Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder.

Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.

Functional Results, Complications Associated with the Serosa-lined Tunnel, and Quality of Life with a Cross-folded Ileal Reservoir Combined with an Afferent Tubular Isoperistaltic Segment for Heterotopic Continent Urinary Diversion: An Observational Long-term Cohort Analysis.

BACKGROUND: In patients who do not qualify for an orthotopic urinary diversion, for example, the urethra cannot be spared or is functionally impaired, a heterotopic continent cutaneous cross-folded ileal reservoir offers a good alternative. OBJECTIVE: To describe the indication, surgical technique, and postoperative management, and to report the reservoir-related outcomes and complications associated with the serosa-lined tunnel. DESIGN, SETTING, AND PARTICIPANTS: Perioperative outcomes of 118 consecutive patients after cystectomy and a heterotopic ileal reservoir adapted from the Studer bladder substitute technique, operated between 2000 and 2018, were evaluated. The catheterisable serosa-lined tunnel was constructed from the appendix (Mitrofanoff, n = 63), an ileal segment (Yang-Monti, n = 48), or a fallopian tube (n = 7). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pre- and postoperative data until last follow-up appointment were entered prospectively in the departmental database. The chi-square test was used to compare proportions. RESULTS AND LIMITATIONS: Median follow-up was 94 (interquartile range 36-152) mo. No peri- or postoperative mortality was observed within 90 d of surgery. Patient satisfaction was high in 77.5% and moderate in 16.9%. Overall, complications associated with the serosa-lined tunnel occurred in 52% (61/118) of patients. Stenosis of the continent outlet developed in 38% (45/118) of patients: 33/45 (75%) were simply dilated/incised at the outpatient clinic, of those 24% (8/33) required additional endoscopic dilatation. Of patients with stenosis of the continent outlet, 27% (12/45) needed open revision surgery. During follow-up, 8% (nine/118) of patients required revision of the serosa-lined tunnel due to incontinence. Twelve months postoperatively, 95% (92/97) patients were continent. A limitation is the retrospective analysis from prospectively assessed data. This could limit the generalisability of these findings, as selection bias cannot be excluded. CONCLUSIONS: The heterotopic continent cutaneous cross-folded ileal reservoir achieves good functional results. Complications associated with the serosa-lined tunnel occur in about half of the patients but generally are easy to manage. As a result, patient satisfaction is high. PATIENT SUMMARY: In patients who do not qualify for an orthotopic bladder substitute, a heterotopic continent cutaneous cross-folded ileal reservoir offers a viable alternative with good postoperative functional results and high patient satisfaction.

Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: correlation with autistic symptomatology.

Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 ± 3.8 years), 17 healthy male children (age 13.6 ± 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 ± 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, η2 = 0.285; plasma concentrations ASD 19.61 ± 7.12 pg/ml, ADHD 8.05 ± 5.49 pg/ml, healthy controls 14.43 ± 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS.