Familial juvenile hyperuricemic nephropathy: Revisiting the SLC8A1 gene, in a family with a novel terminal gross deletion in the UMOD gene.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) comprises a heterogeneous group of rare hereditary kidney diseases characterized by family history of progressive chronic kidney disease (CKD) with bland urine sediment, absence of significant proteinuria and normal or small-sized kidneys. Current diagnostic criteria require identification of a pathogenic variant in one of five genes - UMOD, MUC1, REN, HNF1ß, SEC61A1. The most prevalent form of ADTKD is uromodulin-associated kidney disease (ADTKD-UMOD). Genetic study of a Portuguese family diagnosed with familial juvenile hyperuricemic nephropathy (FJHN), one of the nosological entities in the spectrum of ADTKD, revealed a previously unreported large deletion in UMOD encompassing the entire terminal exon, which strictly cosegregated with CKD and hyperuricemia/gout, establishing the primary diagnosis of ADTKD-UMOD; as well as an ultra-rare nonsense SLC8A1 variant cosegregating with the UMOD deletion in patients that consistently exhibited an earlier onset of clinical manifestations. Since the terminal exon of UMOD does not encode for any of the critical structural domains or amino acid residues of mature uromodulin, the molecular mechanisms underlying the pathogenicity of its deletion are unclear and require further research. The association of the SLC8A1 locus with FJHN was first indicated by the results of a genome-wide linkage analysis in several multiplex families, but those data have not been subsequently confirmed. Our findings in this family revive that hypothesis.

Sacral neuromodulation in pediatric refractory bladder and bowel dysfunction Insights from Canada's first pediatric cohort.

INTRODUCTION: Refractory bladder and bowel dysfunction (BBD) significantly affects the health and quality of life of children and their caregivers, emphasizing the need for effective and minimally invasive treatments. This study aims to present the inaugural Canadian experience using sacral neuromodulation (SNM ) as a therapeutic option for children with refractory BBD. METHODS: Patients <18 years old with refractory BBD were prospectively followed from 2018 to the present. Preoperative evaluation included spinal MRI and video urodynamics. Two-stage SNM implantation was executed with a minimum two-week stage 1 trial. Functional outcomes and complication rates were measured following validated questionnaires. RESULTS: Six patients completed staged implantation at a median age of 10.8 years (range 8.2-18). The median baseline Dysfunctional Voiding Scoring System (DVSS) score was 12.5 (10-22). At six months of followup, only one patient required adjunct bladder medication. Median DVSS at one-year followup was 5.5 (0-7). Symptomatic resolution was noted in three patients at six months, sustained over one year. Early surgical complications were reported in one (infection) and late complications in three (lead fracture, battery depletion, non-traumatic malfunction), requiring reimplantation at a median of 37.5 (1-49) months. Post-SNM reimplantation, oral medication and rectal therapy decreased, and DVSS scores improved by 30% (0-63.6) at six months. CONCLUSIONS: SNM is feasible and offers promising results for refractory pediatric BBD in Canada. The significant improvement of symptoms highlights the treatment's potential, which must be balanced against the high need for revision detected at three years, possibly related to patients' growth and high activity level.

Isolated posterior urethral valves (PUV) and anterior urethral valves (AUV) with and without concomitant PUV: Matched cohort study at a high-risk pediatric center.

OBJECTIVES: To compare postnatal outcomes of AUV and PUV patients to evaluate for potential differences between these conditions, given that anterior urethral valves (AUV) with or without concomitant posterior urethral valves (PUV) is a rare congenital anomaly leading to lower urinary tract obstruction (LUTO). METHODS: We reviewed our LUTO database and included patients with AUV or concomitant AUV+PUV, managed at our institution between 2003 and 2023 matching them to comparable PUV cases. Assessed variables included prenatal diagnosis, gestational age (GA) at birth, initial management, kidney function, presence and degree of hydronephrosis (HN), and need for renal replacement therapy (RRT). RESULTS: The AUV ± PUV group (AUV: n=11, concomitant PUV: n=2) and PUV group (n=26) had similar presenting ages and follow-up times (p>0.05). Only 15.4% of AUV cases presented prenatally compared to 72.0% of PUV cases (p=0.0016), leading to delayed postnatal management in AUV patients (p=0.0260). Findings at presentation included UTI, weak stream or a palpable penile mass. PUV patients demonstrated significantly higher creatinine levels at the initial visit and at last follow-up (p=0.0120 and p=0.0302) than the AUV ± PUV group, with only one patient requiring RRT (p>0.05). At the last follow-up, no patient in the AUV ± PUV group required clean intermittent catheterization compared to 37.5% in the PUV group (p=0.0331) which also demonstrated more patients with persistent HN (p=0.0039). CONCLUSION: AUV with or without concomitant PUV is a rare finding that should be considered in patients presenting with weak stream, UTI, and penile swelling. Our data suggests potential differences in presentation and less severe postnatal outcomes in AUV compared to PUV patients.

Review - Renal transplantation for congenital urological diseases.

INTRODUCTION: Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are structural disorders originating prenatally and present at birth. Affecting 4.2 to 1000 per 10,000 births globally, CAKUT includes conditions like posterior urethral valves, cloacal anomalies, and reflux nephropathy. These anomalies can lead to chronic kidney disease (CKD) or end-stage kidney disease (ESKD) in children, necessitating renal replacement therapy or transplantation. OBJECTIVES: This article aims to provide an updated perspective on pediatric kidney transplantation for children with CAKUT, emphasizing pre-transplant evaluation and management to optimize long-term outcomes. METHODS: A comprehensive urologic evaluation is essential for children with ESKD being considered for kidney transplantation. Key pre-transplant investigations include kidney/bladder ultrasound (US), voiding cystourethrogram (VCUG), uroflowmetry, and urodynamics (UDS)/video-urodynamics (VUDS). Non-operative interventions such as pharmacotherapy and clean intermittent catheterization (CIC) are also considered. Surgical interventions, like augmentation cystoplasty or continent catheterizable channels, are evaluated based on individual patient needs. RESULTS: Kidney/bladder US and VCUG provide essential anatomical information. UDS offers comprehensive functional data, identifying hostile bladders needing pre-transplant optimization. Non-surgical measures like anticholinergics and CIC improve bladder function, while surgical options enhance compliance and capacity. Concurrent interventions during transplantation are feasible but require careful consideration of risks and benefits. DISCUSSION: Children with CAKUT undergoing kidney transplantation exhibit comparable or better graft survival rates than those without CAKUT. However, those with lower urinary tract obstructions (LUTO) may have poorer long-term outcomes. UDS is crucial for evaluating bladder function pre-transplant, guiding the need for interventions. Long-term monitoring for urinary tract infections (UTIs) and bladder dysfunction is essential. CONCLUSION: Optimal outcomes in pediatric kidney transplantation for CAKUT patients require thorough pre-transplant evaluation and management, particularly for those with LUTO. Multidisciplinary approaches ensure careful monitoring and timely interventions, improving graft survival and quality of life for these patients.

Long-Term Kidney Outcomes in Children with Posterior Urethral Valves: A Population-Based Cohort Study.

BACKGROUND: Posterior urethral valves represent the most common cause of lower urinary tract obstruction in male infants (∼1/4000 live births). Long-term kidney outcomes of posterior urethral valves remain uncertain. We aimed to determine the time-varying risk of major adverse kidney events (MAKE) following children with posterior urethral valves into adulthood. METHODS: A population-based retrospective cohort study of all males (<2 years) diagnosed with posterior urethral valves between 1991-2021 in Ontario, Canada. Comparator cohorts were: 1) male general population and 2) male pyeloplasty patients (both <2 years). The primary outcome was MAKE (death, long-term kidney replacement therapy [dialysis or kidney transplant], or chronic kidney disease). Time-to-MAKE was analyzed using multivariable-adjusted Cox proportional hazards models. We censored for provincial emigration, or administrative censoring (March 31, 2022). RESULTS: We included 727 children with posterior urethral valves, 855 pyeloplasty comparators, and 1,013,052 general population comparators. Median follow-up time was 16.6 years (Q1-3 8.6-24.5) overall. Throughout follow-up, 32% of children with posterior urethral valves developed MAKE vs. 1% of the general population and 6% of pyeloplasty comparators. Their adjusted hazard ratio for MAKE was 36.6 (95%CI 31.6-42.4) vs. the general population. The risk of developing MAKE declined over the first 5 years after posterior urethral valves diagnosis but remained elevated for >30-year follow-up. Children with posterior urethral valves were also at higher risk of death, chronic kidney disease, long-term kidney replacement therapy, hypertension, and acute kidney injury than general population or pyeloplasty comparators. CONCLUSIONS: Children with posterior urethral valves are at higher risk of adverse long-term kidney outcomes well into adulthood.

Trehalose mediates salinity-stress tolerance in natural populations of a freshwater crustacean.

Salinization poses an increasing problem worldwide, threatening freshwater organisms and raising questions about their ability to adapt. We explored the mechanisms enabling a planktonic crustacean to tolerate elevated salinity. By gradually raising water salinity in clonal cultures from 185 Daphnia magna populations, we showed that salt tolerance strongly correlates with native habitat salinity, indicating local adaptation. A genome-wide association study (GWAS) further revealed a major effect of the Alpha,alpha-trehalose-phosphate synthase (TPS) gene, suggesting that trehalose production facilitates salinity tolerance. Salinity-tolerant animals showed a positive correlation between water salinity and trehalose concentrations, while intolerant animals failed to produce trehalose. Animals with a non-functional TPS gene, generated through CRISPR-Cas9, supported the trehalose role in salinity stress. Our study highlights how a keystone freshwater animal adapts to salinity stress using an evolutionary mechanism known in bacteria, plants, and arthropods.

Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.

Evaluating Safety of Ring Versus Clamp Devices in Neonatal Circumcision: A Meta-Analysis.

BACKGROUND: While device-based circumcision is considered non-inferior to traditional dissection, there is no consensus on the efficacy and safety of ring devices in comparison with clamp devices. We aimed to compare the safety outcomes of ring-based versus clamp-based circumcision techniques in neonates. METHODS: MEDLINE, EMBASE, Scopus, and CINAHL were searched following the Cochrane collaboration (PRISMA guidelines), without language restrictions, to identify relevant randomized controlled trials. Adverse events, bleeding events, infection events, and procedure time were extracted and analyzed from the selected studies. RESULTS: From 1661 citations, seven trials were included, encompassing 3390 patients. These studies compared ring-based to clamp-based circumcision devices in neonates. No significant difference was found in overall adverse events between the two groups. However, ring devices showed significantly fewer bleeding events compared to clamp devices. Infection events and procedure time were similar for both groups. CONCLUSIONS: Both ring and clamp devices have similar safety profiles, with ring devices potentially offering a reduced risk of bleeding. A comprehensive understanding of ring-specific complications and cosmetic outcomes is necessary for a more complete evaluation of these circumcision techniques. Our analysis is limited from a lack of detailed examination of ring-specific complications and their impact on cosmetic results. The included studies varied in quality, and some exhibited a risk of bias. LEVEL OF EVIDENCE: Level IV Treatment Study.

Bladder Embryonal Rhabdomyosarcoma Presenting in the Perinatal Period: Report of Two Consecutive Cases.

Bladder embryonal rhabdomyosarcomas (ERMS) are malignant soft tissue tumors that rarely present in the perinatal period. Herein, we report 2 cases that were diagnosed in the newborn period (one with concomitant posterior urethral valves [PUV]), managed with chemotherapy and surgical resection to minimize the need for radiation.

The impact of posterior urethral valves on pediatric quality of life and family function: Prospective analysis of serial patients managed in a dedicated multidisciplinary clinic.

INTRODUCTION: Posterior urethral valves (PUV) is a chronic condition that can adversely impact child and family health related quality of life (HRQOL). Surprisingly, to date, the impact of this condition on the QOL of children with PUV has not been studied. Thus, our aim is to evaluate this important aspect of care using validated questionnaires in our institutional PUV clinic. METHODS: From December 2022 to January 2024, the PedsQL Inventory and associated family impact module was distributed in our PUV clinic. Higher scores reflect better HRQoL and less impact on family. Children >8 years old completed the tool themselves, otherwise parents completed the tools on behalf of the child. We compared PUV scores against reported psychometric data from healthy children and other chronic illnesses. RESULTS: A total of 112 families completed the questionnaires. The total HRQoL score was 80 ± 13. Overall, we noted that the domains reflecting psychosocial impact were significantly lower than those of physical well-being (76 ± 16 vs. 89 ± 15 for psychosocial and physical impact, respectively; p < 0.01). There was a significant difference in the psychosocial emotional impact for children managed with clean intermittent catheterization (CIC) compared to those who were not (69 ± 21 vs. 81 ± 16; p = 0.005) (Table 2). In addition, we noted that children with PUV scored similar to healthy controls, but higher than children with other chronic illnesses. With respect to the impact on family, overall, parent, and family impacts were 76 ± 19, 78 ± 21, and 81 ± 21, respectively. DISCUSSION: Chronic illness has been associated with a negative impact on HRQoL in both adults and children. We noted similar findings the present study, particularly for young children and those who are maintained on CIC. To our knowledge, this is the first study to evaluate the impact of PUV on a child's HRQoL as well as the impact on the family, and to document a negative psychosocial impact of CIC in this population. However, there are some important limitations to be addressed including relying on families to complete questionnaires accurately during busy clinic visits and the lack of controls from the same environment. CONCLUSION: When compared to healthy controls, PUV patients score similarly in HRQoL assessment. In addition, children <3years of age report a negative impact on physical well being, and CIC negatively impacts the emotional well-being. These data can be used to advocate for better mental health supports and social work for these children.

The Role of Secondary Conservative Management Strategies in Bladder and Bowel Dysfunction: A Systematic Review and Meta-analysis.

OBJECTIVE: We sought to determine the effect of secondary management strategies in addition to urotherapy on bowel bladder dysfunction outcomes. STUDY DESIGN: The review protocol was prospectively registered (CRD42023422168). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus (database initiation until June 2023) were searched. Comparative studies of secondary management strategies vs conventional urotherapy alone were included. Two authors independently screened titles, abstracts, and reviewed full-text articles. Two authors extracted data related to study characteristics, methodology, subjects, and results. RESULTS: In this systematic review and meta-analysis of 18 studies and 1228 children, secondary management strategies (home-based education, biofeedback, and physical therapy) were associated with reduced symptom burden, fewer recurrent urinary tract infections, and improved uroflowmetry findings than children treated solely with urotherapy for conservative management. CONCLUSIONS: Although there is significant reporting heterogeneity, secondary conservative management strategies such as home education, biofeedback or cognitive behavioral therapy, and physiotherapy-based education are associated with less urinary incontinence, fewer infections, and fewer abnormal uroflowmetry findings.

Assessing safety and tolerability of super selective alpha-1 adrenergic blockers in infants under 3 years: Insights from a single-center study on lower urinary tract obstruction (LUTO).

BACKGROUND: Little is known about alpha blocker use in young children, particularly in those with lower urinary tract obstruction (LUTO). Therefore, we aimed to assess the safety and tolerability of selective alpha-blockers in children under 3 years of age with LUTO. METHODS: A prospectively-collected database captured 93 patients born between 12/2005 and 01/2023. Assessed data included baseline characteristics, ultrasound features, blood pressure (BP), side effects and creatinine values. Primary outcome was side effects or discontinuation of alpha-blockers. Secondary outcomes were BP parameters, growth, and kidney function. Data are shown as median with interquartile range (IQR), Odds Ratio (OR) with 95% CI and mean value with standard deviation (SD). RESULTS: A total of 33 patients less than 3 years of age were started on alpha-blockers at 16.8 ± 11.8 months and followed for 48.9 ± 40.5 months. At last follow-up, no significant effect on systolic/diastolic BP percentiles (p > 0.9 and p > 0.9), creatinine levels (p > 0.9). Weight percentiles increased to the last follow-up (37.8 ± 33.2 vs. 53.6 ± 32.9, p = 0.0133) while height percentiles increased from 28 to 100 days to last follow-up (12.9 ± 18.3 vs. 39.6 ± 35.2, p=0.001). Four patients discontinued alpha-blockers; however, no side-effects were reported during the study period. CONCLUSIONS: No severe clinical or systemic side effects were observed, demonstrating safety and tolerability in young children with LUTO. Although alpha-blockers did not significantly improve kidney function in short term follow-up, and failure to thrive was not observed in these children. Additional studies with more patients are required to assess the optimal dosing and timing leading to maximal benefits for these infants.

Assessment and validation of the pet-owner relationship scale for Brazil.

Introduction: This study aimed to perform a cross-cultural adaptation of the cat-owner/dog-owner relationship scales. The method involved several stages: conceptual, item, semantic, operational, measurement, and functional equivalence. Procedures included translation, synthesis of translations, back-translation, consensus on the English versions, external evaluation by the original authors, expert committee evaluation, and pre-tests. Methods: The study surveyed 234 pet owners across Brazil using a 20-item questionnaire. Data analysis utilized confirmatory factor analysis, covariance-based modeling, and multigroup analysis. Results: The study confirmed the content and construct validity of the model, demonstrating good convergent validity. Hypotheses testing revealed significant inverse relationships between Perceived Cost and Perceived Emotional Closeness, and between Perceived Cost and Pet-Owner Interactions. A positive correlation was found between Perceived Emotional Closeness and Pet-Owner Interactions, with Perceived Emotional Closeness also mediating the relationship between Perceived Cost and Pet-Owner Interactions. No significant differences were found across different pet owner groups, indicating the scale's invariance and reliability across various demographics. Discussion: The study significantly expands understanding of the complex dynamics in pet-owner relationships and emphasizes the interplay between emotional and practical factors. It offers valuable insights for future research and practices in animal and human welfare.

A Cohort Study to Evaluate the Evolution of the Optic Nerve Head Parameters and Inner Retinal Thickness During Childhood.

PURPOSE: To compare children's stereometric optic disc parameters and inner retinal thickness measured by optical coherence tomography (OCT) in two different moments in life in the same children and to establish a correlation between the optic nerve head (ONH) area and the difference of these parameters in the two observations. METHODS: In this observational cohort, children were evaluated on two occasions: at 6.7 ± 1.6 and 13.2 ± 0.7 years of age. Cup volume, neuroretinal rim (NRR) area, average cup-to-disc ratio, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell inner plexiform layer (GCIPL) were measured by the Cirrus HD-OCT (Carl Zeiss Meditec AG). RESULTS: A total of 175 children were included, 89 boys (50.9%) and 86 girls (49.1%). There was a significant decrease of the NRR area (P < .001) and increase of the cup volume (P < .001) on the second observation. The pRNFL thickness and GCIPL thickness also decreased (P < .001 and P = .002, respectively). There was a positive correlation between the ONH area and the difference of the cup volume (P = .047; r = 0.102) and a negative correlation with the difference of the NRR area (P < .001; r = 0.237). CONCLUSIONS: During childhood, there is an increase of the cup volume, a decrease of the NRR area, and a decrease of inner retinal layer thickness (more significant in the superior and inferior quadrants) measured by OCT. This study demonstrates that in children with large discs the enlargement of the cup and decrease of the NRR is more evident. Considering these changes, the physiological enlargement of the cup in a child with a large disc can be misinterpreted as the development of a glaucomatous lesion. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Intradetrusor Versus Suburothelial Onabotulinum Toxin A in Adults with Neurogenic and Non-neurogenic Overactive Bladder Syndrome: A Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB). METHODS: This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I2 statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software. RESULTS: Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) (p = 0.24) and acute urinary retention (p = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies. CONCLUSIONS: Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.

Pediatric Urology Providers' Perceptions and Attitudes on Transitional Urologic Care in a Single-Payer Health Care System.

INTRODUCTION: Advances in health care have improved outcomes for pediatric patients with congenital neurourological conditions, highlighting the need for an effective transition from pediatric to adult care. This study investigates Canada's transitional urologic care within its single-payer health care system, focusing on the active members of Pediatric Urologists of Canada and their practices, perceptions, and attitudes toward transitional urologic care. METHODS: A survey was distributed to 35 Pediatric Urologists of Canada members from July 2023 to January 2024, which collected data on transitional care practices and available transitional urology clinics. It also focused on a service overview, covering aspects such as the responder's geographic and institutional affiliations, clinical practice characteristics involving transitional care, perceived challenges, and strategies for care enhancement. RESULTS: Nationwide engagement emphasized a commitment to improving transitional care, with a significant proportion of respondents (64%) having over 10 years of practice, reflecting substantial experience in addressing transitional care challenges. The survey identified 4 dedicated transitional care clinics, 3 of which are active, pointing to concerted efforts toward specialized service provision. The major challenges identified include the lack of adult transitional care initiatives and governmental support. Recommendations for improvement should focus on standardizing transition protocols and boosting patient education. The survey also underscored the necessity of protocolized care for spina bifida-neurogenic bladder and complex urogenital conditions. CONCLUSIONS: This study highlights the active efforts and existing challenges within Canada's transitional urologic care system, particularly emphasizing operational transitional care clinics as a crucial step forward in catering to transitioning patients' needs.

Toxicity mechanisms of plastic nanoparticles in three terrestrial species: antioxidant system imbalance and neurotoxicity.

The detrimental impacts of plastic nanoparticles (PNPs) are a worldwide concern, although knowledge is still limited, in particular for soil mesofauna. This study investigates the biochemical impact of 44 nm polystyrene PNPs on three soil models-Enchytraeus crypticus (Oligochaeta), Folsomia candida (Collembola) and Porcellionides pruinosus (Isopoda). Exposure durations of 3, 7 and 14 days (d) were implemented at two concentrations (1.5 and 300 mg kg-1 PNPs). Results revealed PNPs impact on the activities of the glutathione-dependent antioxidative enzyme, glutathione S-transferase (GST) and on the neurotransmitter acetylcholinesterase (AChE) for all three species. Catalase (CAT) played a minor role, primarily evident in F. candida at 300 mg kg-1 PNPs (CAT and GST response after 14 d), with no lipid peroxidation (LPO) increase. Even with the antioxidant defence, P. pruinosus was the most sensitive species for lipid oxidative damage (LPO levels increased after 7 d exposure to 300 mg kg-1 PNPs). Significant AChE inhibitions were measured already after 3 d to both PNP concentrations in F. candida and E. crypticus, respectively. Significant AChE inhibitions were also found in P. pruinosus but later (7 d). Overall, the toxicity mechanisms of PNPs involved antioxidant imbalance, being (mostly) the glutathione-associated metabolism part of that defence system. Neurotoxicity, linked to AChE activities, was evident across all species. Sensitivity to PNPs varied: P. pruinosus > F. candida ≅ E. crypticus. This pioneering study on PNPs toxicity in soil invertebrates underscores its environmental relevance, shedding light on altered biochemical responses, that may compromise ecological roles and soil ecosystem fitness.