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Emerging therapeutic options for the management of hepatitis C infection

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World Journal of Gastroenterology 2014年第23期20卷 7079-7088页

作者： J richard Thompson Department of pharmacy practice One University Park DriveLipscomb University College of PharmacyNashvilleTN 37204United States

Until recently the traditional treatment for hepatitis C infection included pegylated interferon and ribavirin combination *** sustained virological response(SVR)seen with this combination is poor and requires lengthy treatment to ***,significant side effects and numerous contraindications prevented many patients from being successfully treated with this *** 2011,two new protease inhibitors,telaprevir and boceprevir,were approved for use with pegylated interferon and ribavirin in the United States by the United States Food and Drug *** agents have significantly improved SVR rates;however significant problems with toxicity remain including severe skin rash and *** are a wide range of compounds in late stage development for the future treatment of hepatitis C that exploit many different mechanisms of viral *** of these compounds include additional protease inhibitors,like telaprevir and boceprevir,as well as inhibitors of other nonstructural proteins in the viral genome such as NS5A and NS5B,and compounds that target host proteins within the *** of these agents are being developed for oral administration once daily and various combinations are being assessed for use without the need for pegylated interferon and *** paper reviews agents in late phase development that may be commercially available within 1-2 years.

关键词： Hepatitis C pharmacotherapy Interferon Ribavirin protease inhibitors polymerase inhibitors Cyclophilin inhibitors

Digital imaging approaches for phenotyping whole plant nitrogen and phosphorus response in Brachypodium distachyon

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Journal of Integrative plant Biology 2014年第8期56卷 781-796页

作者： richard poiré Vincent Chochois Xavier R.R.Sirault John p.Vogel Michelle Watt Robert T.Furbank CSIRO plant Industry High Resolution plant phenomics Centre CSIRO Plant Industry USDA-ARS Western Regional Research Center

This work evaluates the phenotypic response of the model grass （Brachypodium distacbyon （L.） p. Beauv.） to nitrogen and phosphorus nutrition using a combination of imaging techniques and destructive harvest of shoots and roots. Reference line Bd21-3 was grown in pots using 11 phosphorus and 11 nitrogen concentrations to establish a dose-response curve. Shoot biovolume and biomass, root length and biomass, and tissue phosphorus and nitrogen concentrations increased with nutrient concentration. Shoot biovolume, estimated by imaging, was highly correlated with dry weight （R2 〉 0.92） and both biovolume and growth rate responded strongly to nutrient availability. Higher nutrient supply increased nodal root length more than other root types. photochemical efficiency was strongly reduced by low phosphorus concentrations as early as 1 week after germination, suggesting that this measurement may be suitable for high throughput screening of phosphorus response. In contrast, nitrogen concentration had little effect on photochemical efficiency. Changes in biovolume over time were used to compare growth rates of four accessions in response tonitrogen and phosphorus supply. We demonstrate that a time series image-based approach coupled with mathematical modeling provides higher resolution of genotypic response to nutrient supply than traditional destructive techniques and shows promise for high throughput screening and determina- tion of genomic regions associated with superior nutrient use efficiency.

关键词： Nutrients uptake phenomics photosynthesis root shootCitation: poire R, Chochois V, Sirault XRR, Vogel Jp, Watt M, Furbank RT(2o14) Digital imaging approaches for phenotyping whole plantnitrogen and phosphorus response in Brachypodium distachyon.

Two remarkable epimerizations imperative for the success of an asymmetric total synthesis of (+)-aigialospirol

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Science China Chemistry 2011年第1期54卷 31-42页

作者： FIGUEROA Ruth FELTENBERGER John B. GUEVARRA Christle C. HSUNG richard p. Division of pharmaceutical Sciences and Department of Chemistry University of Wisconsin School of pharmaceutical Science and Technology Tianjin University

Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of(+)-aigialospirol featuring a cyclic acetal tethered ring-closing *** modeling,we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis,thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product *** importantly,calculations allowed us to fully understand the nature and the mechanistic course of these two epimerizations that were imperative to the total synthesis efforts.

关键词： cyclic acetal tethered RCM (+)-aigialospirol anomeric effect and epimerization.

Kaempferia parviflora ethanol extract improves self-assessed sexual health in men:a pilot study

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Journal of Integrative Medicine 2018年第4期16卷 249-254页

作者： richard A.Stein Kira Schmid Jowell Bolivar Andrew G.Swick Steven V.Joyal Steven p.Hirsh Life Extension 3600 West Commercial BlvdFort tauderdaleFL 33309USA Life Extension Clinical Research Inc.5990 North Federal HighwayFort LauderdaleFL 33308USA

Background： Sexual health positively correlates with overall wellbeing. Existing therapeutics to enhance male sexual health are limited by factors that include responsiveness, adherence and adverse effects. As the population ages, safe and effective interventions that preserve male sexual function are needed. published research suggests that various preparations of Kaempferia parviflora, a plant in the Zingiberaceae （ginger） family, support cardiovascular health and may ameliorate erectile function. Objective： The aim of this study was to examine the effects of KaempMaxTM, an ethanol extract of the K. parvi]lora rhizome, on erectile function in healthy middle-aged and older men. Design, setting, participants and interventions： We conducted an open-label, one-arm study on 14 generally healthy males aged 50-68 years with self-reported mild erectile dysfunction, who were not using pre- scription treatments. participants took 100 mg KaempMaxTM daily for 30 days. Main outcome measures： Evaluations were conducted at baseline and on the final study assessment. primary efficacy analyses included the International Index of Erectile Function （IIEF）; secondary efficacy analyses included the Global Assessment Question about erectile function. Results： Thirteen participants completed the 30-day study. Supplementation with KaempMaxTM resulted in statistically significant improvements in erectile function, intercourse satisfaction and total scores on the IIEF questionnaire. KaempMaxTM was well tolerated and exhibited an excellent safety profile. Conclusion： Our results suggest that KaempMaxTM may improve erectile function in healthy middle-aged and older men. While the effects were not as pronounced as what might be seen with prescription med- ication, most participants found them satisfactory. Additional, longer and placebo-controlled clinical tri- als will be needed. Trial registration： *** identifier Ncr03389867.

关键词： Sexual health Kaempferia parviflom Complementary therapies KaempMax^TM Global Assessment QuestionInternational Index of Erectile Function

Is cardiac resynchronisation therapy feasible, safe and beneficial in the very elderly？

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Journal of Geriatric Cardiology 2015年第5期12卷 497-501页

作者： Bartosz Olechowski Rebecca Sands Donah Zachariah Neil p Andrews richard Balasubramaniam Mark Sopher John paisey paul R Kalra Royal Bournemouth Hospital NHS Foundation Trust Bournemouth UK Queen Alexandra Hospital Portsmouth Hospitals NHS Trust Portsmouth UK

Objective To evaluate whether cardiac resynchronisation therapy （CRT） implantation was feasible and safe in octogenarians and the asso- ciation with symptoms. Methods Consecutive patients undergoing CRT implantation were recruited from two UK centers. patients grouped according to age：〈 80 ＆ ≥ 80 years. Baseline demographics, complications and outcomes were compared between those groups. Results A total of 439 patients were included in this study, of whom 26% were aged ≥ 80 years. Octogenarians more often received cardiac resynchronization therapy pacemaker in comparison to cardiac resynchronisation therapy-defibrillator. Upgrade from pacemaker was common in both groups （16% 〈 80 years vs. 22% ≥ 80 years, p = NS）. Co-morbidities were similarly common in both groups （overall diabetes： 25%, atrial fibrillation： 23%, hypertension： 45%）. More patient age ≥ 80 years had significant chronic kidney disease （CKD, estimated glomerular filtration rate 〈 45 mL/min per 1.73 m^2, 44% vs. 22%, p 〈 0.01 ）. Overall complication rates （any） were similar in both groups （16% vs. 17%, p = NS）. Both groups demonstrated symptomatic benefit. One-year mortality rates were almost four fold greater in octogenarians as compared with the younger cohort （13.9% vs. 3.7%, p 〈 0.01）. Conclusions CRT appears to be safe in the very elderly despite extensive co-morbidity, and in particular frequent severe CKD. Symptomatic improvement appears to be meaningful. Strategies to increase the appropriate identification of elderly patients with CHF who are potential candidates for CRT are required.

关键词： Cardiac resynchronisation therapy Heart failure Left ventricular dysfunction Safety The elderly

The discovery of magnetotactic/magnetosensitive bacteria

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Chinese Journal of Oceanology and Limnology 2009年第1期27卷 1-2页

作者： richard B. FRANKEL Department of physics California Polytechnic State University San Luis Obispo

Magnetotactic bacteria orient and migrate along magnetic field lines in aquatic habitats. The first paper on this phenomenon was written by richard p. Blakemore （Blakemore, 1975; 1982）.

关键词： magnetotaxis magnetosensitivity bacteria discovery

Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

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World Journal of Gastroenterology 2009年第46期15卷 5867-5870页

作者： Daniel Kaemmerer Vikas prasad Wolfgang Daffner Dieter Hrsch Günter Klppel Merten Hommann richard p Baum Department of General and Visceral Surgery Zentralklinik Bad Berka Department of Nuclear Medicine Center for PETZentralklinik Bad Berka Department of Internal Medicine Gastroen-terologyEndocrinology and OncologyZentralklinik Bad Berka Department of pathology University of Kiel

pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the *** diagnosis many of them are already advanced and diff icult to *** report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman,who received neoadjuvant peptide receptor radionuclide therapy(pRRT)as firstline *** resulted in a signif icant downstaging of the tumor and allowed its subsequent complete surgical ***-up for eighteen months revealed a complete *** is the first report on neoadjuvant pRRT in a neuroendocrine neoplasm with subsequent successful complete resection.

关键词： Endocrine pancreatic carcinoma peptidereceptor radionuclide therapy Neodjuvant treatment pancreatic surgery Molecular imaging Receptor pan-creatic endocrine tumor Computed tomography

RBM20 is an essential factor for thyroid hormone-regulated titin isoform transition

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Journal of Molecular Cell Biology 2015年第1期7卷 88-90页

作者： Chaoqun Zhu Zhiyong Yin Jun Ren richard J.McCormick Stephen p.Ford Wei Guo Department of Animal Science College of Agriculture and Natural ResourcesUniversity of WyomingLaramieWY 82071USA Department of Cardiology XiJing HospitalFourth Military Medical UniversityXi’an 710032China Center for Cardiovascular Research and Alternative Medicine College of Health ScienceUniversityof WyomingLaramieWY 82071USA

Dear Editor,Diastolic heart failure(DHF)and systolic heart failure(SHF)are two main subsets of chronic heart failure that are commonly encountered in clinical practice(Chatterjee and Massie,2007).

关键词： clinical heart systolic

A Numerical Investigation into the Bending of Metallic Laminate Sheet

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World Journal of Engineering and Technology 2019年第2期7卷 314-324页

作者： richard p. Turner School of Metallurgy & Materials University of Birmingham Birmingham United Kingdom

A finite element model to simulate the bending of tri-layer laminate metallic sheet was proposed, and the model?was?developed in the commercial finite element (FE) solver deform. The model was simulated under adiabatic conditions (thus assuming zero heat transfer), with room temperature material properties and an ambient atmosphere assumed throughout. The models used copper as the core layer, whilst the upper and lower face layers were alternated between an aluminium alloy Al 2017, a titanium alloy Ti-6Al-4V, and a stainless steel 316L. Thus, room temperature mechanical properties for Ti-6Al-4V, copper, 316L stainless steel and 2017 Al alloy were entered into the model. FE predictions suggest that the material used in the face layers are of significant design importance, with variation in the peak strain in the face layers of around one-third, whilst significant variation in these layers for peak Von Mises stress, with Ti-6Al-4V and Al 2017 alloys was significantly closer to their ultimate tensile strength (UTS) values than 316L. However in the core copper layer the stress and strain predictions were largely unaffected. In models that mixed Al 2017 and 316L upper and lower face layers, significant differences in peak strains in the face layers were predicted, with the 316L layer suffering greater strains when paired with the Al 2017 alloy than paired with itself. A sensible locating of the materials in upper and lower face layers is predicted to give optimised stress and strain fields.

关键词： Stress Strain Layer Simulation Cockroft-Latham