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Federica Bozzano Mariella Della Chiesa Andrea Pelosi Francesca Antonini Maria Libera Ascierto Genny Del Zotto Francesca Moretta Letizia Muccio Anna Luganini Giorgio Gribaudo Giovanni Cenderello Chiara Dentone Laura Nicolini Alessandro Moretta Lorenzo Moretta Andrea De Maria 《The Journal of allergy and clinical immunology》2021,147(6):2343-2357
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Human cytomegalovirus (HCMV) infection is associated with severe morbidity and mortality in immunocompromised individuals, mainly transplant recipients and AIDS patients, and is the most frequent cause of congenital malformations in newborn children. To date, few drugs are licensed for the treatment of HCMV infections, most of which target the viral DNA polymerase and suffer from many drawbacks, including long-term toxicity, low potency, and poor bioavailability. In addition, the emergence of drug-resistant viral strains is becoming an increasing problem for disease management. Finally, none of the current anti-HCMV drugs have been approved for the treatment of congenital infections. For all these reasons, there is still a strong need for new anti-HCMV drugs with novel mechanisms of action. The first events of the virus replication cycle, including attachment, entry, immediate-early gene expression, and immediate-early functions—in particular that of Immediate-Early 2 protein—represent attractive targets for the development of novel antiviral compounds. Such inhibitors would block not only the expression of viral immediate-early proteins, which play a key role in the pathogenesis of HCMV infection, but also the host immunomodulation and the changes to cell physiology induced by the first events of virus infection. This review describes the current knowledge on the initial phases of HCMV replication, their validation as potential novel antiviral targets, and the development of compounds that block such processes. 相似文献
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Peter B. Lockhart Hillary R. DeLong Ruth D. Lipman Elliot Abt Larry M. Baddour Monica Colvin Craig S. Miller Thomas Sollecito Kelly O’Brien Cameron G. Estrich Marcelo W.B. Araujo Alonso Carrasco-Labra 《Journal of the American Dental Association (1939)》2019,150(9):739-747.e9
BackgroundThe purpose of this systematic review was to determine the potential effect of dental treatment before cardiac valve surgery (CVS) or left ventricular assist device (LVAD) implantation on morbidity and mortality.Types of Studies ReviewedThe authors included relevant studies from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, including randomized controlled trials and cohort studies, published from 1998 through 2019 and involving adults who received dental treatment before CVS or LVAD implantation. The authors assessed bias by using the Newcastle-Ottawa Quality Assessment Scale and evidence certainty by using the Grading of Recommendations Assessment, Development and Evaluation approach. The authors used a meta-analysis with a random-effects model to estimate dichotomous and continuous outcomes, expressed as relative risk (RR) and weighted mean difference.ResultsSix studies met the inclusion criteria for CVS but none for LVAD implantation. Very low certainty in the evidence suggested uncertainty as to whether health outcomes for patients undergoing dental treatment before CVS differed from those who did not. Postsurgical outcomes included all-cause mortality (RR, 1.00; 95% confidence interval [CI], 0.53 to 1.91), infective endocarditis (RR, 1.30; 95% CI, 0.51 to 3.35), postsurgical infection (RR, 1.01; 95% CI, 0.76 to 1.33), and length of stay in the hospital (weighted mean difference, 2.9; 95% CI, ?2.3 to 8.1).Conclusions and Practical ImplicationsFrom the available evidence, it is unclear whether postoperative outcomes differ in patients receiving dental treatment before CVS compared with outcomes in those who do not. Dentists and medical care professionals should collaborate on an appropriate course of action for each patient, weighing any potentially relevant care considerations. 相似文献
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本文报道以成分不同的PEG为载体制成吡罗昔康(PIR)固体分散体(Sd)制剂,与片剂相比,体内外特性存在着显著性差异。Sd用红外光谱、X射线衍射光谱加以证明,由Sd制成两种滴丸DⅠ、DⅡ,用转篮法测定了体外释药速度。用HPLC法测定了家兔的吸收速度。以PEG 4000与1000为混合载体制备的滴丸DⅠ,其体外释药速度远较单纯PEG 4000为载体的滴丸DⅡ为快,两者的T_(50)相差6.4倍。家兔吸收试验中,两种滴丸的T_m相差为6.5倍,与体外释药速度倍数十分吻合。进一步测定了滴丸DⅠ在8名志愿者的体内血药浓度,结果表明,DⅠ的T_m及K_α远较片剂快,而C_m AUC和片剂相近。 相似文献
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Shailee Shah Alaa Alashi Gosta B. Pettersson L. Leonardo Rodriguez A. Marc Gillinov Richard A. Grimm Jose Navia Samir R. Kapadia Lars G. Svensson Brian P. Griffin Milind Y. Desai 《The Journal of thoracic and cardiovascular surgery》2019,157(5):1785-1792.e1
Background
Paravalvular leak (PVL) is often seen after aortic (AV) and mitral valve (MV) surgery, either due to infection or valve dehiscence. We sought to describe predictors of longer-term outcomes in patients who developed PVL after AV and MV surgery and were considered eligible for reoperative cardiac surgery (RCS).Methods
We studied 495 such patients (65 ± 14 years, 65% men, 47% with MV PVL) who presented at our center between January 2003 and December 2011. Patients with severe mitral/aortic stenosis, patients with less than mild PVL, and those with prohibitive risk precluding RCS were excluded. Society of Thoracic Surgeons (STS) score was calculated. Primary endpoint was mortality.Results
At baseline, mean STS score and left ventricular ejection fraction were 5.8 ± 4% and 52 ± 12%, respectively. In total, 105 (21%) had infective PVL and 72% had moderate or greater PVL. At a median of 8 days, 351 (71%) patients underwent RCS to repair PVL (3% in-hospital postoperative mortality), and at 6.6 ± 4 years, 230 (47%) patients died. On multivariable Cox survival analysis, greater STS score (hazard ratio or HR 1.35), mitral versus aortic PVL (HR 1.66), infectious etiology (HR 2.05), and greater right ventricular systolic pressure (HR 1.09) were associated with greater longer-term mortality, whereas surgery (HR 0.58) was associated with improved longer-term survival (all P < .05).Conclusions
Patients who develop mild or greater PVL after AV/MV surgery have a high rate of longer-term mortality, despite excellent perioperative outcomes. Greater STS score, right ventricular systolic pressure, infectious etiology, and MV (vs AV) involvement were all independently associated with long-term mortality, whereas RCS for PVL closure was associated with improved longer-term survival. 相似文献90.
Chien‐Yu Ji Tsung‐Chien Chen Yung‐Lung Lee 《Optimal control applications & methods.》2008,29(2):101-125
In this work, the input‐estimation (IE) algorithm and the linear quadratic Gaussian (LQG) controller are adopted to design a control system. The combined method can maintain higher control performance even when the system variation is unknown and under the influence of disturbance input. The IE algorithm is an on‐line inverse estimation method involving the Kalman filter (KF) and the least‐square method, which can estimate the system input without additional torque sensor, while the LQG control theory has the characteristic of low sensitivity of disturbance. The design and analysis processes of the controller will also be discussed in this paper. The joint control of the flexible‐joint robot system is utilized to test and verify the effectiveness of the control performance. According to the simulation results, the IE algorithm is an effective observer for estimating the disturbance torque input, and the LQG controller can effectively cope with the situation that the disturbance exists. Finally, higher control performance of the combined method for joint control of the robotic system can be further verified. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献