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Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence of good short-term and medium-term outcomes of ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation with pre-transplant positive crossmatches in paediatric practice. However, there remain concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of our study is to show longer-term follow-up on all ABOi and HLAi paediatric kidney transplant recipients (pKTR) in the UK. Methods: Questionnaires specifying kidney transplant type, desensitisation requirement and kidney allograft function were sent to 13 paediatric nephrology centres that performed kidney transplantation in children and young people under 18 years of age who received an ABOi and/or HLAi transplant between 1 January 2006 and 31 December 2016. Patient and kidney allograft survival were compared between ABOi, HLAi and ABO/HLA compatible (ABOc/HLAc) groups. Results: Among 711 living donor kidney transplants performed in the UK, 23 were ABOi and 6 were HLAi. Patient survival was 87%, 100% and 96% in ABOi, HLAi and ABOc/HLAc groups, respectively, at median follow-up of 6.8 (3.6–14.0) years post-transplant. Death-censored kidney allograft survival was 100% in all 3 groups at last follow-up. There were no cases of primary non-function in ABOi or HLAi groups, but 2% in the ABOc/HLAc group. There was one reported case of Epstein-Barr viral-induced post-transplant lymphoproliferative disorder. Conclusion: Longer term follow-up has shown that ABOi and HLAi kidney transplantation are feasible for pKTR where no compatible donors are available, and that minimising desensitisation should be achieved where possible. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Modern public transit systems are often run with automated fare collection (AFC) systems in combination with smart cards. These systems passively collect massive amounts of detailed spatio-temporal trip data, thus opening up new possibilities for public transit planning and management as well as providing new insights for urban planners. We use smart card trip data from Taipei, Taiwan, to perform an in-depth analysis of spatio-temporal station-to-station metro trip patterns for a whole week divided into several time slices. Based on simple linear regression and line graphs, days of the week and times of the day with similar temporal passenger flow patterns are identified. We visualize magnitudes of passenger flow based on actual geography. By comparing flows for January to March 2019 and for January to March 2020, we look at changes in metro trips under the impact of the coronavirus pandemic (COVID-19) that caused a state of emergency around the globe in 2020. Our results show that metro usage under the impact of COVID-19 has not declined uniformly, but instead is both spatially and temporally highly heterogeneous. [ABSTRACT FROM AUTHOR]

Coral holobionts are multi-species assemblages, which adds significant complexity to genotype-phenotype connections underlying ecologically important traits like coral bleaching. Small scale heterogeneity in bleaching is ubiquitous in the absence of strong environmental gradients, which provides adaptive variance needed for the long-term persistence of coral reefs. We used RAD-seq, qPCR and LC-MS/MS metabolomics to characterize host genomic variation, symbiont community and biochemical correlates in two bleaching phenotypes of the vertically transmitting coral Montipora capitata. Phenotype was driven by symbiosis state and host genetic variance. We documented 5 gene ontologies that were significantly associated with both the binary bleaching phenotype and symbiont composition, representing functions that confer a phenotype via host-symbiont interactions. We bred these corals and show that symbiont communities were broadly conserved in bulk-crosses, resulting in significantly higher survivorship under temperature stress in juveniles, but not larvae, from tolerant parents. Using a select and re-sequence approach, we document numerous gene ontologies selected by heat stress, some of which (cell signaling, antioxidant activity, pH regulation) have unique selection dynamics in larvae from thermally tolerant parents. These data show that vertically transmitting corals may have an adaptive advantage under climate change if host and symbiont variance interact to influence bleaching phenotype. Selective breeding of corals with different bleaching phenotypes demonstrates the potential for climate adaptation in vertically transmitting species. [ABSTRACT FROM AUTHOR]

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was the qualitative and quantitative evaluation of osseous graft consolidation using allogeneic bone blocks for vertical bone augmentation in an animal model. Material and methods: Standardised allogeneic and autologous bone blocks were fixed on the frontal skull of 20 adult female pigs and covered with a resorbable collagen membrane. Animals were sacrificed after 2 and 6 months. Specimens were histologically and histomorphometrically analysed focusing on the amount of vital bone, residual bone substitute material and connective tissue. Furthermore, the amount of expression of bone matrix proteins (collagen type I and osteocalcin) and de novo vessel formation (von Willebrand factor) were quantified by immunohistochemistry. Results: Significantly more allogeneic bone blocks failed for both evaluation time points (p < 0.05). Allogeneic blocks showed significantly less vital bone with more connective tissue formation compared to autologous bone blocks. Increased vessel formation could be detected for both evaluation time points in the contact area of autologous bone with local bone. The expression of collagen type I and osteocalcin was significantly lower in the allogeneic bone graft. Conclusions: Allogeneic cancellous bone blocks showed a significantly higher failure rate compared to autologous bone blocks. Allogeneic bone blocks seemed to negatively affect bone formation or negatively influence the host in the long term, and increased connective tissue formation and block loss should be anticipated. Clinical relevance: In order to maintain patient safety and treatment success clinicians should be persuaded to make a conscious choice of the applied biomaterials with regard to their components and structure. [ABSTRACT FROM AUTHOR]

Background: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known. Methods: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels < 4 μg/L (Tac < 4) and the concentration/weight-adjusted dose (C/D) ratio as a proxy marker of tacrolimus metaboliser status. Results: LACR patients had higher CV (median, IQR 44%, 36–61% v. 24%, 19–35%, p < 0.0001) and higher MAD (33%, 25–48% v. 19%, 15–26%, p < 0.0001). The MAD was less affected by outlying tacrolimus results. Receiver operating curve analysis of the MAD resulted in a sensitivity of 76% and specificity of 76% at a threshold of 26% (AUC 0.85, p < 0.05). LACR patients had more Tac < 4 (50% v. 26%, p < 0.05). There was no difference in C/D suggesting that good IPV can be maintained in fast metabolisers. Patients with LACR had significantly increased creatinine at 12-month follow-up despite treatment (108 v. 5 umol/L increase from baseline) and four patients lost their allograft. Conclusions: Monitoring of tacrolimus IPV using the MAD may be a clinical marker for LACR. A threshold IPV of 26% can potentially be used as a therapeutic target pending further validation studies. [ABSTRACT FROM AUTHOR]

Objective: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.Methods: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells.Results: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.Conclusions: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose. [ABSTRACT FROM AUTHOR]

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Molybdenum carbide (Mo2C), an interstitial transition metal carbide, has been used in a myriad of industrial applications due to its refractory nature, extreme hardness and strength, and high electrical and thermal conductivity. It also possesses catalytic activity for many chemical processes such as hydrodeoxygenation, reforming, water-gas shift, and the Fischer-Tropsch reaction. Among the current synthesis methods available to produce β-Mo2C, temperature-programmed reduction yields materials with the highest specific surface areas. The objective of the present work is to perform a detailed investigation of the carburization process and to determine the key intermediate phases that are formed during reduction. To achieve this objective, we performed the carburization process under pulse conditions wherein a small amount of CH4 in each pulse was reacted with a packed bed of MoO2. Our XRD and TEM results demonstrate that the solid-phase transformation from MoO2 to β-Mo2C follows a “plum-pudding” mechanism where Mo metal crystallites are constantly formed as the key intermediate phase throughout the matrix. [ABSTRACT FROM AUTHOR]

The article focuses on the EU Member States' national implementation legislation as the new legislation aims to ensure the EU offers an attractive and favorable environment for carrying out clinical research on a large scale, with high standards of public transparency and safety for clinical trial participants.

Purpose: Chronic kidney disease (CKD) can place restrictions upon biopsychosocial development in children; consequently, assessment of self-reported quality of life (QoL) is important in patient evaluations. This research aimed to evaluate a generic and renal-specific self-report QoL scale, assess children's attitudes towards living with CKD and propose an appropriate tool for future individual clinical use or departmental audit.Methods: Seventy-one children (41 male, 30 female; mean age = 13.60 years, range = 6.00-18.96) with CKD completed the Generic Children's QoL Measure (GCQ), PedsQL 3.0 End Stage Renal Disease Module (PedsQL) and Child Attitude Toward Illness Scale (CATIS). Descriptive and cross-sectional analyses were performed, along with an examination of associations between scores on each measure.Results: The mean GCQ score for patients was comparable with normative data (p = 0.27). Generic QoL, disease-specific QoL and attitudes towards CKD did not vary by CKD stage, age, time since diagnosis or duration of current treatment. Gender was not associated with QoL, although males had more negative CATIS scores than females (p < 0.05). Pre-emptive transplant patients had more positive GCQ and PedsQL scores (p < 0.05 for each), but there was no relationship between treatment and CATIS scores. Scores on all scales were moderately correlated (r = 0.35-0.59), suggesting that clinicians may choose the most appropriate measure for assessment of psychological/psychosocial functioning based on clinical judgement.Conclusions: This study further confirmed that using child self-reported QoL measures is possible and may help psychosocial teams to individualise work. The GCQ is simple and convenient, and could be used as an annual screening tool to facilitate discussion of QoL with children and young people. Further work is necessary before such things as cut-off scores can be recommended. [ABSTRACT FROM AUTHOR]

The article discusses answers to a quiz that appeared within the issue of "Pediatric Nephrology," which focused on renal failure from birth. It is noted that through ultrasonography, having large bright kidneys are suggestive of acute kidney injury (AKI). Information about the Denys-Drash syndrome (DDS) is presented, which is caused by heterozygous mutations on WT1 on chromosome 11p13.

A correction to the article "Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome" that was published online on February 24, 2022 is presented.

In the article by Möst et al., entitled "Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study. [ABSTRACT FROM AUTHOR]

A case is presented of a neonate born at 32 weeks of gestation with intra-uterine growth retardation. The renal scan performed at 31 weeks showed oligohydramnios but normal kidneys. The neonate was oliguric from birth and required early peritoneal dialysis. Her urine showed heavy proteinuria, and the plasma albumin was very low. Post-natal ultrasonography showed large bright kidneys with reduced corticomedullary differentiation but no dysplastia; arterial and venous flow was normal on Doppler ultrasound. The quiz discusses the differential diagnosis with particular reference to whether this picture represents acute kidney injury with expected improvement or chronic kidney disease. Further questions discuss mechanisms of renal failure in this situation. Finally, with reference to previous case reports and series, a correlation between a specific mutation and this severe phenotype is proposed. [ABSTRACT FROM AUTHOR]