The significant public health problem of Hepatitis C virus (HCV) has been partially addressed with the advent of directly acting antiviral agents (DAAs). However, the development of an effective ...preventative vaccine would have a significant impact on HCV incidence and would represent a major advance towards controlling and possibly eradicating HCV globally. We previously reported a genotype 1a HCV viral-like particle (VLP) vaccine that produced neutralizing antibodies (NAb) and T cell responses to HCV. To advance this approach, we produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine to produce broader immune responses. We show that this quadrivalent vaccine produces antibody and NAb responses together with strong T and B cell responses in vaccinated mice. Moreover, selective neutralizing human monoclonal antibodies (HuMAbs) targeting conserved antigenic domain B and D epitopes of the E2 protein bound strongly to the HCV VLPs, suggesting that these critical epitopes are expressed on the surface of the particles. Our findings demonstrate that a quadrivalent HCV VLP based vaccine induces broad humoral and cellular immune responses that will be necessary for protection against HCV. Such a vaccine could provide a substantial addition to highly active antiviral drugs in eliminating HCV.
Objectives:
Although the high rate of erectile dysfunction (ED) following prostatectomy is well recognised, the aetiology and pathophysiology have not yet been fully elucidated. We examined the ...current literature as to aetiology, treatment and possible prevention of ED following prostatectomy.
Method:
Review of the literature by a Medline search.
Keywords:
Radical prostatectomy; Erectile dysfunction; Quality of life; Prevention; Management.
Conclusion:
The most important predictors of erectile function are pre-operative erectile function and the nerve sparing nature of the procedure. The former is determined by age and vascular risk-factors whereas the latter is decided by the stage of the tumour and the skill of the surgeon. The value of intraoperative nerve mapping seems limited and the importance of nerve grafting is uncertain. Natural recovery of erection can take as long as 24 months. Patients complain about a lack of professional support. Symptomatic therapy may be applied according to the current general standards of treatment in men with ED.
The paper presents results of research on an inverse kinematics algorithm that has been used in a functional model of a cucumber-harvesting robot consisting of a redundant P6R manipulator. Within a ...first generic approach, the inverse kinematics problem was reformulated as a non-linear programming problem and solved with a Genetic Algorithm (GA). Although solutions were easily obtained, the considerable calculation time needed to solve the problem prevented on-line implementation. To circumvent this problem, a second, less generic, approach was developed which consisted of a mixed numerical-analytic solution of the inverse kinematics problem exploiting the particular structure of the P6R manipulator. Using the latter approach, calculation time was considerably reduced. During the early stages of the cucumber-harvesting project, this inverse kinematics algorithm was used off-line to evaluate the ability of the robot to harvest cucumbers using 3D-information obtained from a cucumber crop in a real greenhouse. Thereafter, the algorithm was employed successfully in a functional model of the cucumber harvester to determine if cucumbers were hanging within the reachable workspace of the robot and to determine a collision-free harvest posture to be used for motion control of the manipulator during harvesting. The inverse kinematics algorithm is presented and demonstrated with some illustrative examples of cucumber harvesting, both off-line during the design phase as well as on-line during a field test.
Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In the case of shortage of tissue, engineered tissue may enhance urethral ...reconstruction. As the corpus spongiosum (CS) is important in supporting the function of the urethra, tissue engineering of the urethra should be combined with reconstruction of a CS. For that purpose, detailed knowledge of the composition of the CS, more specifically its extracellular matrix (ECM) and vascularization is needed for scaffold design. The objective of this study is to analyze the microarchitecture of the CS through (immuno) histology and scanning electron microscopy (SEM).
The CS including the urethra of patients undergoing male-to-female genital confirming surgery was harvested. This CS was fixed and processed for either (immuno) histology or for SEM.
Four layers could be distinguished in the CS; first a transition zone from urethra epithelium to a collagen rich layer, which was highly vascularized, followed by a second, elastin rich layer. The third layer was formed by veins, arteries and vascular spaces and the last layer showed the transition from this vascular rich region to the collagen rich tunica albuginea. In this layer collagen bundles intertwined with elastic fibres. In the CS different components of the ECM were visible and distinguishable.
This study provides novel and detailed information on the microarchitecture of the CS and the distribution of vascularization, which is important for scaffold design in tissue engineering.
An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and class II CD4+ T-cells together with broad neutralizing antibody ...responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g cm-3. The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8+ T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huh7 cells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8+ T-cell responses and will have important implications for the development of a preventative vaccine for HCV.
This paper describes the concept of an autonomous robot for harvesting cucumbers in greenhouses. A description is given of the working environment of the robot and the logistics of harvesting. It is ...stated that for a 2 ha Dutch nursery, 4 harvesting robots and one docking station are needed during the peak season. Based on these preliminaries, the design specifications of the harvest robot are defined. The main requirement is that a single harvest operation may take at most 10 s. Then, the paper focuses on the individual hardware and software components of the robot. These include, the autonomous vehicle, the manipulator, the end-effector, the two computer vision systems for detection and 3D imaging of the fruit and the environment and, finally, a control scheme that generates collision-free motions for the manipulator during harvesting. The manipulator has seven degrees-of-freedom (DOF). This is sufficient for the harvesting task. The end-effector is designed such that it handles the soft fruit without loss of quality. The thermal cutting device included in the end-effector prevents the spreading of viruses through the greenhouse. The computer vision system is able to detect more than 95% of the cucumbers in a greenhouse. Using geometric models the ripeness of the cucumbers is determined. A motion planner based on the A*-search algorithm assures collision-free eye-hand co-ordination. In autumn 2001 system integration took place and the harvesting robot was tested in a greenhouse. With a success rate of 80%, field tests confirmed the ability of the robot to pick cucumbers without human interference. On average the robot needed 45 s to pick one cucumber. Future research focuses on hardware and software solutions to improve the picking speed and accuracy of the eye-hand co-ordination of the robot.
We revalidate parameters of the cavernous arterial response (peak systolic blood flow velocity) and acceleration time using penile duplex pharmaco-ultrasonography.
Blood flow velocity in the ...cavernous artery following pharmaco-stimulation was determined with duplex ultrasonography in 106 patients with erectile dysfunction. Intima media thickness of the common carotid artery, a valid index for atherosclerosis and clinical diagnosis based on a comprehensive evaluation were used as references. The clinical diagnosis was used to determine cutoff values. For the statistical analysis, Pearson correlation and ROC curves were used.
When correlating peak systolic velocity and acceleration time to intima media thickness, acceleration time (r = 0.51, p <0.01) was the most valid parameter to detect cavernous atherosclerotic pathology (peak systolic velocity r = −0.18, p = 0.12). This finding was confirmed by a comparison of both parameters to the clinical diagnosis. AUC was 0.59, 95% CI 0.49–0.69 for peak systolic velocity and 0.72 (95% CI 0.62–0.80 for acceleration time). The cutoff point for acceleration time to discriminate between atherosclerotic and nonatherosclerotic erectile dysfunction was determined at acceleration time 100 milliseconds or greater. Sensitivity was 66% and specificity was 71%.
The results of this study show that acceleration time has more power than peak systolic velocity to diagnose atherosclerotic erectile dysfunction.
Sildenafil utilization was prospectively evaluated among 153 men with a history of erectile dysfunction (ED)-prescription drug use prior to starting sildenafil and 164 men who were new starters of ...ED-prescription drugs. Further, some determinants of sildenafil discontinuation were identified. During a median follow-up period of 18 months 45% of all patients discontinued sildenafil treatment, regardless of earlier treatment history. However, patients with a history of drug treatment for ED were nearly eight times as likely to switch or re-start another ED-prescription drug after discontinuing sildenafil compared to previously untreated users. Age >60 y, diabetes medication, nitrate use, and use of incontinence pads (a proxy for disease/surgery in the pelvic region) were associated with an increased likelihood of discontinuing sildenafil. Although the introduction of sildenafil reduced the barrier to seek medical help for erectile problems, sildenafil treatment failure in previously untreated patients results in a high dropout rate from further ED drug treatment of any kind.
Sexual dysfunction after renal replacement therapy Diemont, Willem L.; Vruggink, Peter A.; Meuleman, Eric J.H. ...
American journal of kidney diseases,
05/2000, Letnik:
35, Številka:
5
Journal Article
Recenzirano
The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or ...with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.
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