Long-term Potency Research Articles

In Vitro Functionality and Endurance of GMP-Compliant Point-of-Care BCMA.CAR-T Cells at Different Timepoints of Cryopreservation.

The search for target antigens for CAR-T cell therapy against multiple myeloma defined the B-cell maturation antigen (BCMA) as an interesting candidate. Several studies with BCMA-directed CAR-T cell therapy showed promising results. Second-generation point-of-care BCMA.CAR-T cells were manufactured to be of a GMP (good manufacturing practice) standard using the CliniMACS Prodigy® device. Cytokine release in BCMA.CAR-T cells after stimulation with BCMA positive versus negative myeloma cell lines, U266/HL60, was assessed via intracellular staining and flow cytometry. The short-term cytotoxic potency of CAR-T cells was evaluated by chromium-51 release, while the long-term potency used co-culture (3 days/round) at effector/target cell ratios of 1:1 and 1:4. To evaluate the activation and exhaustion of CAR-T cells, exhaustion markers were assessed via flow cytometry. Stability was tested through a comparison of these evaluations at different timepoints: d0 as well as d + 14, d + 90 and d + 365 of cryopreservation. As results, (1) Killing efficiency of U266 cells correlated with the dose of CAR-T cells in a classical 4 h chromium-release assay. There was no significant difference after cryopreservation on different timepoints. (2) In terms of endurance of BCMA.CAR-T cell function, BCMA.CAR-T cells kept their ability to kill all tumor cells over six rounds of co-culture. (3) BCMA.CAR-T cells released high amounts of cytokines upon stimulation with tumor cells. There was no significant difference in cytokine release after cryopreservation. According to the results, BCMA.CAR-T cells manufactured under GMP conditions exerted robust and specific killing of target tumor cells with a high release of cytokines. Even after 1 year of cryopreservation, cytotoxic functions were maintained at the same level. This gives clinicians sufficient time to adjust the timepoint of BCMA.CAR-T cell application to the patient's course of the underlying disease.

Field efficacy of botanicals and beneficial microbes to control banana mealybug (Pseudococcus elisae Borchsenius) (Hemiptera: Pseudococcidae)

The banana mealybug (Pseudococcus elisae Borchsenius) causes significant economic losses to banana production. Prior to the 2019 ban of the organophosphate chlorpyrifos use in commercial banana production systems due to high chlorpyrifos residue levels on banana fruits, chlorpyrifos-treated exclusion bags were commonly used to mitigate mealybug infestation on banana bunches and fingers. Short- and long-term effects of 2 beneficial microbes (Beauveria bassiana and Kosakonia radicincitans), 2 neem-based botanicals (Orgamix and Rata®), 3 chemical insecticides Pyriforce® (Chlorpyriphos-ethyl), Calixine Super® (Acetamipride and Bifenthrin), and Parastar EC40® (Imidachlorpride and Lambda-cyhalothrin), and tap water (Control) were evaluated on mealybug in a newly established and 5-year-old banana farms. Mealybug sampling was conducted for three months after each insecticide application and their population dynamics was calculated using Mann-Kendall trend statistics (S). For the 5-year-old banana farm, except the control, all treatments caused significant (P < 0.05) short-term reduction in mealybug population from pre-treatment application to 5 days in March, July and November samplings. Mealybug population reduction in March was greater than 90% for Calixine Super®, Orgamix and Beauveria, and between 80% and 90% for Kosakonia, Rata and Parastar EC40® (P < 0.05). A similar trend was recorded in July and November, with a higher reduction for Beauveria (52.08%) in July. An increasing linear mealybug trend was observed between March and June (S was positive, P > 0.05) across all treatments, while Orgamix and Rata® caused downward trend between July and October. A downward mealybug trend occurred for Parastar EC40® (S = −1), Rata® (S = −3), Beauveria (S = −6) and Kosakonia (S = −3) between November and January. Biorationals effectively reduced mealybug populations better than chlorpyrifos, while beneficial microbes and neem-based botanicals demonstrated long-term potency on mealybug.

Ketahanan Mortar Ringan Campuran Gula Aren dan Ragi pada Suhu Tinggi: Narrative Review

Lightweight mortar is a specific type of mortar that is made by adding a foaming agent. A lightweight mortar has a lot of pores or cavities filled with air, which reduces the mortar’s weight. The lightweight mortar has better heat insulation than an ordinary mortar with its high porosity. There has been much research and application of lightweight mortar in the last few years. This review focuses on lightweight mortar made with a natural additive that has good high-temperature resistance. Many additives can be used, such as yeast and palm sugar. Yeast is a microorganism that can be used as a foaming agent because it can produce carbon dioxide (CO2) that creates a lot of pores in the mortar through the glycolysis process. Palm sugar is a disaccharide groups sugar, and sucrose, consisting of glucose and fructose. Glucose can reduce gypsum consumption in mortar and ettringite formation. Besides, sugar contains lignin, which can increase the bonding strength of mortar components. This study proves that the innovation of lightweight mortar with organic additives has a long-term potency with its durability at high temperatures.

Self-assembling ferritin nanoparticles coupled with linear sequences from canine distemper virus haemagglutinin protein elicit robust immune responses

BackgroundCanine distemper virus (CDV), which is highly infectious, has caused outbreaks of varying scales in domestic and wild animals worldwide, so the development of a high-efficiency vaccine has broad application prospects. Currently, the commercial vaccine of CDV is an attenuated vaccine, which has the disadvantages of a complex preparation process, high cost and safety risk. It is necessary to develop a safe and effective CDV vaccine that is easy to produce on a large scale. In this study, sequences of CDV haemagglutinin (HA) from the Yanaka strain were aligned, and three potential linear sequences, termed YaH3, YaH4, and YaH5, were collected. To increase the immunogenicity of the epitopes, ferritin was employed as a self-assembling nanoparticle element. The ferritin-coupled forms were termed YaH3F, YaH4F, and YaH5F, respectively. A full-length HA sequence coupled with ferritin was also constructed as a DNA vaccine to compare the immunogenicity of nanoparticles in prokaryotic expression.ResultThe self-assembly morphology of the proteins from prokaryotic expression was verified by transmission electron microscopy. All the proteins self-assembled into nanoparticles. The expression of the DNA vaccine YaHF in HEK-293T cells was also confirmed in vitro. After subcutaneous injection of epitope nanoparticles or intramuscular injection of DNA YaHF, all vaccines induced strong serum titres, and long-term potency of antibodies in serum could be detected after 84 days. Strong anti-CDV neutralizing activities were observed in both the YaH4F group and YaHF group. According to antibody typing and cytokine detection, YaH4F can induce both Th1 and Th2 immune responses. The results of flow cytometry detection indicated that compared with the control group, all the immunogens elicited an increase in CD3. Simultaneously, the serum antibodies induced by YaH4F and YaHF could significantly enhance the ADCC effect compared with the control group, indicating that the antibodies in the serum effectively recognized the antigens on the cell surface and induced NK cells to kill infected cells directly.ConclusionsYaH4F self-assembling nanoparticle obtained by prokaryotic expression has no less of an immune effect than YaHF, and H4 has great potential to become a key target for the easy and rapid preparation of epitope vaccines.Graphical

Potency testing for a recombinant protein vaccine early in clinical development: Lessons from the Schistosoma mansoni Tetraspanin 2 vaccine

IntroductionAs a primary stability-indicating parameter, potency should be strategically evaluated during each phase of vaccine development. Herein, we present potency testing during the early clinical development of the Schistosoma mansoni (Sm) Tetraspanin-2 vaccine formulated on Alhydrogel (Sm-TSP-2/Al). As Sm-TSP-2/Al does not induce sterilizing immunity against its target pathogen (Sm) in animal models, potency is measured by “serological substitution”, a method that can add significant variation to the potency metric, especially when used in a compliance (or ‘single data point’) approach. MethodsPotency data were analyzed using the compliance approach to determine if two clinical lots of Sm-TSP-2/Al retained potency over 84 and 36 months post-release, respectively. These same data were also analyzed by: i) least-squares regression with a joinpoint regression analysis; ii) control charting of stability slopes; and iii) bootstrap modeling. Nested-regression and bootstrapping were used to compare the potency of the first (#11-69F-003) and second (#1975) clinical lots of Sm-TSP-2/Al. ResultsDespite significant variability in the immune assay, both clinical lots of Sm-TSP-2/Al remained potent for 84 and 36 months, respectively, in all four statistical approaches. The first lot of Sm-TSP-2/Al showed a gain in potency starting at 36 months post-release as captured by joinpoint regression. The two clinical lots of Sm-TSP-2/Al had comparable long-term potency. ConclusionWhile a compliance approach can monitor the long-term stability of Sm-TSP-2/Al, it risks putting this critical stability-indicating parameter out of specification with each time point tested due to statistical multiplicity. Alternative statistical methods, such as joinpoint regression or bootstrapping, do not have this limitation and offer even more precise estimations of potency, with the added benefit of also providing predictive analytics. Nested regression and bootstrapping were shown to be a viable alternatives for lot-to-lot comparisons of the stability of Sm-TSP-2/Al. Instructions for implementing both these potency testing approaches are provided.

Harnessing biomaterials for therapeutic strategies against COVID-19.

With the emergence of the coronavirus disease 2019 (COVID-19), the world is experiencing a profound human health crisis. The number of infections and deaths due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to increase every minute, pinpointing major shortcomings in our ability to prevent viral outbreaks. Although several COVID-19 vaccines have been recently approved for emergency use, therapeutic options remain limited, and their long-term potency has yet to be validated. Biomaterials science has a pivotal role to play in pushing the boundaries of emerging technologies for antiviral research and treatment. In this perspective, we discuss how biomaterials can be harnessed to develop accurate COVID-19 infection models, enhance antiviral drug delivery, foster new antiviral strategies, and boost vaccine efficacy. These efforts will not only contribute to stop or mitigate the current pandemic but will also provide unorthodox platforms to understand, prevent, and protect us from future viral outbreaks.

The role of brain-derived neurotrophic factor (BDNF) in the development of vascular cognitive impairment

Brain-derived neurotrophic factor (BDNF) is principally involved in the phenomena of neuroplasticity of the brain and long-term synaptic potency (LTP) in the hippocampus. This article covers the role played by BDNF as a diagnostic marker of vascular cognitive disorders. The relationship between etiology and the degree of cognitive impairment with the level of BDNF is ambiguous. Especially if we take into account the fact that vascular pathology can be a trigger for molecular mechanisms of neurodegeneration. The lowest BDNF level can be found among patients with dementia in Alzheimer’s disease, and there is evidence that patients with neurodegenerative disease without cognitive impairment have a decreased BDNF level. Patients with vascular cognitive impairment have a less expressed decrease of BDNF level, although it can depend on severity of stroke. In case of vascular cognitive impairment, it is possible to improve cognitive state thanks to increased BDNF level in hippocampus after physical activity. That opens new opportunities in rehabilitation. Genetic polymorphism of BDNF leads to the problems with cognitive rehabilitation and increases the risk of post-stroke dementia and dementia in Alzheimer’s disease. Supposedly, changes in the structure of BDNF-propeptide, which is involved in the processes of long-term synaptic depression (LTD) of the hippocampus, are the main cause in this case.

The Stabilizing Excipients in Dry State Therapeutic Phage Formulations.

Phage therapy has gained prominence due to the increasing pathogenicity of "super bugs" and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their "druggability" by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this review focuses on the current classes of excipients used to manufacture dry state phage formulations and their ability to stabilize and protect phage throughout the process, as discussed in the literature. We provide perspective of outstanding challenges involved in the formulation of dry state phage. We suggest strategies to improve excipient identification and selection, optimize the potential excipient combinations to improve phage viability during formulation, and evaluate new methodologies that can provide greater insight into phage-excipient interactions to improve design criteria to improve formulation of dry state phage therapeutics. Addressing these challenges opens up new opportunities to re-design and re-imagine phage formulations for improved efficacy as a pharmaceutical product.

The Current Dietary Risk Assessment of Chemicals in Food Underestimates the Actual Risk.

Dietary risk assessments (DRA) help determine safe exposure levels of toxic substances in food. Of these, Acceptable Daily Intake (ADI), derived from No Observed Adverse Effect Levels (NOAEL) of long-term toxicity studies, is compared to exposure estimates using lifetime-averaged food intakes. These estimates ignore intermittent high exposures exceeding the ADI; toxic effects of such exposures are considered irrelevant, on the assumption that toxic potency increases with exposure duration, which would be reflected by decreasing NOAELs. However, our statistical analysis of thousands of animal toxicology studies shows that NOAELs after short- and long-term exposure are similar if study design factors are considered. Thus, the short- and long-term potency effects of chemicals are similar. Hence, a short-term toxic effect is generally ignored in current DRA. It accounts for lifetime-averaged but not intermittent high food intakes and, therefore, must be revised. Additionally, there is no added value of long-term studies for ADI derivation.

Cytotoxicity of Nubein6.8 peptide isolated from the snake venom of Naja nubiae on melanoma and ovarian carcinoma cell lines

This study was conducted to examine the cytotoxic effects of Nubein6.8 isolated from the venom of the Egyptian Spitting Cobra Naja nubiae on melanoma (A375) and ovarian carcinoma cell lines and to reveal its mode of action. The size of Nubein6.8 (6801.8 Da) and its N-terminal sequence are similar to cytotoxins purified from the venom of other spitting cobras. Nubein6.8 showed a high significant cytotoxic effect on A375 cell line and moderate effect on A2780. A clonogenic assay showed that Nubein6.8 has a significant long-term potency on A375 cell survival when compared to A2780. The molecular intracellular signaling pathways of Nubein6.8 have been investigated using Western blotting analysis, flow cytometry, and microscale protein labeling. This data revealed that Nubein6.8 has DNA damaging effects and the ability to activate apoptosis in both tumor cell lines. Cellular uptake recordings revealed that the labeled-Nubein6.8 was intracellularly present in A375 cells while A2780 displayed resistance against it. SEM examination showed that Nubein6.8 was found to have high accessibility to malignant melanoma cells. The apoptotic effect of Nubein6.8 was confirmed by TEM examination that revealed many evident characteristics for Nubein6.8 apoptotic efficacy on A375 cell sections. Also, TEM reflected many resistant characteristics that faced Nubein6.8 acquisition through ovarian carcinoma cell sections. Accordingly, the snake venom peptide of Nubein6.8 is a promising template for developing potential cytotoxic agents targeting human melanoma and ovarian carcinoma.

PT383 - Hot or cold: No difference in long-term potency between touch-cautery and athermic suture-ligation in control of pedicle during robot-assisted radical prostatectomy

PT383 - Hot or cold: No difference in long-term potency between touch-cautery and athermic suture-ligation in control of pedicle during robot-assisted radical prostatectomy

Patient-Reported Sexual Survivorship Following High-Dose Image-Guided Proton Therapy for Prostate Cancer

ObjectiveTo help guide individualized treatment, we sought to identify baseline predictive factors that impact long-term erectile function following high-dose image-guided radiotherapy (HD-IGRT). MethodsPotent men with localized prostate cancer treated with radiotherapy alone were enrolled in an institutional review board-approved prospective cohort study. Men received HD-IGRT as primary treatment of prostate cancer. Patient-reported inventories were used to assess erectile function at baseline, 6 months, 2 years, and 5 years after treatment. Long-term potency rates were compared to validated models, and baseline factors were used to create a novel, internally validated nomogram for predicting long-term function. Results1,159 men were treated with HD-IGRT. Among 676 men who were potent at baseline and did not receive hormone therapy, the potency rates at 6 months, 2 years, and 5 years were 81%, 68%, and 61%. Recursive partitioning categorized patients into 3 groups based on two factors: baseline response to EPIC Q57 (ability to have an erection) and pre-existing heart disease. At 5 years, the most favorable group reported “very good” on Q57 and had an 80% potency rate (n = 137; p = 0.83); the intermediate group reported “good” on Q57 and had no baseline cardiac disease with a 62% potency rate (n = 145; p = 0.86); and the remaining poor risk group had a 37% potency rate (n = 117; p = 0.19). ConclusionsPatient-reported pretreatment sexual function and comorbidities enables stratification and prediction of erectile function. EPIC subset questions with baseline comorbidities may potentially serve as a quick and practical clinical tool for predicting sexual survivorship.

Incorporation of CD40 ligand or granulocyte-macrophage colony stimulating factor into Hantaan virus (HTNV) virus-like particles significantly enhances the long-term immunity potency against HTNV infection.

Hantavirus infections cause severe haemorrhagic fever with renal syndrome (HFRS) in humans and are associated with high fatality rates. In 2017, numerous outbreaks were reported in China and Germany. This represents a significant public-healthcare issue with no effective HFRS vaccines that offer a long-term immune response. In this study, we investigated the long-term humoral and cellular immune responses and protective immunity of Hantaan virus (HTNV) granulocyte-macrophage colony stimulating factor (GM-CSF) and CD40 ligand (CD40L) virus-like particles (VLPs) in mice. GM-CSF and CD40L VLPs were constructed via co-transfection of pCI-S and pCI-M-CD40L, and pCI-S and pCI-M-GM-CSF, into dihydrofolatereductase (dhfr)-deficient Chinese hamster ovary cells, respectively. Mice were immunized with HTNV VLPs 2 weeks apart. The animals were challenged 6 months after immunization. Specific and neutralizing antibodies were assessed by ELISA; IFN-γ was measured by enzyme-linked immunospot (ELISpot) assay and effectiveness by cytotoxic T lymphocyte (CTL) cytotoxicity assays. Nucleic acid loads of HTNV were tested by quantitative real-time PCR and viral antigen was detected via indirect ELISA. Pathological alterations were detected via haematoxylin-eosin staining. GM-CSF and CD40L VLPs provided stable, long-term protection with a high titre of neutralizing antibody in mice 6 months after immunization. Furthermore, VLPs increased HTNV-specific cellular immune responses via higher expression of IFN-γ and CTL responses. HTNV challenge assay results showed long-term protection against HFRS. No significant pathological alteration was observed in the organs of mice after immunization. This is, to the best of our knowledge, the first report demonstrating the long-term potency of HTNV VLP vaccines against HTNV infection and offers new insights into HTNV vaccine development.

Reconstituted Bay 81-8973 Factor VIII Stability Supports Its Suitability for Continuous Infusion for up to 24 Hours

Continuous infusion (CI) is used in many treatment centers as an option at the time when patients with hemophilia A undergo major surgical procedures. Benefits of CI versus bolus infusion (BI) of factor VIII (FVIII) in patients undergoing surgery include avoiding unnecessarily high peaks and low troughs of FVIII levels and reducing FVIII consumption during and after surgery, partially due to decreased clearance. Stability and long-term potency of FVIII products under CI conditions have been shown to exhibit variability. Thus, it is important to demonstrate stability for each product used in CI applications.BAY 81-8973 (Kovaltry®, Bayer, Berkeley, CA) is an unmodified, full-length recombinant human FVIII product with a primary amino acid sequence identical to that of sucrose-formulated recombinant FVIII (rFVIII-FS; Kogenate® FS, Bayer). rFVIII-FS was shown previously to be stable in solution for up to 7 days, to be safe and effective for CI during surgery, and to be suitable for pediatric and adult patients. The present study investigated whether BAY 81-8973 has adequate potency and purity up to 24 hours after reconstitution, which may indicate suitability for CI applications.BAY 81-8973 drug product in 250-IU and 500-IU vial sizes was tested 0, 4, 8, 12, and 24 hours after reconstitution with sterile water for injection and storage at room temperature in 30-mL polypropylene syringes (BD Plastipak™, BD, Franklin Lakes, NJ). The drug product was tested for potency (chromogenic assay), purity (high performance liquid chromatography - size exclusion chromatography [HPLC-SEC]), total protein content, pH, solution clarity, and subvisible particulates (high accuracy liquid particle counting - subvisible particles [HIAC-SVP]).There were no changes in potency, pH, clarity, aggregation, chain dissociation, subvisible particles, or total protein with either 250- or 500-IU BAY 81-8973 for up to 24 hours. Results were also consistent with the demonstrated safety and efficacy of rFVIII-FS for CI during surgery. These data indicate that BAY 81-8973 may be suitable for CI applications for up to 24 hours. DisclosuresTeare:Bayer: Employment. Trefethen:Bayer: Employment. Garger:Bayer: Employment. Mathew:Bayer: Employment.

Penile rehabilitation for postprostatectomy erectile dysfunction.

Despite efforts to preserve the neurovascular bundles with nerve-sparing surgery, erectile dysfunction remains common following radical prostatectomy. Postoperative penile rehabilitation seeks to restore erectile function but results have been conflicting. To evaluate the effects of penile rehabilitation strategies in restoring erectile function following radical prostatectomy for prostate cancer. We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase), the Cochrane Library, Web of Science, clinical trial registries (ClinicalTrials.gov, International Clinical Trials Registry Platform) and a grey literature repository (Grey Literature Report) from their inception through to 3 January 2018. We also searched the reference lists of other relevant publications and abstract proceedings. We applied no language restrictions. We included randomised or quasi-randomised trials with a parallel or cross-over design. We used standard Cochrane methodological procedures. Two review authors independently screened the literature, extracted data, assessed risk of bias and rated quality of evidence according to GRADE on a per-outcome basis. Primary outcomes were self-reported potency, erectile function measured by validated questionnaires (with potency defined as an International Index of Erectile Function (IIEF-EF) score of 19 or greater and or an IIEF-5 of score of 17 or greater) and serious adverse events. For all quality of life assessments on a continuous scale, higher values indicated better quality of life. We included eight randomised controlled trials with 1699 participants across three comparisons. This abstract focuses on the primary outcomes of this review only.Scheduled phosphodiesterase type 5 inhibitors (PDE5I) versus placebo or no treatmentScheduled PDE5I may have little or no effect on short-term (up to 12 months) self-reported potency (risk ratio (RR) 1.13, 95% confidence interval (CI) 0.91 to1.41; very low quality evidence), which corresponds to 47 more men with self-reported potency per 1000 (95% CI 33 fewer to 149 more) and short-term erectile function as assessed by a validated instrument (RR 1.11, 95% CI 0.80 to 1.55; very low quality evidence), which corresponds to 28 more men per 1000 (95% CI 50 fewer to 138 more), but we are very uncertain of both of these findings. Scheduled PDE5I may result in fewer serious adverse events compared to placebo (RR 0.32, 95% CI 0.11 to 0.94; low quality evidence), though this does not appear biologically plausible and may represent a chance finding. We are also very uncertain of this finding. We found no long-term (longer than 12 months) data for any of the three primary outcomes.Scheduled PDE5I versus on-demand PDE5I Daily PDE5I appears to result in little to no difference in both short-term and long-term (greater than 12 months) self-reported potency (short term: RR 0.97, 95% CI 0.62 to 1.53; long term: RR 1.00, 95% CI 0.60 to 1.67; both very low quality evidence); this corresponds to nine fewer men with self-reported short-term potency per 1000 (95% CI 119 fewer to 166 more) and zero fewer men with self-reported long-term potency per 1000 (95% CI 153 fewer to 257 more). We are very uncertain of these findings. Daily PDE5I appears to result in little to no difference in short-term and long-term erectile function (short term: RR 1.00, 95% CI 0.65 to 1.55; long term; RR 0.74, 95% CI 0.48 to 1.14; both very-low quality evidence), which corresponds to zero men with short-term erectile dysfunction per 1000 (95% CI 80 fewer to 125 more) and 119 fewer men with long-term erectile dysfunction per 1000 (95% CI 239 fewer to 64 more). We are very uncertain of these findings. Scheduled PDE5I may result in little or no effects on short-term adverse events (RR 0.69 95% CI 0.12 to 4.04; very low quality evidence), which corresponds to seven fewer men with short-term serious adverse events (95% CI 18 fewer to 64 more), but we are very uncertain of these findings. We found no long-term data for serious adverse events.Scheduled PDE5I versus scheduled intraurethral prostaglandin E1At short-term follow-up, daily PDE5I may result in little or no effect on self-reported potency (RR 1.10, 95% CI 0.79, to 1.52; very low quality evidence), which corresponds to 46 more men per 1000 (95% CI 97 fewer to 241 more). Daily PDE5I may result in a small improvement of erectile function (RR 1.64, 95% CI 0.84 to 3.20; very low quality evidence), which corresponds to 92 more men per 1000 (95% CI 23 fewer to 318 more) but we are very uncertain of both these findings. We found no long-term (longer than 12 months) data for any of the three primary outcomes.We found no evidence for any other comparisons and were unable to perform any of the preplanned subgroup analyses based on nerve-sparing approach, age or baseline erectile function. Based on mostly very-low and some low-quality evidence, penile rehabilitation strategies consisting of scheduled PDE5I use following radical prostatectomy may not promote self-reported potency and erectile function any more than on demand use.

Identification of potential crucial genes and pathways associated with vein graft restenosis based on gene expression analysis in experimental rabbits.

Occlusive artery disease (CAD) is the leading cause of death worldwide. Bypass graft surgery remains the most prevalently performed treatment for occlusive arterial disease, and veins are the most frequently used conduits for surgical revascularization. However, the clinical efficacy of bypass graft surgery is highly affected by the long-term potency rates of vein grafts, and no optimal treatments are available for the prevention of vein graft restenosis (VGR) at present. Hence, there is an urgent need to improve our understanding of the molecular mechanisms involved in mediating VGR. The past decade has seen the rapid development of genomic technologies, such as genome sequencing and microarray technologies, which will provide novel insights into potential molecular mechanisms involved in the VGR program. Ironically, high throughput data associated with VGR are extremely scarce. The main goal of the current study was to explore potential crucial genes and pathways associated with VGR and to provide valid biological information for further investigation of VGR. A comprehensive bioinformatics analysis was performed using high throughput gene expression data. Differentially expressed genes (DEGs) were identified using the R and Bioconductor packages. After functional enrichment analysis of the DEGs, protein–protein interaction (PPI) network and sub-PPI network analyses were performed. Finally, nine potential hub genes and fourteen pathways were identified. These hub genes may interact with each other and regulate the VGR program by modulating the cell cycle pathway. Future studies focusing on revealing the specific cellular and molecular mechanisms of these key genes and pathways involved in regulating the VGR program may provide novel therapeutic targets for VGR inhibition.

Long-term effect of tendering on prices of branded pharmaceutical products

Tendering has proven its efficacy mainly in generic procurement, however due to several impediments, its penetration among European Countries is low and data regarding its long-term effect are scarce. MethodsWe assess the long-term effect of tendering on prices of branded products in Cyprus through the utilization of a repeated measures generalized linear model. We used products that were continuously included in Cyprus formulary for seven consecutive years. ResultsTendering demonstrates a statistically significant reduction, superior to reduction reached with official external price referencing scheme, and it retains its long-term potency on price reduction. It is mediated by other variables such as interchangeability, in-patient status and indication of the product. Volume of sales is not related to the rate of reduction. ConclusionsTendering can be considered as a potent pricing and reimbursement method in the long-term. It is a context sensitive scheme, therefore it must be applied with regards to each country׳s operational health policy framework.

LONG-TERM POTENCY, STERILITY, AND STABILITY OF VANCOMYCIN, CEFTAZIDIME, AND MOXIFLOXACIN FOR TREATMENT OF BACTERIAL ENDOPHTHALMITIS

To determine the long-term potency, sterility, and stability of vancomycin, ceftazidime, and moxifloxacin prepared in single-use polypropylene syringes for intravitreal injection. Experimental study. Vancomycin 1 mg/0.1 mL, ceftazidime 2 mg/0.1 mL, and moxifloxacin 160 μg/0.1 mL were compounded and prepared in 1-mL polypropylene syringes and stored at 4 °C, -20 °C, and -80 °C. Antibiotic potency, sterility, pH, osmolality, and concentration were tested at baseline and at 1, 2, 4, 8, 12, and 24 weeks after preparation. Potency, sterility, and stability were preserved for all 3 antibiotics at all temperatures out to 24 weeks, although there was a trend toward reduced potency at Week 24 for vancomycin and ceftazidime stored at 4°C. The largest zones of inhibition for Staphylococcus epidermidis and S. aureus were consistently demonstrated by moxifloxacin. Vancomycin, ceftazidime, and moxifloxacin prepared in single-use polypropylene syringes retain potency, sterility, and stability out to 24 weeks when stored at -20 °C or -80 °C. The results of this study may have important implications for the current management of endophthalmitis.

Long‐term potency after early use of a vacuum erection device following radical prostatectomy

To evaluate the long-term potency after radical prostatectomy (RP) with the early use of a vacuum erection device (VED), and reasons for sexual inactivity and long-term attrition and maintenance of sexual activity, as RP is one of the most common treatments for prostate cancer but erectile dysfunction (ED) is a common side-effect. We identified 141 sexually active patients who underwent RP at Cleveland Clinic Foundation. Patients were offered various non-oral treatment options to prevent ED and were also motivated for early penile rehabilitation. At 5 years 62% remained sexually active, of whom 71% had natural erections sufficient for intercourse without assistance, 8.5% were still using sildenafil, 10% were using combined therapy (sildenafil plus VED). At 5 years 38% (43/113) men were sexually inactive. The reasons included loss of interest in 17 (40%), cardiovascular/neurological diseases in 18 (42%), hormonal therapy in three (7%), loss of partner in three (7%) and two had other surgery. The natural rate of erections for sufficient vaginal penetration without an erection aid were preserved and maintained in the early-prophylaxis group, and almost 60% of them had used a VED as early prophylaxis. Despite current phosphodiesterase-5 inhibitor treatments for ED, VED is becoming recognized again as having a primary role in early penile rehabilitation in many patients, specifically those treated for prostate cancer.

Long-term Potency Preservation following Brachytherapy for Prostate Cancer

To assess potency preservation in men following brachytherapy for prostate cancer with or without external beam radiation therapy (EBRT) and/or androgen deprivation therapy (ADT) and to evaluate the factors that significantly impact this rate.