Histomorphometry of the Sural Nerve for Use as a CFNG in Facial Reanimation Procedures

Facial palsy (FP) is a debilitating nerve pathology. Cross Face Nerve Grafting (CFNG) describes a surgical technique that uses nerve grafts to reanimate the paralyzed face. The sural nerve has been shown to be a reliable nerve graft with little donor side morbidity. Therefore, we aimed to investigate the microanatomy of the sural nerve. Biopsies were obtained from 15 FP patients who underwent CFNG using sural nerve grafts. Histological cross-sections were fixated, stained with PPD, and digitized. Histomorphometry and a validated software-based axon quantification were conducted. The median age of the operated patients was 37 years (5–62 years). There was a significant difference in axonal capacity decrease towards the periphery when comparing proximal vs. distal biopsies (p = 0.047), while the side of nerve harvest showed no significant differences in nerve caliber (proximal p = 0.253, distal p = 0.506) and axonal capacity for proximal and distal biopsies (proximal p = 0.414, distal p = 0.922). Age did not correlate with axonal capacity (proximal: R = −0.201, p = 0.603; distal: R = 0.317, p = 0.292). These novel insights into the microanatomy of the sural nerve may help refine CFNG techniques and individualize FP patient treatment plans, ultimately improving overall patient outcomes

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Verzicht auf Drainagen bei der Abdominoplastik – eine randomisiert-kontrollierte Studie

Introduction There is insufficient scientific evidence from randomised controlled trials to support the routine use of closed-suction drains in body contouring procedures. The aim of this study was to evaluate cumulative seroma volume, length of hospital stay and complication rates in abdominoplasty patients without drains in direct comparison with a cohort receiving drains. Material and Methods Abdominoplasty patients were prospectively randomised in two study groups with (MD) and without (OD) placement of closed-suction drains. Patients with a BMI = 3. Cumulative seroma volume over a four-week follow-up period was assessed as the primary outcome measure. Secondary outcome measures were complications requiring surgical revision and length of hospital stay. Results This trial did not identify a statistically significant difference in cumulative seroma volume between the MD (30/53) and OD (23/53) cohorts in 53 patients (M(MD)493 +/- SD 407 ml; M(OD)459 +/- SD 624 ml; p = 0.812). However, a significantly shorter average length of hospital stay was observed in the OD population (M(MD)5.1 +/- SD 1.4 d; M(OD)4.2 +/- SD 1.5 d; p = 0.023). Complication rates were equal in both study groups (n(MD) = 1; n(OD) = 1). Conclusion The results of this trial do not justify routine placement of closed-suction drains in abdominoplasty procedures (horizontal or combined horizontal/vertical incision) in the pre-obese patient cohort (BMI <= 30 kg/m(2)). Drain placement should be evaluated on an individual patient-specific basis

Standard doses of Triamcinolone do not affect fibroblast cell migration of abdominoplasty patients in-vitro1

BACKGROUND:Recent studies have demonstrated that local application of corticosteroids reduces wound exudation following abdominoplasty and other reconstructive surgical procedures. On the other hand, corticosteroids might provoke wound healing disturbances due to their immunosuppressive effects. OBJECTIVE:The main objective of this study was to gain further information about the impact of the corticosteroid triamcinolone on cell migration in abdominoplasty patients. METHODS:An in-vitro scratch assay wound healing model was applied to observe cell migration of fibroblasts cultured with nutrient medium containing human seroma aspirate±triamcinolone. RESULTS:There were no significant differences regarding cell migration when fibroblasts were incubated with triamcinolone + seroma containing culture medium compared to seroma containing culture medium without triamcinolone. CONCLUSIONS:The performed in-vitro study suggests that triamcinolone does not decelerate fibroblast cell migration which is considered as a surrogate of wound healing

Clinical Impact of DIEP Flap Perforator Characteristics – A Prospective Indocyanine Green Fluorescence Imaging Study

Background: The question to what extent perfusion in deep inferior epigastric perforator (DIEP) flaps depends on specific perforator characteristics has been raised. Anatomical studies and previous clinical trials focussing on DIEP flap perfusion resulted in discrepancies. This prospective study investigates how perforator row, number and diameter affect DIEP flap microperfusion via Indocyanine Green (ICG) fluorescence angiography. Methods: The fractional weight of insufficiently perfused flap tissue in Zone 4 related to the total DIEP flap weight was measured based on ICG fluorescence angiography and defined as Zone 4 %. As a surrogate for overall DIEP flap perfusion, Zone 4 % was assessed according to the row, number and diameter of perforators included in the flap. Results: In 42 unilateral DIEP flap breast reconstructions, neither medial (33.6 +/- 14.2 %)/lateral perforator row (29.9 +/- 7.5 %, p = 0.683) nor the parameter perforator number (single perforator 31.5 +/- 14.4 %, two perforators 30.2 +/- 10.2 %, p = 0.727) had a statistically significant effect on flap tissue availability as measured via Zone 4 %. A negative correlative trend between perforator diameter and Zone 4 % (r = -0.096, p = 0.588) was observed. Conclusion: Zone 4 % provides a novel method for an objective assessment of DIEP flap perfusion. Medial/lateral row selection and other perforator properties (number, diameter) within the standard ranges, did not affect Zone 4 % as indicated by ICG fluorescence angiography. (C) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved