghGeorge SquareEdinburgh EH89LDUK Health in Humanitarian Crises Centre London School of Hygiene&Tropical MedicineKeppel StreetLondon WC1E 7HTUK.

Background:The recent development of rapid diagnostic tests(RDTs)for human African trypanosomiasis(HAT)enables elimination programmes to decentralise serological screening services to frontline health ***,patients must still undertake multiple onwards referral steps to either be confirmed or discounted as *** surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient *** study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile,***:Between August 2013 and june 2015,85%(295/346)people who screened RDT-positive were examined by microscopy at least once;10 cases were *** interviewed 20 RDT-positive suspects who had not completed referral(16 who had not presented for their first microscopy examination,and 4 who had not returned for a second to dismiss them as cases after receiving discordant[RDT-positive,but microscopy-negative results]).Interviews were analysed thematically to examine experiences of each step of the referral ***:Poor provider communication about HAT RDT results helped explain non-completion of referrals in our *** patients were unaware they were tested for HAT until receiving results,and some did not know they had screened *** HAT testing and treatment is free,anticipated costs for transportation and ancillary health services fees deterred *** expected a positive RDT result would lead to HAT *** results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health *** the four individuals who missed their second examination,complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was ***:An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably sub

关键词： Human African trypanosomiasis Sleeping sickness Uganda Passive screening Diagnostics Case detection Referral completion Rapid diagnostic tests Elimination

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Controlling schistosomiasis with praziquantel:How much longer without a viable alternative?

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Infectious Diseases of Poverty 2017年第1期6卷 654-663页

作者： Robert Bergquist jürg Utzinger jennifer Keiser Ingerod BrastadSweden Swiss Tropical and Public Health Institute P.O.BoxCH-4002 BaselSwitzerland University of Basel P.O.BoxCH-4003 BaselSwitzerland

The current approach of morbidity control of schistosomiasis,a helminth disease of poverty with considerable public health and socioeconomic impact,is based on preventive chemotherapy with *** is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 *** argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug *** drugs already approved for other diseases provides a shortcut to clinical trials,as it is expected that such drugs rapidly pass the regulatory *** antischistosomal properties of antimalarial drugs(e.g.,semisynthetic artemisinins,synthetic trioxolanes,trioxaquines and mefloquine)and of drugs being developed or registered for other purposes(e.g.,moxidectin and miltefosin),administered alone or in combination with praziquantel,have been tested in the laboratory and clinical *** avenue to follow is the continued search for new antischistosomal properties in ***,we summarise recent progress made in schistosomiasis chemotherapy,placing particular emphasis on repositioning of existing drugs against schistosomiasis.

关键词： Chemotherapy Drug repositioning Elimination Morbidity control Praziquantel Schistosomiasis

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Superconvergence and the Numerical Flux: a Study Using the Upwind-Biased Flux in Discontinuous Galerkin Methods

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Communications on Applied Mathematics and Computation 2020年第3期2卷 461-486页

作者： Daniel j.Frean jennifer K.Ryan School of Mathematics University of East AngliaNorwichUK Applied Mathematics and Statistics Colorado School of MinesGoldenCOUSA

One of the beneficial properties of the discontinuous Galerkin method is the accurate wave propagation *** is,the semi-discrete error has dissipation errors of order 2k+1(≤Ch2k+1)and order 2k+2 for dispersion(≤Ch2k+2).Previous studies have concentrated on the order of accuracy,and neglected the important role that the error constant,C,plays in these *** this article,we show the important role of the error constant in the dispersion and dissipation error for discontinuous Galerkin approximation of polynomial degree k,where k=0,1,2,*** gives insight into why one may want a more centred flux for a piecewise constant or quadratic approximation than for a piecewise linear or cubic *** provide an explicit formula for these error *** is illustrated through one particular flux,the upwind-biased flux introduced by Meng et al.,as it is a convex combination of the upwind and downwind *** studies of wave propagation are typically done through a Fourier *** higher order Fourier information can be extracted using the smoothness-increasing accuracy-conserving(SIAC)*** SIAC filter ties the higher order Fourier information to the negative-order norm in physical *** show that both the proofs of the ability of the SIAC filter to extract extra accuracy and numerical results are unaffected by the choice of flux.

关键词： Discontinuous Galerkin Smoothness-increasing accuracy-conserving(SIAC)filtering Superconvergence

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