Longtime behavior of nonlocal Cahn-Hilliard equations

Here we consider the nonlocal Cahn-Hilliard equation with constant mobility in a bounded domain. We prove that the associated dynamical system has an exponential attractor, provided that the potential is regular. In order to do that a crucial step is showing the eventual boundedness of the order parameter uniformly with respect to the initial datum. This is obtained through an Alikakos-Moser type argument. We establish a similar result for the viscous nonlocal Cahn-Hilliard equation with singular (e.g., logarithmic) potential. In this case the validity of the so-called separation property is crucial. We also discuss the convergence of a solution to a single stationary state. The separation property in the nonviscous case is known to hold when the mobility degenerates at the pure phases in a proper way and the potential is of logarithmic type. Thus, the existence of an exponential attractor can be proven in this case as well

Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome

Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients

BACKGROUND AND OBJECTIVES: Many kidney transplant recipients suffer from fatigue and poor health-related quality of life. Airflow limitation may be an underappreciated comorbidity among kidney transplant recipients, which could contribute to fatigue and lower health-related quality of life in this population. In this study, we compared the prevalence of airflow limitation between kidney transplant recipients and healthy controls and investigated associations of airflow limitation with fatigue and health-related quality of life in kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the ongoing TransplantLines Biobank and Cohort study were used. Airflow limitation was defined as forced exhaled volume in 1 second less than the fifth percentile of the general population. Fatigue and health-related quality of life were assessed using checklist individual strength 20 revised (CIS20-R) and Short Form-36 (SF-36) questionnaires. RESULTS: A total of 539 kidney transplant recipients (58% men; mean age 56±13 years) and 244 healthy controls (45% men; mean age 57±10 years) were included. Prevalence of airflow limitation was higher in kidney transplant recipients than in healthy controls (133 [25%] versus 25 [10%]). In multinomial regression models, airflow limitation was independently associated with fatigue severity (odds ratio moderate fatigue, 1.68; 95% confidence interval, 0.92 to 3.09 and odds ratio severe fatigue, 2.51; 95% confidence interval, 1.39 to 4.55; P=0.007) and lower physical health-related quality of life (-0.11 SDs; 95% confidence interval, -0.19 to -0.02; P=0.01) in kidney transplant recipients. In exploratory mediation analyses, fatigue accounted for 79% of the association of airflow limitation with physical health-related quality of life. CONCLUSIONS: Airflow limitation is common among kidney transplant recipients. Its occurrence is associated with more than two times higher risk of severe fatigue, and it is associated with lower physical health-related quality of life. Mediation analyses suggest that airflow limitation causes fatigue, which in turn, decreases physical health-related quality of life. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: TransplantLines: The Transplantation Biobank, NCT03272841 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN06600521.mp3

Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients

Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9–10.6] ppm vs. 16.0 [8.0–45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea. View Full-Tex

“White Flight” or positive contact? Local diversity and attitudes to immigration in Britain

Does the local presence of immigrant groups increase White hostility to immigration? Most research finds that diverse neighborhoods reduce White opposition to minorities and immigration. However, most studies at higher geographies find the reverse effect. We confirm this pattern for England and Wales for 2009-2012. Yet, contextual studies are open to selection bias, which is where this article makes its main contribution. Is White tolerance in diverse neighborhoods the result of a positive effect of inter-ethnic contact, or does it arise from White flight, with anti-immigrant Whites exiting diverse areas but remaining within wider geographies as radicalized opponents of immigration? We provide the first attempt we are aware of to track the opinions of in- and out-migrants, as well as stayers, from local areas over an extended period. We use 20 years of large-scale geocoded British longitudinal data and find only limited evidence of selection effects associated with White flight

Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients:A Post-Hoc Analysis of the MECANO Trial

The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. beta = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. beta = 0.24 and 0.23, respectively) (p <0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required

Rationale and design of TransplantLines:a prospective cohort study and biobank of solid organ transplant recipients

Introduction In the past decades, short-term results after solid organ transplantation have markedly improved. Disappointingly, this has not been accompanied by parallel improvements in long-term outcomes after transplantation. To improve graft and recipient outcomes, identification of potentially modifiable risk factors and development of biomarkers are required. We provide the rationale and design of a large prospective cohort study of solid organ transplant recipients (TransplantLines). Methods and analysis TransplantLines is designed as a single-centre, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. Data will be collected from transplant candidates before transplantation, during transplantation, at 3 months, 6 months, 1 year, 2 years and 5 years, and subsequently every 5 years after transplantation. Data from living organ donors will be collected before donation, during donation, at 3 months, 1 year and 5 years after donation, and subsequently every 5 years. The primary outcomes are mortality and graft failure. The secondary outcomes will be cause-specific mortality, cause-specific graft failure and rejection. The tertiary outcomes will be other health problems, including diabetes, obesity, hypertension, hypercholesterolaemia and cardiovascular disease, and disturbances that relate to quality of life, that is, physical and psychological functioning, including quality of sleep, and neurological problems such as tremor and polyneuropathy. Ethics and dissemination Ethical approval has been obtained from the relevant local ethics committee. The TransplantLines cohort study is designed to deliver pioneering insights into transplantation and donation outcomes. The study design allows comprehensive data collection on perioperative care, nutrition, social and psychological functioning, and biochemical parameters. This may provide a rationale for future intervention strategies to more individualised, patient-centred transplant care and individualisation of treatment

Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder

Background: Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. Method: We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results: Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. Conclusions: These outcomes demonstrate that symptoms of MDD were reduced following effective treatment with an SSRI, and further, stress physiology was unlikely to be a key factor in this outcome. Further research is required to discriminate potential differences in underlying stress physiology for individuals with MDD who respond to antidepressant treatment, relative to those who experience treatment resistance.Charlotte Keating, Tye Dawood, David A Barton, Gavin W Lambert and Alan J Tilbroo

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Practical consensus guidelines for the management of enuresis

Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. Conclusion: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis