Long-term Acceptance Research Articles

Efficacy and Patient Satisfaction from Homoeopathic Treatment in Gynecological Disorders

Background: Homeopathy was discovered in the year 1790 by German physician Christian Friedrich Samuel Hahnemann. Homeopathy is based on the principle of Similia Similibus Currentur” which means ‘likes cures likes’. The process of preparation of homeopathic medicines is known as “Potentization”. There are many types of research and studies which prove the positive effects of homeopathic remedies in various chronic disorders including gynecological disorders such as fibroids, PCOD, Menstrual disorders, PMS, etc. Many gynecological disorders are treatable by homeopathic remedies. Homeopathy requires an active collaboration on the part of the patient as it has an intrinsic difficulty of long-term acceptance. Methodology: The study was conducted as an observational and prospective study to check the Efficacy and Patient Satisfaction from Homoeopathic Treatment in Gynecological Disorders.110 samples in which females with age more than 13years who had gynecological disorders and undergoing homeopathic treatment for gynecological disorders were taken, a pre-tested and standardized questionnaire was used and samples were selected by non-probability convenient sampling method. Results: Efficacy and patient satisfaction from homeopathic treatment in gynecological disorders was 68.8%. Conclusion: The overuse of contraceptive and hormonal pills is showing bad effects on patients' health and more often the hormonal treatment which shows carcinogenic effects. So, as to overcome and reduce all these side effects of modern medicine the alternative system of treatment Homoeopathy was tossed up. Homeopathy is a very beneficial and potent alternative to synthetic hormones. This research paper has the clinical findings of homeopathic appointments in the 3 clinics of the Faridabad area Gynecological disorders.

FPAES: A Hybrid Approach for the Optimal Placement and Sizing of Reactive Compensation in Distribution Grids

Reactive power compensation with Capacitor Banks (CBs) is one of the most successful approaches used in distribution systems, mainly due to their versatility, long-term acceptance in the power industry, and reduced costs. Most allocation methods, however, lack specific strategies to handle the limited discrete nature of CBs sizes seeking to improve the overall optimization and computational performance. We present an algorithm for the Optimal Placement of Capacitor Banks (OPCB) in distribution systems by means of a hybrid Flower Pollination Algorithm (FPA)–Exhaustive Search (ES) approach. The pollination process itself determines the sets of buses for placement, while CBs sizes and the final fitness values of each pollen are selected after a full-search is conducted in the sizing space. As the sizing phase works on the limited search space of predetermined discrete bank values, the computational effort to find the optimum CB capacity is greatly reduced. Tests were performed on distribution systems of 10, 34, and 85 buses with respect to the objective function, final losses, and voltage profile. The algorithm offers an excellent compromise between solution quality and computational effort, when compared to similar approaches.

Delayed non-myeloablative irradiation to induce long-term allograft acceptance in a large animal lung transplantation model

We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol.

Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. A retrospective cohort study. An urban, academic medical institution. Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. None. The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Extracellular Vesicles as a Novel Therapeutic Option in Liver Transplantation.

Longterm liver graft dysfunction and immunological rejection remain common adverse events, in part due to early acute rejection episodes initiated by ischemia/reperfusion injury (IRI) immediately following transplantation. Novel treatment methods are therefore required to ameliorate liver IRI and to promote longterm allograft acceptance. Extracellular vesicles (EVs) derived from tolerogenic phenotype cells may serve as a novel therapeutic option in liver transplantation due to their immunomodulatory and proregenerative effects. Studies of hepatic IRI along with animal liver allograft models have demonstrated that EVs isolated from mesenchymal stem/stromal cells, immature dendritic cells, and hepatocytes can reduce graft injury through mechanisms including enhancement of mitochondrial autophagy, inhibition of immune response, and promotion of tissue regeneration. These preclinical models may soon move translationally into clinical practice, necessitating the generation of robust methods to generate clinical-grade EVs. These methods must address issues of reproducibility and ability to scale up the tolerogenic cell cultivation, EV isolation, and EV characterization. Once generated, the efficient delivery of EVs to the donor organ prior to transplantation remains an issue that could be resolved through the novel organ storage method ex vivo machine perfusion (EVMP). In this review, we summarize studies that have used tolerogenic cell-derived EVs to ameliorate hepatic IRI and promote liver allograft acceptance, discuss the steps toward generation of clinical-grade EVs, and introduce EVMP as a novel method to efficiently deliver EVs.

Kidney-induced systemic tolerance of heart allografts in mice

In swine and nonhuman primates, kidney allografts can induce tolerance of heart allografts, leading to their long-term, immunosuppression-free survival. We refer to this phenomenon as kidney-induced cardiac allograft tolerance (KICAT). In this study, we have developed a murine model for KICAT to determine the underlining cellular/molecular mechanisms. Here, we show that spontaneously accepted DBA/2J kidneys in C57BL/6 recipients induce systemic tolerance that results in the long-term acceptance of DBA/2J heart allografts but not third-party cardiac allografts. The state of systemic tolerance of hearts was established 2 weeks after transplantation of the kidney, after which time, the kidney allograft is no longer required. Depletion of Foxp3+ T cells from these mice precipitated rejection of the heart allografts, indicating that KICAT is dependent on Treg function. Acceptance of kidney allografts and cotransplanted heart allografts did not require the thymus. In conclusion, these data show that kidney allografts induce systemic, donor-specific tolerance of cardiac allografts via Foxp3 cells, and that tolerance is independent of the thymus and continued presence of the kidney allograft. This experimental system should promote increased understanding of the tolerogenic mechanisms of the kidney.

Humanitarian Assistance and Permanent Settlement of Asylum Seekers in Greece: The Role of Sympathy, Perceived Threat, and Perceived Contribution

During the recent inflow of asylum seekers from the Middle East and North Africa to Europe, the native population in Greek frontier islands largely offered humanitarian assistance to these immigrants, while support for their permanent settlement in the area was low. To explain this discrepancy, we investigated whether sympathy toward asylum seekers, perceptions of threat posed by asylum seekers, and asylum seekers’ perceived societal contributions relate differently to native Greeks’ self-reported provision of humanitarian assistance and to their support for asylum seekers’ permanent settlement in Greece. Using data from a representative sample of 1,220 Greek participants, we found that Greeks who showed more sympathy toward asylum seekers were more likely to report having offered humanitarian assistance. Further, participants who felt more sympathy and those who perceived higher asylum seekers’ contributions were more positive toward asylum seekers’ permanent settlement, whereas participants who perceived more threat from asylum seekers showed less support for their permanent settlement. We conclude that policies geared toward motivating people to provide humanitarian aid to asylum seekers should focus on generating sympathy, whereas policies geared toward increasing long-term acceptance of asylum seekers need to additionally consider lowering threat perceptions and highlighting asylum seekers’ contributions.

Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma.

Although once daily anti-glaucoma drug therapy is a current clinical reality, most therapies require multiple dosing and there is an unmet need to develop convenient, safe, and effective sustained release drug delivery systems for long-term treatment to improve patient adherence and outcomes. One of the first sustained release drug delivery systems was approved for the reduction of intraocular pressure in glaucoma patients. It is a polymeric reservoir-type insert delivery system, Ocusert™, placed under the eyelid and on the ocular surface for zero-order drug release over one week. The insert, marketed in two strengths, released pilocarpine on the eye surface. While many clinicians appreciated this drug product, it was eventually discontinued. No similar sustained release non-invasive drug delivery system has made it to the market to date for treating glaucoma. Drug delivery systems under development include punctal plugs, ring-type systems, contact lenses, implants, microspheres, nanospheres, gels, and other depot systems placed in the extraocular, periocular, or intraocular regions including intracameral, supraciliary, and intravitreal spaces. This article discusses the advantages and disadvantages of the various routes of administration and delivery systems for sustained glaucoma therapy. It also provides the reader with some examples and discussion of drug delivery systems that could potentially be applied for glaucoma treatment. Interestingly, one intracamerally injected implant, Durysta™, was approved recently for sustained intraocular pressure reduction. However, long-term acceptance of such devices has yet to be established. The ultimate success of the delivery system will depend on efficacy relative to eye drop dosing, safety, reimbursement options, and patient acceptance. Cautious development efforts are warranted considering prior failed approaches for sustained glaucoma drug delivery. Neuroprotective approaches for glaucoma therapy including cell, gene, protein, and drug-combination therapies, mostly administered intravitreally, are also rapidly progressing towards assessment in humans.

Telehealth in Uro-oncology Beyond the Pandemic: Toll or Lifesaver?

BackgroundTelehealth services are rapidly embraced in uro-oncology due to the current coronavirus disease 2019 (COVID-19) pandemic. ObjectiveTo determine patients’ perspective on adoption of telehealth as a response to the pandemic and its sustainability in the future. Design, setting, and participantsFollowing a COVID-19 outbreak, 101 patients with advanced genitourinary cancers are currently managed “virtually” for therapy administration at our tertiary care unit. They were surveyed about the current situation, and current and long-term employment of telehealth. InterventionRapid implementation of virtual patient management. Outcome measurements and statistical analysisPatients’ perception of anxiety of COVID-19 and cancer, perspective on telehealth measures as a reaction to the current COVID-19 pandemic, and long-term acceptance were used as outcomes. Wilcoxon matched-pair signed rank test, chi-square test, and Mann-Whitney U test were performed. Results and limitationsOf 101 patients, 92 answered the questionnaire, with 71 (77.2%) responding virtually by e-mail or phone call. Anxiety of cancer (6/10, interquartile range [IQR] 3–8) superseded that of COVID-19 (four/10, IQR 2–5.25, p<0.001), and patients oppose temporary treatment interruption. Of the patients, 66.0% perceive their susceptibility to COVID-19 as equal to or lower than the general population and 52.2% believe that COVID-19 will not affect their therapy. In future, patients (62.6%) prefer to maintain in-person appointments as opposed to complete remote care, but accept remote care during the pandemic (eight/10, IQR 5–9). Beyond the crisis, maintaining telehealth has low preference rates (four/10, IQR 2–7), with high acceptance for external laboratory controls (60.9%) and online visit management (48.9%), but lower acceptance for remote treatment planning including staging discussions (44.6%) and for referral to secondary care oncologists (17.4%). ConclusionsDespite the pandemic, cancer remains the key concern and patients are not willing to compromise on their treatment. Rapid implementation of telehealth is tolerated well during the need of social distancing, with a clear “red line” concerning changes in existing patient-physician relationships. Balancing future implementation of telehealth while considering patients’ demand for personal relationships will ensure human dignity in uro-oncology. Patient summaryWe queried patients with genitourinary cancers treated in an almost virtual setting following a local coronavirus outbreak. Acceptance of telehealth during the current situation is high; however, long-term implementation of the adapted services is less favored. We deduce that patient-physician relationship is crucial for cancer patients and needs to be balanced against measures for social distancing to forge the future management.

Efficacy and Acceptance of a Lombard-response Device for Hypophonia in Parkinson's Disease.

The purpose of this study was to examine the effectiveness, satisfaction, and acceptance of a low-cost Lombard-response (LR) device in a group of individuals with Parkinson's disease (IWPD) and their communication partners (CPs). Sixteen IWPD and hypophonia and their CPs participated in the study. The IWPD wore a LR device that included a small MP3 player (Sony Walkman) and headphones playing a multi-talker noise audio file at 80 dB during lab-based speech tasks and during their daily conversational speech over a 2-week device trial period. Outcome measures included average conversational speech intensity and scores on a questionnaire related to speech impairment, communication effectiveness, and device satisfaction. Conversational speech intensity of the IWPD is increased by 7 to 10 dB with the LR device. Following a 2-week trial period, eight of the IWPD (50%) gave the LR device moderate-to-high satisfaction and effectiveness ratings and decided to purchase the device for long-term daily use. At the 4-month follow-up, none of the IWPDs were still using the LR device. Device rejection was related to discomfort (loudness), headaches, interference with cognition, and difficulty controlling device. Short-term acceptance and satisfaction with the LR device was moderate, but long-term acceptance, beyond 4 months, was absent. Future studies are required to determine if other types of low-cost LR devices can be developed that improve long-term efficacy and device acceptance in IWPD and hypophonia.

Coreceptor blockade targeting CD4 and CD8 allows acceptance of allogeneic human pluripotent stem cell grafts in humanized mice

We have previously demonstrated that short-term coreceptor blockade with non-lytic monoclonal antibodies enables the long-term survival of fully allogeneic embryonic stem cell (ESC) transplants in mice. Here, we describe the use of Hu-PBL humanized mice to determine whether short-term coreceptor blockade with humanized anti-human CD4 and CD8 antibodies can achieve the same outcome towards human ESC derivatives. While control Hu-PBL mice rejected allogeneic hESC-derived transplants within weeks, mice treated with coreceptor blocking antibodies held their grafts for 7 weeks, the duration of the study. Rejection in the control mice was associated with demonstrable infiltrates of human CD45 white blood cells, predominantly of CD8 T-cells, whereas anti-CD4, but not anti-CD8 antibody treated mice showed remarkably reduced lymphocyte infiltration and prolonged allograft survival, indicating that the CD4+ T-cells were crucial to the rejection process. Our results give support to the principle that short-term blockade of T-cell co-receptors can achieve long-term acceptance of regenerative cell transplants in humans.

Automatic Estimation of Taste Liking Through Facial Expression Dynamics

The level of taste liking is an important measure for a number of applications such as the prediction of long-term consumer acceptance for different food and beverage products. Based on the fact that facial expressions are spontaneous, instant and heterogeneous sources of information, this paper aims to automatically estimate the level of taste liking through facial expression videos. Instead of using handcrafted features, the proposed approach deep learns the regional expression dynamics, and encodes them to a Fisher vector for video representation. Regional Fisher vectors are then concatenated, and classified by linear SVM classifiers. The aim is to reveal the hidden patterns of taste-elicited responses by exploiting expression dynamics such as the speed and acceleration of facial movements. To this end, we have collected the first large-scale beverage tasting database in the literature. The database has 2,970 videos of taste-induced facial expressions collected from 495 subjects. Our large-scale experiments on this database show that the proposed approach achieves an accuracy of 70.37 percent for distinguishing between three levels of taste-liking. Furthermore, we assess the human performance recruiting 45 participants, and show that humans are significantly less reliable for estimating taste appreciation from facial expressions in comparison to the proposed method.

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation.

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5mg/kg) for 14days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1×106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500µL ip, POD 1, 5). Banff grade III or 120days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28days in CTRL (n=7), 34 in ASC (n=6), and 27.5 in ASC-CYP (n=4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.

Peripheral CD19+CD24highCD38high B-regulatory cells in lung transplant recipients

BackgroundThe role of CD19+CD24highCD38high B-regulatory cells in solid-organ Transplant (Tx) in acceptance are still scarce. In previous studies on kidney transplant recipients may suggest a protective role of this cell subtype in graft tolerance and the existence of a cross talk between B-and T-regulatory clones. In lung transplantation, the role of B-regulatory cells has never been investigated. In a murine tracheal transplantation model, this subset seems able to prevent tracheal obliteration when in combination with rapamycin. Aim of this study is to analyze peripheral CD19+CD24highCD38high B-reg cells counts in a cohort of lung recipients, their association with several clinical and pharmacological variables and their possible association with T regulatory cell. MethodsFrom Jan 2009 to Dec 2014, 117 lung Tx recipients were submitted to an immunological follow up I-FU(median: 108.7 months (6.7–310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD19+CD24highCD38high B-cells (globally 1106 determinations). We tested the association between B-reg and relevant variables by linear or regression models for repeated measures, adjusting for time from Tx. ResultsAmong all variables analyzed at multivariate analysis: chronic rejection (OR − 0.19, p = .039), use of Mycophenolate (OR − 0.38, p < .001) and the presence of a concomitant pulmonary infection of S. aureus (OR 0.66, p = .002) and A. fumigatus (OR 0.50, p = .009) were significantly associated to B-reg cell.No significant correlation between CD19+CD24highCD38high B-reg cells and T-reg cells counts was found in our cohort. ConclusionsOur present data highlight, for the first time, that this cell subset might participate in long-term lung graft acceptance mechanisms.

Blood CD9+ B cell, a biomarker of bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome is the main limitation for long-term survival after lung transplantation. Some specific B cell populations are associated with long-term graft acceptance. We aimed to monitor the B cell profile during early development of bronchiolitis obliterans syndrome after lung transplantation. The B cell longitudinal profile was analyzed in peripheral blood mononuclear cells from patients with bronchiolitis obliterans syndrome and patients who remained stable over 3years of follow-up. CD24hi CD38hi transitional B cells were increased in stable patients only, and reached a peak 24months after transplantation, whereas they remained unchanged in patients who developed a bronchiolitis obliterans syndrome. These CD24hi CD38hi transitional B cells specifically secrete IL-10 and express CD9. Thus, patients with a total CD9+ B cell frequency below 6.6% displayed significantly higher incidence of bronchiolitis obliterans syndrome (AUC=0.836, PPV=0.75, NPV=1). These data are the first to associate IL-10-secreting CD24hi CD38hi transitional B cells expressing CD9 with better allograft outcome in lung transplant recipients. CD9-expressing B cells appear as a contributor to a favorable environment essential for the maintenance of long-term stable graft function and as a new predictive biomarker of bronchiolitis obliterans syndrome-free survival.

Alloresponses of Mixed Lymphocyte Hepatocyte Culture to Immunosuppressive Drugs as an In-Vitro Model of Hepatocyte Transplantation.

BackgroundHepatocyte transplantation (HCTx) has the potential for the treatment of end-stage liver disease. However, failure of engraftment and the long-term acceptance of cellular allografts remain significant challenges for its clinical application. The aim of this study was to investigate the efficacy of the immunosuppressive agents, Cyclosporine, Everolimus, and Belatacept to suppress the alloresponse of primary human hepatocytes in a mixed lymphocyte-hepatocyte culture (MLHC) and their potential hepatotoxicity in vitro.Material/MethodsPrimary human hepatocytes were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an MLHC. Proliferative alloresponses were determined by flow cytometry, and cytokine secretion was measured using Luminex-based multiplex technology. Using an MLHC, the alloresponses of primary human hepatocytes were compared in the presence and absence of Cyclosporine, Everolimus, and Belatacept. Cultured primary human hepatocytes were assessed for the production of albumin, urea, aspartate transaminase (AST) and DNA content. Metabolic activity was determined with the MTT assay.ResultsImmune responses induced by primary human hepatocytes were effectively suppressed by Cyclosporine, Everolimus, and Belatacept. Everolimus significantly reduced the metabolic activity of primary human hepatocytes in vitro, suggesting impairment of cell viability. However, further functional analysis showed no significant differences between treated and untreated controls.ConclusionsCyclosporine, Everolimus, and Belatacept suppressed the alloresponse of primary human hepatocytes in an MLHC without significant cytotoxicity or functional cell impairment.

Effect of Timing and Complement Receptor Antagonism on Intragraft Recruitment and Protolerogenic Effects of Mesenchymal Stromal Cells in Murine Kidney Transplantation.

Mesenchymal stromal cells (MSCs) have protolerogenic effects in renal transplantation, but they induce long-term regulatory T cells (Treg)-dependent graft acceptance only when infused before transplantation. When given posttransplant, MSCs home to the graft where they promote engraftment syndrome and do not induce Treg. Unfortunately, pretransplant MSC administration is unfeasible in deceased-donor kidney transplantation. To make MSCs a therapeutic option also for deceased organ recipients, we tested whether MSC infusion at the time of transplant (day 0) or posttransplant (day 2) together with inhibition of complement receptors prevents engraftment syndrome and allows their homing to secondary lymphoid organs for promoting tolerance. We analyzed intragraft and splenic MSC localization, graft survival, and alloimmune response in mice recipients of kidney allografts and syngeneic MSCs given on day 0 or on posttransplant day 2. C3a receptor (C3aR) or C5a receptor (C5aR) antagonists were administered to mice in combination with the cells or were used together to treat MSCs before infusion. Syngeneic MSCs given at day 0 homed to the spleen increased Treg numbers and induced long-term graft acceptance. Posttransplant MSC infusion, combined with a short course of C3aR or C5aR antagonist or administration of MSCs pretreated with C3aR and C5aR antagonists, prevented intragraft recruitment of MSCs and graft inflammation, inhibited antidonor T-cell reactivity, but failed to induce Treg, resulting in mild prolongation of graft survival. These data support testing the safety/efficacy profile of administering MSCs on the day of transplant in deceased-donor transplant recipients and indicate that complement is crucial for MSC recruitment into the kidney allograft.

Cellular mechanism in support of allogenic human amnion epithelial cell transplantation without immunosuppression

Background & Aim Placenta is a non-controversial and readily available source of stem cells for regenerative medicine. We previously reported that human amnion epithelial cells (hAEC) from term placenta are not tumorigenic, have immunomodulatory and anti-inflammatory properties and once transplanted differentiate into functional hepatocyte-like cells. In preclinical studies with immune-competent mice, hAEC engrafted and survived without administration of immunosuppressive drugs, resulting in correction of metabolic liver diseases or the reversal of acute liver failure. In clinical settings allogenic hAEC have been transplanted without immunosuppression. However, little or null is known about immunomodulatory cells, as hAEC. During the past years we studied and identified molecular pathways this novel stem cells has, driving immunoregulatory capacity. Methods, Results & Conclusion We performed a complete surface screening of hAEC, profiling all the molecules commonly described on other stem as well as somatic cells. Amnion characteristically lacks HLA class 2 expression and expresses both class 1a and non-polymorphic class 1b (responsible for maternal immune-toleration of the fetus). We quantified the level of expression of HLA-G and HLA-E molecules both as membrane-bound and soluble forms. Recently, purinergic mediators, hydrolyzed by plasma membrane nucleotidases, have also been identified to regulate immune cell response, thus we quantified the level of expression of all ecto-enzymes in hAEC preparations. Surprisingly, hAEC constitutively express all known ecto-enzymes. In addition, we proved constitutive expression of of CD47 (‘don't-eat-me’ signal) and complement system (CD55/CD59). Immunogenicity of the hAEC was confirmed on purified immune effector cells (T-, B- and NK-cells). Conclusions High level expression of ecto-enzymatic axis and non-canonical HLA molecules likely play a key role in immunological tolerance and long-term acceptance of the human xeno-cell graft in immunocompetent mice. The ability to treat the most common (liver) diseases with one stem cell therapy without the administration of immunosuppressive drugs could be a “game changer” and will greatly expand the number of patients who could receive cellular therapy. Based on their safety and the successful preclinical studies, approval was granted to begin banking of hAEC under cGMP condition at Karolinska Institutet, and to perform hAEC transplants on 10 patients with liver disease without immunosuppression.

Security Aware Virtual Network Embedding Algorithm Using Information Entropy TOPSIS

Network virtualization is an effective manner to address the ossification issue of Internet architecture. Virtual network embedding is one of the most critical techniques in network virtualization environments. Several security problems about virtual network embedding are introduced due to the fact that virtual network embedding adds a virtual layer into the internet architecture. In this paper, we proposed an approach for security aware virtual network embedding called SA-VNE to address the security problems in virtual network embedding process. Firstly, we use the information entropy TOPSIS method to rank the importance of substrate nodes with an aim to choose the most appropriate substrate node for accommodating the virtual node. Secondly, we use the shortest path algorithm to perform the link mapping process. Simulation results demonstrated that our proposed SA-VNE algorithm behaves better that those of state-of-the-art existing security aware virtual network embedding algorithms in terms of the long-term average revenue, the long-term average VN acceptance ratio, the long-term average revenue to cost ratio and the running time.

New Empirical Data Findings for Student Experiences of E-Learning analytics Recommender Systems and their Impact on System Adoption

This article examines Saudi Arabian students' experiences of using an e-learning analytics recommender system during their study and the extent to which their experiences were predictors of their adoption and post-adoption of the system. A sample of 353 students from various universities in Saudi Arabia completed a survey questionnaire for data collection. Results showed that user experience is a significant predictors of student adoption and post-adoption of an e-learning recommender system. Based on these findings, this study concluded that universities must support students to develop their awareness of, and skills in using an e-learning recommender system to support students' long-term acceptance and use of the system.