A growing recognition that uneven-aged silviculture can offer multiple benefits to forested ecosystems has encouraged some landowners in the southern region of the United States to convert even-aged pine stands into m...A growing recognition that uneven-aged silviculture can offer multiple benefits to forested ecosystems has encouraged some landowners in the southern region of the United States to convert even-aged pine stands into multi-aged stands.For shade-intolerant pines of the southern United States,however,few studies have examined residual tree growth following silvicultural treatments that convert even-aged stands to multi-aged stands.Understanding the growth response of residual trees to different kinds of stand conversion treatments is critical to stand development and sustainability,as trees must be recruited into larger size classes during the conversion process to develop the desired stand structure and maintain productivity.In this study,we utilized a replicated,long-term silvicultural experimental trial in the southeastern United States to assess the effects of two cutting treatments(dispersed"single tree cutting"that created small canopy gaps and the"patch cutting"that created 0.1-0.8ha patch openings)and an uncut control on the 14-year growth(~cutting cycle length)of residual longleaf pine(Pinus palustris Mill.)trees.We found that tree growth,measured as mean basal area increment(BAI),was significantly higher following patch cutting(mean BAI of 16.97cm^(2))compared to both the single tree cutting(13.33cm^(2))and the uncut control(12.68cm^(2))(p<0.001).In patch cutting,the size of the patch opening,the location of trees surrounding the patch opening,and the position of the tree canopy all had a significant effect on BAI.Trees surrounding patch openings of 0.4ha exhibited greater growth,with a mean BAI of 19.24cm^(2),compared to those surrounding 0.1 and 0.8ha patch openings,which had mean BAI values of 15.89 and 15.71cm^(2),respectively(p<0.001).The position of a tree around the patch opening also influenced tree growth,as residual trees more to the North,South,and East sides exhibited significantly higher mean BAI than trees on the West side of the patch openings(p<0.001).However,distance from the patch opening border did not significantly affect the mean BAI(p=0.522).In all treatments,dominant and co-dominant trees exhibited higher BAI than intermediate and overtopped trees,indicating that tree canopy position significantly influenced tree growth(p<0.001).Understanding how residual trees grow after these silvicultural treatments is crucial for thoroughly assessing their efficacy with longleaf pine.This study's findings will enhance our understanding of stand dynamics during stand conversion and help land managers anticipate the growth of longleaf pine into larger size categories after single tree and patch cuttings.展开更多
In recent years,Speech Emotion Recognition(SER)has developed into an essential instrument for interpreting human emotions from auditory data.The proposed research focuses on the development of a SER system employing d...In recent years,Speech Emotion Recognition(SER)has developed into an essential instrument for interpreting human emotions from auditory data.The proposed research focuses on the development of a SER system employing deep learning and multiple datasets containing samples of emotive speech.The primary objective of this research endeavor is to investigate the utilization of Convolutional Neural Networks(CNNs)in the process of sound feature extraction.Stretching,pitch manipulation,and noise injection are a few of the techniques utilized in this study to improve the data quality.Feature extraction methods including Zero Crossing Rate,Chroma_stft,Mel⁃scale Frequency Cepstral Coefficients(MFCC),Root Mean Square(RMS),and Mel⁃Spectogram are used to train a model.By using these techniques,audio signals can be transformed into recognized features that can be utilized to train the model.Ultimately,the study produces a thorough evaluation of the models performance.When this method was applied,the model achieved an impressive accuracy of 94.57%on the test dataset.The proposed work was also validated on the EMO⁃BD and IEMOCAP datasets.These consist of further data augmentation,feature engineering,and hyperparameter optimization.By following these development paths,SER systems will be able to be implemented in real⁃world scenarios with greater accuracy and resilience.展开更多
Objective:To investigate the antioxidant enicacy of a biologically active dilerpenoid compound sugiol isolated from Metasequoia glyptostroboides(M.glyptostroboides)in various antioxidant models.Methods:An abietane typ...Objective:To investigate the antioxidant enicacy of a biologically active dilerpenoid compound sugiol isolated from Metasequoia glyptostroboides(M.glyptostroboides)in various antioxidant models.Methods:An abietane type diterpenoid sugiol,isolated from ethyl acetate extract of M.glyptostroboides cones,was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl radicals.Results:The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities.Consequently,the sugiol exerted lipid peroxidation inhibitory effect by 76.3%as compared to a-tocopherol(80.13%)and butylaled hydroxyanisole(76.59%).In addition,the sugiol had significant scavenging activities of l,l-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%,72.42%,72.99%and 85.04%,when compared to the standard compound ascorbic acid(81.69%,74.62%,73.00%and 73.79%)and a-tocopherol/butylated hydroxyanisole(84.09%,78.61%,74.45%and 70.02%),respectively.Conclusions:These findings justify the biological and traditional uses of M.glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.展开更多
Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in...Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.展开更多
Renal transplantation remains the best option for patients suffering from end stage renal disease(ESRD).Given the worldwide shortage of organs and growing population of patients with ESRD,those waitlisted for a transp...Renal transplantation remains the best option for patients suffering from end stage renal disease(ESRD).Given the worldwide shortage of organs and growing population of patients with ESRD,those waitlisted for a transplant is ever expanding.Contemporary crossmatch methods and human leukocyte antigen(HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients.Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome.Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology.This review aims to provide a worked example using a clinical vignette.Furthermore,each technique is discussed in detail with its pros and cons.The index case is that of a young male with ESRD secondary to Lupus nephritis.He is offered a deceased donor kidney with a 1-0-0 mismatch.His complement dependent cytotoxicity(CDC) crossmatch reported positive for B lymphocyte,but flow cytometry crossmatch(FCXM) was reported negative for both B and T lymphocytes.Luminex-SAB(single antigen bead) did not identify any donor specific antibodies(DSA).He never had a blood transfusion.The positive CDCcrossmatch result is not concordant with DSA status.These implausible results are due to underlying lupus erythematosus,leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors.False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus,that may lead to inadvertent refusal of adequate kidney grafts.Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors.Based on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.展开更多
The glomerular diseases after renal transplantation can occur de novo,i.e.,with no relation to the native kidney disease,or more frequently occur as a recurrence of the original disease in the native kidney.There may ...The glomerular diseases after renal transplantation can occur de novo,i.e.,with no relation to the native kidney disease,or more frequently occur as a recurrence of the original disease in the native kidney.There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease.However,structural alterations in transplanted kidney add to dilemma in diagnosis.These changes in architecture of histopathology can happen due to:(1) exposure to the immunosuppression specifically the calcineurin inhibitors(CNI);(2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cellmediated immunological onslaught;(3) post-transplant viral infections;(4) ischemia-reperfusion injury; and(5) hyperfiltration injury.The pathogenesis of the de novo glomerular diseases differs with each type.Stimulation of B-cell clones with subsequent production of the monoclonal Ig G,particularly Ig G3 subtype that has higher affinity to the negatively charged glomerular tissue,is suggested to be included in PGNMID pathogenesis.De novo membranous nephropathy canbe seen after exposure to the cryptogenic podocyte antigens.The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology.The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported.The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups,immune complex mediated MPGN and complement-mediated MPGN.The latter comprises of the dense deposit disease and the C3 GN disease.De novo C3 disease is rather rare.Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent.展开更多
Adequate intravenous fluid therapy is essential in renal transplant recipients to ensure a good allograft perfusion.Central venous pressure(CVP)has been cons-idered the corners-tone to guide the fluid therapy for deca...Adequate intravenous fluid therapy is essential in renal transplant recipients to ensure a good allograft perfusion.Central venous pressure(CVP)has been cons-idered the corners-tone to guide the fluid therapy for decades;it was the only available simple tool worldwide.However,the revolutionary advances in assessing the dynamic preload variables together with the availability of new equipment to precisely measure the effect of intravenous fluids on the cardiac output had created a question mark on the future role of CVP.Des-pite the critical role of fluid therapy in the field of tra-nsplantation.There are only a few clinical studies that compared the CVP guided fluid therapy with the other modern techniques and their relation to the outcome in renal transplantation.Our work sheds some light on the available published data in renal transplantation,together with data from other disciplines evaluating the utility of central venous pressure measurement.Although lager well-designed studies are still required to consolidate the role of new techniques in the field of renal transplantation,we can confidently declare that the new techniques have the advantages of providing more accurate haemodynamic assessment,which results in a better patient outcome.展开更多
In view of the availability of new immunosuppression strategies,the recurrence of allograft glomerulonephritis(GN) are reported to be increasing with time post transplantation.Recent advances in understanding the path...In view of the availability of new immunosuppression strategies,the recurrence of allograft glomerulonephritis(GN) are reported to be increasing with time post transplantation.Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence.Recurrent GN diseases manifest with a variable course,stubborn behavior,and poor response to therapy.Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis.This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival.Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries,and pathogenesis of individual glomerulonephritis is discussed.The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.展开更多
Urological complications, especially urine leaks, remain the most common type of surgical complication in the early post-transplant period. Despite major advances in the field of transplantation, a small minority of k...Urological complications, especially urine leaks, remain the most common type of surgical complication in the early post-transplant period. Despite major advances in the field of transplantation, a small minority of kidney transplants are still being lost due to urological problems. Many of these complications can be traced back to the time of retrieval and implantation. Serial ultrasound examination of the transplanted graft in the early post-operative period is of key importance for early detection. The prognosis is generally excellent if recognized and managed in a timely fashion. The purpose of this narrative review is to discuss the different presentations, compare various ureterovesical anastomosis techniques and provide a basic overview for the management of post-transplant urological complications.展开更多
AIM To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin(m TOR) inhibitors with or without calcineurin inhibitors(C...AIM To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin(m TOR) inhibitors with or without calcineurin inhibitors(CNIs) in renal transplant recipients.METHODS We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, m TOR inhibitors as an alternative to CNI within six months of renal transplant by searching the Pub Med, EMBASE, Cochrane, Crossref, and Scopus using Me SH terms. RESULTS Six articles of early withdrawal of CNI and introduction of m TOR-inhibitors within six months of renal transplantation were sought. Glomerular filtration rate(GFR) and serum creatinine were significantly better in m TOR inhibitor group with equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was significantly higher in m TOR-inhibitor group. CONCLUSION The evidence reviewed in this meta-analysis suggests that early introduction m TOR-inhibitors substantial CNI minimization. The m TOR inhibitors such as everolimus and sirolimus, due to their complementary mechanism of action and favourable nephrotoxicity profile; better glomerular filtration, lower serum creatinine with equivalent survival. Having said that, due to the higher rejection rate, may influence the use of these regimens to patients with moderate to high immunological risk patients.展开更多
Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant.Posttransplant lymphoproliferative disorders(PTLD)include a wide ...Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant.Posttransplant lymphoproliferative disorders(PTLD)include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior.Two main risk factors of PTLD are:Firstly,the cumulative immunosuppressive burden,and secondly,the oncogenic impact of the Epstein-Barr virus.The latter is a key pathognomonic driver of PTLD evolution.Over the last two decades,a considerable progress has been made in diagnosis and therapy of PTLD.The treatment of PTLD includes reduction of immunosuppression,rituximab therapy,either isolated or in combination with other chemotherapeutic agents,adoptive therapy,surgical intervention,antiviral therapy and radiotherapy.In this review we shall discuss the prevalence,clinical clues,prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.展开更多
For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy(a subtype of membranoproliferative glomerulonephritis), have mostly been comp...For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy(a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases.Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.展开更多
Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms o...Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.展开更多
Due to the increased burden of infectious complications following solid organ transplantation,vaccination against common pathogens is a hugely important area of discussion and application in clinical practice.Reductio...Due to the increased burden of infectious complications following solid organ transplantation,vaccination against common pathogens is a hugely important area of discussion and application in clinical practice.Reduction in infectious complications will help to reduce morbidity and mortality post-transplantation.Immunisation history is invaluable in the work-up of potential recipients.Knowledge of the available vaccines and their use in transplant recipients,donors and healthcare providers is vital in the delivery of quality care to transplant recipients.This article will serve as an aide-memoire to transplant physicians and health care professionals involved in managing transplant recipients as it provides an overview of different types of vaccines,timing of vaccination,vaccines contraindicated post solid organ transplantation and travel vaccines.展开更多
The risk of contrast-induced nephropathy(CIN) in renal transplant recipients is increased in diabetics, patients with impaired basal kidney function, patients in shock, patients presenting with acute emergency and in ...The risk of contrast-induced nephropathy(CIN) in renal transplant recipients is increased in diabetics, patients with impaired basal kidney function, patients in shock, patients presenting with acute emergency and in old age recipients. Approximately one-third of all hospitalized patients with acute kidney injury is attributed to CIN. In the United States, it is the third leading cause of hospital-acquired renal failure. Therefore, efforts should be directed to minimize CIN-related morbidity and mortality as well as to shorten hospital stay. While the role of peri-procedural prophylactic hydration with saline is unequivocal; the use of acetyl cysteine is not based on robust evidence. The utility of theophylline, aminophylline, calcium channel blockers, natriuretic peptide, and diuretics does not have proven role in attenuating CIN incidence. We aim to analyze the evidence for using various protocols in published literature to limit CIN-associated morbidity and mortality, particularly during surveillance of the renal allograft survival.展开更多
Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney t...Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation.Pancreatic transplantation in humans was first introduced in 1966.The initial outcome was disappointing.However,this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies.Combined kidney and pancreas transplantation will not only solve the problem of organ failure,but it will also stabilise or even reverse the metabolic complications of diabetes.Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure.Nevertheless,at the cost of an initial increase in morbidity and risk of mortality.Other transplantation options include pancreas after kidney transplantation and islet cell transplantation.We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease.Our work will provide a simplified,yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.展开更多
Chronic kidney disease(CKD),especially in advanced stages,is an important cause of infertility.In CKD patients,infertility has been linked to multiple factors.The pathophysiology of infertility related to CKD is compl...Chronic kidney disease(CKD),especially in advanced stages,is an important cause of infertility.In CKD patients,infertility has been linked to multiple factors.The pathophysiology of infertility related to CKD is complex and forked.Correction of modifiable factors can improve fertility in both genders.In males as well as females,successful kidney transplantation offers good chances of restoration of reproductive function.In female renal allograft recipients,recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and ovulation.Owing to this improvement,there is a significant risk of unplanned pregnancy,hence the need to discuss methods of contraception before transplantation.In kidney transplant recipients,different contraceptive options for pregnancy planning,have been used.The selection of one contraception over another is based on preference and tolerability.Pregnancy,in renal transplanted females,is associated with physiologic changes that occur in pregnant women with native kidneys.Immunosuppressive medications during pregnancy,in a recipient with a single functioning kidney,expose the mother and fetus to unwanted complications.Some immunosuppressive drugs are contraindicated during pregnancy.Immunosuppressive medications should be discussed with renal transplant recipients who are planning to breastfeed their babies.In addition to antirejection drugs,other medications should be managed accordingly,whenever pregnancy is planned.展开更多
Smoking is one of the preventable leading causes of death worldwide. Most of the studies focused on the association between smoking and cardiovascular disease, pulmonary diseases, malignancy and death. However, the di...Smoking is one of the preventable leading causes of death worldwide. Most of the studies focused on the association between smoking and cardiovascular disease, pulmonary diseases, malignancy and death. However, the direct effect of smoking on the renal system was undermind. There are emerging evidence correlating tobacco use with pathological changes in the normal kidneys. The effect is more obvious on the renal allograft most probably due to the chronic immune suppression status and the metabolic effect of the drugs. Several studies have documented a deleterious effect of smoking on the renal transplant recipients. Smoking was associated with lowering patient and graft survival. Smoking cessation proved to improve graft survival and to a lesser extent recipient survival. Even receiving a renal transplant from a smoker donor increases the risk of death for the recipient and carries a poorer graft survival compared to non-smoking donors. Most of the studies investigating the effect of smoking were based on self-reporting questioners, which may be misleading due to poor recall or the desire to give socially acceptable answers. This made the need of a reliable biomarker of ultimate importance. Cotinine was proposed as a promising biomarker that may help to provide objective evidence regarding the status of smoking and the dose of nicotine exposure, yet there are still some limitations of its use. The aim of this work is to review the current evidence to improve our understanding of this critical topic. Indeed, this will help to guide better-designed studies in the future.展开更多
AIM To explore the benefits and harms of corticosteroid(CS)minimization following renal transplantation.METHODS CS minimization attempts to improve cardiovascular risk factors(hypertension,diabetes,dyslipidemia),to en...AIM To explore the benefits and harms of corticosteroid(CS)minimization following renal transplantation.METHODS CS minimization attempts to improve cardiovascular risk factors(hypertension,diabetes,dyslipidemia),to enhance growth in children,to ameliorate bone disease and to lead to better compliance with immunosuppressive agents.Nevertheless,any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival.RESULTS Complete CS avoidance or very early withdrawal(i.e.,no CS after post-transplant day 7)seems to be associated with better outcomes in comparison with later withdrawal.However,an increased incidence of CS-sensitive acute rejection has been observed with all CS minimization strategies.Among the prerequisites for the safe application of CS minimization protocols are the administration of induction immunosuppression and the inclusion of calcineurin inhibitors in maintenance immunosuppression regimens.CONCLUSION Transplant recipients at low immunological risk(primary transplant,low panel reactive antibodies)arethought as optimal candidates for CS minimization.CS avoidance may also be undesirable in patients at risk for glomerulonephritis recurrence or with severe delayed graft function and prolonged cold ischemia time.Thus,CS minimization is not yet ready for implementation in the majority of transplant recipients.展开更多
Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and...Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and associated cancers by impairing immune response against viruses and cancer immunoediting.This review reflects the magnitude,etiology and immunological characteristics of various virus-related post-transplant malignancies,emphasizing the need for future research.A multidisciplinary and strategic approach may serve best but overall literature evidence targeting it is sparse.However,the authors attempted to provide a more detailed update of the literature consensus for the prevention,diagnosis,management and surveillance of post-transplant viral infections and associated malignancies,with a focus on the current role of adoptive immunotherapy and the way forward.In order to achieve long-term patient and graft survival as well as superior post-transplant outcomes,collaborative research on holistic care of organ recipients is imperative.展开更多
基金The USDA NIFA McIntire Stennis project#1014653 and the University of Florida Institute of Food and Agricultural Sciences funded the research presented in this publication.
文摘A growing recognition that uneven-aged silviculture can offer multiple benefits to forested ecosystems has encouraged some landowners in the southern region of the United States to convert even-aged pine stands into multi-aged stands.For shade-intolerant pines of the southern United States,however,few studies have examined residual tree growth following silvicultural treatments that convert even-aged stands to multi-aged stands.Understanding the growth response of residual trees to different kinds of stand conversion treatments is critical to stand development and sustainability,as trees must be recruited into larger size classes during the conversion process to develop the desired stand structure and maintain productivity.In this study,we utilized a replicated,long-term silvicultural experimental trial in the southeastern United States to assess the effects of two cutting treatments(dispersed"single tree cutting"that created small canopy gaps and the"patch cutting"that created 0.1-0.8ha patch openings)and an uncut control on the 14-year growth(~cutting cycle length)of residual longleaf pine(Pinus palustris Mill.)trees.We found that tree growth,measured as mean basal area increment(BAI),was significantly higher following patch cutting(mean BAI of 16.97cm^(2))compared to both the single tree cutting(13.33cm^(2))and the uncut control(12.68cm^(2))(p<0.001).In patch cutting,the size of the patch opening,the location of trees surrounding the patch opening,and the position of the tree canopy all had a significant effect on BAI.Trees surrounding patch openings of 0.4ha exhibited greater growth,with a mean BAI of 19.24cm^(2),compared to those surrounding 0.1 and 0.8ha patch openings,which had mean BAI values of 15.89 and 15.71cm^(2),respectively(p<0.001).The position of a tree around the patch opening also influenced tree growth,as residual trees more to the North,South,and East sides exhibited significantly higher mean BAI than trees on the West side of the patch openings(p<0.001).However,distance from the patch opening border did not significantly affect the mean BAI(p=0.522).In all treatments,dominant and co-dominant trees exhibited higher BAI than intermediate and overtopped trees,indicating that tree canopy position significantly influenced tree growth(p<0.001).Understanding how residual trees grow after these silvicultural treatments is crucial for thoroughly assessing their efficacy with longleaf pine.This study's findings will enhance our understanding of stand dynamics during stand conversion and help land managers anticipate the growth of longleaf pine into larger size categories after single tree and patch cuttings.
文摘In recent years,Speech Emotion Recognition(SER)has developed into an essential instrument for interpreting human emotions from auditory data.The proposed research focuses on the development of a SER system employing deep learning and multiple datasets containing samples of emotive speech.The primary objective of this research endeavor is to investigate the utilization of Convolutional Neural Networks(CNNs)in the process of sound feature extraction.Stretching,pitch manipulation,and noise injection are a few of the techniques utilized in this study to improve the data quality.Feature extraction methods including Zero Crossing Rate,Chroma_stft,Mel⁃scale Frequency Cepstral Coefficients(MFCC),Root Mean Square(RMS),and Mel⁃Spectogram are used to train a model.By using these techniques,audio signals can be transformed into recognized features that can be utilized to train the model.Ultimately,the study produces a thorough evaluation of the models performance.When this method was applied,the model achieved an impressive accuracy of 94.57%on the test dataset.The proposed work was also validated on the EMO⁃BD and IEMOCAP datasets.These consist of further data augmentation,feature engineering,and hyperparameter optimization.By following these development paths,SER systems will be able to be implemented in real⁃world scenarios with greater accuracy and resilience.
基金supported by a grant(NRF-2011-0008199)from the Basie Science Research Program through the National Research Foundation of Korea
文摘Objective:To investigate the antioxidant enicacy of a biologically active dilerpenoid compound sugiol isolated from Metasequoia glyptostroboides(M.glyptostroboides)in various antioxidant models.Methods:An abietane type diterpenoid sugiol,isolated from ethyl acetate extract of M.glyptostroboides cones,was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl radicals.Results:The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities.Consequently,the sugiol exerted lipid peroxidation inhibitory effect by 76.3%as compared to a-tocopherol(80.13%)and butylaled hydroxyanisole(76.59%).In addition,the sugiol had significant scavenging activities of l,l-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%,72.42%,72.99%and 85.04%,when compared to the standard compound ascorbic acid(81.69%,74.62%,73.00%and 73.79%)and a-tocopherol/butylated hydroxyanisole(84.09%,78.61%,74.45%and 70.02%),respectively.Conclusions:These findings justify the biological and traditional uses of M.glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.
文摘Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.
文摘Renal transplantation remains the best option for patients suffering from end stage renal disease(ESRD).Given the worldwide shortage of organs and growing population of patients with ESRD,those waitlisted for a transplant is ever expanding.Contemporary crossmatch methods and human leukocyte antigen(HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients.Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome.Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology.This review aims to provide a worked example using a clinical vignette.Furthermore,each technique is discussed in detail with its pros and cons.The index case is that of a young male with ESRD secondary to Lupus nephritis.He is offered a deceased donor kidney with a 1-0-0 mismatch.His complement dependent cytotoxicity(CDC) crossmatch reported positive for B lymphocyte,but flow cytometry crossmatch(FCXM) was reported negative for both B and T lymphocytes.Luminex-SAB(single antigen bead) did not identify any donor specific antibodies(DSA).He never had a blood transfusion.The positive CDCcrossmatch result is not concordant with DSA status.These implausible results are due to underlying lupus erythematosus,leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors.False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus,that may lead to inadvertent refusal of adequate kidney grafts.Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors.Based on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.
文摘The glomerular diseases after renal transplantation can occur de novo,i.e.,with no relation to the native kidney disease,or more frequently occur as a recurrence of the original disease in the native kidney.There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease.However,structural alterations in transplanted kidney add to dilemma in diagnosis.These changes in architecture of histopathology can happen due to:(1) exposure to the immunosuppression specifically the calcineurin inhibitors(CNI);(2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cellmediated immunological onslaught;(3) post-transplant viral infections;(4) ischemia-reperfusion injury; and(5) hyperfiltration injury.The pathogenesis of the de novo glomerular diseases differs with each type.Stimulation of B-cell clones with subsequent production of the monoclonal Ig G,particularly Ig G3 subtype that has higher affinity to the negatively charged glomerular tissue,is suggested to be included in PGNMID pathogenesis.De novo membranous nephropathy canbe seen after exposure to the cryptogenic podocyte antigens.The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology.The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported.The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups,immune complex mediated MPGN and complement-mediated MPGN.The latter comprises of the dense deposit disease and the C3 GN disease.De novo C3 disease is rather rare.Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent.
文摘Adequate intravenous fluid therapy is essential in renal transplant recipients to ensure a good allograft perfusion.Central venous pressure(CVP)has been cons-idered the corners-tone to guide the fluid therapy for decades;it was the only available simple tool worldwide.However,the revolutionary advances in assessing the dynamic preload variables together with the availability of new equipment to precisely measure the effect of intravenous fluids on the cardiac output had created a question mark on the future role of CVP.Des-pite the critical role of fluid therapy in the field of tra-nsplantation.There are only a few clinical studies that compared the CVP guided fluid therapy with the other modern techniques and their relation to the outcome in renal transplantation.Our work sheds some light on the available published data in renal transplantation,together with data from other disciplines evaluating the utility of central venous pressure measurement.Although lager well-designed studies are still required to consolidate the role of new techniques in the field of renal transplantation,we can confidently declare that the new techniques have the advantages of providing more accurate haemodynamic assessment,which results in a better patient outcome.
文摘In view of the availability of new immunosuppression strategies,the recurrence of allograft glomerulonephritis(GN) are reported to be increasing with time post transplantation.Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence.Recurrent GN diseases manifest with a variable course,stubborn behavior,and poor response to therapy.Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis.This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival.Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries,and pathogenesis of individual glomerulonephritis is discussed.The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.
文摘Urological complications, especially urine leaks, remain the most common type of surgical complication in the early post-transplant period. Despite major advances in the field of transplantation, a small minority of kidney transplants are still being lost due to urological problems. Many of these complications can be traced back to the time of retrieval and implantation. Serial ultrasound examination of the transplanted graft in the early post-operative period is of key importance for early detection. The prognosis is generally excellent if recognized and managed in a timely fashion. The purpose of this narrative review is to discuss the different presentations, compare various ureterovesical anastomosis techniques and provide a basic overview for the management of post-transplant urological complications.
文摘AIM To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin(m TOR) inhibitors with or without calcineurin inhibitors(CNIs) in renal transplant recipients.METHODS We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, m TOR inhibitors as an alternative to CNI within six months of renal transplant by searching the Pub Med, EMBASE, Cochrane, Crossref, and Scopus using Me SH terms. RESULTS Six articles of early withdrawal of CNI and introduction of m TOR-inhibitors within six months of renal transplantation were sought. Glomerular filtration rate(GFR) and serum creatinine were significantly better in m TOR inhibitor group with equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was significantly higher in m TOR-inhibitor group. CONCLUSION The evidence reviewed in this meta-analysis suggests that early introduction m TOR-inhibitors substantial CNI minimization. The m TOR inhibitors such as everolimus and sirolimus, due to their complementary mechanism of action and favourable nephrotoxicity profile; better glomerular filtration, lower serum creatinine with equivalent survival. Having said that, due to the higher rejection rate, may influence the use of these regimens to patients with moderate to high immunological risk patients.
文摘Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant.Posttransplant lymphoproliferative disorders(PTLD)include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior.Two main risk factors of PTLD are:Firstly,the cumulative immunosuppressive burden,and secondly,the oncogenic impact of the Epstein-Barr virus.The latter is a key pathognomonic driver of PTLD evolution.Over the last two decades,a considerable progress has been made in diagnosis and therapy of PTLD.The treatment of PTLD includes reduction of immunosuppression,rituximab therapy,either isolated or in combination with other chemotherapeutic agents,adoptive therapy,surgical intervention,antiviral therapy and radiotherapy.In this review we shall discuss the prevalence,clinical clues,prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.
文摘For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy(a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases.Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.
文摘Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.
文摘Due to the increased burden of infectious complications following solid organ transplantation,vaccination against common pathogens is a hugely important area of discussion and application in clinical practice.Reduction in infectious complications will help to reduce morbidity and mortality post-transplantation.Immunisation history is invaluable in the work-up of potential recipients.Knowledge of the available vaccines and their use in transplant recipients,donors and healthcare providers is vital in the delivery of quality care to transplant recipients.This article will serve as an aide-memoire to transplant physicians and health care professionals involved in managing transplant recipients as it provides an overview of different types of vaccines,timing of vaccination,vaccines contraindicated post solid organ transplantation and travel vaccines.
文摘The risk of contrast-induced nephropathy(CIN) in renal transplant recipients is increased in diabetics, patients with impaired basal kidney function, patients in shock, patients presenting with acute emergency and in old age recipients. Approximately one-third of all hospitalized patients with acute kidney injury is attributed to CIN. In the United States, it is the third leading cause of hospital-acquired renal failure. Therefore, efforts should be directed to minimize CIN-related morbidity and mortality as well as to shorten hospital stay. While the role of peri-procedural prophylactic hydration with saline is unequivocal; the use of acetyl cysteine is not based on robust evidence. The utility of theophylline, aminophylline, calcium channel blockers, natriuretic peptide, and diuretics does not have proven role in attenuating CIN incidence. We aim to analyze the evidence for using various protocols in published literature to limit CIN-associated morbidity and mortality, particularly during surveillance of the renal allograft survival.
文摘Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation.Pancreatic transplantation in humans was first introduced in 1966.The initial outcome was disappointing.However,this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies.Combined kidney and pancreas transplantation will not only solve the problem of organ failure,but it will also stabilise or even reverse the metabolic complications of diabetes.Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure.Nevertheless,at the cost of an initial increase in morbidity and risk of mortality.Other transplantation options include pancreas after kidney transplantation and islet cell transplantation.We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease.Our work will provide a simplified,yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.
文摘Chronic kidney disease(CKD),especially in advanced stages,is an important cause of infertility.In CKD patients,infertility has been linked to multiple factors.The pathophysiology of infertility related to CKD is complex and forked.Correction of modifiable factors can improve fertility in both genders.In males as well as females,successful kidney transplantation offers good chances of restoration of reproductive function.In female renal allograft recipients,recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and ovulation.Owing to this improvement,there is a significant risk of unplanned pregnancy,hence the need to discuss methods of contraception before transplantation.In kidney transplant recipients,different contraceptive options for pregnancy planning,have been used.The selection of one contraception over another is based on preference and tolerability.Pregnancy,in renal transplanted females,is associated with physiologic changes that occur in pregnant women with native kidneys.Immunosuppressive medications during pregnancy,in a recipient with a single functioning kidney,expose the mother and fetus to unwanted complications.Some immunosuppressive drugs are contraindicated during pregnancy.Immunosuppressive medications should be discussed with renal transplant recipients who are planning to breastfeed their babies.In addition to antirejection drugs,other medications should be managed accordingly,whenever pregnancy is planned.
文摘Smoking is one of the preventable leading causes of death worldwide. Most of the studies focused on the association between smoking and cardiovascular disease, pulmonary diseases, malignancy and death. However, the direct effect of smoking on the renal system was undermind. There are emerging evidence correlating tobacco use with pathological changes in the normal kidneys. The effect is more obvious on the renal allograft most probably due to the chronic immune suppression status and the metabolic effect of the drugs. Several studies have documented a deleterious effect of smoking on the renal transplant recipients. Smoking was associated with lowering patient and graft survival. Smoking cessation proved to improve graft survival and to a lesser extent recipient survival. Even receiving a renal transplant from a smoker donor increases the risk of death for the recipient and carries a poorer graft survival compared to non-smoking donors. Most of the studies investigating the effect of smoking were based on self-reporting questioners, which may be misleading due to poor recall or the desire to give socially acceptable answers. This made the need of a reliable biomarker of ultimate importance. Cotinine was proposed as a promising biomarker that may help to provide objective evidence regarding the status of smoking and the dose of nicotine exposure, yet there are still some limitations of its use. The aim of this work is to review the current evidence to improve our understanding of this critical topic. Indeed, this will help to guide better-designed studies in the future.
文摘AIM To explore the benefits and harms of corticosteroid(CS)minimization following renal transplantation.METHODS CS minimization attempts to improve cardiovascular risk factors(hypertension,diabetes,dyslipidemia),to enhance growth in children,to ameliorate bone disease and to lead to better compliance with immunosuppressive agents.Nevertheless,any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival.RESULTS Complete CS avoidance or very early withdrawal(i.e.,no CS after post-transplant day 7)seems to be associated with better outcomes in comparison with later withdrawal.However,an increased incidence of CS-sensitive acute rejection has been observed with all CS minimization strategies.Among the prerequisites for the safe application of CS minimization protocols are the administration of induction immunosuppression and the inclusion of calcineurin inhibitors in maintenance immunosuppression regimens.CONCLUSION Transplant recipients at low immunological risk(primary transplant,low panel reactive antibodies)arethought as optimal candidates for CS minimization.CS avoidance may also be undesirable in patients at risk for glomerulonephritis recurrence or with severe delayed graft function and prolonged cold ischemia time.Thus,CS minimization is not yet ready for implementation in the majority of transplant recipients.
文摘Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and associated cancers by impairing immune response against viruses and cancer immunoediting.This review reflects the magnitude,etiology and immunological characteristics of various virus-related post-transplant malignancies,emphasizing the need for future research.A multidisciplinary and strategic approach may serve best but overall literature evidence targeting it is sparse.However,the authors attempted to provide a more detailed update of the literature consensus for the prevention,diagnosis,management and surveillance of post-transplant viral infections and associated malignancies,with a focus on the current role of adoptive immunotherapy and the way forward.In order to achieve long-term patient and graft survival as well as superior post-transplant outcomes,collaborative research on holistic care of organ recipients is imperative.
