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Understanding the spatial distribution of elephant carcasses in relation to ecological characteristics and human activities is critical to developing targeted management strategies for reducing poaching. We employ a spatial modelling approach to quantify the relative contribution of multiple climatic, ecological, human and protected area management predictors of the number of elephant carcasses in a recognized poaching hotspot: the Ruvuma landscape of northern Mozambique and southern Tanzania. This includes the Niassa Reserve in the south and the Selous Game Reserve in the north. In Mozambique, the number of elephant carcasses is positively associated with State-managed protected areas such as Niassa Reserve, but particularly with environmental variables including low rainfall and high temperatures. In Tanzania, elephant carcasses are positively associated with community-managed sites. A strong focus on effective management of protected areas in the Ruvuma landscape is crucial to reducing the killing of elephants. [ABSTRACT FROM AUTHOR]

Aichi Target 11 (AT11), adopted by 193 Parties to the Convention on Biological Diversity (CBD) in 2010, states that protected areas (PAs) must be equitably managed by 2020. However, significant challenges remain in terms of actual implementation of equitable management in PAs. These challenges include, among others, the lack of a standardized approach to assess and monitor social equity and the difficulty of reducing social equity to a series of metrics. This perspective addresses these challenges and it proposes a minimum set of ten indicators for assessing and monitoring the three dimensions of social equity in protected areas: recognition, procedure and distribution. The indicators target information on social equity regarding cultural identity, statutory and customary rights, knowledge diversity; free, prior and informed consent mechanisms, full participation and transparency in decision-making, access to justice, accountability over decisions, distribution of conservation burdens, and sharing of conservation benefits. The proposed indicator system is a first step in advancing an approach to facilitate our understanding of how the different dimensions of social equity are denied or recognized in PAs globally. The proposed system would be used by practitioners to mainstream social equity indicators in PAs assessments at the site level and to report to the CBD on the ‘equitably managed’ element of AT11. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to determine the distribution of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) promoter region T-275A and C-2152T single-nucleotide polymorphisms (SNPs) in stable transplant patients and to investigate the impact of these SNPs on the evolution of this population after 10 years of follow-up. Methods White renal transplant recipients (n = 873) were studied. The median time of follow-up was 91.8 months (P25–75 46–146). Amplification with specific “primers” to delimit the study area was performed for each polymorphism. Amplification was performed with the use of real-time polymerase chain reaction. Results T-275A promoter mutation was detected in 13% of patients and C-2152T in 12% of patients. Survival analysis was performed on 873 renal transplants, carried out between 2004 and 2013. We found a higher frequency of death from cancer among polymorphism carriers ( P = .001). Conclusions It appears that carriers of T-275A and C-2152T SNPs of the UGT1A9 gene promoter region show a greater incidence of death from cancer, with a significantly higher cumulative incidence of death from gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

Abstract: In this paper the numerical solution of a highly nonlinear model for the thermomechanical behavior of polythermal glaciers is presented. The modeling follows the shallow ice approximation (SIA) for glaciers introduced in Fowler (1997) . The model has been extended to incorporate additional moving boundaries and other nonlinear features. Moreover, a fixed domain formulation is proposed to avoid the computational drawbacks of a time-dependent domain in the numerical simulation with front tracking methods. In this setting, the coupled problem is decomposed into different nonlinear problems which allow one to obtain sequentially the profile evolution, the velocity field, the glacier surface and atmospheric temperatures, basal magnitudes and the temperature distribution inside the ice mass. A fixed point iteration algorithm converges to the solution of the nonlinear coupled problem. Among different numerical methods involved in the solution of the subproblems, characteristic schemes for time discretization, finite elements for spatial discretization, duality methods for the nonlinearities associated to maximal monotone operators and a Newton scheme for the nonlinear viscous term are proposed. Several numerical simulation examples illustrate the performance of the numerical methods and the behavior of the involved physical magnitudes. [Copyright &y& Elsevier]

Abstract: We compared the response to repeated social defeat in rats selected as high (HR) and low (LR) responders to novelty. In experiment 1, we investigated the behavioral and neuroendocrine effects of repeated social defeat in HR-LR rats. By the last defeat session, HR rats exhibited less passive-submissive behaviors than LR rats, and exhibited higher corticosterone secretion when recovering from defeat. Furthermore, in the forced swim test, while HR defeated rats spent more time immobile than their undefeated controls, LR rats'' immobility was unaffected by defeat. In experiment 2, we compared the effects of repeated social defeat on body, adrenal, thymus, and spleen weights in HR-LR rats; moreover, we compared the effects of repeated social defeat on stress related molecules gene expression in these two groups of rats. Our results show that HR rats exhibited a decrease in thymus weight after repeated social defeat that was not present in LRs. Analyses of in situ hybridization results found HR-LR differences in 5-HT2a mRNA levels in the parietal cortex and 5-HT1a mRNA levels in the dorsal raphe. Moreover, LR rats had higher glucocorticoid receptor (GR) mRNA expression than HR rats in the dentate gyrus, and repeated social defeat decreased this expression in LR rats to HR levels. Finally, hippocampal mineralcorticoid receptor (MR)/GR ratio was reduced in HR rats only. Taken together, our results show a differential response to social defeat in HR-LR rats, and support the HR-LR model as a useful tool to investigate inter-individual differences in response to social stressors. [Copyright &y& Elsevier]

The here presented GLAciology NUmerical SImulation Toolbox (GLANUSIT) is a software application which provides a user friendly environment for the numerical simulation of large ice masses evolution. The graphical user interface has been developed in MATLAB while the core of GLANUSIT contains the original FORTRAN codes, which develop the specific numerical methods for the solution of the complex shallow ice model. This highly nonlinear model governs the coupled thermodynamical and hydrodynamical processes. The global algorithm mainly consists on a fixed point iteration between the different subproblems. The numerical solution of each subproblem requires specific techniques, which are not common in present software packages, as for example the part of moving boundaries solvers included in the code. Finally, a practical case study with real data is presented. [Copyright &y& Elsevier]

This work deals with the numerical solution of a complex mathematical model arising in theoretical glaciology. The global moving boundary problem governs thermomechanical processes jointly with ice sheet hydrodynamics. One major novelty is the inclusion of the ice velocity field computation in the framework of the shallow ice model so that it can be coupled with profile and temperature equations. Moreover, the proposed basal velocity and shear stress laws allow the integration of basal sliding effects in the global model. Both features were not taking into account in a previous paper (Math. Model. Methods Appl. Sci. 12 (2) (2002) 229) and provide more realistic convective terms and more complete Signorini boundary conditions for the thermal problem. In the proposed numerical algorithm, one- and two-dimensional piecewise linear Lagrange finite elements in space and a semi-implicit upwinding scheme in time are combined with duality and Newton''s methods for nonlinearities. A simulation example involving real data issued from Antarctic shows the temperature, profile and velocity qualitative behaviour as well as the free boundaries and basal effects. [Copyright &y& Elsevier]

Abstract: Introduction: The incidence of candiduria in renal transplant recipients is unknown. In clinical practice, the indications for antifungal therapy are not well established. Furthermore, there is the problem of the choice of the antifungal drug since some of them may select resistant Candida species, or interact with immunosuppressive agents or only be used intravenously. Aim: We sought to study the incidence, clinical repercussions and effectiveness of antifungal treatment to prevent recurrence of candiduria. Materials and methods: We examined all episodes of Candida-positive urine cultures (>50,000 cfu/mL) in 996 recipients over 2 years. We considered the Candida species, administered treatment, presence of fever, requirement for hospital admission versus outpatient case, occurrence of simultaneous bacterial urinary tract infection (UTI), antibiotic use during the week before candiduria, and presence of an indwelling urinary catheter. Results: Among 996 subjects, 34 displayed 83 episodes of candiduria, yielding an accumulated incidence of 3.4% after 2 years. The frequency was higher among women (6.3% vs 1.7%, P < .001). Of the 45 outpatient episodes (54.2%), 17 were treated and one required hospitalization (5.9%). Of the 28 nontreated outpatients, two were hospitalized (7.1%, P = .68 vs treated patients). All cases of hospital admission presented simultaneous bacterial UTI, none developed candidemia, and two patients did not receive any antifungal therapy. With respect to the first episodes of each patient (n = 34), 5/11 treated (45.5%) and 4/23 untreated (17.4%) patients developed recurrences (P = .095). Selection of more resistant Candida species was not observed. Fifty cases (60%) were associated with antibiotic therapy and 34 (41%) the presence of a urinary catheter. Conclusions: It does not seem necessary to treat candiduria in this setting. Antifungal therapy was not associated with either a reduction in recurrence or the appearance of more resistant species in this study. We observed no important clinical repercussions. [Copyright &y& Elsevier]

Abstract: Introduction: mTOR inhibitors (imTOR) are immunosuppressive drugs that have a concentration-related effects on hematopoiesis, potentially resulting in anemia. The reason is uncertain, but a pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we studied whether everolimus influenced iron homeostasis. Methods: We studied iron homeostasis in 43 patients after late introduction of everolimus into the immunosuppressive treatment. Thirty-seven patients (86%) were receiving mycophenolate. Hemoglobin concentration, red blood cell count, mean corpuscular volume, serum iron, ferritin, C-reactive protein levels, and transferrin saturation were evaluated 3 months before and 1, 3, and 6 months after the switch. Results: The percentage of anemic patients preconversion was 18.6% and it was 34.9% at 3 months and 18.6% at 6 months. We did not observe a significant reduction in hemoglobin, but there was increased red blood cell count after everolimus introduction, with a significant reduction in mean corpuscular volume. Serum iron and transferrin saturation levels were also markedly reduced after the switch, while ferritin serum concentrations remained stable. An improvement in renal function was observed. Conclusions: The anemia caused by everolimus—microcytosis, low serum iron, despite high ferritinemia, and elevated C-reactive protein levels—was consistent with the anemia of a chronic inflammatory state. This alteration occurred within the first months postconversion and disappeared at 6 months. The combination of mycophenolate and everolimus seemed to be useful without significant secondary effects. [Copyright &y& Elsevier]

Abstract: Introduction: Enteric-coated mycophenolate sodium (EC-MPS) is the enteric-coated salt form of mycophenolic acid (MPA), the active component of the prodrug mycophenolate mofetil. EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. There are no studies available comparing trough plasma levels in patients with GI intolerance to MMF when they are converted to EC-MPS. Aim: To compare the GI tolerance and the MPA levels in patients previously treated with MMF in whom this drug was replaced by EC-MPS. Materials and methods: A prospective study was conducted in 133 renal transplant patients after conversion from MMF to EC-MPS (median time posttransplant 42 months, range 1 to 240 months). The causes for EC-MPS switching were GI intolerance to MMF (51.9%; group A), low trough plasma levels with MMF (29.3%; group B), and others (18.8%; group C). These patients were converted to equipotent doses of EC-MPS. Results: The trough plasma MPA levels increased from 1.5 ± 1.1 μg/mL at baseline to 2.5 ± 2.0 μg/mL at 1 month postconversion despite the equipotent EC-MPS doses not being increased. These higher plasma levels were maintained throughout the study. In group A, this increase was from 1.8 ± 1.0 to 2.7 ± 2.1 μg/mL (P = .01) and in group B from 0.8 ± 0.4 to 2.4 ± 1.4 μg/mL (P < .001). The doses and levels of calcineurin inhibitor decreased from baseline. Creatinine clearance improved from 56.5 ± 24.7 mg/dL at baseline to 61.9 ± 28.6 at 6 months postconversion (P = .02). There was a statistically significant increase in hemoglobin levels. In group A, the GI tolerance improved in 78% of the patients. Conclusions: At equipotent doses, patients converted to EC-MPS have higher and more adequate levels of MPA. At 6 months postconversion, we observed an improvement of the renal function, probably due to a reduction of calcineurin inhibitor drugs. However, the possibility that a better immunosuppressive efficacy as demonstrated by more suitable trough plasma levels may have been a contributing factor cannot be discarded. [Copyright &y& Elsevier]

Abstract: The introduction of mycophenolate mofetil (MMF) was an important advance in immunosuppressive therapy, although its use is limited by adverse gastrointestinal events. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed to avoid these side effects. Recent clinical trials have demonstrated that EC-MPS is a safe drug in both de novo and maintenance renal transplant patients. In this prospective study, therapeutically equivalent doses of EC-MPS were administered to 39 stable kidney transplant patients receiving MMF. After 3 months of treatment with EC-MPS the incidence of adverse gastrointestinal events was lower (15.8% of the patients). There were higher levels of mycophenolic acid after conversion to EC-MPS, probably due to better absorption. These factors allowed decreased doses and levels of calcineurin inhibitors without increasing the risk of graft rejection. At 3 months postconversion, serum creatinine improved from the mean baseline value of 1.83 ± 0.12 mg/dL to 1.70 ± 0.10 mg/dL. In conclusion, EC-MPS was well tolerated in maintenance renal transplant patients with adverse gastrointestinal events secondary to MMF. [Copyright &y& Elsevier]

Background Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or humoral rejection (AHR) has dissimilar outcomes. The aim of this study was to examine the association between subtypes of AVR and graft loss. Methods We assessed patients who provided biopsy samples for acute allograft rejection from 1998 to 2014. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology as well as donor-specific anti-HLA antibodies when available. Results A total of 1,004 patients were biopsied and included in the main analyses, of which 259 (32.87%) had acute biopsy-proven rejection. We identified three patterns of graft rejection defined according to the presence of peritubular capillaritis (ptc): a) T-cell–mediated acute vascular rejection if ptc free; b) humoral-mediated acute vascular rejection if ptc >0; and c) T-cell–mediated rejection if vasculitis = 0 and ptc = 0 (148 [57%], 70 [27%], and 41 [16%], respectively). At 5 years, graft survival was lower among patients with ptc-vascular rejection than those with T-cell vascular rejection (72.3% vs 83.2%; P = .010). T-cell–mediated rejection without vasculitis had similar survival compared with rejection absence (89.3% vs 8 9.2%; P = .698). Multivariate analysis adjusted by age and sex showed that risk of graft loss was higher in biopsies with high scores of glomerulitis (g2-g3); vasculitis (v2-v3), capillaritis (ptc2-ptc3), or interstitial inflammation (i2-i3). However, tubulitis and C4d were not statically significant. Conclusions We conclude that antibody-mediated AVR involves a poorer prognosis than T-cell–mediated AVR. The presence of tubulitis does not seem to determine a poor long-term renal graft prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Persistence of inappropriately high serum levels of fibroblast growth factor-23 (FGF23), a recently discovered phosphaturic hormone, has been reported to play an important role in the pathogenesis of posttransplant hypophosphatemia. The aim of the present study was to evaluate FGF23 in the early posttransplant period and study the complex associations between FGF23, parathyroid hormone (PTH), 1,25(OH)2 vitamin D, and phosphate in transplant patients. Materials and methods: We performed a cross-sectional observational study of 42 adult kidney recipients in the early posttransplant period (<6 months). Fasting serum samples and 24-hour urine samples were collected during a routine follow-up outpatient visit. Serum creatinine, calcium, phosphate, magnesium and urinary creatinine, calcium, magnesium, and phosphate were measured using standard assays. We also studied concentrations of 25 hydroxyvitamin D, 1,25(OH)2 vitamin D, intact PTH, and circulating FGF23. Results: Median values for the different parameters studied were as follows: 9.9 ± 0.6 mg/dL, phosphatemia 3.3 ± 0.7 mg/dL, estimated glomerular filtration rate (eGFR; 41.1 ± 14.0 mL/min, phosphate reabsorption rate 68.4% ± 10.7%, PTH 94.5 ng/L (53.8–199.5), calcitriol 33.0 pg/mL (24.0–44.1), calcidiol 27.3 ng/mL (17.0–38.0), FGF23 139 pg/mL (88–221), and calciuria 62.5 mg/d (40.3–101.3). The variables significantly associated with serum FGF23 levels were phosphate reabsorption rate (r = .493; P = .001), calcitriol (r = .399; P = .009), eGFR (r = .557; P < .001), PTH (0.349; P = .024). Conclusions: Elevated serum levels of FGF23 could explain the deficiency of calcitriol and elevated renal phosphorus wasting in the early posttransplant period. All treatments that can lead to increased serum phosphate levels (eg, oral medication or calcitriol) should be carefully evaluated, since increased phosphatemia could further stimulate secretion of FGF23 and prolong high phosphorus loss. [Copyright &y& Elsevier]

Abstract: Objectives: We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. Methods: We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. Results: Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P = .004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P = .035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. Conclusion: There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of these entities, which are related to poor cardiovascular outcomes. [Copyright &y& Elsevier]

Abstract: Everolimus has recently been introduced into clinical practice with promising perspectives due to its efficacy, lack of nephrotoxicity, and antitumor effects. Experience in clinical trials associated with low-dose cyclosporine showed good results, but there is almost no experience in calcineurin inhibitor (CNI) elimination learning it as the primary immunosuppressant. We describe our experience in a series of 78 stable renal transplant patients who were switched to Everolimus with complete and quick elimination of the CNI: the procedure of conversion, pharmacokinetic results after conversion, evolution of renal parameters (renal function, proteinuria, and others), and safety data (acute rejection and adverse events). An initial dose of 3 mg/d was adequate to obtain the recommended trough levels between 5 and 10 ng/mL. Our results demonstrated that conversion to Everolimus was a simple, safe procedure that must be considered in patients CNI toxicity, especially those with malignant neoplasms and progressive deterioration of renal function due to chronic allograft nephropathy. [Copyright &y& Elsevier]

Abstract: Disseminated varicella-zoster virus (VZV) infection in adult renal allograft recipients is a rare but potentially fatal illness. We retrospectively collected the cases of VZV infection that occurred in 812 adult renal transplant recipients, performed between 1995 and 2004 at our institution. Eight patients developed varicella (1%), seven men and one woman. The overall median age was 38 years (range = 31 to 64). The median time from transplantation to infection was 32 months (range = 2 to 92). Four cases were primary infections and four disseminated VZV reactivations. Immunosuppression consisted of prednisone (PDN) + cyclosporine (CSA) + mycophenolate (MF; n = 4); PDN + CSA + azathioprine (n = 1); PDN + tacrolimus (FK) + MF (n = 1); FK + MF (n = 1); PDN + rapamycin + MF (n = 1). Seven patients (87%) required hospital admission for a median duration of 11 days (range = 3 to 21). Four patients were previously diagnosed with chronic hepatitis virus infection: two type B (HBV) and two type C (HCV). The last cohort required longer admission than the negative patients (11.5 ± 3 vs 7.5 ± 9 days; P = .1). The only clinical manifestation in four patients was general malaise, fever, and a disseminated vesicular rash; the other four patients also showed visceral involvement: two pneumonitis, one hepatitis, and thrombotic microangiopathy, and one developed multiorgan failure and died due to a delayed diagnosis in a patient positive for HBVs. The diagnosis was established according to the symptoms, IgG-IgM seroconversion and VZV polymerase chain reaction quantification in vesicle contents. Treatment consisted of reduced immunosuppression, antiviral drugs (acyclovir or gancyclovir), and in six patients, a varicella-zoster immunoglobulin dose. We concluded that varicella infection in adult renal allograft recipients is unusual but highly morbid. A vaccination program in seronegative pretransplant candidates should be attempted. Early diagnosis and treatment may improve the prognosis. Although further studies are required, chronic HBV or HCV infection seemed to be a risk factor for the disease. [Copyright &y& Elsevier]

Abstract: Background: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). Aim: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. Patients and Methods: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 ± 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. Results: The types of donors in both groups were: non–heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 ± 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 ± 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 ± 0.2 in the preemptive group versus 1.7 ± 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. Conclusion: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes. [Copyright &y& Elsevier]

Background Renal transplantation has been established as the treatment of choice for end-stage renal disease (ESRD) due to diabetic nephropathy. This study aimed to investigate the risk factors for recurrence of diabetic nephropathy (RDN) in renal allografts. Methods We studied 1,011 renal transplant patients from 1986 to 2003, of which 95 had ESRD due to diabetic nephropathy. We retrospectively analyzed the clinical characteristics and outcomes of RDN after renal transplantation. Results Of the 95 recipients with ESRD due to diabetic nephropathy, 41 developed RDN and 11 of those 41 underwent graft biopsy. The mean durations from transplantation to RDN and to renal replacement therapy was 81.58 months (range, 54–120 mo), and 109.66 months (range, 27–188.4 mo), respectively. At 5 years, treatment on statins and renin-angiotensin-aldosterone system (RAAS) blockers were associated with a higher survival free from RND (82.2% vs 63.2% [ P = .070] and 100% vs 80% vs 0.6% [ P = .013], respectively). Compared with cyclosporine, tacrolimus was associated with a higher risk for RND (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.75–5.13; P = .047). High doses of prednisone (>0.06 mg/kg) were also associated with a higher risk of RDN (OR, 3.03; 95% CI, 1.19–8.30; P = .029). The combination of calcineurin inhibitor and mammalian target of rapamycin inhibitor (mTORi) demonstrated the highest risk of RDN (OR, 14.08; 95% CI, 3.72–53.29; P < .01). Conclusions Treatment with tacrolimus and mTORi is the most diabetogenic immunosuppressive regimen. Treatment with tacrolimus entails a greater risk of RDN than with cyclosporine. The administration of statins or RAAS blockers could delay the progression of RDN. [ABSTRACT FROM AUTHOR]

Abstract: To date there is a substantial experience with rapamycin conversion in stable renal transplant recipients with respect to the procedure of conversion, initial doses, and target blood levels as well as adverse events, but in the case of Everolimus there is almost no experience with conversion and calcineurin inhibitor (CNI) withdrawal. We describe an initial experience among 32 renal transplant recipients who were converted to Everolimus with complete suspension of CNI in two Spanish transplant centers. Our results emphasised the procedure for conversion, the target levels, the adverse events, and the initial efficacy, over the first month after conversion. Our conclusions were that conversion from CNI to Everolimus was a simple, safe procedure with a predictable profile of adverse events, which were, in general, of mild intensity. There was a good correlation between initial dose and blood level. Initial doses of about 3 mg/d combined with rapid reduction in CNI exposure seemed to be adequate. The target range levels between 5 and 10 ng/mL seemed to be sufficient for complete CNI elimination, especially in patients also receiving antiproliferative drugs (such as mycophenolate mofetil or azathioprine) in whom levels near the lower end of the range might be adequate. [Copyright &y& Elsevier]

Abstract: Background: Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) is an option for renal transplant patients who develop a tumor. This strategy, however, may be associated with an increased risk of rejection. Aim: We sought to evaluate a series of renal transplant patients who underwent conversion from CNI to SRL because they developed a tumor during the posttransplant period. Methods: This prospective study of 29 patients included 2 patients with skin cancer (1 melanoma and 1 squamous cell carcinoma) and 27 patients who developed other tumors: lung (n = 6), prostate (n = 4), lymphoma (n = 2), colon adenocarcinoma (n = 2), kidney (n = 2), Kaposi sarcoma (n = 2), urothelium (n = 1), parotid (n = 1), larynx (n = 1), gastric (n = 1), breast (n = 1), tongue (n = 1), liver (n = 1), xanthoastrocytoma (n = 1), and aggressive angiomyxoma of the perineum (n = 1). Results: CNI were withdrawn in 28 patients and reduced in the remaining patient. Renal function was better when CNI were rapidly or abruptly suspended, with maintenance of cyclosporine (CsA) + SRL for more than 3 months being especially detrimental. Proteinuria worsened in patients whose preconversion levels were >0.5 g/d, particularly those treated with CsA. There was no episode of rejection. Conclusions: SRL is a promising option for the management of posttransplant tumors. The switch in immunosuppression should be undertaken quickly, especially in patients under treatment with CsA. [Copyright &y& Elsevier]

Abstract: Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 ± 4.3 vs 59.8 ± 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 ± 4.6 vs 68.4 ± 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation. [Copyright &y& Elsevier]

Neuroticism has frequently been associated with Chronic Fatigue Syndrome (CFS). Other studies have shown that CFS patients are less extraverted than non-CFS patients, although the results are inconsistent. The objective of this study is twofold: To assess the personality profile of adults with CFS under the AFFM and to test the discriminant validity of the ZKPQ. The CFS group consisted of 132 consecutive patients. A cross-validation procedure, using logistic regression, was executed. Low levels on Activity and high on Neuroticism-Anxiety showed the best discriminant capacity between CFS and controls. The results of this study are concordant with previous literature on the relevance of Neuroticism in CFS characterization, but it extends the scarce existing literature in a significant manner in relation to the Activity trait. For a better conceptualization of this medical condition, we encourage researchers to take into account the facets of Extraversion rather than the dimension itself. [ABSTRACT FROM AUTHOR]