Different botanical sources of starch  were fed either raw or cooked. In the controls (C), there was an almost complete pcD (>92%) except for potato starch (61.5%) which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%). Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI), enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with ( The pancreatic duct ligated (PL) pig or minipig is an established model for studying pancreatic exocrine insufficiency (PEI) in humans and for obtaining information about effects of PEI on digestive processes and for optimising enzyme substitution therapy –5.Coefficients of absorption for fat and protein over the total tract are much more decreased in the case of PEI than that of starch. Overall, the topic of carbohydrate malabsorption in the case of PEI has still to be quantified accurately , 7. AmylOn the one hand, the fermentation of carbohydrates contributes to the patients' energy supply by providing short chain fatty acids , 14, butAs observed in a former study, the botanical origin of the starch had a marked effect on praecaecal digestibility in PL-pigs , but in The results of this study should contribute to optimising dietary recommendations for human patients suffering from PEI.All efforts were made to minimise both the stress for the individual animal and the numbers of animals used. The procedures used in this study were conducted in accordance with the German Animal Welfare Act and with the European Council Directive of 24 November 1986 (86/609/EEC) and were approved by the Ethics Committee on Animal Welfare of the Hannover District Government.n = 3), additionally, a ligation of the ductus pancreaticus accessorius was performed to induce the PEI experimentally. In all pigs activity of faecal chymotrypsin was measured  and only minipigs with a chymotrypsin activity < 0.900 U/g faeces were defined and used as PL-pigs. The other minipigs (n = 3) with an intact pancreas served as controls (C). The body weight of the minipigs used in the present study was 37.0 ± 2.50 kg (C) and 37.7 ± 5.74 kg (PL).Altogether, 6 adult female minipigs, fitted with an ileocaecal reentrant fistula , were uStarch of different botanical origin was chosen to include starch sources of different granula size in this study .2O3 as a marker) was fed only once without any adaptation period and chyme collection was performed over 8 h after the first occurrence of the green colour of the chyme indicated the arrival of the test diet at the fistula at the terminal ileum. In PL-pigs enzyme replacement therapy with Creon was stopped at least three days before the trial started and no enzymes were given during the test. In the evening before the test started the pigs were fed only 400 mL of a liquid diet  to optimise gastric emptying and to avoid a carryover of nutrients of the diet from the previous evening into the test. A wash-out period of at least 48 h between two screening-tests was used to ensure a washout of Cr2O3 out of the praecaecal gastrointestinal tract. The different sources of starch were tested in a randomised order with every pig receiving all diets. For reasons of low palatability and incomplete feed intake one pig had to be replaced by another for the test diet containing raw amaranth.The different starch sources were tested in a screening-test established by Becker . Therefo2O3 . Isolated starch and test diets were analysed using standard methods according to Naumann and Bassler [The test meal consisted of 150 g of the starch to be tested, 25 mL of olive oil , 30 g of methylcellulose , and 0.625 g CrChemical composition of the test diets is described in Thermal treatment of starch was performed by cooking over 20 minutes. The amount of water was adapted to allow continuous stirring of the starch mash with amounts of water differing from 2.5 (amaranth) up to 5 litres (potato) per kg starch. After cooking, starch was dried by freeze drying .Ileal chyme was collected by opening the reentrant fistula, closing the caecal fistula with a cover containing a membrane, and fixing a flexible bin to the ileal fistula. These bins were emptied frequently and replaced by new ones. Water and electrolytes were substituted (1 mL per gramme chyme collected) into the caecal fistula every two hours according to the method described by Tabeling et al. .2O3 was determined according to the method of Petry and Rapp [Samples of ileal chyme were weighed and frozen immediately after collection, freeze-dried , and analysed regarding dry matter and starch  according to Naumann and Bassler . Cr2O3 wand Rapp . The pcDand Rapp  and Mößeand Rapp . t-test was used while for the comparison of the results of the control and PL-pigs an unpaired t-test was used. Significant effects of the group were stated when P < 0.05.Statistical analysis was performed using SAS version 9.31 . For testing the effects of botanical origin and thermal processing of the starch within one group of animals a pairedThe pcD of starch was significantly reduced in the PL-pigs compared to the controls for amaranth, potato starch, and pea starch. When raw rice starch was fed, there was also a large numerical difference regarding pcD between the controls and PL-pigs but due to high individual variation in the PL-pigs (69.6 ± 23.7) this difference reached no significance see .The pcD of starch was significantly reduced in PL-pigs compared to controls for cooked amaranth, while there was no significant effect of PEI when rice starch, potato starch, and pea starch were fed see .In C-pigs the pcD of raw starch was high in general (>96%) but was significantly lower when raw potato starch was fed (61.5%), while there was no significant effect of botanical origin when the different sources of starch were fed cooked, with values varying from 91 to 99% see .P < 0.005) than pcD observed after feeding amaranth (87.9 ± 3.50). When cooked starch was fed, the values differed between 87.5% (amaranth) and 91.7% (rice starch).In PL-pigs feeding of the raw potato starch resulted in the lowest pcD with values (43.9 ± 2.71%) being significantly lower (P < 0.05) of pcD of potato starch. While thermal treatment did not affect pcD of starch in controls (except for potato starch), in the group PL-pigs, cooking of starch resulted in a significant increase in pcD for all sources of starch tested except for amaranth. It is worth mentioning that variation regarding pcD was very high in the PL-pigs for raw rice starch and raw pea starch. When these sources of starch were fed cooked the variation was much lower  nor in the PL-pigs (81.3 ± 5.12) did the increased amount of the raw amaranth per meal  have any effect on the pcD compared to the values observed after feeding 150 g of amaranth per meal.As determining praecaecal digestibility is of greatest relevance to evaluate the nutritive value of starch , use of The part of starch being digested and absorbed in praecaecal parts of the GIT is of special interest as postileal degradation of resistant starch is only performed by intestinal microflora, having beneficial effects on colonic health by degradation to butyric acid  but alsoThe digestibility of starch is influenced by botanical origin  with conπr2 but the volume is 4/3πr3 the right hand curve is consistent with a role for particle size determining the surface area for enzymatic attack.Furthermore, the digestibility was affected by granula size of the starch. The pcD of starch was lower for starch sources with larger granula size as a result of lower surface area . AlthougCooking starch has been well known for a very long time and is a traditional method to increase praecaecal digestibility of starch and to reduce negative side effects of fermentation. It is well accepted that necessity of thermal processing is dependent on the source of starch; for example, raw potato starch (high proportion of resistant starch) is not adequate for human nutrition while most grains  can be used as food without thermal processing in healthy individuals.P < 0.05) in C-pigs. This finding tallies well with that of Rerat [ in vitro tests fermentation of 1 g of starch in ileal chyme of PL-pigs resulted in a production of up to 160 mL of gas [The results of this study are of special interest for dietary treatment of human patients with PEI. Adult healthy minipigs are able to digest starch of different origin quite efficiently praecaecally; even the starch was not heat treated. Only raw potato starch was digested to a lower extent (of Rerat  and is pof Rerat . In PL-pof Rerat ) there mL of gas . AlthougL of gas , there i in vivo [The screening-test model used in this study seems to be an interesting and suitable method not only for testing pancreatic enzyme preparations in vivo  but alsoThis study clearly underlines the need for botanic characterisation of starch in nutrition and dietetics. The fact that ranking of starch pcD differed between C- and PL-pigs emphasises the need for investigations on specific animal models or patients when trying to optimise diet formulation for special dietetic purposes.


Journal of Negative Results in Biomedicine, for their invaluable assistance with review of manuscripts for the journal in Volume 13 (2014).A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers, whose efforts often go unrecognized. Although final decisions are always editorial, they are greatly facilitated by the deeper technical knowledge, scientific insights, understanding of social consequences, and passion that reviewers bring to our deliberations. For these reasons, the Editor-in-Chief and Managing Editor of the journal warmly thank the reviewers whose comments helped to shape  Courtney AldrichUSAPraveen BallabhUSAMarkus BiburgerGermanyTrevor BirminghamCanadaFrederick ColbourneCanadaPeter CrouchAustraliaJean-Pierre DavidGermanySolange L. De CastroBrazilChetana S. DeshpandeIndiaJulia EtichGermanyYoshiaki FurukawaJapanKolja GelseGermanyFelipe Goñi-de-CerioSpainBettina GroetschGermanyUlrike HarreGermanyGordon HowarthAustraliaDirk HubmacherUSAPan JihongChinaDimitrios KanakisGreeceMasashi KanayamaUSAShunsuke KanbaraJapanAndre Pascal KengneSouth AfricaMichio KurosuUSAAlexander Benedikt LeichtleSwitzerlandRoberto MarciItalyDavid McGheeUKDirk MielenzGermanyTetsuryu MitsuyamaJapanEvelyn Marielle MonninkhofNetherlandsJennifer MoylanUSATakashi NagasawaJapanEdin NevzatiSwitzerlandNikoletta PapadopoulouGermanyRui PredigerBrazilHaibo QiuChinaJaqueline RinaldiBrazilJuan RodriguezArgentinaCelena Scheede-BergdahlCanadaJe Kyung SeongSouth KoreaVishnumurthy Shushrutha HednaUSAMitsutoshi TsukimotoJapanStephanie WohlgemuthUSAFumihiko YoshinoJapanTi-Fei YuanChina


Journal of Foot and Ankle Research would like to thank all our reviewers who have contributed to the journal in Volume 7 (2014).The Editors of  Pippa AndersonUnited KingdomJohn ArnoldAustraliaStuart BairdUnited KingdomChristian John BartonAustraliaHeiner BaurSwitzerlandPaul BennettAustraliaShan BerginAustraliaAdam BirdAustraliaChris BishopAustraliaDaniel BonannoAustraliaKatherine BurgessUnited KingdomJoshua BurnsAustraliaJohn BurstonUnited KingdomPaul ButterworthAustraliaMatthew CarrollNew ZealandAlex ChamberlainAustraliaGraham ChapmanUnited KingdomAngus ChardAustraliaNicole ChimeraUSALisa ChinnUSAVivienne ChuterAustraliaMark CornwallUSAMatthew CotchettAustraliaEmma CowleyUnited KingdomSarah CurranUnited KingdomHamish CurryAustraliaAnnette DavisAustraliaSophie De MitsBelgiumSharon DixonUnited KingdomStephen DuckettCanadaAngela EvansAustraliaLisa FarndonUnited KingdomGwen FernandesUnited KingdomJill FerrariUnited KingdomJoseph FioritoUSAAlex ForresterUnited KingdomJacqueline ForssUnited KingdomAndrew Franklyn-MillerAustraliaNicoletta FrescosAustraliaTetsuo FukunagaJapanAlfred GattMaltaKathleen GattMaltaMoshi GesoAustraliaPaul GibbonsAustraliaUri GivonIsraelKelly GrayAustraliaJoel GurrAustraliaDavid GutekunstUSAJill HalsteadUnited KingdomJoseph HamillUSAFarina HashmiUnited KingdomFiona HawkeAustraliaGordon HendryUnited KingdomClaire HillerAustraliaHiroaki HobaraJapanSheree HurnAustraliaKasper JanssenThe NetherlandsRobert KiddAustraliaTim KilmartinIrelandKevin KirbyUSADorit KunkelUnited KingdomToshiyuki KuriharaJapanPeter LazzariniAustraliaAlberto LeardiniItalySzu-Ping LeeUSAPazit LevingerAustraliaRod LingAustraliaAnmin LiuUnited KingdomAnna LorimerNew ZealandJody LucasUnited KingdomJohn LudlowUSAClaire MacGilchristIrelandNicola MaffulliUnited KingdomRyan MahaffeyUnited KingdomNele MahieuBelgiumMatthew MaloneAustraliaIan MathiesonUnited KingdomJulie McDonaldAustraliaAndrew McMillanAustraliaKaren MickleAustraliaStewart MorrisonUnited KingdomGeorge S MurleyAustraliaVanessa NubeAustraliaSusan PagerAustraliaKade PatersonAustraliaCraig PayneAustraliaByron PerrinAustraliaCarlos Pique-VidalSpainCameron PowdenUSATrevor D PriorUnited KingdomSmita RaoUSAAnita RaspovicAustraliaMichael Skovdal RathleffDenmarkAnthony RedmondUnited KingdomEdward RoddyUnited KingdomKeith RomeNew ZealandThomas RoukisUSAHagen SchmalGermanyDebbie SharmanUnited KingdomZhongmin ShiChinaSorin SieglerUSAElizabeth SkinnerAustraliaSimon SmithAustraliaJinsup SongUSAMartin SpinkAustraliaJulie StebbinsUnited KingdomMartijn SteultjensUnited KingdomRobert StoekenbroekThe NetherlandsGeoff SuissmanAustraliaLuke TaylorAustraliaScott TelferUnited KingdomDominic ThewlisAustraliaKirsten Tulchin-FrancisUSAStephen UrryAustraliaBabette Corine van der ZwaardThe NetherlandsTom van RaaijThe NetherlandsWesley VernonUnited KingdomScott WearingAustraliaAnita WilliamsUnited KingdomSebastian WolfGermanyDavid WylieUnited KingdomYayi XiaChinaMaria YoungUnited KingdomBernhard ZipfelSouth Africa


Elderly patients with end-stage renal disease have become the fastest growing population of kidney transplant candidates in recent years. However, the risk factors associated with long-term outcomes in these patients remain unclear.We retrospectively analyzed 166 recipients aged 60 years or older who underwent primary deceased kidney transplantation between 2002 and 2013 in our center. The main outcomes included 1-, 3- and 5-year patient survival as well as overall and death-censored graft survival. The independent risk factors affecting graft and patient survival were analyzed using Cox regression analysis.The 1-, 3-, 5-year death-censored graft survival rates were 93.6%, 89.4% and 83.6%, respectively. Based on the Cox multivariate analysis, panel reactive antibody (PRA)>5% , delayed graft function  and acute rejection  were independent risk factors for graft failure. The 1-, 3-, 5-year patient survival rates were 84.8%, 82.1% and 77.1%, respectively. Longer dialysis time , graft loss  and low-dose ganciclovir prophylaxis (1.5 g/d for 3 months)  were risk factors associated with patient death.The five-year results show an excellent graft and patient survival in elderly kidney transplant recipients aged ≥60 years. PRA>5%, delayed graft function, and acute rejection are risk factors for graft failure, while longer duration of dialysis, graft loss and low-dose ganciclovir prophylaxis are risk factors for mortality in elderly recipients. These factors represent potential targets for interventions aimed at improving graft and patient survival in elderly recipients. Kidney transplantation is considered to be the best treatment option for patients with end-stage renal disease (ESRD), regardless of their age. Currently, the mean age of patients undergoing renal transplantation has increased. This trend is observed not only in western countries such as America but also in Asian countries. Patients ≥60 years with ESRD have become the fastest growing population of wait-listed individuals and kidney transplant candidates However, despite the known benefits of kidney transplantation over dialysis in the elderly patients, long-term outcomes of the recipients and their grafts are still limited Therefore, the aim of this study was to evaluate graft and patient survival in kidney transplant recipients aged ≥60 years and to determine the possible recipient-related risk factors associated with clinical outcome.This retrospective cohort study was approved by the Institutional Review Board/Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University, and all aspects of the study complied with the Helsinki Declaration of 1975. The Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University specifically approved that not informed consent was required because all data were going to be analyzed anonymously. All of the organs were from donation after brain death (DBD) or donation after cardiac death (DCD), and all of the organ donors had provided informed written consent. No prisoner organs were used in this study.All patients aged 60 years or older who underwent first-time kidney transplantation from deceased donors in our center between January 2002 and June 2013 were collected. We excluded patients who had received another organ besides the kidney. The recipient characteristics included age, gender, causes of ESRD, pre-transplant comorbidities , type and time on dialysis, and panel reactive antibody (PRA) level at transplantation. The induction agents, basic maintained immunosuppressive regimens, and regimens for cytomegalovirus (CMV) prophylaxis were also recorded. After surgery, the number and frequency of adverse events including delayed graft function (DGF), acute rejection (AR) and chronic rejection (CR) at any time, leucopenia, infectious events, graft loss and patient death, malignancy and other new onset diseases were recorded. The causes of graft failure and mortality were also recorded.Patients received IL-2 receptor antagonist  or rabbit anti-thymocyte globulin (rATG) as induction agents. The maintained immunosuppressive regimens consisted of cyclosporine or tacrolimus, mycophenolate mofetil (MMF) and prednisone. From 2002 to 2006, most of the recipients received a low-dose ganciclovir (1.5 g/d for 3 months) for CMV prophylaxis, whereas patients mainly received a high-dose ganciclovir (3.0 g/d for 3 months) since 2007. Sulfamethoxazole was administered orally for 3 months for Pneumocystis jirovecii pneumonia prophylaxis.DGF was defined as the need for dialysis in the first week after transplantation. AR was diagnosed based on clinical manifestations such as fever, oliguria, and serum creatinine elevation of >25% from the baseline value and was confirmed by a subsequent renal allograft biopsy. Biopsy-proven acute rejections (BPAR) included all acute rejections which were graded borderline or higher by Banff'97 criteria. CR was diagnosed by clinical findings with a decrease in kidney function and developing a gradual rise in serum creatinine, and was confirmed by renal allograft biopsy with histological features including thickening of the intima of arterioles and arteries, sclerosis of glomeruli, and tabular atrophy.P<0.2 level in the univariate Cox analysis were included in the final multivariate model. A P-value <0.05 was considered to indicate statistical significance.All data were analyzed by SPSS for Windows Version 19.0 . Continuous variables are expressed as counts and percentages, and categorical variables are expressed as the means with standard deviations (mean ± SD). Actuarial graft and patient survival were calculated using Kaplan–Meier analysis. To assess variables associated with transplant outcome, univariate and multivariate Cox proportional hazards regression models were employed. The association between outcomes and all co-variables were tested separately in univariate Cox analyses. To evaluate the potential independent risk factors for transplant outcomes, all variables associated with graft loss or patient death at a We collected data from 166 primary deceased kidney transplant recipients aged 60 or older between January 2002 and June 2013. The demographic and baseline characteristics of these elderly patients are shown in The adverse events during the 5-year follow-up are shown in During a 5-year follow-up, there were 36 cases of graft loss in the cohort. More than half of the graft losses (52.8%) were due to patient death. Univariate analysis showed that longer dialysis time, PRA>5%, DGF and AR were risk factors for death-censored graft loss. Based on the Cox multivariate models, a PRA>5% , DGF  and AR  remained independent risk factors for death-censored graft loss, except for longer dialysis time . The staThere were 29 deaths during the 5-year follow-up. The risk factors for patient death were shown in The rapid increase in elderly patients with ESRD has raised an important issue regarding the optimization of long-term outcomes in this population. Despite a higher percentage of cadaveric kidney donors being allocated to older patients, the short-term graft survival is excellent in the majority of these patients. However, longer-term graft survival in the elderly recipients is less than expected due to death with a functioning graft, which is the major cause of graft loss. Elderly renal transplant recipients are at increased risk of graft loss and death compared with younger cohorts In this study, we retrospectively analyzed 166 cases of renal transplantation from deceased donors in recipients aged ≥60 years and identified the possible risk factors predicting poor clinical outcome. Consistent with previous studies, death with a functioning graft is the leading cause of graft loss in elderly patients, with a percentage of more than 50% In our study, we found that patients aged ≥60 years experienced a low incidence of AR episodes, which were similar to previous findings The literature on the association between duration of dialysis and transplant outcome is rich and at times inconsistent. Most of the studies reported that longer duration of dialysis was associated with poorer patient and graft outcome in kidney transplant recipients Graft failure was a significant risk factor for mortality for patients aged ≥60 years in our study, which was confirmed in previous studies CMV infection is a common problem in immunocompromised hosts and an important cause of morbidity and mortality in kidney transplant recipients CAD was one of the most common comorbidities and causes of death in elderly recipients. Faravardeh et al. Our study has certain limitations inherent in its retrospective nature because data were collected from patients transplanted from 2002 to June 2013. There were certain patients missing in the follow-up , which may reduce potential adverse effects of various risk factors that would be observed over a longer-term. In addition, the relatively small sample size might have less power to detect the effect of variables that have a smaller impact on the poor clinical outcome.In conclusion, the transplant outcomes are excellent among recipients aged 60 years or older. We found that PRA>5%, DGF and AR were risk factors for graft failure, while longer time on dialysis, failed grafts and low-dose ganciclovir prophylaxis were risk factors for mortality in recipients aged ≥60 years. These factors represent potential targets for interventions aimed at improving graft and patient survival in elderly recipients. Therefore, reducing PRA level and decreasing the incidence of DGF and AR may result in longer graft survival, while shortening the duration of dialysis may lead to longer patient survival. In addition, high-dose ganciclovir prophylaxis should be widely used in elderly recipient to decrease the incidence of CMV infection. Nevertheless, further prospective, randomized and multicenter studies are needed to confirm these findings.


The mammalian neocortex generally has a repetitious, laminar structure and performs functions integral to higher cognitive processes, including sensory perception, memory, and coordinated motor output. What computations does this circuitry subserve, that might connect these unique structural elements with their biological function? Potjans and Diesmann  parameteThis population statistic approach lends itself to quickly analyzing the response properties of population-scale dynamics of neural tissue. We use this strategy to examine the input-output relationship of the Potjans and Diesmann column model , in an


Dear Sir,,Skin stapling devices are widely used to secure skin graft because they are easy to use and useful—especially for large grafting areas. They can save operating time and improve graft taking.3


The state-of-the-art immunosuppression drugs do not ensure indefinite transplant survival, and most transplants are continuously lost to chronic rejection even years posttransplantation. This form of rejection is responsible for long-term failure of transplanted organs. The mechanisms involved in development of chronic rejection are not well-understood. One of the main features of chronic rejection is progressive luminal narrowing of graft vessels, which results in compromised blood flow, ischemia, cell death, and finally graft failure. All the existing immunosuppressive regimens are targeting acute rejection, and at present there is no available therapy for prevention of chronic rejection. Chronic rejection involves two major, but interrelated responses: The first is the host immune response against the transplant mediated primarily by alloreactive T and B cells, and the second is injury and repair of the graft (vasculopathy of graft vessels). Here we focus on recent advances in understanding the cellular and molecular aspects of chronic transplant vasculopathy and function of macrophages, topics pivotal for development of novel antichronic rejection therapies. There are three major types of allograft rejection: Hyperacute, acute, and chronic rejection. HyperacuChronic rejection develops within months to years after transplantation and is the major cause of long-term graft loss. The main feature of chronic rejection is accelerated arteriosclerosis or progressive luminal narrowing of graft vessels (vasculopathy or graft vascular disease (GVD)) often accompanied by graft tissue  fibrosis. These, in turn, result in ischemia, cell death, and graft failure. All the existing immunosuppressive regimens are highly focused on prevention of acute rejection, and at present there are no available antichronic rejection therapies. Thus, understanding the cellular and molecular events contributing to chronic rejection of transplanted organs is pivotal for development of novel antichronic rejection therapies.One of the most distinctive features of chronic rejection of heart, kidney, liver, and lung allografts is the progressive occlusion or intimal hyperplasia of the blood vessels, which compromises blood flow and results in ischemia and eventual failure of the graft.Normal blood vessel is built of several distinct layers .1] The  The 1] TAlthough the narrowing of vessel lumen can be caused by one of the three major types of vascular remodeling: Thickening of the intima (through the recruitment of extraneous smooth muscle cells and some leukocytes), constrictive remodeling , and vasoThere are two major hypotheses concerning the initiation of vascular remodeling and inflammatory response. Traditional concept called the “inside-out” response assumes that the inflammatory response to various types of injuries (including immune injury during chronic rejection) is initiated at the endothelial layer of the intima, that is, at the luminal (inside) surface of the vessel . Accordiet al., –24 et aligration.,20,23 an vessels.,25 Inter vessels.,27 and p vessels.,28 In vi vessels., it stilAlthough very little is known about the route and mechanisms, operating in the migration of SMCs into the intima during chronic rejection per se, a plethora of information on the SMC movement in various model systems may apply to the SMC movement during vessel wall remodeling in chronic rejection. It is well-established that the cell migration starts when cell surface receptors are stimulated, which, in turn, initiates a cascade of cytoskeleton remodeling events such as actin polymerization, repositioning of the microtubule organizing center (MTOC), changing the adhesiveness to the substratum, and eventually the emergence of the actin-rich leading and trailing edge (uropod) of the motile cell .18,29,3,329,30 NIt is well-established that after migration to the intima SMCs undergo extensive proliferation. Although the signaling pathways responsible for SMCs proliferation during alloimmune response are not fully understood, it seems that platelet-derived growth factor (PDGF) is one of the regulators involved.,41 RecenOver the years, several therapeutically important drugs have been identified that prevent vessel wall thickening by either inhibiting SMC migration or inhibiting cell cycle-progression, and thus decreasing SMC proliferation or both. For example, sabiporide, a new Na/H exchanger inhibitor, rapamyciMacrophages are one of the most plastic and mysterious cell types of immune response and allograft injury. Macrophages are professional phagocytes and antigen-presenting cells , which dMacrophages present within the transplanted organs derive from two main sources: 1. Donor-derived macrophages, which are present in the organ during transplantation, and 2. recipient-derived macrophages; which enter the graft after transplantation. Within first few weeks posttransplantation donor-derived macrophages proliferate, and subsequently, in non-rejecting graft, their number gradually declines. Studies on kidney transplant models showed that during acute rejection there are massive accumulation of recipient-derived macrophages and their proliferation within the allograft and thus amplify rejection response. AlthoughMacrophage functions such as cell polarity, motility, interactions with extracellular matrix, phagocytosis, and antigen presentation; are all actin cytoskeleton-dependent, and as such they are regulated by small GTPase RhoA/ROCK and Rac1 pathways , 6 and 7Chronic allograft rejection is a major hurdle to transplant success in the clinic and overcoming this hurdle is critical to advance transplant medicine. One of the most striking features of chronic rejection is the concentric neointima formation affecting virtually all blood vessels in the transplanted organs. The mechanisms behind this distinct pathology remain incompletely defined and multiple mechanisms, pathways, and cell types have been implicated in this process. Further understanding of the fundamental mechanisms related to cell motility, migration, and polarization as well as tissue repair and remodeling may lead to the development of new therapies to treat or prevent chronic allograft rejection.


Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs.t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations.Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) : 25.1–161.1; p = 0.008), eotaxin , monocyte chemoattractant protein (MCP)-1 , and vitamin D–binding protein (VDBP) .Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other . These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.The online version of this article (doi:10.1186/s13058-015-0599-7) contains supplementary material, which is available to authorized users. Aromatase inhibitors (AIs) are an important component of the standard treatment of hormone receptor–positive breast cancer, but a high incidence of arthralgia (joint pain) may lead to premature therapy discontinuation and increased mortality , 2. AlthMenopause and other estrogen withdrawal syndromes are associated with an increase is systemic inflammation, which can exacerbate joint pain syndromes –8. GivenWe aimed to evaluate the association of moderate to severe arthralgia with plasma inflammatory biomarker concentrations among postmenopausal women with early-stage breast cancer who were currently taking AIs. We hypothesized that the presence of moderate to severe arthralgia would be associated with elevated serum inflammatory biomarker concentrations. Because arthralgia often coexists with fatigue and insomnia , we thenWe conducted a cross-sectional study, drawing our sample from an ongoing cohort study of patients receiving adjuvant AI therapy in the outpatient breast oncology clinic in the Abramson Cancer Center at the University of Pennsylvania between 2008 and 2013. Eligible participants were aged 18 years or older, had a diagnosis of early-stage breast cancer (stages I–III), were taking an AI, and had a Karnofsky score ≥60 . Additional inclusion criteria required the completion of all chemotherapy and radiation therapy at least 1 month before enrollment, approval of the patient’s treating oncologist, and the ability of the patient to understand and provide informed consent in English. After providing informed consent, patients completed a series of patient-reported outcome instruments and provided a non-fasting blood sample for analysis. Self-report questionnaires and chart abstraction were used for demographic and clinical information. For the present study, we included 203 participants who had had both survey data and a blood sample available during the time of biomarker analyses. The Institutional Review Board at the University of Pennsylvania approved this study.Arthralgia was measured using a modified version of the Brief Pain Inventory (BPI). Because we were focused on arthralgia, the questions were modified to evaluate pain in and around joints. The BPI is validated in patients with cancer and is one of the most commonly used instruments used to measure pain. Domains measured are pain severity (four items) and interference (seven items), with Cronbach’s α ranging from 0.8 to 0.87 and from 0.89 to 0.92, respectively . The useFatigue was measured using the Brief Fatigue Inventory (BFI). The BFI has been validated in cancer populations (Cronbach’s α = 0.96). Similar to the BPI, the “worst fatigue” item has been validated as a single-item dichotomous variable, with a cut point ≥4 indicating moderate to severe fatigue . Insomni2-microglobulin, C-reactive protein (CRP), haptoglobin, and vitamin D–binding protein (VDBP or Gc globulin). Sera were diluted as suggested to a 1:8000 concentration. The diluted sample was added to the magnetic beads, followed by incubation and washing per assay specifications.Serum levels of cytokines, chemokines, and inflammatory molecules were determined using the Cytokine Human Magnetic 30-Plex Panel for the Luminex platform  and the Acute Phase Human 4-Plex Panel for the Luminex platform (Life Technologies). With the 30-plex assay, we examined the following serum cytokine and chemokine levels: interleukin (IL)-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40/p70, IL-13, IL-15, IL-17, vascular endothelial growth factor, tumor necrosis factor α, interferon (IFN)-α, IFN-γ, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1α, MIP1-β, IFN-γ-inducible protein 10, monokine induced by interferon gamma, eotaxin, the regulated on activation, normal T expressed and secreted protein (RANTES), monocyte chemoattractant protein (MCP)-1, epidermal growth factor, granulocyte colony-stimulating factor, basic fibroblast growth factor, and hepatocyte growth factor. Sera were defrosted on ice and added undiluted to the beads. Incubation and washing were carried out per assay specifications. With the 4-plex acute phase panel, we examined β2 analysis to assess pairwise correlations among the three symptoms.Descriptive statistics were used to evaluate the distribution of scores on each of the three patient-reported outcome instruments, with which we measured arthralgia, fatigue, and insomnia. Patients were then dichotomized into the presence or absence of moderate to severe arthralgia, fatigue, and insomnia, as defined by the cut points described above. We performed χp value ≤0.1 was included in our final model.We explored the variability in each inflammatory biomarker using box plots. We identified 20 biomarkers with limited intersubject variability. These were excluded from further analyses. We assessed pairwise correlations among the 14 remaining biomarkers, which revealed a significant association. To understand whether the variability in inflammatory biomarkers could be explained by clinical and demographic variables, we performed a series of linear regressions to evaluate the association of our collected clinical and demographic variables with inflammatory biomarker concentration. With our identified inflammatory biomarkers, we specifically assessed the association of each cytokine marker with age, race, non-steroidal anti-inflammatory drug (NSAID) use in the last 7 days, body mass index (BMI), education, years since last menstrual period, history of chemotherapy administration , cancer stage, and years on AIs. Any variable with a t tests to compare the mean concentration of each inflammatory biomarker for patients with and without moderate to severe arthralgia. The Bonferroni adjustment was applied to adjust for multiplicity in testing (p < 0.004). For the secondary hypothesis, we created a composite binary variable to identify patients with all three symptoms versus those with fewer symptoms. We then conducted two-sided t tests to compare the mean concentration of each inflammatory biomarker for patients with and without comorbid symptoms. Finally, we performed multivariate linear regression analysis to reevaluate the associations between symptoms and inflammatory biomarkers after adjusting for confounding variables.For the primary hypothesis, we conducted two-sided The demographic and clinical characteristics of study participants are shown in Table r = 0.56, p < 0.001), and 88.4 % of patients with arthralgia also had fatigue. Arthralgia was also significantly correlated with insomnia , and 83.7 % of patients with arthralgia also had insomnia. Of the overall population, 16.8 % of patients had all three symptoms. The demographic and clinical characteristics of study participants, as a function of the presence or absence of all three symptoms, are shown in Table Using the cut points of moderate to severe symptoms defined above, 21.3 % of patients had arthralgia, 41.6 % of patients had fatigue, and 33.2 % had insomnia. Arthralgia was significantly correlated with fatigue (p = 0.0026), eotaxin (p = 0.0002), MCP-1 (p = 0.0017), and VDBP (p = 0.0006) were associated with moderate to severe arthralgia. These results were all statistically significant after correction for multiple comparisons. In an exploratory analysis of fatigue and insomnia, all of these biomarkers also showed an association with fatigue and insomnia, with the exception of a trend toward significance for CRP and insomnia. Additional file t tests done to evaluate the association of each symptom with inflammatory biomarkers.The biomarkers exhibited significant pairwise correlation , eotaxin , MCP-1 , and VDBP  were strongly associated with the presence of all three symptoms in multivariate analyses , whereas chemotherapy and age have been shown in other series to impact arthralgia and inflammatory biomarker concentrations , 24, 25.Arthralgia is a common side effect among women taking AIs and is associated with premature discontinuation of therapy . Non-adhOur findings are consistent with prior research tying estrogen deprivation to inflammation. Estrogen α- and β-receptors in the nucleus alter gene expression of various inflammatory biomarkers, leading to immunomodulation . Indeed,On the basis of this biological plausibility, others have evaluated the contribution of inflammation to AI-associated arthralgia. In a genome-wide association study, Ingle et al. identified a series of SNPs that were correlated with the presence of AI-associated arthralgia . These SOur research found that arthralgia is significantly associated with fatigue and insomnia. Among those experiencing moderate to severe arthralgia, 88.4 % also had fatigue and 83.7 % also had insomnia. Bower et al. have evaluated the association of inflammatory biomarkers with fatigue both during  and afteOur identification of VDBP, eotaxin, and MCP-1 as relevant inflammatory biomarkers for AI-related symptom burden is novel. VDBP is the primary binding protein for vitamin D, but it is also an acute-phase reactant subject to significant genetic variability –31. VDBPOur study has a number of important limitations. First, it was cross-sectional in nature. As such, we are unable to establish the causal relationship between symptom burden and inflammatory biomarkers. Further prospective work is needed to clarify whether systemic inflammation leads to symptoms or if the persistent symptoms cause inflammation. Second, we examined numerous biomarkers in this study, and there is a risk of false-positive discovery. We adjusted our primary analysis using Bonferroni corrections for those biomarkers that demonstrated variability in our sample. A future replication study is needed to verify the results identified in our study. Third, our biomarker sampling was non-fasting, and we did not have complete data on comorbid conditions or other medications patients may have used, including statins and bisphosphonates. As described above, concurrent autoimmune conditions may also affect biomarker concentrations . Future In spite of these limitations, this study is, to the best of our knowledge, the largest study to date evaluating the association of patient-reported symptoms with inflammatory biomarkers. We demonstrated that patient-reported arthralgia and co-morbid fatigue and insomnia are associated with elevated serum inflammatory biomarkers among women taking AIs. A better understanding of this novel finding will allow clinicians to develop strategies to manage these symptoms to improve quality of life, adherence to AI therapies, and potentially survival outcomes for women with breast cancer.Patient-reported arthralgia and co-morbid fatigue and insomnia were associated with elevated CRP, eotaxin, MCP-1, and VDBP among a group of breast cancer survivors taking AIs. A better understanding of symptomatic causes of distress will allow clinicians to develop strategies to manage these symptoms to improve quality of life, adherence to therapy, and potentially survival outcomes for women with breast cancer.


In the present study, corn Starch-Neusilin UFL2 conjugates were prepared by physical, chemical, and microwave methods with the aim of using the conjugates as tablet superdisintegrant. Various powder tests, namely, angle of repose, bulk density, tapped density, Hausner's ratio, Carr's index, swelling index, and powder porosity were conducted on the samples. The conjugates were characterized by ATR-FTIR, XRD, DSC, and SEM techniques. Heckel and Kawakita models were applied to carry out compression studies for the prepared conjugates. Fast disintegrating tablets of domperidone were prepared using corn starch and corn Starch-Neusilin UFL2 conjugates as tablet superdisintegrants in different concentrations. Conjugates were found to possess good powder flow and tabletting properties. Heckel analysis indicated that the conjugates prepared by microwave method showed the slowest onset of plastic deformation while Kawakita analysis indicated that the conjugates prepared by microwave method exhibited the highest amount of total plastic deformation. The study revealed that the corn Starch-Neusilin UFL2 conjugates possess improved powder flow properties and could be a promising superdisintegrant for preparing fast disintegrating tablet. Also, the results sugessted that the microwave method was found to be most effective for the preparation of corn Starch-Neusilin UFL2 conjugates. Amongst innumerable applications, starch and its derivatives are one of the most widely used excipients in the pharmaceutical industry as they are incorporated in the manufacture of assorted dosage forms due to their biodegradability and biocompatibility. Starches have become a valuable ingredient because of their inertness, abundance, and cost effectiveness in the food industry, where they are used as thickeners, bulking, water retention, and gelling agents, in the pharmaceutical industry where they are used as fillers, binders, and disintegrants in tablet formulations. Commercially, starches are obtained from a variety of cereals  and from the tubers and roots (predominantly potato and cassava). In the pharmaceutical formulations, starch can be used both as a disintegrant and as a binder depending on the explicit attributes crucial for the formulation. As a disintegrant, the mechanism of action of starch includes wicking, the imbibitions of water into the tablet matrix via capillary action. The concentration of starch used is crucial; if it is below the optimum concentration then there are insufficient channels for capillary action and if it is above the optimum concentration then it is difficult to compress the compacts. Generally, starch can be used at a concentration range of 2–10% w/w. As a binding agent in tablet formulations, starch is heated in solution enhancing its conversion into a paste before addition to the formula powder blend –5. RashiIn recent times, advancement in budding new excipients with multifunctional capabilities  has exploited the use of silicates produced synthetically. Silication of excipients resulted in improvement in various properties of the materials, namely, mechanical strength, compressibility, disintegration, and sensitivity towards lubrication. Thus silicate/starch preparations have the potential to fulfil the requirements of a multifunctional excipient. In this context the physical properties of compacts produced  and sensitivity towards lubrication need to be investigated. On this basis, the current study reports the application of silicates as an effective tabletting aid when used with corn starch , 9.Neusilin is a synthetic, amorphous form of magnesium aluminometasilicate which can be used as a multifunctional excipient in both direct compression and wet granulation of solid dosage forms. Neusilin is widely used in improving the quality of tablets (in the terms of its compaction and disintegration properties), powders, granules, and capsules. It does not develop gels with aqueous solutions unlike other magnesium aluminium silicates. The different grades of Neusilin available are alkaline  and neutral  .22H24ClN5O2, MW-425.91), poorly water-soluble drug [The aim of the present study is to evaluate the efficiency of a new conjugate of corn starch and Neusilin, as super disintegrating agent in the tablets. The corn Starch-Neusilin UFL2 conjugates were prepared by three different methods, namely physical, chemical, and microwave, and were used as a superdisintegrant in domperidone tablet formulation and the tablet properties were compared with a standard marketed fast disintegrating tablet. Domperidone  was supplied as gift sample by Gangwal Chemicals, Mumbai, India. Domperidone was gifted by Dr. Reddy's Laboratories, Baddi (H.P), India. NaOH was procured from Merck Specialities Pvt. Ltd., Mumbai, India. All reagents used were of analytical grade. physical method involved simple mixing of corn starch and Neusilin UFL2 in the ratio 1 : 1. To ensure proper mixing tumbling method was used and the weighed starch and Neusilin were transferred into a beaker and the mouth of the beaker was closed ensuring that there is no spillage of the contents from the beaker while the mixing is carried out. The mixing was carried out for 15 minutes. In chemical method corn starch and Neusilin UFL2 were incorporated in the ratio 1 : 1. Corn starch was suspended in distilled water (q.s) and kept on magnetic stirrer at 270 rpm and temperature not more than 40°C. To this, solution of Neusilin UFL2 in NaOH (q.s) was gradually added with constant stirring. After 15–20 minutes the precipitated conjugate was filtered using Whatman filter paper  having a pore size of 125 mm and dried in oven at a temperature not more than 50 ± 2°C. In microwave method physical mixture of corn starch and Neusilin UFL2 was subjected to microwave radiation at 590 watt for not more than 5 minutes.Three methods were used in the formulation of the corn Starch-Neusilin UFL2 conjugate: physical, chemical, and microwave methods. Theμm opening size), and mixed by tumbling method for 15 to 20 min (contents were transferred into a beaker and the mouth of the beaker was closed ensuring that there is no spillage of the contents from the beaker while mixing is carried out). The blend was lubricated with talc and magnesium stearate and mixing was done for additional 5 minutes and the resulting powder mixture was compressed into tablets using multipunch tabletting machine  using 6.75 mm biconcave round die-punches. The compression force was adjusted to give tablet hardness in the pharmacopoeial range of fast disintegrating tablets (3–5 kg/cm2). For each batch 200 tablets were formulated.Fast disintegrating tablets of domperidone (10 mg) were formulated by direct compression method using corn starch and the corn Starch-Neusilin UFL2 conjugates as superdisintegrant, according to the formulae given in The angle of repose of powder blends was determined by the funnel method. Accurately weighed powder blends were taken in a funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touched the apex of the heap of the powder blends (2 cm). The powder blends were allowed to flow through the funnel freely onto its surface. The diameter of the powder cone was measured and angle of repose was calculated . Three dBoth loose bulk density (LBD) and tapped bulk density (TBD) were determined. A quantity of 1 gm of powder was introduced into a 10 mL measuring cylinder. After the initial volume was determined, the cylinder was tapped onto a hard surface from the height of 2.5 cm at 2 seconds intervals. Tapping was continued until no further change in volume was noted. The LBD and TBD were calculated . The detThe compressibility index of the powder blends was determined by Carr's compressibility index or Carr's index (CI). Hausner ratio (HR) was also determined for each powder blend .V1 and V2 are initial volumes of the powder before and after hydration, respectively.Initial bulk volume of the powder was evaluated using 100 mL stoppered graduated cylinder. Water was added in sufficient quantity to produce uniform dispersion. The sediment volume of the swollen mass was measured after 24 hours. The swelling index was calculated asDispersion (1% w/v) of the sample was prepared in distilled water and the pH was determined individually using digital pH meter at 37 ± 2°C.W1) and heated in an oven at 100 ± 5°C for 2 hrs. Sample was cooled in the dry atmosphere of a desiccator and then reweighed (W2). %LOD was calculated byLoss on drying (LOD) is used to determine the levels of moisture or solvents present in the sample. The sample was weighed (Wi). Then n-hexane (surface tension (γ) is 18.4 mN/m) was poured drop wise on bed top till the solvent filtered out at the bottom of the tip. The tip was reweighed (Wf) and effective pore radius was calculated byEffective pore radius of the powder was determined using method reported by Goel et al. . A micro−1 to 400 cm−1 by KBr pellet method.The infrared (IR) spectra of samples were obtained using an Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectrophotometer . The samples were scanned in the spectral region of 4000 cmμm were randomly placed on a glass slide, respectively. The signals of the reflection angle of 2θ were recorded from 0° to 60° at a scanning rate 0.21°/sec.The X-ray powder diffractograms were registered in an X-Pert Pro (USA) in Bragg-Brentano geometry, using glass tubing with a Cu anode and graphite monochromator. The diffractometer was operated at 40 mA and 40 kV. All the samples being a size of less than 250 The scanning electron micrographs were taken to study the surface morphology using a Hitachi  at an accelerator potential of 10 kV. The samples were stuck on a specimen holder using a silver plate and then coated with palladium in a vacuum evaporator.The thermal transitions of starch samples were investigated with the use of a Perkin Elmer DSC 8000 apparatus (USA), calibrated by using a high purity indium standard. Samples about 10 mg were hermetically sealed in flat bottomed aluminium pans and heated in an atmosphere of nitrogen to eliminate the oxidative and pyrolytic effects. The heating rate was 5°C/min in a temperature range of 25–300°C. The DSC thermograms were recorded.The two well-known compression models The Heckel and The Kawakita were used to carry out the studies .D0, of each formulation was obtained from the ratio of its bulk density to its particle density [The bulk density of each sample at zero pressure was determined by pouring the granules through a funnel into a glass measuring cylinder with a 24 mm diameter and a volume of 50 mL at an angle of 45°. Determinations were done in triplicate. The relative density,  density .m) and dimensions were then determined, respectively, and their relative densities (R) were calculated using the equationVt is the volume (cm3) of the tablet and ρs is the particle density (g/cm3) of the solid material [Tablets (400 mg) were prepared by compressing the prepared conjugates for 30 seconds with predetermined loads on a hydraulic press . After ejection, the tablets were stored over silica gel for 24 hours. Their masses . The force values were converted into pressures and the displacement values  and the true density of the material (determined before compaction) were used to calculate the apparent density of the powder bed, 1/(1 − D). Using the Heckel plot, the compression stage was subjected to linear regression analysis. It is denoted asK, is the reciprocal of the mean yield pressure, Py, of the material. From the intercept A, the relative density, DA, can be calculated using the following equation:D0, is used to describe the initial rearrangement phase of densification as a result of die filling;DB, describes the phase of rearrangement at low pressures and is the difference between DA and D0 [The deformation mechanism of the material was determined using the Heckel model, as it is widely used for relating the relative density,  and D0 , 16.V0. The Kawakita equation is used to study powder compression using the degree of volume reduction (C) and is written asV0 is the initial bulk volume of the powder and Vp is the bulk volume after compression. Constant “a” is equal to the minimum porosity of the material before compression while constant “b” is related to the plasticity of the material. The reciprocal of “b” gives the pressure term, Pk, which is the pressure required to reduce the powder bed by 50% [In the Kawakita equation, the particle density is not introduced in the calculations since the model operates on the relative change in volume which gives the same result whether the relative or the absolute volume is used. The problem in calculation of this equation is to find the correct initial volume, d by 50% , 15.A calibrated vernier calliper  was used for diameter and thickness evaluation of tablets.The tablet hardness is the force required to break a tablet in a diametric compression force. Hardness tester  was used to determine the force required to break the tablet diametrically. The test was performed on six tablets and the average was calculated.F) of a sample of 20 tablets was measured using Roche Friabilator . Twenty tablets were weighed and rotated at 25 rpm for 4 min. Tablets were reweighed after removal of fines (dusted) and the percentage of weight loss was calculated. Friability below 1% was considered acceptable.The friability  [The content uniformity was assessed according to USP method. Ten tablets were pulverized and quantity of powder equivalent to 10 mg of domperidone was shaken with 100 mL of 0.1 N HCl for 30 minutes. The contents were filtered through a 0.45 , India) .d = 6.5 cm) containing 6 mL of water (containing a water soluble dye eosin). A tablet was carefully placed on the surface of tissue paper and the time required for water to reach the upper surface of the tablet was noted as the wetting time [A piece of tissue paper (10.75 × 12 mm) folded twice was placed in a culture dish (ing time .Wa) was measured before its placement on the wet tissue and the final weight (Wb) was taken after complete wetting. Water absorption ratio, R, was determined using the equation [The same procedure used for the wetting time was used for the water absorption ratio. Initial weight of the tablet (equation (10)R=10ρtrue is the true density of the mixture and m and V are the weight and volume of the tablet, respectively. The true density of the powder was found using true density meter .Porosity is a measure of the void spaces in a material and is a fraction of the volume of voids over the total volume, between 0 and 1, or as a percentage between 0 and 100 percent. The porosity of the tablets was calculated as follows:Pf, is a measure of the degree of consolidation/compactness of the tablet. Tablet packing fraction was determined by the equationw is the weight of a tablet, r is radius, t is thickness, and ρ is the particle density.The tablet packing fraction, Pf [The radius and thickness of 10 tablets were measured using a vernier calliper. The apparent particle density of the drug powder was determined using liquid paraffin displacement method. Firstly, the weight of a specific gravity bottle filled with liquid paraffin and the weight of the specific gravity bottle containing a sample of the drug powder were noted. The final weight was determined. The determination was executed in triplicate, and mean results were used in the calculation of Pf .In vitro disintegration time for the tablets was determined using USP disintegration apparatus  using 0.1 N HCl  as the disintegrating medium.In vitro dissolution of the fast disintegrating tablets was studied in USP XXIV dissolution apparatus II  employing a paddle stirrer at 50 rpm using 900 mL of pH 1.2 0.1 N HCl at 37 ± 0.5°C as a dissolution medium. Aliquots of 5 mL each were withdrawn at predetermined time intervals and replaced with equal volume of fresh medium. Aliquots were filtered through a 0.45 μm membrane filter and analyzed for drug content using a UV/VIS double beam spectrophotometer  at 284 nm. Drug concentration was calculated and expressed as cumulative percent of the drug released. The similarity factor (f2) is a logarithmic transformation of the sum-squared error of differences between the test (Tj) and reference (Rj) products over all time points. It is a useful tool for comparison of dissolution profiles when more than three or four dissolution time points are available. It is calculated asWj) is an optional weight factor. The similarity factor fits result between 0 and 100. It is 100 when the test and reference profiles are identical and tends to be 0 as the dissimilarity increases. In order to consider similar dissolution profiles, f2 values should be close to 100.θ°) is a characteristic of the internal friction or cohesion of the particles. Its value will be high if the powder is cohesive and low if the powder is non-cohesive. Flow property of the corn starch was improved by the addition of Neusilin UFL2 as compared formulations with conjugates showed good to excellent flow properties as indicated by the values of angle of repose (36.69–27.67°) to the corn starch (43.25°). Carr's index showed values 22.5 to 12.5 denoting that these formulations were of acceptable to good flowability compared to the corn starch (34.28). Hausner's ratio showed that powders, with low interparticle friction, had ratios of approximately 1.29 to 1.14, indicating good flow properties as compared to the corn starch (1.52). Swelling index of the conjugates prepared by physical, chemical, and microwave method were found to be 40, 65, and 95%, respectively, which was far better than the swelling index of corn starch, that is, 18%, which is in context with the effective pore radius of the conjugates and corn starch. The results of both swelling and effective pore radius point towards more wicking action capability and hence disintegration potential of the conjugates over the pure corn starch. The result of micromeritic study indicates that conjugates prepared by microwave method were the most effective method followed by chemical and physical method as they gave better micromeritic properties as evidenced from the The result of the micromeritic studies for corn starch and the prepared corn Starch-Neusilin UFL2 conjugates were conducted and results are listed in −1 and 2931 cm−1 representing O–H and C–H stretching, respectively. The absorption band at 1652 cm−1 is due to absorbed water in amorphous region of starch. Peak at 1241 cm−1 represents CH2OH group whereas peak at 1159 cm−1 represents coupling mode of C–C and C–O stretching vibrations. The band at 1080 cm−1 represents C–O–H bending vibration whereas peak at 929 cm−1 could be ascribed to the skeletal mode vibration of α-1,4-glycosidic linkage. The corn Starch-Neusilin UFL2 conjugates prepared by different methods, namely physical, microwave, and chemical, exhibit a sharp peak near 3480 cm−1 which is otherwise observed at 3434 cm−1 in the pure corn starch. This shift and sharpening of peak indicate the formation of Si–O–C bridging bond between corn starch and Neusilin UFL2. Moreover reduction in the intensity of peak at 1241 cm−1, 1159 cm−1, and 1080 cm−1 confirms intermolecular bridging between corn starch and Neusilin UFL2. Thus, the addition of Neusilin changed the properties of corn starch forming a new excipient with different functional properties.Corn starch and Neusilin UFL2 interactions studies were carried out using ATR-FTIR spectrophotometer and the spectra for the samples are shown in θ angle. Appearance of sharp peak at 27.40°2θ, 31.72°2θ, 45.60°2θ, 53.91°2θ, and 56.47°2θ angles, respectively, in case of conjugates prepared by microwave method gives clear indication of reduction in amorphous nature or otherwise increase in the crystalline behavior of the corn starch that could be correlated with the increase in swelling and hence superdisintegrant potential of conjugates prepared by different methods. Crystallinity and hence the superdisintegrant property  gives the initial relative density of the starch, DI, while Pk values were obtained from the reciprocal of values of b. The values of DI and Pk are shown in DI is a measure of the packed initial relative density of the formulation with the application of small pressure or tapping. The ranking of DI for the conjugates was chemical method > microwave method > physical method. The value of Pk which is an inverse measure of the amount of plastic deformation occurring during the compression process was found to be maximum for tablets formulated using conjugates prepared by chemical method followed by microwave method and physical method [Py values. It has been shown that while Py relates to the onset of plastic deformation during compression, the Pk relates to the amount of plastic deformation that occurs during the compression process. Thus, the conjugates prepared by physical method showed the slowest onset of plastic deformation but the highest total amount of plastic deformation.The Kawakita plots for the conjugates are presented in l method . Thus, c2 compared to 3.15 to 3.09 kg/cm2 of tablets formulated using the native corn starch. Percentage friability of all formulations was less than 1% indicating good mechanical characteristics. Wetting time was observed to be decreased from 68 seconds for the tablets incorporating native corn starch to 33, 22, and 14 seconds for the tablets incorporating conjugates prepared by physical, chemical, and microwave methods. Disintegration time was also observed to decrease from 83 seconds for the tablets incorporating native corn starch to 40, 35, and 22 seconds for the tablets incorporating conjugates prepared by physical, chemical, and microwave methods, respectively. Water absorption ratio was found to be inversely proportional to the wetting and disintegrating time of the tablets. The increase in water absorption ratio and decrease in wetting and disintegration times in all formulations may be attributed to the modification of the corn starch by Neusilin UFL2 to yield a novel conjugate which acts as superdisintegrant which absorbs water and swells, causing rupture of the tablets. Tablet properties such as mechanical strength, tablet packing fraction, and disintegration are in turn affected by the porosity [Tablets require certain amount of strength and resistance to friability to withstand mechanical shock of handling during manufacturing, shipping, and packaging. Hardness of the tablets formulated using the corn starch-Neusilin UFL2 conjugates as superdisintegrant was found to vary from 4.3 to 3.5 kg/cmporosity . Tabletsporosity . Tablet  in vitro dissolution study are presented in Figures f2) is a logarithmic transformation of the sum-squared error of differences between test and reference products over all time points. It was observed that the three different approaches used for the preparation of conjugate in this study, namely, physical, chemical, and microwave methods, increased the dissolution rate of the drug compared to the tablet prepared with the native corn starch and standard marketed formulation of the drug. The order of increased drug dissolution using the different approaches was as follows: microwave > chemical > physical. In case of the FDTs prepared by using native corn starch (F1–F4) the percentage cumulative drug release was found to be very poor as compared to the standard marketed formulation of domperidone (MKTD). The f2 value for formulation (F1–F4) was below 50 depicting the dissimilarity between the drug releases. Formulations (F5–F8), (F9–F12), and (F13–F16) were containing corn starch-Neusilin UFL2 conjugate prepared by physical, chemical, and microwave methods. The percentage cumulative drug release for these formulations were found to be comparable to the standard marketed formulation of domperidone. The f2 values for these formulations were found to be over 50 evidencing the similarity between the drug releases. Results of various tablet evaluation tests as evidenced from The results obtained from the in vitro disintegration time, drug content, in vitro dissolution, and stability studies. Extensive swelling, porosity, and wicking action of the prepared corn Starch-Neusilin UFL2 conjugates in the prepared fast disintegrating tablets were found to be contributing to its superdisintegrant action.In present work, an attempt was made to modify the corn starch to develop corn starch-Neusilin UFL2 conjugates using different methods, namely physical, chemical, and microwave. The prepared conjugates and the corn starch were characterised for powder flow, pH, viscosity, swelling, and effective pore radius. Evaluation of precompression parameter indicates good flow properties. The prepared conjugates were also subjected to the compression studies, namely Heckel and Kawakita function. The Heckel plot is usually correlated with the speed of the tablet machine while the Kawakita plot is related to the crushing or tensile strength of the tablet. Fast disintegrating tablets of domperidone were formulated by direct compression technique employing the corn starch and the prepared conjugates. The tablets were evaluated for physical parametric tests, wetting time, water absorption ratio, porosity, tablet packing fraction,In conclusion, the prepared conjugates can be effectively used as superdisintegrant in order to develop a faster disintegrating tablet formulation. Future challenges for many fast disintegrating tablet manufacturers include reducing costs by finding ways to manufacture, with conventional equipment, using versatile packaging, and improving mechanical strength. Such products provide an opportunity for the product line extension in the market place and extension of patent term of innovator. Due to its wide significance, this drug delivery system may lead to better patient compliance and ultimate clinical output. Future might witness novel technologies for development and utilization of the modified starches as tablet superdisintegrant for cost effective formulation of fast disintegrating tablets.


DEFB126 rs140685149 mutation was shown to cause sperm dysfunction and subfertility. Indel rs11467497 is another 4-nucleotide frame-shift mutation (151bp upstream of rs140685149) that leads to the premature termination of translation and the expression of peptide truncated at the carboxyl terminus. In the present study, we performed a comprehensive association study to check the contribution of rs140685149 and rs11467497 to male infertility. Our results confirmed the previous findings that there was no association between rs140685149 and sperm motility. In contrast, we found a significant association of another indel rs11467497 with male infertility. Moreover, rs11467497 was shown to be associated with higher number of round cells in the infertile males with low sperm motility. Surprisingly, the two mutations commonly existed in the sperm donors (n = 672), suggesting a potential application of the two indels in the screening for eligible sperm donors. Western blotting assays showed the sperms with rs140685149 2-nt deletion tended to have unstable DEFB126 protein in contrast of no DEFB126 protein expressed in the sperms with rs11467497 4-nt deletion, suggesting a more severe consequence caused by rs11467497 mutation. In conclusion, our study presented a significant contribution of another functional frame-shift polymorphism of DEFB126 (rs11467497) to male infertility. Defensins are small microbicidal peptide toxins that are active against bacteria, fungi and enveloped viruses Approximately 15% of couples fail to attempt their first pregnancy. Male factor is at least partly responsible in about 50% of infertile couples. Among the many aspects, beta-defensins are found to play a primary role in the male infertility. Beta-defensin Defb42 mRNAs are found to be downregulated in mice model with male infertility DEFB126 frame-shift indels among 2682 individuals from Shanghai Jiai Genetics & IVF Institute and Shanghai Human Sperm Bank. The goal of our study was to explore whether two common frame-shift indels of DEFB126 gene contributed to the risk of male infertility in Han Chinese.In the current study, we genotyped two 6/ml) were recruited from Shanghai Jiai Genetics & IVF Institute. The infertile males consisted of 750 with normal sperm progressive motility (PR ≥ 40%) and 611 with much lower sperm motility (PR ≤ 20%). In addition, a total of 642 fertile males were recruited as controls from Shanghai Jiai Genetics & IVF Institute. We also obtained the blood samples of 679 Han Chinese males who donated their sperms in the Shanghai Human Sperm Bank. Genomic DNA was extracted from peripheral blood lymphocytes using DNA-isolation kits . All the individuals have signed the informed consent forms.As shown in Table S1, a total of 1361 infertile Chinese males with normal sperm counts  according to WHO laboratory manual for the examination and processing of human semen. The temperature of sperm process was maintained at 37°C.DEFB126, we used the primers  to amplify DNA fragment containing the two indels. PCR amplifications were carried out in a total volume of 50 μl buffered solution containing the primer mixture, 100 ng genomic DNA, 200 μmol/l deoxyribonucleotide triphosphates each, 1.5 mmol/l Mg2+ and 1.0 U Taq polymerase which was modified with anti-Taq antibody . The cycling conditions were as follows: 95°C for 10 min., followed by 95°C for 10 sec., 57°C for 15 sec. and 72°C for 45 sec. for 40 cycles, a final extension at 72°C for 10 min. Products of the amplification were sequenced with sequencing primer (5′-AATTGGAAACTAAAAGTGAGCC-3′) provided by Biosun Limited Company .According to the genomic DNA sequence of 2O. The cycling conditions were as follows: 94°C for 10 min., followed by 94°C for 10 sec. and 60°C for 1 min. for 35 cycles. Based on the melting temperature shift genotyping assay, the loci of interest were genotyped. Our results showed there was 100% concordance between the results of DNA sequencing and the melting temperature shift genotyping. The sequences of the genotyping primers were shown in We used allele-specific PCR assay based on the SYBR Green to genotype the two indels of DEFB126 gene. The PCR cocktail solution contained 1.5 μl genomic DNA, 0.5 μl false-paired or right-paired primer, 5 μl Sharpvue 2× universal qPCR Master Mix  and 3 μl nuclease-free dHSperm cells were treated by the 10× lysis buffer  at 95°C for 3–5 min. DNA was then sheared by sonication to reduce the viscosity of the sample. The lysates were centrifuged at 16,000 × g for 5 min., and the supernatants were stored at −80°C. The concentration of protein extract was measured using BCA Protein Assay kit Thermo Fisher Scientific, Waltham, Massachusetts, USA. Protein samples (50 μg/lane) were analysed on 15% SDS-PAGE gels and transferred to polyvinylidene difluoride (PVDF) membranes Amersham Pharmacia Biotech with GE Healthcare, Little Chalfont, United Kingdom in a continuous buffer system at 20 V for 40 min. using semidry blotter . The blotted PVDF membrane was blocked with 1× NET  and the immune-detection was carried out using the ECL plus (ECL plus™) Western blotting detection system  with a 1:100 dilution of rabbit anti-DEFB126 polyclonal antibody  and 1:1000 dilution of secondary antibody (HRP-conjugated Goat anti-Rabbit IgG).www.r-project.org) for its citation statistical software. A two-sided P < 0.05 was considered to be significant.Tests of Hardy–Weinberg equilibrium (HWE) and genetic association on the genotype and allele levels were described in our previous studies DEFB126 indels among four different groups, comprising 750 infertile males with normal sperm motility, 611 infertile males with low sperm motility, 679 healthy sperm donors and 642 fertile males . However, there was a significant excess of heterozygotes for rs140685149 in the fertile males , implying an advantage for the heterozygotes of rs140685149 in the fertile males. This agreed to the previous observation P > 0.05). This observation also met with the previous findings Our results showed that there was no departure of HWE for the two indels in the sperm donors . We also observed significant contribution of rs11467497-del to male infertility under the dominant inheritance model . Not surprisingly, much higher number of round cells was observed in the infertile males with low sperm motility than in the infertile males with normal sperm motility . In addition, rs11467497-del was significantly associated with higher number of round cells in the infertile males with low sperm motility , but not in the infertile males with normal sperm motility .Surprisingly, we observed a significant association of another indel rs11467497 with male infertility on both genotype and allele levels  was found to be associated with male infertility, although it was only 151bp away from rs140685149, 2-nt frame-shift indel. Moreover, these two indels were commonly found in the sperm donors, suggesting a potential application of these markers in screening for eligible sperm donors in the future. In addition, our results confirmed that DEFB126 mutations were not related to sperm production and motility. We also showed there was a significant excess of rs140685149 heterozygote genotype in the fertile males, suggesting a selective advantage of this mutation.In the present study, we investigated the two P = 0.018, Fig.DEFB126 gene diminished the expression of DEFB126 in the sperms  was found to be associated with the protection of male infertility. This 4-nt indel  has been found in multiple HapMap populations  as reported in the 1000 genomes project 1467497 werms Fig.. We specDEFB126 gene was found to affect its lectin binding property, thereby causing a defective sperm penetration P < 0.001). This suggests that there is likely to have a selective advantage for rs140685149 in/del heterozygote, although further work needs to reveal the underlying mechanism of this observation.This dinucleotide indel  of DEFB126, DEFB103A, DEFA4, DEFB1, DEFB4A, DEFA5 and DEFA6) are expressed in epididymis. Among these defensins, the expression level of DEFB126 gene is 30 times of DEFB103A gene, and 40 times of DEFA4 gene, and 48 times of DEFB1 gene, and much higher than the rest defensin genes . Interestingly, DEFB126 were down regulated in the caput epididymides of non-obstructive azoospermic men DEFB126 gene in the sperm activity in the epididymis.According to an online gene expression dataset (GSE740) DEFB126 SNPs contribute to the male infertility. Future analyses of other genetic variants or epigenetic modifications may help elaborate the contribution of DEFB126 gene to the male infertility.DEFB126 protein has a conserved β-defensin core and a unique long glycosylated peptide tail. The carbohydrates of this domain contribute substantially to the sperm glycocalyx. Although DEFB126 protein is conserved in structure DEFB126 gene is highly polymorphic according to the records in the NCBI dbSNP database. Altogether there are 77 known SNPs in the gene region, including 44 intronic SNPs, 11 synonymous SNPs, 18 missense SNPs, 6 frame-shift SNPs (rs200807952 (-/GCAA); rs11467497 (-/CAAA); rs74380987 (CAAA/-/C); rs11469647 (CAAA/-); rs11467417 (-/CC/C); rs140685149 (-/CC)) and 1 UTR SNP. As only two frame-shift SNPs  were involved in the present study, we cannot exclude the possibility that other etc.) that may be important for the sperm migration to oviduct The sperm surface proteomics has enabled researchers to search for the coverage of the proteins at the sperm surface that may help understand the milieu of the sperm cell during transit from the testis to the oviduct DEFB126 gene for the association with male infertility. Our results showed that rs11467497-del was associated with male infertility and higher number of round cells in the infertile males with low sperm motility. We also found a lack of association between rs140685149 and sperm motility through the comparison between two types of infertile males with different sperm motility. Further work is needed to elucidate the selection advantage of rs140685149 del/ins heterozygotes in the fertile males.In conclusion, we performed a large scale genetic testing of two functional mutations of


Which graft material is the optimal graft material for the treatment of infected aortic aneurysms and aortic graft infections is still a matter of controversy. Orthotopic aortic reconstruction with intraoperatively prepared xenopericardial roll grafts without omentopexy was performed as the “initial” operation to treat aortic infection or as a “rescue” operation to treat graft infection. Mid-term outcomes were evaluated.Between 2009 and 2013, orthotopic xenopericardial roll graft replacement was performed to treat eight patients . Graft material: equine/bovine pericardium: 2/6; type of operation: initial 4/rescue 4; omentopexy 0. Additional operation: esophagectomy 2. Mean follow-up period: 2.6 ± 1.6 (1.1–5.1) years.Replacement: ascending 3, arch 1 , descending 3, and thoracoabdominal 1. Pathogens: MRSA 2, MSSA 1, Candida 1, E. coli 1, oral bacillus 1, and culture negative 2. Postoperative local recurrence of infection: 0. Graft-related complications: stenosis 0, calcification 0, non-infectious pseudoaneurysm of anastomosis 2 . In-hospital mortality: 2 ; Survival rate exclusive of in-hospital deaths (~3 y): 100 %, but one patient died of lung cancer (3.6 yr).Because xenopericardial roll grafts are not composed of synthetic material, the replacement procedure is simpler and less invasive than the standard procedure. Based on the favorable results obtained, this procedure may have the possibility to serve as an option for the treatment of aortic infections and aortic graft infections not only as a “rescue” treatment but as an “initial” treatment as well.The online version of this article (doi:10.1186/s13019-015-0343-5) contains supplementary material, which is available to authorized users. The standard procedure for treating infected aortic aneurysms and aortic graft infection after aortic procedures is resection of the infected aorta/graft, debridement of the surrounding tissue, in situ graft replacement. Rifampicin-soaked Dacron grafts, cryopreserved arterial homografts are clinically accepted. The omentopexy is the most reliable barrier to the infection. However, for a variety of reasons, we often face the patients whose omentum cannot be used. Xenopericardial roll graft replacement has been performed to treat native aorta/graft infections without omentopexy.Between 2009 and 2013, orthotopic xenopericardial roll graft replacement was performed to treat eight patients, six male and two female; mean age of 69.5 (55–80) years old  patients. Methicillin resistant staphylococcus aureus (MRSA) and Escherichia coli were detected in two patients, and methicillin-sensitive Staphylococcus aureus, Candida albicans, Candida glabrata, Streptococcus anginosus, and an oral bacillus were detected in one patient each. Simple esophagectomy, esophagectomy with cervical esophagostomy and jejunpstomy were performed in one patient each.Aortic infection and aortic graft infection were diagnosed on the basis of blood cultures, the leukocyte count, serum C-reactive protein level, serum procalcitonin level, and clinical findings taken together. Pericardial effusion, perigraft air and abscess formation, and rapid growth of the “punched out” area were important local image signs of aorta/graft infection Fig. .Fig. 1a Written informed consent was obtained from all patients before the procedure.We followed the ‘Prevention and Treatment of Infective Endocarditis (Japanese Circulation Society 2008)’ guidelines in regard to the antibiotic regimen. In accordance with the guidelines for active infective ‘native’ valve endocarditis, the infection control team of Kyorin University administered the most appropriate antibiotic treatment to the patients in whom the causative organism had been identified. In culture-negative situations, we administered empiric antibiotic treatment. When inflammatory marker values had become normal and the diagnostic images no longer showed evidence of the infection, antibiotic treatment was stopped until 4 to 6 weeks. Otherwise, antibiotic treatment was continued.Four patients underwent replacement of the ascending aorta or aortic arch with an open distal anastomosis during deep hypothermic circulatory arrest with intermittent-pressure-augmented retrograde cerebral perfusion –5. The mAdditional file 1:Replacemenet of the ascendingaorta. (WMV 9844 kb)The inflow route of the cardiopulmonary bypass was inserted via the femoral artery. A 10 cm × 10 cm unbranched xenopericardial sheet  was used . It was Additional file 2:Replacement of the aortic arch. (WMV 10647 kb)Three holes in a row, two 10-mm holes and one15-mm hole, were made 5 mm apart in a 10 cm × 10 cm equine pericardial sheet so that the last hole . Then thA 10-mm hole was created, and a 3.5 × 10 cm rectangular pericardial sheet cut from another 10 × 10 cm pericardial sheet was sutured to the circumference of the hole in the same fashion. After completing proximal anastomosis, the roll graft was clamped, and antegrade perfusion was restored via the branch. While warming the patient, the distal anastomosis was performed. One patient (Case 6) underwent simple replacement of the infected aorta; one patient (Case 4) underwent esophagectomy and creation of a cervical esophagostomy and jejunostomy concomitant with replacement of an infected Dacron graft  years. No patients showed any evidence of a postoperative thromboembolic event. Antibiotic treatment could be ceased within 10 weeks in all patients. The patient in case 3, who had multiple organ failure (MOF) secondary to DSWI preoperatively, died on postoperative day (POD) 8. In case 8, it took a long time to dissect the adhesion of the pleural cavity. A long cardiopulmonary bypass time and deep hypothermia time caused excessive bleeding after ceasing the cardiopulmonary bypass and difficult hemostasis and led to early death (POD 1). The other five patients are alive and well.One patient (Case 4) underwent esophageal reconstruction with a stomach roll 3 months postoperatively. One patient Case 2) died of lung cancer 45 months postoperatively. All patients who survived have been followed up by means of regular computed tomography examinations, but none of the patients showed evidence of local recurrence of the infection or graft stenosis, calcification, or dilatation, including of the branches. One patient (Case 4) required thoracic endovascular aortic repair (TEVAR) to treat pseudoaneurysms of the anastomoses and the suture line between the two edges of the pericardial sheet Fig. . Another died of Complete removal of the infected graft or infected aortic aneurysm, extensive debridement, and in situ replacement with a Dacron graft, rifampicin-soaked Dacron graft, or cryopreserved homograft is the standard procedure for treating aortic graft infections and aortic infections –11. HoweYamamoto et al. used equine pericardium in a locally-infected field when repairing a ruptured infected abdominal aortic aneurysm and confirmed excellent durability of the graft and absence of graft infection during long-term follow-up . They alLine break Pericardial sheets are soft and easy to handle. They can be formed into cylinders intraoperatively by rolling them up, and they provided us with a good operative field. It was easy to adjust the diameter of the roll graft to the diameter of the transected aorta. 10 cm of side length of the pericardium is ideal for construction of a neo-aorta without trimming. When we make a 30 mm diameter of the graft, a margin length to sew up was calculated as (10–3 π) / 2 = 0.3 cm. Graft dilatation, mural thrombus formation, shrinkage, calcification, and recurrence of the infection are concerns during long-term follow up. Contrast-enhanced computed tomography may be the most suitable imaging examination for follow-up. None of the above complications occurred in any of our cases. Two patients required TEVAR or direct closure to treat pseudoaneurysms of the anastomoses and to treat pseudoaneurysms of the suture line between the two edges of the pericardial sheet. Based on a comparison of the intraoperative photographs and computed tomography findings, the main cause of the pseudoaneurysms appeared to be a coarse continuous suture that had loosened. Although it is unclear why these pseudoaneurysms did not develop soon after the operation, we think that closer sutures may prevent the occurrence of the pseudoaneurysms in the long-term.Czerny et al. reported the results of using bovine pericardial tube grafts to treat prosthetic graft infection or endovascular graft infection in 15 patients . They coThe pathogen and graft material also affect the prognosis. The case of a patient who died of septic shock in the early postoperative period in which histological examination revealed MRSA colonization and a damaged inner layer of the equine pericardial roll graft has been reported . The autMcMillan et al. used bovine pericardial patches to repair infected fields of 51 peripheral arteries that required removal of infected polytetrafluoroethylene grafts, and although MRSA accounted for 22 % of all organisms detected, 50 of the 51 patches remained in place during a mean follow-up period of 2.1 years without evidence of recurrent infection, rupture, or revision . They coNeck vessel reconstruction with xenopericardial branches in our patient has been challenging. A search of the literature retrieved no publications that described the same procedure. A case of aortic arch replacement with a crimped bovine pericardial graft has been reported, but the arch vessels were anastomosed as an “island” . In viewIn addition to the graft materials commonly used thus far, bioengineered tissue produced from pluripotent or multipotent stem cells, so-called tissue-engineered vascular graft (TEVG) tissue, may provide ideal vascular conduits .The most important advantage of tissue-engineered implants is that the tissue can grow, remodel, rebuild, and respond to injury. According to the first U.S. Food and Drug Administration-approved human clinical trial in the United States of TEVG use in children with congenital heart defects, although asymptomatic graft stenosis developed in the patients with small diameter (<18-mm) conduits, there were no reported thromboembolic, hemorrhagic, or infectious complications, and there was significant growth of the TEVG. Application of TEVG to the creation of neo-aorta is a future task. Accumulation of clinical cases and confirmation of the long-term durability of xenopericardial branched grafts may demonstrate their advantages as an option for the treatment for infected aortic aneurysms.Xenopericardial roll graft replacement is simple and less invasive than the standard procedure. Accumulation of clinical cases and confirmation of the long-term durability of xenopericardial branched grafts may show that this procedure has the potential to serve as an option for the treatment of aortic infections and aortic/graft infections as an “initial” treatment as well as a “rescue” treatment.


Background: Renal transplantation is the procedure of choice for most of patients with end-stage renal disease. The graft, however can be procured from either cadaver or living donors.Objective: To compare graft and patient survival among patients who underwent kidney transplantation from cadaver donor vs. living donor.Methods: From April 2002 to February 2010, we performed 138 cadaver kidney transplantations. We reviewed and compared one-year graft and patient survival with 138 living kidney transplantations.Results: One-year graft and patient survivals in cadaveric groups were 93% and 96%, respectively, and in living groups were 92% and 97%, respectively. Conclusion: There was no significant difference in one-year graft and patient survival between living and cadaver donor kidney transplantation. There is increasing number of patients with end-stage renal disease (ESRD), and renal transplantation is the procedure of choice for most of them, since it improves the quality of life and is cost-effective compared with dialysis -3.The short-term outcome of renal transplantation has been improved substantially in the past 15 years [Generally, it has been assumed that living donor kidney transplantation (LDKT) grafts are superior to deceased donor kidney transplantation (DDKT) grafts in terms of graft survival and a lesser recipients’ morbidity. Moreover, relative insufficient supply of cadaver kidneys can be compensated with living donors. Furthermore, specific planning for the operation, say pre-emptive transplantation, or limitation of the time on dialysis are all possible during living donor program , 4.vs. living donors.Since 1985, we have performed 3512 kidney transplantations in our department. The majority of these transplantations were living unrelated. We have previously found that the result of living related  and unrelated kidney transplantation are similar [In this retrospective study, 138 patients who had received renal grafts from deceased donors were surveyed from April 2002 to February 2010. One-year graft and patient survival were compared to 138 patients who had received the grafts from living donors.In living kidney transplantation group, all donors underwent laparoscopic donor nephrectomy (LDN). Live donors underwent extensive medical evaluation and were accepted for donation only if they were in good health. Those with hypertension, diabetes and proteinouria—even very mild—were not accepted for kidney donation. Donors underwent computerized or rarely conventional angiography for evaluation of renal vascular anatomy and those with multiple vessels were also excluded except if they were related with the recipient.To increase the cost-effective of LDN, pure LDN was done without using endovascular staplers. Instead hemolock and titanium clips were used to ligate the renal artery and vein separately . The firAll cadaver kidneys were harvested in the same city but in another hospital specialized for cadaver surgery. Harvesting surgery and the recipient operation were coordinated in a way that the harvested kidney could be transferred to the recipient’s operating room in less than two hours with cold ischemia time less than three hours. Two pediatric cadavers less than six years were accepted and two kidneys were transplanted en bloc to adult recipients successfully.Immunosuppression protocols were similar for the two groups, namely cyclosporine, azathioprine and prednisolone. Antithymocyte globulin (ATG) was used if needed.Graft failure was defined as the need for renal function replacement therapy from any cause. Delay graft function (DGF) was defined as a serum creatinine level >3.5 mg/dL on the third day post-transplantation.Patient and graft survival rates were analyzed by the Kaplan-Meier survival analysis for differences in patient and graft survivals as assessed by the Log-Rank test. A p value <0.05 was considered statistically significant.The studied patients included 276 kidney transplant patients (138 from cadaver donors and 138 from living donors). Demographic data of patients are shown in In cadaveric group, number of patients who had ureteral fistula and acute rejection were one and two, respectively. Three patients (2%) suffered from DGF in living group and five (3%) in cadaveric group. There were no conversions to open nephrectomy or reoperation in any of LDNs. In the living group, the mean duration of cold ischemia was 42 (range: 32–55) min and warm ischemia was 8.6 (range: 5–17) min. In cadaveric group, the mean duration of cold ischemia was less than three hours and warm ischemia was almost zero.The results of one-year graft and patient survival were similar in cadaveric and living group. One-year graft and patient survivals in cadaveric groups were 93% and 96%, respectively, and in living groups were 92% and 97%, respectively. Using the Log-Rank test, these differences were not statistically significant .vs. living groups.In this study, we analyzed the outcome of 138 patients who had received cadaver renal grafts and compared with that of 138 patients who had received living renal grafts. The results of this study demonstrated that one year after transplantation, the patient and graft survivals were similar in cadaveric In 2005, we reported on the first randomized clinical trial comparing 100 LDNs with a similar number of open donor nephrectomies (ODNs) and concluded that compared to ODN, LDN was associated with a greater donor satisfaction, less donor morbidity and similar graft outcome .et al, [Our results differed from other studies, which reported that living kidney transplantation had a better outcome than cadaveric transplantations. Mehrabi, et al,  reportedet al, [et al, [Lee, et al,  reportedet al, . Harihar [et al,  reported [et al, .We think that one of the reasons for obtaining similar results in our study was the short period between harvesting and transplantation <3 hrs) that was near to living transplantation. In contrast to popular belief  hrs that, 7, 8, iWe therefore concluded that with improved harvesting techniques and early grafting of the harvested kidneys, graft and patient survival similar to living kidney transplantation could be obtained in cadaver transplantation.