Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.

BACKGROUND: This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. METHODS: This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. RESULTS: Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P < 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P < 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P < 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P < 0.001) and peri-tubular capillaritis (r = 0.344, P < 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). CONCLUSIONS: Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.

Predicting Perceptions of the Built Environment using GIS, Satellite and Street View Image Approaches.

BACKGROUND: High quality built environments are important for human health and wellbeing. Numerous studies have characterized built environment physical features and environmental exposures, but few have examined urban perceptions at geographic scales needed for population-based research. The degree to which urban perceptions are associated with different environmental features, and traditional environmental exposures such as air pollution or urban green space, is largely unknown. OBJECTIVE: To determine built environment factors associated with safety, lively and beauty perceptions across 56 cities. METHODS: We examined perceptions collected in the open source Place Pulse 2.0 dataset, which assigned safety, lively and beauty scores to street view images based on crowd-sourced labelling. We derived built environment measures for the locations of these images (110,000 locations across 56 global cities) using GIS and remote sensing datasets as well as street view imagery features (e.g. trees, cars) using deep learning image segmentation. Linear regression models were developed using Lasso penalized variable selection to predict perceptions based on visible (street level images) and GIS/remote sensing built environment variables. RESULTS: Population density, impervious surface area, major roads, traffic air pollution, tree cover and Normalized Difference Vegetation Index (NDVI) showed statistically significant differences between high and low safety, lively, and beauty perception locations. Visible street level features explained approximately 18% of the variation in safety, lively, and beauty perceptions, compared to 3-10% explained by GIS/remote sensing. Large differences in prediction were seen when modelling between city (R2 67-81%) versus within city (R2 11-13%) perceptions. Important predictor variables included visible accessibility features (e.g. streetlights, benches) and roads for safety, visible plants and buildings for lively, and visible green space and NDVI for beauty. CONCLUSION: Substantial within and between city differences in built environment perceptions exist, which visible street level features and GIS/remote sensing variables only partly explain. This offers a new research avenue to expand built environment measurement methods to include perceptions in addition to physical features.

Induction therapy with thymoglobulin or interleukin-2 receptor antagonist for Chinese recipients of living donor renal transplantation: a retrospective study.

BACKGROUND: Recipients of living donor renal transplantation are typically considered to have a relatively lower immunological risk. This retrospective study aimed to compare the therapeutic efficacy and safety between rabbit antithymocyte globulin (rATG) or interleukin-2 receptor antagonist (IL2-RA) induction therapies in Chinese population. METHODS: A total of 188 patients receiving living donor renal transplantation between February 2004 and December 2013 were included and divided into the rATG group and based on their induction therapy. The primary outcome was clinically-suspected rejection. The incidences of de novo donor-specific antigen (dn-DSA), graft survival, and infection were also compared between groups. A multivariate Cox regression analysis was performed to investigate the influential factors associated with clinically-suspected acute rejection and graft survival. RESULTS: The rATG group had a higher panel reactive antibody (PRA) score and more complete HLA mismatches than the IL2-RA group (both P < 0.001). The incidences of clinically-suspected acute rejection (9.8% vs. 8.8%; P = 0.832) and dn-DSA formation (4.9% vs. 5.4%, P = 0.44) were not significantly different between groups. Kaplan-Meier curve analysis demonstrated that the graft survivals of two groups were comparable (P = 0.857). After adjusting for patients' age, sex, PRA, HLA mismatch confounders, and the use of corticoids, the multivariate Cox regression analysis showed that methods of induction therapy were not associated with clinically-suspected acute rejection and graft survival (both P > 0.05). The incidences of complications (infections, pneumonia, liver injury and myelosuppression) were all comparable between groups (all P > 0.05). CONCLUSIONS: These results suggested that rATG could be a safe and efficient immunosuppressant when used in a Chinese recipient population with a higher immunological risk in living donor renal transplantation.

Graft failure of IgA nephropathy in renal allografts following living donor transplantation: predictive factor analysis of 102 biopsies.

BACKGROUND: To investigate predictive factors related to graft failure of IgA nephropathy(IgAN) in renal allografts following living donor transplantation. METHODS: We identified a series of 102 biopsies diagnosed as IgAN in renal allografts following living donor transplantation from July 2004 to January 2017 at our center, and assess the predict value of the Lee's classification and the 2009 Oxford classification in IgAN in renal allografts, clinical, ultrasonic and pathological characteristics at biopsy and the outcomes were retrospectively analyzed. RESULTS: The 5-year graft cumulative survival rate after transplantation was 91.4%. The 4-year graft cumulative survival rate after biopsy diagnosis of IgAN in renal allografts was 59.6%. The mean time ± SD to disease was 4.7 ± 3.5 years. The color doppler ultrasound and blood flow imagine showed the echo enhancement, the reduced blood flow distribution, the reduced peak systolic velocity of main renal artery, and the increased resistance index of arcuate renal artery were valuable in evaluating the graft dysfunction. The Cox multivariate analysis revealed that the 24-h urinary protein level (HR 1.6 for 1-g increase, 95%CI 1.2-2.0), estimated glomerular filtration rate (eGFR) (HR 1.0 for 1-mL/min/1.73 m^2 decline, 95%CI 1.0-1.1), and mesangial C1q deposition (HR 3.0, 95%CI 1.2-7.4) at biopsy were independent predictive factors of graft failure of IgAN in renal allografts. CONCLUSIONS: IgAN in renal allografts occurred frequently within 5 years after transplantation. The risk of graft failure should be taken seriously in patients who exhibit heavy proteinuria and/or a declined eGFR as the initial symptoms; a high lesion grade (grade IV-V of Lee's classification) and/or mesangial C1q deposition may also indicated a poor outcome.

The potential of microRNAs as human prostate cancer biomarkers: A meta-analysis of related studies.

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta-analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007-2017. According to the inclusion criteria, 104 records were included for this meta-analysis. The pooled or stratified analyze showed 10 up-regulated miRNAs (miR-18a, miR-34a, miR-106b, miR-141, miR-182, miR-183, miR-200a/b, miR-301a, and miR-375) and 14 down-regulated miRNAs (miR-1, miR-23b/27b, miR-30c, miR-99b, miR-139-5p, miR-152, miR-187, miR-204, miR-205, miR-224, miR-452, miR-505, and let-7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR-32 and low expression of let-7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR-21, miR-30c, miR-129, miR-145, and let-7c) could predict poor RFS of PC, while the evaluation of miR-375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large-scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.

Evaluation of quality of kidneys from donation after circulatory death/expanded criteria donors by parameters of machine perfusion.

AIM: To investigate whether the parameters of machine perfusion could predict the quality of kidneys from donation after circulatory death (DCD) donors and expanded criteria donors (ECD). METHODS: Fifty-eight kidneys from DCD/ECD donors were harvested in our hospital from July 2011 to August 2014. All kidneys were preserved with machine perfusion (Life Port), and parameters of machine perfusion were collected. All kidneys were biopsied before transplantation. The primary endpoints were delayed graft function (DGF), graft loss and patient death. RESULTS: After kidney transplantation, 26 patients (44.8%) had DGF. We chose 1 h RI as a predictive parameter to predict DGF after transplant, and made the ROC curve. The ROC curve showed that 1 h RI = 0.4 was the best cut-off point for predicting DGF after transplant. The sensitivity was 61.54%, and the specificity was 81.25%. Fifty-eight recipients were divided into two groups according to 1 h RI of machine perfusion. 22 cases in high RI group (RI > 0.4) and 36 cases in low RI group (RI ≤0.4). DGF rate was significantly higher in the high RI group (72.7% vs. 27.8%). One year serum creatinine levels were also significantly higher in the high RI group (P < 0.05). Acute rejection rate and 1 year graft and patient survival were comparable. CONCLUSIONS: One hour RI of machine perfusion is associated with DGF and 1 year graft function in DCD/ECD kidney transplantation, and may be a non-invasive tool for evaluating quality of DCD/ECD kidneys.

Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies.

AIM: The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes. METHODS: We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema. RESULTS: Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively. CONCLUSIONS: A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.

Comparison of outcomes of kidney transplantation from donation after brain death, donation after circulatory death, and donation after brain death followed by circulatory death donors.

BACKGROUND: There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors. METHODS: We retrospectively reviewed 469 recipients who received deceased kidney transplantation in our hospital from February 2007 to June 2015. The recipients were divided into three groups according to the source of their donor kidneys: DBD, DCD, or DBCD. The primary endpoints were delayed graft function (DGF), graft loss, and patient death. RESULTS: The warm ischemia time was much longer in DCD group compared to DBCD group (18.4 minutes vs 12.9 minutes, P < .001). DGF rate was higher in DCD group than in DBD and DBCD groups (22.5% vs 10.2% and 13.8%, respectively, P = .021). Urinary leakage was much higher in DCD group (P = .049). Kaplan-Meier analysis showed that 1-, 2-, and 3-year patient survivals were all comparable among the three groups. CONCLUSION: DBCD kidney transplantation has lower incidences of DGF and urinary leakage than DCD kidney transplant. However, the overall patient and graft survival were comparable among DBD, DCD, and DBCD kidney transplantation.

Ethylene carbodiimide-fixed donor splenocytes combined with α-1 antitrypsin induce indefinite donor-specific protection to mice cardiac allografts.

Peritransplant infusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs) induces protection of islet and cardiac allografts. However, pro-inflammatory cytokine production during the peritransplantation period may negate the effect of ECDI-SPs. Therefore, we hypothesized that blocking pro-inflammatory cytokine secretion while increasing levels of anti-inflammatory cytokines would enhance the tolerance-induced efficacy of ECDI-SPs. The objective of this study was to determine the effectiveness of using ECDI-SPs combined with a short course of α1-antitrypsin (AAT) for induction of tolerance. Using a mice cardiac transplant model, we demonstrated that ECDI-SPs + AAT effectively induced indefinite mice cardiac allograft protection in a donor-specific fashion. This effect was accompanied by modulation of cytokines through decreasing levels of pro-inflammatory cytokines (including IFN-γ, TNF-α, IL-1ß, IL-6, IL-17, and IL-23) and increasing levels of anti-inflammatory cytokines (including IL-10, IL-13, and TGF-ß), and by inhibition of effector T cells (Teff) and expansion of regulatory T cells (Tregs). Therefore, we concluded that combined ECDI-SPs and AAT appeared to modulate the expression of cytokines and regulate the Teff:Treg balance to create a support milieu for graft protection. Our strategy of combining ECDI-SPs and AAT provides a promising approach for inducing donor-specific transplant tolerance.

Transforming growth factor-ß activated long non-coding RNA ATB plays an important role in acute rejection of renal allografts and may impacts the postoperative pharmaceutical immunosuppression therapy.

AIM: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. The lncRNA activated by transforming growth factor ß (TGF-ß) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in renal transplantation. This study aimed to assess lncRNA-ATB expression in renal transplant patients with acute kidney injury and explore its role in postoperative pharmaceutical immunosuppression therapy. METHODS: We detected lncRNA-ATB expression in the kidney biopsies of a cohort of 72 patients with renal allograft rejection and 36 control transplant patients. lncRNA-ATB were overexpressed from lentiviral vectors in renal cells. RESULTS: We found that lncRNA-ATB was remarkably upregulated in patients with acute rejection compared with controls. Meanwhile, lncRNA-ATB could influence the kidney cell phenotypes and impact the nephrotoxicity of immunosuppressive drug. CONCLUSION: In conclusion, lncRNA-ATB are strongly altered in patients with acute rejection and may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

Comparison of efficacy and safety between rabbit anti-thymocyte globulin and anti-T lymphocyte globulin in kidney transplantation from donation after cardiac death: a retrospective cohort study.

AIM: To compare the efficacy and safety between rabbit anti-thymocyte globulin (Thymoglobulin) and anti-T lymphocyte globulin (ATG-Fresenius, ATG-F) in donation after cardiac death (DCD) kidney transplantation. METHODS: We retrospectively analyzed 255 cases of DCD kidney transplantation performed at our hospital from February 2007 to October 2013. The patients were divided into two groups based on their induction therapies with Thymoglobulin (n = 188) or ATG-F (n = 67). Clinical data were collected and compared between the two groups. RESULTS: Delayed graft function (DGF) occurred in 36 (19.1%) patients in the Thymoglobulin group versus 17 (25.4%) patients in the ATG-F group (P = 0.281). However, if we subgroup the patients with increased risk factors for DGF, the DGF rate was 9/40 (22.5%) in the Thymoglobulin group versus 9/16 (56.3%) in the ATG-F group (P = 0.015). Duration of DGF was significantly shorter in the Thymoglobulin group (11.7 days vs. 16.1 days). The acute rejection rate was significantly lower in the Thymoglobulin group (9.6% vs. 19.4%, P = 0.035). One-year graft and patient survival were both comparable between the Thymoglobulin and ATG-F groups. The adjusted odds ratio of DGF was 4.283 (1.137-16.13) between the ATG-F and Thymoglobulin groups in patients with increased risk factors for DGF. CONCLUSION: Compared with ATG-F, Thymoglobulin may reduce duration of DGF and acute rejection rate after DCD kidney transplantation. Moreover, Thymoglobulin significantly reduced DGF in patients with increased risk factors for DGF.

Effect of donor age and parent-to-child transplant on living-related donor kidney transplantation: a single center's experience of 236 cases.

To study the impact of parent-to-child transplant and older donor age on recipients' post-transplant creatinine levels, a total of 236 patients who received living donor kidney transplantation were evaluated for kidney viability based on creatinine (Cr) level. Of the 236 pairings, 113 (48%) were parent-to-child followed by sibling transplants (66, 30%). Recipient Cr levels were significantly higher at 6 months and 3 years post-transplant in the parent-to-child transplants compared to other donor-recipient relationships. In addition, donor age (average age: 44.1 ± 11.5; range: 19-66) contributed to higher recipient post-transplant Cr levels (p < 0.01). Pre-transplant donor and recipient Cr levels tended to result in higher post-transplant Cr levels in recipients (p < 0.05). Multivariate logistic regression analysis revealed that the presence of both parent-to-child transplant and older donor significantly increased the risk of elevated post-transplant Cr levels in recipients with an estimated odds ratios ranging from 3.46 (95% CI: 1.71-6.98) at 6 months to 8.04 (3.14-20.56) at 3 years post-transplant. Donor age significantly affected transplant survival as measured by higher recipient post-transplant Cr levels. In addition, parent-to-child transplant pairings, along with older donor age, significantly increased the risk of elevated post-transplant Cr levels in recipients.

[Analysis of BK viruria on the long term graft survival in renal transplant recipients].

OBJECTIVE: To observe the clearance of BK viruria and long-term graft survival in renal transplant recipients with BK virus (BKV) infection under the protocol of our center. METHODS: Urine was taken from 229 renal transplant recipients,who were transplanted between March 2006 to October 2008, for BKV cytological testing and real-time PCR for BKV DNA at 1, 3, 6, 9, and 12 months after transplantation. Graft biopsies were analyzed for SV40-T by immunohistochemical method. Recipients were treated according to the BKV infection protocol of our center and were monitored for BKV and graft function. All the patients were followed for at least 5 years. RESULTS: By 1 year post-transplant, urinary decoy cells, BK viruria, and BKV associated nephropathy (BKVAN) occurred in 78, 99, and 7 patients, respectively. The median followed-up time was 63.6 (3.0-88.0) months. After reduction of immunosuppression, 81 (81.8%) patients cleared BK viruria with a mean time of (12.1 ± 1.9) months. When compared with non-BKVAN patients, BKVAN patients had a higher median peak level of BK viruria (2.07 × 109 vs 9.28 × 105 copies/ml, P=0.002), lower frequency of clearance (3/7 vs 78/92, P=0.006), longer BK viruria clearance time ((45.4 ± 6.4) vs (8.7 ± 1.5) months, P=0.001). The 1, 3, 5-year graft survival in BK viruria patients were 99.0%, 95.9% and 89.6% respectively, which were not significantly different from those in non-BK viruria patients (97.7%, 95.5% and 93.7%, P=0.289). Graft function of BK viruria patients were not statistical significance compared with non-BK viruria patients (serum creatinine level 5 years post-transplant: (105.7 ± 30.9) vs (111.3 ± 4.6) µmol/L, P=0.322). Graft function of BKVAN patients at 5 years post-transplant was stable without significantly difference from non-BKVAN patients (serum creatinine level: (127.6 ± 41.0) vs (108.3 ± 39.3) µmol/L, P=0.204). CONCLUSION: On the premise of intensively and regularly BKV monitoring and preemptive reduction of immunosuppression, BK viruria and BKVAN can not impact on the long-term graft survival in renal transplant recipients.

[Analysis on BK virus associated nephropathy related risk factors in renal transplant recipients].

OBJECTIVE: To analyze the risk factors affecting BK virus associated nephropathy (BKVAN) after kidney transplantation. METHODS: Three screening methods for BKVAN including quantitative PCR assay for BK virus (BKV) DNA load in urine and plasma and quantitative assay of urine cytology concurrently with renal transplant biopsies for the evaluation of 615 patients from January 2006 to December 2014 were used. The renal allograft biopsy specimens were analyzed by routine histologic examination, immunohistochemistry and classified into three categories of BKVAN. Potential variables were analyzed by Logistic regression model multivariate analysis to assess and rank BKVAN related risk factors. RESULTS: The positive rate of urine decoy cell , BKV viruria and viremia in 615 renal recipients were 13.7% (84/615), 29.3% (180/615), and 8.8% (54/615), respectively. BKVAN were diagnosed in 49 recipients. The incidence and the median level of the number of the decoy cell, BK viral load in urine and plasma were higher in the BKVAN group than those in non-BKVAN group (all P<0.05). Tacrolimus (Tac) combined with mycophenolic acid (MPA) protocol (OR=12.4, P=0.001) and severe pneumonia post-transplant (OR=3.7, P=0.001) were the independent risk factors impacting on BKVAN in renal recipients. CONCLUSIONS: The renal recipients with high level of BKV replication, whose immunosuppressant protocol include Tac and MPA, should be suspected the diagnosis of BKVAN.

Adenoid cystic carcinoma of the retromolar pad region: A case report.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignancies, mostly occurs in the major and minor salivary glands in the oral and maxillofacial region. The development of ACC in the retromolar pad is extremely rare, which limits establishing proper diagnosis and management. PRESENTATION OF CASE: A patient described a 2-month history of finding a mass behind the lower left posterior teeth. Based on the physical examination and radiographic findings, we got an initial impression of a benign mucocele, the nature of which was to be investigated further. Pathological examination of the resected tissue resulted in a diagnosis of ACC. Follow-up visits showed no recurrence during the subsequent 54 months. DISCUSSION: In cases with an uncertain diagnosis based on medical history, clinical features and imaging examinations, it is important to proceed carefully with the possibility of a tumor in mind. CONCLUSION: ACC in the retromolar pad is rare and can be easily misdiagnosed. Clinical, radiographic, and pathological evidence confirm a definitive diagnosis. Long-term follow-up is important for the full analysis of ACC treatment.

A novel accelerated rejection model for mouse cardiac transplantation involving presensitization with donor splenocytes.

BACKGROUND: Accelerated rejection is a type of refractory rejection. Animal models of accelerated rejection are widely employed in research on transplant immunity. METHODS: We divided 36 C57BL/6 mice into six groups that underwent heart transplant. To select the ideal number of splenocytes for the presensitization to induce accelerated rejection, were transferred 0.5 × 10(7), 1 × 10(7), 5 × 10(7), or 10 × 10(7) donor splenocytes 7 d before transplantation. We confirmed successful presensitization by increases in donor-reactive antibodies. We performed 12 additional heart transplants in the accelerated rejection group and the control groups for a histological examination, immunohistochemical staining for C3d, and a splenocyte test using flow cytometry. RESULTS: The transfer of 5 × 10(7) donor splenocytes effectively and efficiently induced an accelerated rejection in the BALB/c→C57BL/6 heart transplant, with an allograft survival time that was decreased from 7.4 ± 0.5 d to 3.5 ± 0.8 d compared with the allogenic controls (P < 0.05, log-rank test). An analysis of this model indicated that compared with acute rejection, the number of donor-reactive antibodies was significantly increased, and the proportions of effector memory CD8(+) T cells and plasmacytes in the spleen were significantly increased (7.81% ± 1.2% versus 2.96% ± 1.0%, P = 0.006; 1.27% ± 0.13% versus 0.71% ± 0.22%, P = 0.018, respectively). We found the histological characteristics of both cellular and humoral rejection in the accelerated rejection model. CONCLUSIONS: Presensitization via the transfer of donor splenocytes facilitates the establishment of an accelerated rejection model. Our findings with this model indicate that humoral rejection and cellular rejection are coexistent, and that the proportions of effector memory CD8(+) T cells and plasmacytes in the spleen increase significantly during accelerated rejection.

Kidney transplantation from living related donors aged more than 60 years: a single center experience.

OBJECTIVES: To evaluate whether the outcomes of renal grafts from living related donors more than 60 years old are acceptable, in terms of renal function and patient/graft survival. MATERIAL AND METHODS: Twenty-one patients who received kidneys from donors older than 60 years constituted the study group (Group 1). The control group (Group 2) consisted of 110 patients who received renal transplants from ideal donors, aged 18 to 45 years. The recipients were analyzed for posttransplantation serum creatinine, the number of acute rejection episodes and delayed graft function, and patient/graft survival. RESULTS: The mean age of donors was 62.6 ± 2.2 years in Group 1 and 32.8 ± 7.0 years in Group 2. Recipient serum creatinine was higher on postoperative day 1, year 1, year 5 in Group 1 than that in Group 2 (536.8 ± 203.3 vs. 409.8 ± 213.8, 142.4 ± 38.2 vs. 100.3 ± 22.9, 152.6 ± 42.7 vs. 107.1 ± 22.1, respectively; all p < 0.05). Acute rejection was seen in 4 cases in Group 1 (19.0%) and in 15 cases in Group 2 (13.6%; p = 0.759). Delayed graft function was seen in two cases in Group 1 (9.5%) and in four cases in Group 2 (3.6%; p = 0.540). One-, 3- and 5-year patient survival was 100%, 100% and 100% for Group 1, and 97%, 97% and 97% for Group 2. Corresponding death-censored graft survival was 100%, 100% and 100% for Group 1, and 98%, 98% and 96% for Group 2. No significant difference was observed in terms of patient/graft survival. CONCLUSIONS: Although compromising renal function, donor age did not affect patient and graft survival in the 5-year follow-up in our study. Age alone seems not to be an exclusion criterion to living kidney donation.

Measuring and modelling perceptions of the built environment for epidemiological research using crowd-sourcing and image-based deep learning models.

BACKGROUND: Perceptions of the built environment, such as nature quality, beauty, relaxation, and safety, may be key factors linking the built environment to human health. However, few studies have examined these types of perceptions due to the difficulty in quantifying them objectively in large populations. OBJECTIVE: To measure and predict perceptions of the built environment from street-view images using crowd-sourced methods and deep learning models for application in epidemiologic studies. METHODS: We used the Amazon Mechanical-Turk crowdsourcing platform where participants compared two street-view images and quantified perceptions of nature quality, beauty, relaxation, and safety. We optimized street-view image sampling methods to improve the quality and resulting perception data specific to participants enrolled in the Washington State Twin Registry (WSTR) health study. We used a transfer learning approach to train deep learning models by leveraging existing image perception data from the PlacePulse 2.0 dataset, which includes 1.1 million image comparisons, and refining based on new WSTR perception data. Resulting models were applied to WSTR addresses to estimate exposures and evaluate associations with traditional built environment measures. RESULTS: We collected over 36,000 image comparisons and calculated perception measures for each image. Our final deep learning models explained 77.6% of nature quality, 68.1% of beauty, 72.0% of relaxation, and 64.7% of safety in pairwise image comparisons. Applying transfer learning with the new perception labels specific to the WSTR yielded an average improvement of 3.8% for model performance. Perception measures were weakly to moderately correlated with traditional built environment exposures for WSTR participant addresses; for example, nature quality and NDVI (r = 0.55), neighborhood area deprivation (r = -0.16), and walkability (r = -0.20), respectively. SIGNIFICANCE: We were able to measure and model perceptions of the built environment optimized for a specific health study. Future applications will examine associations between these exposure measures and mental health in the WSTR. IMPACT STATEMENT: Built environments influence health through complex pathways. Perceptions of nature quality, beauty, relaxation and safety may be particularly import for understanding these linkages, but few studies to-date have examined these perceptions objectively for large populations. For quantitative research, an exposure measure must be reproducible, accurate, and precise--here we work to develop such measures for perceptions of the urban environment. We created crowd-sourced and image-based deep learning methods that were able to measure and model these perceptions. Future applications will apply these models to examine associations with mental health in the Washington State Twin Registry.

Improved erectile function and sex hormone profiles in male Chinese recipients of kidney transplantation.

BACKGROUND: Few studies have reported the relationship between duration of dialysis and effect of kidney transplantation on sex hormone levels and erectile dysfunction (ED) in Chinese patients. METHODS: Our study included 24 patients with uremia who underwent kidney transplantation. Erectile function in these patients was assessed using the 5-item version of the International Index of Erectile Function (IIEF-5), and serum sex hormone levels were measured pre- and post-transplantation. Post-transplantation changes in IIEF-5 scores were analyzed according to duration of dialysis. RESULTS: Twenty-one (87.5%) and 11 (45.9%) of the 24 patients suffered from varying degrees of ED during the pre- and post-transplantation periods, respectively. The pre- vs. post-transplantation IIEF-5 scores were significantly different (p < 0.05) among patients who had undergone dialysis for less than six months. Following transplantation, serum levels of prolactin and ß-estradiol decreased significantly (24.35 ± 11.62 vs. 13.93 ± 7.16 ng/mL, p = 0.027; 42.20 ± 15.04 vs. 17.7 ± 7.15 pg/mL, p = 0.000, respectively), whereas levels of testosterone increased (3.07 ± 0.94 vs. 6.54 ± 3.14 ng/mL, p = 0.004). CONCLUSIONS: Successful kidney transplantation can significantly ameliorate ED in Chinese patients, especially in individuals with a shorter time on dialysis. Changes in sex hormone levels may contribute to this improvement in ED.

The role of interleukin-17 in murine cytomegalovirus interstitial pneumonia in mice with skin transplants.

We hypothesized that the T helper (Th)17 response plays an important role in murine cytomegalovirus (MCMV) interstitial pneumonia. BALB/c mice with skin grafts from C57/BJ6 mice were intranasally inoculated with 1.0 × 10(5) PFU MCMV. Lung tissues and skin grafts were histologically evaluated and expression of interleukins (IL)-17, -6 and -8, monocyte chemotactic protein (MCP)-1 and interferon (IFN)-γ in serum and bronchoalveolar lavage (BAL) fluid, intracellular IL-4, -17, and IFN-γ, in spleen lymphocytes were analysed. The levels of IL-17 in the serum and BAL fluid were significantly higher in MCMV-infected mice versus not-infected mice (P = 0.0286 and P = 0.007, respectively) and the BAL levels of IL-17 peaked in 9 days (P = 0.001). The IL-17 level in the BAL was correlated with the grade of lung interstitial inflammation (r = 0.554, P = 0.0144). Serum IFN-γ levels were also higher after infection than that in the not-infected mice (P = 0.0286). IL-17 production increases locally and systemically during MCMV interstitial pneumonia. Neutralization of IL-17 significantly suppressed lung inflammation at day14 as assessed by histology. These findings suggest that IL-17 is important in the pathology of MCMV interstitial pneumonia.