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The European Commission has asked EU Member States for comments on a French law notification demanding plant varieties produced with the help of in vitro mutagenesis have to be eliminated from the national catalog of approved varieties because of missing legal authorization deemed required by genetic engineering law. Primary target are herbicide-tolerant Clearfield oilseed rape varieties. The scientific reasoning is questionable, traceability is illusive, and law enforcement is likely to be impossible.

The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity (using Low-Resolution Brain Electromagnetic Tomography (LORETA)) for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after ten weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week ten, patients were divided into responders and non-responders (according to a reduction of symptom severity > 50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t=2.86, p

Representing statistical information in terms of natural frequencies rather than probabilities improves performance in Bayesian inference tasks. This beneficial effect of natural frequencies has been demonstrated in a variety of applied domains such as medicine, law, and education. Yet all the research and applications so far have been limited to situations where one dichotomous cue is used to infer which of two hypotheses is true. Real-life applications, however, often involve situations (e.g., medical tests) where cues have more than one value, where more than two hypotheses are considered, or where more than one cue is available. In Study 1, we show that natural frequencies, compared to information stated in terms of probabilities, consistently increase the proportion of Bayesian inferences made by medical students in four conditions—three cue values, three hypotheses, two cues, or three cues—by an average of 37 percentage points. In Study 2, we show that teaching natural frequencies for simple tasks with one dichotomous cue and two hypotheses leads to a transfer of learning to complex tasks with three cue values and two cues, with a proportion of 40% and 81% correct inferences, respectively. Thus, natural frequencies facilitate Bayesian reasoning in a much broader class of situations than previously thought.

In research on Bayesian inferences, the specific tasks, with their narratives and characteristics, are typically seen as exchangeable vehicles that merely transport the structure of the problem to research participants. In the present paper, we explore whether, and, if so, how task characteristics that are usually ignored influence participants’ responses in these tasks. We focus on both quantitative dimensions of the tasks, such as their base rates, hit rates and false-alarm rates, as well as qualitative characteristics, such as whether the task involves a norm violation or not, whether the stakes are high or low, and whether the focus is on the individual case or on the numbers. Using a data set of 19 different tasks presented to 500 different participants who provided a total of 1,773 responses, we analyze these responses in two ways: First, on the level of the numerical estimates themselves, and second, on the level of various response strategies, Bayesian and non-Bayesian, that might have produced the estimates. We identified various contingencies, and most of the task characteristics had an influence on participants’ responses. Typically, this influence has been stronger when the numerical information in the tasks was presented in terms of probabilities or percentages, compared to natural frequencies – and this effect cannot be fully explained by a higher proportion of Bayesian responses when natural frequencies were used. One characteristic that did not seem to influence participants’ response strategy was the numerical value of the Bayesian solution itself. Our exploratory study is a first step towards an ecological analysis of Bayesian inferences, and highlights new avenues for future research.

Visual aids can improve comprehension of risks associated with medical treatments, screenings, and lifestyles. Do visual aids also help decision makers accurately assess their risk comprehension? That is, do visual aids help them become well calibrated? To address these questions, we investigated the benefits of visual aids displaying numerical information and measured accuracy of self-assessment of diagnostic inferences (i.e., metacognitive judgment calibration) controlling for individual differences in numeracy. Participants included 108 patients who made diagnostic inferences about three medical tests on the basis of information about the sensitivity and false-positive rate of the tests and disease prevalence. Half of the patients received the information in numbers without a visual aid, while the other half received numbers along with a grid representing the numerical information. In the numerical condition, many patients --especially those with low numeracy-- misinterpreted the predictive value of the tests and profoundly overestimated the accuracy of their inferences. Metacognitive judgment calibration mediated the relationship between numeracy and accuracy of diagnostic inferences. In contrast, in the visual aid condition, patients at all levels of numeracy showed high-levels of inferential accuracy and metacognitive judgment calibration. Results indicate that accurate metacognitive assessment may explain the beneficial effects of visual aids and numeracy --a result that accords with theory suggesting that metacognition is an essential part of risk literacy. We conclude that well-designed risk communications can inform patients about health-relevant numerical information while helping them assess the quality of their own risk comprehension.

In Bayesian inference tasks, information about base rates as well as hit rate and false-alarm rate needs to be integrated according to Bayes’ rule after the result of a diagnostic test became known. Numerous studies have found that presenting information in a Bayesian inference task in terms of natural frequencies leads to better performance compared to variants with information presented in terms of probabilities or percentages. Natural frequencies are the tallies in a natural sample in which hit rate and false-alarm rate are not normalized with respect to base rates. The present research replicates the beneficial effect of natural frequencies with four tasks from the domain of management, and with management students as well as experienced executives as participants. The percentage of Bayesian responses was almost twice as high when information was presented in natural frequencies compared to a presentation in terms of percentages. In contrast to most tasks previously studied, the majority of numerical responses were lower than the Bayesian solutions. Having heard of Bayes’ rule prior to the study did not affect Bayesian performance. An implication of our work is that textbooks explaining Bayes’ rule should teach how to represent information in terms of natural frequencies instead of how to plug probabilities or percentages into a formula.

Larval zebrafish (Danio rerio) have become favored subjects for studying the neural bases of behavior. Here, we report a highly stereotyped response of zebrafish larvae to hydrodynamic stimuli. It involves positive taxis, motion damping and sustained responsiveness to flows derived from local, non-stressful water motions. The response depends on the lateral line and has a high sensitivity to stimulus frequency and strength, sensory background and rearing conditions - also encompassing increased threshold levels of response to parallel input. The results show that zebrafish larvae can use near-field detection to locate sources of minute water motions, and offer a unique handle for analyses of hydrodynamic sensing, sensory responsiveness and arousal with accurate control of stimulus properties.

The paraventricular nucleus (PVN) of the hypothalamus in mammals coordinates neuroendocrine, autonomic and behavioral responses pivotal for homeostasis and the stress response. A large amount of studies in rodents has documented that the PVN contains diverse neuronal cell types which can be identified by the expression of distinct secretory neuropeptides. Interestingly, PVN cell types often coexpress multiple neuropeptides whose relative coexpression level are subject to environment-induced plasticity.Due to their small size and transparency, zebrafish larvae offer the possibility to comprehensively study the development and plasticity of the PVN in large groups of intact animals, yet important anatomical information about the larval zebrafish PVN-homologous region has been missing. Therefore we recently defined the location and borders of the larval neurosecretory preoptic area (NPO) as the PVN-homologous region in larval zebrafish based on transcription factor expression and cell type clustering. To identify distinct cell types present in the larval NPO, we also generated a comprehensive 3D map of 9 zebrafish homologs of typical neuropeptides found in the mammalian PVN (arginine vasopressin, corticotropin-releasing hormone, proenkephalin a/b, neurotensin, oxytocin, vasoactive intestinal peptide, cholecystokinin, and somatostatin). Here we extend this chemoarchitectural map to include the degrees of coexpression of two neuropeptides in the same cell by performing systematic pairwise comparisons. Our results allowed the subclassification of NPO cell types, and differences in variability of coexpression profiles suggest potential targets of biochemical plasticity. Thus, this work provides an important basis for the analysis of the development, function, and plasticity of the primary neuroendocrine brain region in larval zebrafish.

Background-Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).Methods and Results- In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF) and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions-After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

The recovery of functional movements following injury to the central nervous system (CNS) is multifaceted and is accompanied by processes occurring in the injured and non-injured hemispheres of the brain or above/below a spinal cord lesion. The changes in the CNS are the consequence of functional and structural processes collectively termed neuroplasticity and these may occur spontaneously and/or be induced by movement practice. The neurophysiological mechanisms underlying such brain plasticity may take different forms in different types of injury, for example stroke vs. spinal cord injury (SCI). Recovery of movement can be enhanced by intensive, repetitive, variable and rewarding motor practice. To this end, robots that enable or facilitate repetitive movements have been developed to assist recovery and rehabilitation. Here, we suggest some elements of robot-mediated training such as assistance, perturbation and unloading may have the potential to enhance neuroplasticity. Together the elemental components for developing integrated robot-mediated training protocols may form part of a neurorehabilitation framework alongside those methods already employed by therapists. Robots could thus open up a wider choice of options for delivering movement rehabilitation grounded on the principles underpinning neuroplasticity in the human CNS.

Maintenance of genetic stability is crucial for all organisms in order to avoid the onset of deleterious diseases such as cancer. One of the many proveniences of DNA base damage in mammalian cells is oxidative stress, arising from a variety of endogenous and exogenous sources, generating highly mutagenic oxidative DNA lesions. One of the best characterized oxidative DNA lesion is 7,8-dihydro-8-oxoguanine (8-oxo-G), which can give rise to base substitution mutations (also known as point mutations). This mutagenicity is due to the miscoding potential of 8-oxo-G that instructs most DNA polymerases (pols) to preferentially insert an Adenine (A) opposite 8-oxo-G instead of the appropriate Cytosine (C). If left unrepaired, such A:8-oxo-G mispairs can give rise to CG->AT transversion mutations. A:8-oxo-G mispairs are proficiently recognized by the MutY glycosylase homologue (MUTYH). MUTYH can remove the mispaired A from an A:8-oxo-G, giving way to the canonical base excision repair (BER) that ultimately restores undamaged Guanine (G). The importance of this MUTYH-initiated pathway is illustrated by the fact that biallelic mutations in the MUTYH gene are associated with a hereditary colorectal cancer syndrome termed MUTYH-associated polyposis (MAP). In this review, we will focus on MUTYH, from its discovery to the most recent data regarding its cellular roles and interaction partners. We discuss the involvement of the MUTYH protein in the A:8-oxo-G BER pathway acting together with pol , the pol that can faithfully incorporate C opposite 8-oxo-G and thus bypass this lesion in a correct manner. We also outline the current knowledge about the regulation of MUTYH itself and the A:8-oxo-G repair pathway by posttranslational modifications (PTM). Finally, to achieve a clearer overview of the literature, we will briefly touch on the rather confusing MUTYH nomenclature. In short, MUTYH is a unique DNA glycosylase that catalyzes the excision of an undamaged base from DNA.

Sodium reabsorption is tightly coupled to calcium reabsorption in the proximal tubule via the action of the Na + /H + exchanger isoform 3 (NHE3). Poulsen et al. provide evidence of reduced proximal calcium reabsorption in kidney tubule-specific NHE3-deficient mice that is compensated distally, unaltered phosphate homeostasis, and NHE3 involvement in the hypocalciuric effect of thiazides. These results provide support that gastrointestinal NHE3 inhibitors, used for hyperphosphatemia treatment, are unlikely to cause long-term impact on bone mineralization., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute kidney injury (AKI) is common in hospitalised adults and children and is associated with significantly increased mortality and worse short-term and long-term outcomes. This systematic review and meta-analysis will evaluate the cost associated with AKI., Methods and Analysis: This health economic analysis will be performed using systematic search of databases, including MEDLINE, EMBASE, CINAHL, Scopus and Cochrane Library from 2009 to the present (search completed on 27 May 2024). Two reviewers will independently complete study selection, data extraction and bias assessment. Inclusion criteria will be randomised controlled trials (RCTs) and observational studies (cohort or case-control) from all countries of hospitalised adults and children. The exposure will be AKI based on definitions using serum creatinine and/or urine output criteria, relative to patients without AKI. The primary outcome studied will be the cost of index hospitalisation associated with AKI episode. Other secondary outcomes will include the cost of intensive care unit admission during index hospitalisation, direct costs related to inpatient and outpatient care) and indirect (time) costs related to loss of productivity. Pooled random-effect meta-analysis ORs with 95% CIs will be reported., Ethics and Dissemination: Ethics approval was not required due to study methodology. The authors have no competing interests to report. The results will be disseminated in peer-reviewed publications according to guidelines by the Cochrane and Centre for Reviews and Dissemination., Prospero Registration Number: CRD42024512658., Competing Interests: Competing interest: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Acute kidney injury (AKI) is common in critically ill children and associated with adverse short-term outcomes; however, long-term outcomes are not well described., Methods: This longitudinal prospective cohort study examined the prevalence of chronic kidney disease (CKD) and hypertension (HTN) 11 vs. 6 years after pediatric intensive care unit (PICU) admission and association with AKI. We examined children (age < 19 years) without pre-existing kidney disease 11 ± 1.5 years after PICU admission at a single center. AKI was defined using serum creatinine criteria. The primary outcome was a composite of CKD or HTN. CKD was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 or albuminuria. Multivariable analyses compared outcomes at 11- vs. 6-year follow-up and association with AKI during PICU admission., Results: Of 96 children evaluated 11 years after PICU admission, 16% had evidence of CKD or HTN (vs. 28% at 6 years, p < 0.05). Multivariable analysis did not show improvement in outcomes from 6- to 11-year follow-up. eGFR decreased from 6- to 11-year follow-up (adjusted coefficient - 11.7, 95% CI - 17.6 to - 5.9) and systolic and diastolic blood pressures improved. AKI was associated with composite outcome at 6-year (adjusted odds ratio (aOR) 12.7, 95% CI 3.2-51.2, p < 0.001), but not 11-year follow-up (p = 0.31). AKI was associated with CKD (aOR 10.4, 95% CI 3.1-34.7) at 11 years., Conclusions: This study provides novel data showing that adverse kidney and blood pressure outcomes remain highly prevalent 10 years after critical illness in childhood. The association with AKI wanes over time., Competing Interests: Declarations. Dr. Zappitelli reported receiving personal fees from Bioporto Inc. for consulting work, and from Baxter Inc. for a talk on CRRT for sepsis and citrate anticoagulation. Dr. Zappitelli is Chair of the Data Safety Monitoring Board for an Eloxx Pharmaceuticals clinical trial. All involvement has no impact on the current manuscript. We declare that we do not have any conflicts of interest., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objectives: The objective of this Prospective Register of Systematic Reviews (CRD42022384192) registered systematic review and meta-analysis was to determine whether prophylactic peritoneal dialysis (PD) catheter insertion at the time of pediatric cardiac surgery is associated with improved short-term outcomes., Data Sources: Databases search of the MEDLINE, EMBASE, CINAHL, and Cochrane Library completed in April 2021 and updated October 2023., Study Selection: Two reviewers independently completed study selection, data extraction, and bias assessment. Inclusion criteria were randomized controlled trials (RCTs) and observational studies of children (≤ 18 yr) undergoing cardiac surgery with cardiopulmonary bypass. We evaluated use of prophylactic PD catheter versus not., Data Extraction: The primary outcome was in-hospital mortality, as well as secondary short-term outcomes. Pooled random-effect meta-analysis odds ratio with 95% CI are reported., Data Synthesis: Seventeen studies met inclusion criteria, including four RCTs. The non-PD catheter group received supportive care that included diuretics and late placement of PD catheters in the ICU. Most study populations included children younger than 1 year and weight less than 10 kg. Cardiac surgery was most commonly used for arterial switch operation. In-hospital mortality was reported in 13 studies; pooled analysis showed no association between prophylactic PD catheter placement and in-hospital mortality. There were mixed results for ICU length of stay and time to negative fluid balance, with some studies showing shortened duration associated with use of prophylactic PD catheter insertion and others showing no difference. Overall, the studies had high risk for bias, mainly due to small sample size and lack of generalizability., Conclusions: In this meta-analysis, we have failed to demonstrate an association between prophylactic PD catheter insertion in children and infants undergoing cardiac surgery and reduced in-hospital mortality. Other relevant short-term outcomes, including markers of fluid overload, require further study., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge., Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy., Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations., Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy., Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Background: Hypercalciuria is the most common risk factor for kidney stone formation, including in pediatric patients. However, the etiology is often unknown and children are frequently diagnosed with idiopathic hypercalciuria. Nearly 50% of children with hypercalciuria have a first-degree relative with kidney stones, suggesting a strong genetic basis for this disease. A failure of calcium reabsorption from the proximal nephron is implicated in the pathogenesis of hypercalciuria. Claudin-2 is a tight junction protein abundantly expressed in the proximal tubule. It confers paracellular permeability to calcium that is essential for transport across the proximal tubule where the majority of filtered calcium is reabsorbed., Objective: Our objective was to examine the frequency of coding variations in CLDN2 in a cohort of children with idiopathic hypercalciuria., Design: Mixed method including retrospective chart review and patient interview, followed by genetic sequencing., Setting: Three tertiary care centers in Canada., Patients: Children (age 1-18 years) with idiopathic hypercalciuria. Patients with other causes of hypercalciuria were excluded., Methods: Data were collected from 40 patients with idiopathic hypercalciuria. Informed consent to collect DNA was obtained from 13 patients, and the final and only coding exon of CLDN2 was sequenced., Results: The majority of patients were male, white, and had a positive family history of kidney stones. Parathyroid hormone levels were significantly lower than the reference range ( P < .001). The levels of 1,25-dihydroxyvitamin D were also significantly higher in our patient cohort, relative to the reference range ( P < .001). Sequence analysis of CLDN2 did not identify any coding variations., Limitations: Sequencing analysis was limited to the final coding exon and small sample size., Conclusions: CLDN2 coding variations are not a common cause of idiopathic hypercalciuria in Canadian children. Further study is needed to determine the causes of hypercalciuria in pediatric patients and develop targeted therapies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RTA work closely with Dr Hartwig as a member of the KRESCENT leadership team (she is a handling editor)., (© The Author(s) 2022.)

Acute kidney injury is common in critically ill children, but the long-term outcomes are not well defined., Objectives: Evaluated whether nonrecovery of kidney function, following acute kidney injury, was associated with postdischarge mortality, healthcare utilization, and chronic kidney disease., Design: Retrospective, two-center, observational study., Setting: Two ICUs at tertiary children's hospitals in Montreal, QC., Participants: Pediatric patients (age ≤ 18 yr) with index admission to intensive care between January 1, 2003, and March 31, 2005. Children were excluded if they 1) died during admission, 2) did not have serum creatinine or urine output measured, 3) did not develop acute kidney injury, 4) could not be linked to administrative health data, and 5) (for chronic kidney disease outcome) had pre-existing renal disease by chart review, baseline estimated glomerular filtration rate measurement, or administrative health data codes., Main Outcomes and Measures: Three-hundred seventy-eight patients' data were included for long-term mortality and healthcare utilization outcomes; 316 patients for long-term chronic kidney disease outcome. Outcomes were defined using provincial administrative healthcare data diagnosis, procedure, and billing codes., Main Results: Nonrecovery of kidney function, defined as serum creatinine greater than or equal to 1.5× baseline at ICU discharge, occurred in 51 patients (13%). Nonrecovery of kidney function was not associated with long-term mortality (at 5-7 yr following hospital discharge), increased hospitalizations or emergency department visits (at 30-days, 1-year, and 5-yr follow-up), or increased physician visits (at 1- and 5-yr follow-up). Nonrecovery was associated with increased 30-day physician visits (adjusted relative risk, 1.40; 95% CI, 1.13-1.73) and chronic kidney disease diagnosis within 5 years of discharge (adjusted hazard ratio, 4.92, 95% CI, 1.77-13.70)., Conclusions and Relevance: Nonrecovery of kidney function following an episode of acute kidney injury in critically ill children is associated with nearly five-fold increased risk for long-term chronic kidney disease. Acute kidney injury nonrecovery may be a useful marker to identify patients that are particularly important to follow-up post discharge for chronic kidney disease detection., Competing Interests: Dr. Zappitelli was provided with an operating grant from the Fonds de Recherche du Quebec-Sante to perform this work and with SickKids Research Institute and SickKids Department of Pediatrics Start up Funds to pay for statistical analyses related to this work. The remaining authors have not disclosed any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Administrative health care databases contain valuable patient information generated by health care encounters. These "big data" repositories have been increasingly used in epidemiological health research internationally in recent years as they are easily accessible and cost-efficient and cover large populations for long periods. Despite these beneficial characteristics, it is also important to consider the limitations that administrative health research presents, such as issues related to data incompleteness and the limited sensitivity of the variables. These barriers potentially lead to unwanted biases and pose threats to the validity of the research being conducted. In this review, we discuss the effectiveness of health administrative data in understanding the epidemiology of and outcomes after acute kidney injury (AKI) among adults and children. In addition, we describe various validation studies of AKI diagnostic or procedural codes among adults and children. These studies reveal challenges of AKI research using administrative data and the lack of this type of research in children and other subpopulations. Additional pediatric-specific validation studies of administrative health data are needed to promote higher volume and increased validity of this type of research in pediatric AKI, to elucidate the large-scale epidemiology and patient and health systems impacts of AKI in children, and to devise and monitor programs to improve clinical outcomes and process of care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ulrich, So, Zappitelli and Chanchlani.)

Objectives: Acute kidney injury occurs frequently in children during critical illness and is associated with increased morbidity, mortality, and health resource utilization. We aimed to examine the association between acute kidney injury duration and these outcomes., Design: Retrospective cohort study., Settings: PICUs in Alberta, Canada., Patients: All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015., Interventions: None., Measurements and Main Results: In total, 1,017 children were included, and 308 (30.3%) developed acute kidney injury during PICU stay. Acute kidney injury was categorized based on duration to transient (48 hr or less) or persistent (more than 48 hr). Transient acute kidney injury occurred in 240 children (77.9%), whereas 68 children (22.1%) had persistent acute kidney injury. Persistent acute kidney injury had a higher proportion of stage 2 and stage 3 acute kidney injury compared with transient acute kidney injury and was more likely to start within 24 hours from PICU admission. Persistent acute kidney injury occurred more frequently in those with higher illness severity and in those admitted with shock, sepsis, or with a history of transplant. Mortality varied significantly according to acute kidney injury status: 1.8% of children with no acute kidney injury, 5.4% with transient acute kidney injury, and 17.6% with persistent acute kidney injury died during hospital stay (p < 0.001). On multivariable analysis adjusting for illness and acute kidney injury severity, transient and persistent acute kidney injury were both associated with fewer ventilation-free days at 28 days (-1.28 d; 95% CI, -2.29 to -0.26 and -4.85 d; 95% CI, -6.82 to -2.88), vasoactive support-free days (-1.07 d; 95% CI, -2.00 to -0.15 and -4.24 d; 95% CI, -6.03 to -2.45), and hospital-free days (-1.93 d; 95% CI, -3.36 to -0.49 and -5.25 d; 95% CI, -8.03 to -2.47), respectively., Conclusions: In critically ill children, persistent and transient acute kidney injury have different clinical characteristics and association with outcomes. Acute kidney injury, even when its duration is short, carries significant association with worse outcomes. This risk increases further if acute kidney injury persists longer independent of the degree of its severity., Competing Interests: Dr. Bagshaw received funding from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

The prevalence of hypertension in children with type 1 diabetes is reported to be between 6% and 16%. This potentially modifiable cardiovascular risk factor may go undiagnosed and undertreated, particularly in children with type 1 diabetes. Recent updated Canadian clinical practice guidelines recommend blood pressure screening every 2 years in children with type 1 diabetes as well as routine use of ambulatory blood pressure monitoring. Risk factors for hypertension in type 1 diabetes include poor glycemic control, overweight and obesity and genetic predisposition for hypertension. In terms of pathophysiology, sustained hyperglycemia, angiotensin I and II and inflammatory cytokines have been implicated. Endothelial and vascular dysfunction, with impaired endothelial-dependent vasodilation and increased carotid artery intima-media thickness, are evident in preclinical and clinical studies of children and not just in adults with type 1 diabetes. Early targeted therapy is critical to the control of hypertension and the development of related morbidity. As with hypertension in adults with type 1 diabetes, lifestyle modifications remain first-line therapy, including diet and glycemic control. Initial antihypertensive therapy should be an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker because of their associated effects of reducing microalbuminuria and improving renovascular outcomes. Pediatric hypertension in type 1 diabetes is an area of evolving study and opinion; identification and appropriate treatment is critical for the prevention of micro- and macrovascular complications in adulthood., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)