Transcultural adaptation and validation of IMPACT-III and IMPACT-III-P in Spanish families: a multicenter study from SEGHNP.

IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform a transcultural adaptation and validation for the Spanish context. Translation, back-translation, and evaluation of the questionnaires were performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett's sphericity test (p-value < 0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser's criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, and CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92). CONCLUSION: The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families. WHAT IS KNOWN: • IMPACT-III and parent-proxy IMPACT-III (IMPACT-III-P) are useful questionnaires for assessing health-related quality of life (HRQoL) in pediatric inflammatory bowel disease (p-IBD) patients and their parents/caregivers and have been translated and validated in several countries. • To date, no transcultural adaptation and validation of these questionnaires have been published for Spanish patients with p-IBD and their families. WHAT IS NEW: • This is the first transcultural adaptation and validation of IMPACT-III and IMPACT-III-P for Spanish p-IBD families. • These are valid and reliable instruments for assessing HRQoL in Spanish families of patients with p-IBD.

A sustainable approach for cotton bioscouring: reuse of the pectate lyase containing treatment bath.

Enzymatic scouring of cotton has established itself (slowly) as a green alternative to alkaline scouring in the textile industry, mostly due to more environmentally friendly processing at lower pH and temperatures and its less aggressive action on the cotton fibers. However, among other limitations, enzyme costs have contributed to impeding its wide acceptance and use. For the first time, in this study, the recycling of the bioscouring bath was evaluated, unlike most current bioscouring that is performed using fresh enzyme solution. Bioscouring of raw knitted cotton fabric was carried out for 30 min with a commercial pectinase (BioPrep® 3000L) at 55 °C and pH 8.5. About 89% of the recovered pectate lyase-containing scouring bath was completed with 11% of fresh enzyme solution and reused in a new bioscouring process under the same conditions. Up to ten reuse cycles were possible maintaining the level of pectin removal and without significant loss in quality of subsequent dyeing. A detailed analysis of the pretreated fabrics is presented. Reusing the scouring bath, reducing the intensive consumption of input materials (enzyme, water, and chemicals) and wastewater generation can be possible, making bioscouring a more attractive and sustainable technique. The process demonstrated is promising and its industrial application is feasible.

Urinary Plasminogen Activator Inhibitor-1: A Biomarker of Acute Tubular Injury.

INTRODUCTION: Acute kidney injury (AKI) is a threatening, multiaetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events underlying each case, which limits personalized and optimized handling. Therefore, a pathophysiological diagnosis based on new urinary biomarkers is sought for practical (readiness and noninvasiveness) and conceptual reasons, as the urine is a direct product of the kidneys. However, biomarkers found in the urine may also have extrarenal origin, thus conveying pathophysiological information from other organs or tissues. Urinary plasminogen activator inhibitor-1 (PAI-1) has been associated to AKI, although its origin and traffic to the urine are not known. METHODS: Herein, we studied the blood or renal origin of urinary PAI-1 (uPAI-1) in experimental AKI in Wistar rats, by means of the in situ renal perfusion method. For this purpose, urine was collected while the kidneys of rats with AKI showing increased uPAI-1 excretion, and controls, were in situ perfused with a saline solution. RESULTS: Our results show that during perfusion, PAI-1 remained in the urine of AKI rats, suggesting that renal cells shed this protein directly to the urine. PAI-1 is also significantly increased in the urine of AKI patients. Its low correlation with other urinary markers such as NGAL or NAG suggests that PAI-1 provides complementary and distinct phenotypical information. CONCLUSION: In conclusion, uPAI-1 is a biomarker produced by damaged kidneys following AKI, whose precise pathophysiological meaning in AKI needs to be further investigated.

Secondary antibody deficiency is associated with development of infection in kidney transplantation: Results of a multicenter study.

BACKGROUND: We performed a multicenter study to assess the association between secondary antibody deficiency (immunoglobulin G [IgG] hypogammaglobulinemia combined with low levels of specific antibodies) and development of infection in kidney transplantation. METHODS: We prospectively analyzed 250 adult kidney recipients at four centers. The assessment points were before transplantation and 7 and 30 days after transplantation. The immune parameters were as follows: IgG, IgA, and IgM and complement factors C3 and C4 tested by nephelometry; specific IgG antibodies to cytomegalovirus (CMV) and IgG and IgG2 antibodies to pneumococcal polysaccharide (anti-PPS) determined using enzyme-linked immunosorbent assay. The clinical follow-up period lasted 6 months. The clinical outcomes were CMV disease and recurrent bacterial infections requiring antimicrobial therapy. STATISTICS: Multivariate logistic regression. RESULTS: At day 7, IgG hypogammaglobulinemia (IgG levels < 700 mg/dL) combined with low IgG anti-CMV antibody titers (defined as levels < 10 000 units) was present in 12% of kidney recipients. IgG hypogammaglobulinemia combined with low IgG anti-PPS antibody titers (defined as levels < 10 mg/dL) at 1 month after kidney transplantation were recorded in 16% of patients. At day 7 the combination of IgG hypogammaglobulinemia and low anti-CMV titers was independently associated with the development of CMV disease (odds ratio [OR], 6.95; 95% confidence interval [CI], 1.17-41.31; P = .033). At day 30 after transplantation, the combination of IgG < 700 mg/dL and IgG anti-PPS < 10 mg/dL, was independently associated with recurrent bacterial infection (OR, 5.942; 95% CI, 1.943-18.172; P = .002). CONCLUSION: In a prospective multicenter study, early immunologic monitoring of secondary antibody deficiency proved useful for the identification of kidney recipients who developed severe infection.

Management of small intestinal bacterial overgrowth by pediatric gastroenterologists in Spain.

BACKGROUND: small intestinal bacterial overgrowth (SIBO) is a heterogeneous condition with nonspecific symptoms. This study aimed to report its management by pediatric gastroenterologists in Spain. METHODS: a descriptive study was performed by means of a survey sent to 184 active members of the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP). RESULTS: one hundred and forty-eight responses (80.4 %) were received. Forty-four patients had no predisposing condition, 31.1 % used antibiotics followed by probiotics, 33.1 % antibiotherapy concomitant with probiotics, 24.3 % only antibiotics and 10.8 % only probiotics. The diagnosis was established via clinical parameters in 73.8 % of participants and the therapeutic response was checked only by clinical data in 90 %. CONCLUSIONS: there is high variability in the management of SIBO among pediatric population in Spain.

Simulating Nonlinear Dynamics of Collective Spins via Quantum Measurement and Feedback.

We study a method to simulate quantum many-body dynamics of spin ensembles using measurement-based feedback. By performing a weak collective measurement on a large ensemble of two-level quantum systems and applying global rotations conditioned on the measurement outcome, one can simulate the dynamics of a mean-field quantum kicked top, a standard paradigm of quantum chaos. We analytically show that there exists a regime in which individual quantum trajectories adequately recover the classical limit, and show the transition between noisy quantum dynamics to full deterministic chaos described by classical Lyapunov exponents. We also analyze the effects of decoherence, and show that the proposed scheme represents a robust method to explore the emergence of chaos from complex quantum dynamics in a realistic experimental platform based on an atom-light interface.

Comparison of Assays for the Diagnosis of Mycoplasma genitalium and Macrolide Resistance Mutations in Self-Collected Vaginal Swabs and Urine.

BACKGROUND: The objective was to compare commercial assays on clinical specimens for Mycoplasma genitalium (MG) detection and macrolide resistance mutation (MRM) frequency. METHODS: Three self-collected vaginal swabs (VS) and a first-void urine (FVU) from 300 consented women were tested by Aptima MG (AMG), ResistancePlus MG (RPMG) and Seeplex STD6 ACE (STD6) for detection of MG. Aptima MG and STD6 MG positives were tested for MRM using MG 23S rRNA polymerase chain reaction with Sanger sequencing (23SMGSS) compared with MRM determination in the RPMG assay. Unique AMG positives were tested with confirmatory Aptima assays. RESULTS: M. genitalium prevalence ranged from 7.1% to 19.7%, influenced by the assay used and the specimen tested. Overall agreements for MG detection were 96.3% (κ = 0.91) for VS and 93.3% (κ = 0.72) for FVU between AMG and RPMG with lower agreements with STD6. Using a rotating reference standard, sensitivities on VS and FVU were 100% and 100% for AMG, 100% and 83.3% for RPMG, and 54.2% and 48.4% for STD6. Specificities were high for RPMG and STD6 and AMG detected extra positives, most of which were confirmed. Macrolide resistance mutation frequency rates testing VS and FVU were 50% (24/48) and 58.1% (18/31) by RPMG compared with 52.5% (31/59) and 23.5% (12/51) by 23SMGSS. MRM overall agreements between RPMG and 23SMGSS were 73.2% (κ = 0.41) for VS and 76.0% (κ = 0.52) for FVU. CONCLUSIONS: Aptima MG detected more cases of MG infections. ResistancePlus MG detection was more effective on VS than on FVU. Seeplex STD6 ACE performance was inferior. The MRM detection component of RPMG agreed with results from 23SMGSS most of the time.

In vitro susceptibility of microorganisms isolated from cold stored corneas: increased gentamicin-resistance in cornea banking.

Donor cornea contamination is one of the major risks for corneal transplants. The use of antibiotics in storage media remains as one of the most important security measurements to minimize the contamination risk in corneal preservation. Since antibiotic resistance among microorganisms have been rising gradually, it is important to gain knowledge about the antimicrobial susceptibility pattern for choosing the most suitable antimicrobial agents. Thus, we evaluated the in vitro susceptibility of microorganisms isolated in donor corneas processed at the Center for Blood Transfusion, Tissues and Cells (Córdoba, Spain) during 4 years in order to evaluate the efficiency, and to promote changes for further antibiotics use. Our results show the high rate of resistance to gentamicin, an antibiotic used in corneal preservation media such as Optisol GS and Eusol-C. Conversely, all the analyzed microorganisms were sensitive to vancomycin. This suggests the possibility of replacing gentamicin with another more effective antibacterial agent such as vancomycin.

Brain Electrical Activity Associated With Visual Attention and Reactive Motor Inhibition in Patients With Fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a generalized chronic pain condition associated with multiple cognitive impairments, including altered inhibitory processes. Inhibition is a key component of human executive functions and shares neural substrate with pain processing, which may explain the inhibitory deficits in FM. Here, we investigated the integrity of brain inhibitory mechanisms in these patients. METHODS: We recorded the electroencephalographic activity of 27 patients with FM and 27 healthy controls (HCs) (all women) while they performed a reactive motor inhibition task (the stop-signal paradigm). We analyzed task-induced modulations in electrophysiological markers related to inhibition (N2, P3, and midfrontal theta oscillations) and visual attention (posterior alpha oscillations). RESULTS: The FM group performed the task correctly, with no differences relative to HCs at the behavioral level. We did not find any between-group differences in N2 amplitude (F(1,52) = 0.01, p = .93), P3 amplitude (F(1,52) = 3.46; p = .068), or theta power (F(1,52) = 0.05; p = .82). However, modulation of posterior alpha power after presentation of either the go or stop stimuli was lower in patients than in HCs (F(1,52) = 7.98; p = .007). CONCLUSIONS: N2, P3, theta power, and behavioral results indicate that the mechanisms of motor inhibition are sufficiently preserved to enable correct performance of the stop-signal task in patients with FM. Nevertheless, the lower modulation of alpha suggests greater difficulty in mobilizing and maintaining visual attentional resources, a result that may explain the cognitive dysfunction observed in FM.

Mycoplasma genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae Detected With Aptima Assays Performed on Self-Obtained Vaginal Swabs and Urine Collected at Home and in a Clinic.

Self-obtained vaginal swabs, first-void urine and pooled specimens were collected at home and in a clinic. Percent prevalence and collection site concordance was 30.3 and 100 for Mycoplasma genitalium (74.4% azithromycin resistant) 15.1 and 96.7 for Chlamydia trachomatis and 6.6 and 100 for Neisseria gonorrhoeae (27% ciprofloxacin-resistant).

CCL20 blockade increases the severity of nephrotoxic folic acid-induced acute kidney injury.

The chemokine CCL20 activates the CCR6 receptor and has been implicated in the pathogenesis of glomerular injury. However, it is unknown whether it contributes to acute kidney injury (AKI). We identified CCL20 as upregulated in a systems biology strategy combining transcriptomics of kidney tissue from experimental toxic folic acid-induced AKI and from stressed cultured tubular cells and have explored the expression and function of CCL20 in experimental and clinical AKI. CCL20 upregulation was confirmed in three models of kidney injury induced by a folic acid overdose, cisplatin or unilateral ureteral obstruction. In injured kidneys, CCL20 was expressed by tubular, endothelial, and interstitial cells, and was also upregulated in human kidneys with AKI. Urinary CCL20 was increased in human AKI and was associated with severity. The function of CCL20 in nephrotoxic folic acid-induced AKI was assessed by using neutralising anti-CCL20 antibodies or CCR6-deficient mice. CCL20/CCR6 targeting increased the severity of kidney failure and mortality. This was associated with more severe histological injury, nephrocalcinosis, capillary rarefaction, and fibrosis, as well as higher expression of tubular injury-associated genes. Surprisingly, mice with CCL20 blockade had a lower tubular proliferative response and a higher number of cells in the G2/M phase, suggesting impaired repair mechanisms. This may be related to a lower influx of Tregs, despite a milder inflammatory response in terms of chemokine expression and infiltration by IL-17+ cells and neutrophils. In conclusion, CCL20 has a nephroprotective role during AKI, both by decreasing tissue injury and by facilitating repair. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Urinary Meatal Swabbing Detects More Men Infected With Mycoplasma genitalium and Four Other Sexually Transmitted Infections Than First Catch Urine.

Urinary meatal swabs compared with urine showed higher infection rates for Mycoplasma genitalium (15.3% vs 12.6%, P = 0.035), Chlamydia trachomatis (11.3% vs 9.3%, P = 0.039), Neisseria gonorrhoeae (1.4% vs 1.1%, P = 1.00), Trichomonas vaginalis (8.0% vs 1.7%, P < 0.001), and high-risk human papillomavirus (5.9% vs 3.4%, P = 0.078) respectively.

Comparison of cobas 4800, m2000, Viper XTR, and Infinity 80 Automated Instruments When Processing Urine Specimens for the Diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae.

OBJECTIVES: North American and European advisory groups recommend testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) with nucleic acid amplification tests. Testing is often performed on automated instruments. The objectives of this study were to process urines for the diagnosis of CT and NG and to examine workflow procedures and outcomes. METHODS: While processing 1, 24, 48, 96, and 192 urine specimens on 3 batch-mode systems which use 96-well plates: cobas 4800, m2000, and Viper XTR and the random access cartridge testing GeneXpert Infinity 80, we measured assay performance, hands-on time for processing and maintenance, reagents and plastics consumption, time required to obtain results, and testing accuracy. RESULTS: The Infinity 80 required the least hands-on time for single specimens and smaller batches, whereas the Viper XTR and m2000 required the most hands-on time for all batch sizes. Cumulative daily, weekly, and monthly maintenance was highest for the Viper XTR and lowest for Infinity 80. All batch-mode instruments consumed large amounts of disposables. Time to results was shortest for the Infinity 80, and the Viper XTR provided the shortest time for the batch-mode instruments. All systems showed similar diagnostic accuracy. CONCLUSIONS: Because detection performances were similar, issues of hands-on time, maintenance, time to results, and consumables are important operational factors for the diagnosis and treatment of CT/NG infections.

PET and MRI detection of early and progressive neurodegeneration in spinocerebellar ataxia type 36.

BACKGROUND: The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans. METHODS: Twenty SCA36 patients underwent a study consisting of FDG-PET and MRI scans. Clinical motor evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA). FDG-PET was carried out using a voxel-by-voxel and region-of-interest analysis. MRI evaluation was based on visual inspection and volumetric analysis. RESULTS: SARA ranged from 0 to 24.5 (4 patients asymptomatic, 3 with unspecific symptoms, and 13 with cerebellar signs). FDG-PET revealed hypometabolism in the asymptomatic stage in the vermis and right cerebellar hemisphere. In the ataxic stage, hypometabolism spread to both cerebellar hemispheres and the brain stem. MRI was normal in asymptomatic and preataxic individuals and showed superior cerebellar vermis atrophy early in the ataxic stage, diffuse cerebellar atrophy some years into the disease course, and a pattern of olivopontocerebellar atrophy in the oldest patients. There was no significant cerebellar atrophy in patients younger than 50 years. CONCLUSIONS: We present the first FDG-PET study of SCA36 and one of the largest neuroimaging study of SCAs. Our results revealed neuronal dysfunctions in the vermis and right cerebellar hemisphere as soon as a decade before the onset of motor symptoms. In the ataxic stage, dysfunctions spread to both hemispheres and the brain stem. © 2016 International Parkinson and Movement Disorder Society.

Electroencephalographic Evidence of Altered Top-Down Attentional Modulation in Fibromyalgia Patients During a Working Memory Task.

Fibromyalgia (FM) is a chronic syndrome involving widespread pain of unclear pathophysiology. FM patients frequently complain about cognitive symptoms that interfere with their daily life activities. Several studies have reported attentional deficits and working memory impairment in FM patients. Nevertheless, the mechanisms involved in these alterations are still poorly understood. In this study we recorded electroencephalographic activity in 32 women with FM and 30 matched controls while they performed a 2-back working memory task. We analyzed behavioural data, posterior alpha and midfrontal theta frequency power, and theta phase synchronization between midfrontal locations and the remaining scalp-recorded areas. Task performance was similar in patients and controls; however, time-frequency analysis showed a smaller decrease in the amplitude of the posterior alpha (related to attentional processing) and a smaller increase in midfrontal theta power (related to mental effort) in FM patients than in healthy controls. The FM patients also showed lower functional connectivity between midfrontal locations and rest of the scalp-recorded areas in the theta band (related to information transfer across distant brain regions when top-down control is required). To our knowledge, this is the first study relating alterations in oscillatory activity and impaired connectivity to attentional working memory complaints in FM patients. Reduced power in the theta band during performance of the task suggests that the medial frontal cortex may play an important role in the attentional deficits reported in FM.

An ontology-aware integration of clinical models, terminologies and guidelines: an exploratory study of the Scale for the Assessment and Rating of Ataxia (SARA).

BACKGROUND: Electronic rating scales represent an important resource for standardized data collection. However, the ability to exploit reasoning on rating scale data is still limited. The objective of this work is to facilitate the integration of the semantics required to automatically interpret collections of standardized clinical data. We developed an electronic prototype for the Scale of the Assessment and Rating of Ataxia (SARA), broadly used in neurology. In order to address the modeling challenges of the SARA, we propose to combine the best performances from OpenEHR clinical archetypes, guidelines and ontologies. METHODS: A scaled-down version of the Human Phenotype Ontology (HPO) was built, extracting the terms that describe the SARA tests from free-text sources. This version of the HPO was then used as backbone to normalize the content of the SARA through clinical archetypes. The knowledge required to exploit reasoning on the SARA data was modeled as separate information-processing units interconnected via the defined archetypes. Each unit used the most appropriate technology to formally represent the required knowledge. RESULTS: Based on this approach, we implemented a prototype named SARA Management System, to be used for both the assessment of cerebellar syndrome and the production of a clinical synopsis. For validation purposes, we used recorded SARA data from 28 anonymous subjects affected by Spinocerebellar Ataxia Type 36 (SCA36). When comparing the performance of our prototype with that of two independent experts, weighted kappa scores ranged from 0.62 to 0.86. CONCLUSIONS: The combination of archetypes, phenotype ontologies and electronic information-processing rules can be used to automate the extraction of relevant clinical knowledge from plain scores of rating scales. Our results reveal a substantial degree of agreement between the results achieved by an ontology-aware system and the human experts.

Different in vitro proliferation and cytokine-production inhibition of memory T-cell subsets after calcineurin and mammalian target of rapamycin inhibitors treatment.

Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi) are the main immunosuppressants used for long-term maintenance therapy in transplant recipients to avoid acute rejection episodes. Both groups of immunosuppressants have wide effects and are focused against the T cells, although different impacts on specific T-cell subsets, such as regulatory T cells, have been demonstrated. A greater knowledge of the impact of immunosuppression on the cellular components involved in allograft rejection could facilitate decisions for individualized immunosuppression when an acute rejection event is suspected. Memory T cells have recently gained focus because they might induce a more potent response compared with naive cells. The impact of immunosuppressants on different memory T-cell subsets remains unclear. In the present study, we have studied the specific impact of CNI (tacrolimus) and mTORi (rapamycin and everolimus) over memory and naive CD4(+) T cells. To do so, we have analysed the proliferation, phenotypic changes and cytokine synthesis in vitro in the presence of these immunosuppressants. The present work shows a more potent effect of CNI on proliferation and cytokine production in naive and memory T cells. However, the mTORi permit the differentiation of naive T cells to the memory phenotype and allow the production of interleukin-2. Taken together, our data show evidence to support the combined use of CNI and mTORi in transplant immunosuppression.