Structure-Activity Relationships and Molecular Pharmacology of Positive Allosteric Modulators of the Mu-Opioid Receptor.

Positive allosteric modulation of the mu-opioid receptor is a promising strategy to address the ever-growing problem of acute and chronic pain management. Positive allosteric modulators (PAMs) of the mu-opioid receptor could be employed to enhance the efficacy of endogenous opioid peptides to a degree that provides pain relief without the need for traditional opioid drugs. Alternatively, PAMs might be used to enhance the action of opioid drugs and so provide an opioid-sparing effect, allowing for the use of lower doses of opioid agonists and potentially decreasing associated side effects.

Evaluation of predictive performance of fetal urinary inflammatory markers of postnatal kidney function in fetuses with posterior urethral valves.

Background: There are proposed roles for inflammation in the development of congenital obstructive uropathy in the setting of posterior urethral valves (PUV). However, the value of inflammatory proteins as predictive markers of postnatal kidney function, key in the management of fetuses with PUV, has not been explored. We screened fetal urine of fetuses with PUV with a panel of inflammatory proteins to determine their predictive value of postnatal kidney function.

Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.

Mitochondria play a crucial role in maintaining the energy status and redox homeostasis of eukaryotic cells. They are responsible for the metabolic efficiency of cells, providing both ATP and intermediate metabolic products. They also regulate cell survival and death under stress conditions by controlling the cell response or activating the apoptosis process.

Aperiodic activity differences in individuals with high and low temporal processing efficiency.

It is known that Temporal Information Processing (TIP) underpins our cognitive functioning. Previous research has focused on the relationship between TIP efficiency and oscillatory brain activity, especially the gamma rhythm; however, non-oscillatory (aperiodic or 1/f) brain activity has often been missed. Recent studies have identified the 1/f component as being important for the functioning of the brain.

Kidney volume normative values in Central European children aged 0-19 years: a multicenter study.

Background And Objecitves: The currently available kidney volume normative values in children are restricted to small populations from single-centre studies not assessing kidney function and including none or only a small number of adolescents. This study aimed to obtain ultrasound-based kidney volume normative values derived from a large European White/Caucasian paediatric population with normal kidney function.

Methods: After recruitment of 1427 children aged 0-19 years, 1396 individuals with no history of kidney disease and normal estimated glomerular filtration rate were selected for the sonographic evaluation of kidney volume.

Are the Classical Symptoms of Hypertension in Children Still Sensitive Enough?

The available literature is scarce on the initial symptoms of arterial hypertension in children. Our study aimed to analyze the initial clinical profile of patients referred to the hospital with suspected hypertension and those diagnosed with hypertension for the first time during a hospitalization for other reasons. This study was a retrospective analysis of medical records in 471 patients.

A common timing mechanism across different millisecond domains: evidence from perceptual and motor tasks.

Temporal information processing (TIP) constitutes a complex construct that underlies many cognitive functions and operates in a few hierarchically ordered time domains. This study aimed to verify the relationship between the tens of milliseconds and hundreds of milliseconds domains, referring to perceptual and motor timing, respectively. Sixty four young healthy individuals participated in this study.

Cognitive training incorporating temporal information processing improves linguistic and non-linguistic functions in people with aphasia.

People with aphasia (PWA) often present deficits in non-linguistic cognitive functions, such as executive functions, working memory, and temporal information processing (TIP), which intensify the associated speech difficulties and hinder the rehabilitation process. Therefore, training targeting non-linguistic cognitive function deficiencies may be useful in the treatment of aphasia. The present study compared the effects of the novel Dr.

Ten-Eleven Translocation 1 and 2 Enzymes Affect Human Skin Fibroblasts in an Age-Related Manner.

Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC), first to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxycytosine (5caC). Evidence suggests that changes in TET expression may impact cell function and the phenotype of aging. Proliferation, apoptosis, markers of autophagy and double-strand DNA break repair, and the expression of Fibulin 5 were assessed by flow cytometry in TET1 and TET2-overexpressing fibroblasts isolated from sun-unexposed skin of young (23-35 years) and age-advanced (75-94 years) individuals.

A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months.

Kidney length normative values - new percentiles by age and body surface area in Central European children and adolescents.

Background: Kidney size evaluation is an essential examination in pediatric nephrology. While body length/height is the best predictor of kidney length, age-based and body surface area (BSA)-based normative values may be useful in clinical practice or research. This study aimed to establish ultrasound-based kidney length lambda-mu-sigma (LMS) percentiles by age and BSA in healthy children.

Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy.

Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6 or COQ8B. We performed a systematic literature review, PodoNet, mitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.

Burnout Syndrome among Pediatric Nephrologists-Report on Its Prevalence, Severity, and Predisposing Factors.

Background And Objectives: Burnout is an occupation-related syndrome comprising emotional exhaustion, depersonalization, and reduced feelings of work-related personal accomplishments. There are reports on burnout among adult nephrologists and general pediatricians, but little is known about burnout among pediatric nephrologists. The aim of our study was to assess the prevalence and severity of burnout syndrome among Polish pediatric nephrologists.

Sub- and Supra-Second Timing in Auditory Perception: Evidence for Cross-Domain Relationships.

Previous studies indicate that there are at least two levels of temporal processing: the sub- and supra-second domains. The relationship between these domains remains unclear. The aim of this study was to test whether performance on the sub-second level is related to that on the supra-second one, or whether these two domains operate independently.

Age as a moderator of the relationship between planning and temporal information processing.

Planning is a fundamental mental ability related to executive functions. It allows to select, order and execute subgoals to achieve a goal. Studies have indicated that these processes are characterised by a specific temporal dynamics reflected in temporal information processing (TIP) in some tens of millisecond domain.

An Anhydrous Sodium Chloride Skin Preservation Model for Studies on Keratinocytes Grafting into the Wounds.

Background: Human skin is needed for covering large body areas lost by trauma. The shortcomings of contemporary methods of skin storage are limited preservation time and high immunogenicity if allogeneic.

Methods: We investigated whether long-lasting skin preservation in anhydrous sodium chloride (NaCl) may be the source of keratinocytes (KCs) for transplantation.

Kidney length normative values in children aged 0-19 years - a multicenter study.

Background: Currently used pediatric kidney length normative values are based on small single-center studies, do not include kidney function assessment, and focus mostly on newborns and infants. We aimed to develop ultrasound-based kidney length normative values derived from a large group of European Caucasian children with normal kidney function.

Methods: Out of 1,782 children aged 0-19 years, 1,758 individuals with no present or past kidney disease and normal estimated glomerular filtration rate had sonographic assessment of kidney length.

Serum intact fibroblast growth factor 23 in healthy paediatric population.

Introduction: It is believed that fibroblast growth factor 23 (FGF23) can become an early biomarker of chronic kidney disease progression. Data on FGF23 age dependency are inconsistent. We present the results of the cross-sectional study concerning FGF23 levels in healthy Polish children.

A unique case of diagnosis of a heterotopic pregnancy at 26 weeks - case report and literature review.

Background: Heterotopic pregnancy (HP) is a rare condition when at least two pregnancies are present simultaneously at different implantation sites and only one located in the uterine cavity. The majority of cases are diagnosed in the first trimester.

Case Presentation: We present a unique case of HP diagnosed at 26 weeks of spontaneous pregnancy in a patient without any relevant risk factors.

Interfamilial clinical variability in four Polish families with cranioectodermal dysplasia and identical compound heterozygous variants in WDR35.

Cranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED.