Neurocognitive Profile in Pediatric Kidney Transplant Candidates: Effects of Medical and Sociodemographic Factors.

Background: We evaluated the effects of kidney failure etiology, dialysis, and sociodemographic factors on the subdomains of intellectual functioning in pediatric kidney transplant candidates. Methods: This retrospective study included 78 pediatric kidney transplant candidates who completed a Wechsler Intelligence Scale assessment during pre-transplant neuropsychological evaluation between 1/1/2010 and 10/31/2022. Linear regression models were employed to examine the effects of kidney failure etiology, dialysis status, neighborhood area deprivation, and race on subdomains of intellectual functioning. Results: The mean scores of various intellectual functioning domains in pediatric kidney transplant candidates were significantly lower than in the general population (ps <0.001). After adjusting for covariates, patients with congenital anomalies of the kidney and urinary tract had significantly lower processing speed (M=85; 95% CI: 79-91) compared to patients with nephrotic syndrome (M=99; 95% CI: 90-107) and other etiologies (M=84; 95% CI: 78-90) (p=0.003). Patients living in high-level deprivation neighborhoods showed lower working memory performance (M=84, 95% CI: 77-91) than patients living in median-level (M=91, 95% CI: 87-95) and low-level (M=98, 95% CI: 92-104) neighborhood area deprivation (p=0.03). Patients from marginalized racial groups demonstrated lower verbal skills (M=80, 95% CI: 74-87) than White patients (M=92, 95% CI: 88-97) (p=0.02). Additionally, patients receiving dialysis showed higher reasoning skills (M=98, 95% CI: 90-104) than patients without dialysis (M= 90, 95% CI: 86-95) (p=0.04). Conclusions: Neurocognitive development in pediatric kidney transplant candidates is associated with medical and sociodemographic factors. Strategies to monitor, treat, and accommodate neurocognitive concerns need to be considered to optimize long-term medical and social outcomes.

Common mental health conditions and considerations in pediatric chronic kidney disease.

The mental health of youth with chronic kidney disease (CKD) has been increasingly recognized as an area of clinical need. The development of mental health concerns is influenced by a range of physiological, psychological, and environmental factors. Some of these factors are common across child development, but some are more unique to youth with CKD. Mental health concerns are associated with increased risk for a range of poor medical outcomes (e.g., adherence, risk of transplant rejection) and quality of life concerns. In this educational review, we discuss the current evidence base regarding the development of mental health concerns in youth with CKD. The review covers multiple domains including mood and anxiety disorders, traumatic stress, and neurodevelopmental disorders. Estimated prevalence and hypothesized risk factors are outlined, and the potential impact of mental health on medical care and functional outcomes are reviewed. Finally, we introduce options for intervention to support positive mental health and offer recommendations for building access to mental health care and improving the mental health education/training of medical professionals.

Neurodevelopmental profile of infants and toddlers awaiting a kidney transplant.

BACKGROUND: Infants and toddlers with kidney failure are susceptible to neurodevelopmental delays due to medical comorbidities and rapid brain development in early childhood. However, research on the neuropsychological development of this patient population has been limited over the past 10 years. METHODS: We performed a retrospective study to evaluate the neurodevelopmental functioning of infants/toddlers with kidney failure who completed the Bayley Scales of Infant and Toddler Development (3rd and 4th Edition) as part of a pretransplant evaluation between 2010 and 2022 (n = 23; Mage = 18 months, SD = 8.53; 16 males) using t-tests, linear model, and Pearson correlations. RESULTS: Mean Bayley scores of participants were below normative means for cognition (M = 86.74, 95% CI = 80.53-92.94, p < 0.001), language (M = 79.20, 95% CI = 73.32-85.08, p < 0.001), and motor (M = 78.00, 95% CI = 70.15-85.85, p < 0.001) domains. After adjusting for prematurity and epilepsy, patients on dialysis had significantly lower cognitive (78.7 vs. 93.8; p = 0.001) and motor scores (67.1 vs. 85.5; p = 0.01) compared to no dialysis. Pretransplant cognitive scores were positively correlated with posttransplant Full-Scale IQ (r(8) = 0.65 p = 0.04), verbal comprehension (r(8) = 0.75 p = 0.02), and fluid reasoning (r(7) = 0.68 p = 0.045). Similarly, pretransplant language scores were positively correlated with posttransplant Full-Scale IQ (r(7) = 0.74 p = 0.03) and verbal comprehension (r(7) = 0.73 p = 0.03). Of the 16 participants who reached age > 5 years during the study period, seven were diagnosed with a neurodevelopmental disorder, including three with autism spectrum disorder. CONCLUSIONS: Infants and toddlers with kidney failure are at risk of developmental delays and later neurodevelopmental disorders. Dialysis is associated with cognitive and motor delays independent of prematurity and epilepsy.

Naringin protects against inflammation and apoptosis induced by intestinal ischemia-reperfusion injury through deactivation of cGAS-STING signaling pathway.

Effective amelioration of ischemia/reperfusion (I/R)-induced intestinal injury and revealing its mechanisms remain the challenges in both preclinic and clinic. Potential mechanisms of naringin in ameliorating I/R-induced intestinal injury remain unknown. Based on pre-experiments, I/R-injured rat intestine in vivo and hypoxia-reoxygenation (H/R)-injured IEC-6 cells in vitro were used to verify that naringin-alleviated I/R-induced intestinal injury was mediated via deactivating cGAS-STING signaling pathway. Naringin improved intestinal damage using hematoxylin and eosin staining and decreased alanine aminotransferase and aspartate aminotransferase contents in plasma. Naringin decreased inflammation characterized by reducing IL-6, IL-1ß, TNF-α, and IFN-ß contents in both plasma and IEC-6 cells. Naringin mitigated oxidative stress via recovering superoxide dismutase, glutathione, and malondialdehyde levels in the I/R-injured intestine. Naringin reduced the expression of apoptotic proteins, including Bax, caspase-3, and Bcl-2, and reduced terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells both in vivo and in vitro, and decreased Hoechst 33342 signals in vitro. cGAS, STING, p-TBK1, p-IRF3, and NF-κB expressions were up-regulated both in vivo and in vitro respectively and the up-regulated indexes were reversed by naringin. Transfection of cGAS-siRNA and cGAS-cDNA significantly down-regulated and up-regulated cGAS-STING signaling-related protein expressions, respectively, and partially weakened naringin-induced amelioration on these indexes, suggesting that deactivation of cGAS-STING signaling is the crucial target for naringin-induced amelioration on I/R-injured intestine.

MicroRNA-122a aggravates intestinal ischemia/reperfusion injury by promoting pyroptosis via targeting EGFR-NLRP3 signaling pathway.

Multiple studies have confirmed the significance of microRNA (miR)-122a in disease regulation. However, its impact on ischaemia/reperfusion (I/R) injury is unknown. In this study, we propose that the promoting role of miR-122a exists in I/R injuries. Two models, including hypoxia/reoxygenation (H/R)-injured IEC-6 cells in vitro and ischemia/reperfusion (I/R)-injured C57BL/6 mice intestinal tissues in vivo, were used to verify our purpose. Applying dual-luciferase reporter assays and transfection tests, the regulatory impacts of miR-122a were examined by promoting pyroptosis on intestinal I/R injury via targeting epidermal growth factor receptor (EGFR)-NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) signaling pathway. Both H/R-injured IEC-6 cells and I/R-injured mice intestinal tissues had elevated miR-122a expression, which targeted EGFR directly. Increased miR-122a expression significantly inhibited EGFR activity, decreased EGFR mRNA and protein expression, increased NLRP3 mRNA and protein expression, and up-regulated caspase 1, N-GSDMD, ASC, IL-1ß, and IL-18 protein expression to promote pyroptosis. Furthermore, in IEC-6 cells, a miR-122a inhibitor and an EGFR-overexpression plasmid significantly reduced pyroptosis and alleviated intestinal I/R injury via activating the EGFR-NLRP3 signaling pathway, showing that miR-122a is very essential for regulating intestinal I/R injury. In brief, miR-122a promotes pyroptosis by inhibiting the EGFR-NLRP3 signaling pathway, which should be evaluated as a therapeutic target for intestinal I/R injury.

A Predictive Study of the Dynamic Development of the P-Wave Terminal Force in Lead V1 in the Electrocardiogram in Relation to Long-Term Prognosis in Non-ST-Segment Elevation Acute Coronary Syndrome Patients during Hospitalization.

BACKGROUND: Changes in the ECG indicator PtfV1 reflect left atrial pressure and left ventricular diastolic function in NSTE-ACS patients during hospitalization. The value of PtfV1 in the evaluation of long-term prognosis in NSTE-ACS is still not clear. The purpose of this study was to investigate the relationship between the dynamic changes in P-wave terminal force in lead V1(PtfV1) in the ECG of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients during hospitalization and the long-term major adverse cardiovascular events (MACEs) of patients. METHODS: A total of 595 patients who received coronary angiography and were confirmed as NSTE-ACS in the coronary heart disease database of Department of Cardiology of West China Hospital were continuously included. The PtfV1 and other clinical data at admission and discharge were collected and dynamically observed. The end events of follow-up observation were MACEs. RESULTS: Follow-up was performed on 595 patients for 24.71 ± 1.95 months. There were 127 PtfV1(+) and 468 PtfV1(-) at admission, and the incidences of MACEs were 14.2% and 11.1%, respectively (P = 0.731). Compared with patients with persistent PtfV1(-) ECG at admission and discharge, 53 patients with persistent PtfV1(+) ECG at admission and discharge had increased risk for MACEs (HR: 2.221, 95% CI: 1.072-4.601, P = 0.032); 94 patients with new PtfV1(+) ECG at discharge also had significantly increased risk for MACEs (HR: 2.993, 95% CI: 1.660-5.397, P = 0.000). CONCLUSIONS: NSTE-ACS patients with persistent PtfV1(+) ECG indicators at admission and discharge and new PtfV1(+) at discharge had significantly increased risk of MACEs.

Boundary issues and multiple relationships in genetic counseling supervision: supervisor, non-supervisor, and student perspectives.

Boundary issues and multiple relationships potentially affect all supervision interactions. Boundary crossings are departures from the strictest professional role and may or may not benefit supervisees. Boundary violations are outside common practice and may place supervisees at significant risk. Multiple relationships occur when supervisors concurrently or consecutively hold two or more roles with supervisees. Studies in other fields indicate supervisors and supervisees may be uncertain about professional conduct regarding these issues. In this study, genetic counselor supervisors (n = 126), non-supervisors (n = 72), and genetic counseling students (n = 129) completed an anonymous survey investigating four major questions: 1) Are various boundary issues and multiple relationships perceived as differentially appropriate? 2) Do supervisor, non-supervisor, and student perceptions differ? 3) What challenging situations have respondents experienced? and 4) What management strategies did they use? There was general agreement among groups in their appropriateness ratings of 56 hypothetical supervisor behaviors, although supervisor ratings tended to reflect stricter boundaries regarding the appropriateness of interactions than student ratings. A majority rated unavoidable boundary crossings and supervisor multiple relationships involving an academic relationship as most appropriate, and romantic/sexual multiple relationships and/or boundary violations as least appropriate. Analysis of respondents' actual challenging situations revealed many involved boundary violations, placed students at risk of harm, and often resulted in student compliance.