Spinal versus General Anaesthesia in Postoperative Pain Management during Transurethral Procedures

We compared the analgesic efficacy of spinal and general anaesthesia following transurethral procedures. 97 and 47 patients underwent transurethral bladder tumour resection (TUR-B) and transurethral prostatectomy (TUR-P), respectively. Postoperative pain was recorded using an 11-point visual analogue scale (VAS). VAS score was greatest at discharge from recovery room for general anaesthesia (P = 0.027). The pattern changed significantly at 8 h and 12 h for general anaesthesia's efficacy (P = 0.017 and P = 0.007, resp.). A higher VAS score was observed in pT2 patients. Patients with resected tumour volume >10 cm3 exhibited a VAS score >3 at 8 h and 24 h (P = 0.050, P = 0.036, resp.). Multifocality of bladder tumours induced more pain overall. It seems that spinal anaesthesia is more effective during the first 2 postoperative hours, while general prevails at later stages and at larger traumatic surfaces. Finally, we incidentally found that tumour stage plays a significant role in postoperative pain, a point that requires further verification

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.Peer reviewe

Η έκφραση του h-TERT στα κύτταρα του αμνιακού υγρού και στα κύτταρα του ενδομητρίου μετά από καλλιέργεια

Στο αμνιακό υγρό έχουν βρεθεί Πολυδύναμα Βλαστικά Kύτταρα (Multipotent Stem Cells) που έχουν τη τάση του πολλαπλασιασμού, της αυτοανανέωσης και της διαφοροποίησής τους προς νευρικά κύτταρα, οστεοβλάστες και λιποκύτταρα. Επίσης περισσότερο ενδείκνυται να παρουσιάζουν ιδιότητες Ολοδυνάμων Βλαστικών κυττάρων (Pluripotent Stem Cells) της γαμετικής σειράς (Germ Stem Cells), γεγονός ελπιδοφόρο για τη δημιουργία γαμετών. Εκτός από δείκτες μεσεγχυματικής προέλευσης έχουν και δείκτες που ανευρίσκονται στα εμβρυικά κύτταρα όπως Octamer binding transcription factor ¾ (OCT ¾), Stage – specific embryonic antigen – 4 (SSEA-4), Sex Determining region Y-box 2 (SOX-2), Nanogen (NANOG), C- Myelocytomatosis (C-myc) και CD117(C-kit), όπου ο cluster of differentiation – 117 (CD117 ή C-kit) εμφανίζεται και στα Germ Cells. Το h-TERT (5p15.33) είναι το γονίδιο έκφρασης της αντίστροφης τρανσκριπτάσης της Τελομεράσης, του ενζύμου της αθανασίας καθώς προσθέτει αλληλουχίες DNA TTAGGG στα τελομεριδιακά άκρα των χρωμοσωμάτων ώστε τα κύτταρα να έχουν αυξημένο δυναμικό πολλαπλασιασμού και να μην οδηγούνται στην κυτταρική απόπτωση. Έχει αυξημένη έκφραση στα Εμβρυονικά Βλαστικά Κύτταρα (Embryonic Stem Cells), στα Αρχέγονα Γεννητικά Κύτταρα (Primordial Germ Cells) και στα Βλαστικά Καρκινικά Κύτταρα (Cancer Stem Cells). Επομένως είναι πιθανό όσο αυξάνει το δυναμικό και η πλαστικότητα των Stem Cells και λιγότερο διαφοροποιημένα είναι τα κύτταρα, να υπάρχει αυξημένη έκφραση του πυρηνικού h-TERT των αμνιοκυττάρων (Amniotic Fluid Cells - AFCs) αλλά και του κυτοσολικού h-TERT που είναι ενσωματωμένο σε εξωκυττάρια κυστίδια (Extracellular vesicles – EVs) που τα αμνιοκύτταρα (AFCs) κρύβουν. Επίσης η ανίχνευση αυτού του γονιδίου και στα Μεσεγχυματικά κύτταρα του ενδομητρίου στην Εκφυλιστική φάση – Εμμηνόρροια (Menstrual - blood derived Stem Cells – MenSCs) είναι σημαντική ένδειξη της αναπλαστικής ιδιότητας αυτών των κυττάρων για θεραπεία διαφόρων νοσημάτων και ανάπλαση ιστών. Διαφοροποιούνται σε κύτταρα του μυοκαρδίου, αναπνευστικά επιθηλιακά κύτταρα, ενδοθηλιακά, μυϊκά, νευρικά, ηπατικά, παγκρεατικά κύτταρα, οστεοβλάστες και λιποκύτταρα. Επίσης πρόσφατα έχει αποδεικτεί ότι εμφανίζουν και δείκτες που εκφράζονται στα Ολοδύναμα Εμβρυικά Βλαστικά κύτταρα όπως Oct-4, S0X-2, και SSEA-4, γεγονός πολύ σημαντικό για την Αναγεννητική Ιατρική.The amniotic fluid (AF) has been knowledged as an important fluid because in this have been isolated Stem Cells (Amniotic Fluid Stem Cells –AFCs), those cells show high plasticity, self – renewal and the capacity to differentiate into Nerve cells, Osteoblasts cells and Adipoce cells. AFCs, primarily, have been suggested to be categorized as Multipotent Stem Cells but nevertheless they express some genes of Pluripotent Stem Cells (Embryonic Stem Cells) and mainly in germ stem cell line as CD117 (c-kit), something very important and highly promising for the future. These markers are OCT 3/4, SSEA-4, SOX-2, NANOG, C-myc and CD117(C-kit), which has been mentioned. The h-TERT gene (5p15.33) is the gene of expression human telomerase reverse transcriptase. Telomerase is the enzyme responsible for maintenance of the length of telomeres at the end of chromosomes by addition of repetitive sequences as TTAGGG. The h-TERT expression has been exhibited in Embryonic Stem Cells, Primordial Germ Cells and Cancer Stem Cells as result to be the key of organ and tissue regeneration. So, the expression of this gene in AFCs is very significant because antibody-forming cells (AFCs) express the gene h-TERT at different levels with the the higher transcript levels of expressing the h-TERT protein that is present in the nuclear and cytoplasmic compartment, where the cytosolic h-TERT is embodied in the Extracellular vesicles (EVs) that AFCs secrete in the extracellular mileu. Menstrual - blood derived Stem Cells – MenSCs are Endometrial Mesenchymal Regenerative Cells are capable of differentiating into nine lineages, as Cardiomyocytic, Respiratory Epithelial, Neurocytic, Myocytic, Endothelial, Pancreatic, Hepatic, Adipocytic and Osteogenic. Recently, MenSCs have been known that they show some markers of Embryonic Pluripotent Stem Cells as Oct-4, S0X-2, και SSEA-4, something also promising in Regenerative Medicine.

First Case of Complete Bladder Duplication in the Coronal Plane with Concomitant Duplication of the Urethra in an Adult Male

Duplication of the lower urinary tract is a very rare congenital anomaly which is diagnosed either at birth or during early childhood. These rare malformations are most of the times accompanied by other concomitant anomalies and are therefore diagnosed immediately after birth. In some even rarer cases there are no concomitant anomalies and symptoms thus leading to a diagnosis later in childhood. This is the first case in the literature of complete bladder duplication in the coronal plane with concomitant duplication of the urethra and no other associated anomalies in a 52-year-old male who remained asymptomatic and therefore undiagnosed for more than 5 decades

Antibiotics after Simple (Acute) Appendicitis Are Not Associated with Better Clinical Outcomes: A Post-Hoc Analysis of an EAST Multi-Center Study

Background:The post-operative management of simple (acute) appendicitis differs throughout the United States. Guidelines regarding post-operative antibiotic usage remain unclear, and treatment generally is dictated by surgeon preference. We hypothesize that post-operative antibiotic use for simple appendicitis is not associated with lower post-operative complication rates. Methods:In a post-hoc analysis in a large multi-center observational study, only patients with an intra-operative diagnosis of AAST EGS Grade I were included. Subjects were classified into those receiving post-operative antibiotics (POST) and those given pre-operative antibiotics only (NONE). Clinical outcomes examined were length of stay (LOS), 30-day emergency department (ED) visits and hospital re-admissions, secondary interventions, surgical site infection (SSI), and intra-abdominal abscess (IAA). Results:A total of 2,191 subjects were included, of whom 612 (28%) received post-operative antibiotics. Compared with the NONE group, POST patients were older (age 37 [range 26-50] versus 33 [26-46] years; p < 0.001), weighed more (82 [70-96] versus 79 [68-93] kg (p = 0.038), and had higher white blood cell counts (13.5 +/- 4.2 versus 13.1 +/- 4.4/10(3)/mcL (p = 0.046), Alvarado Scores (6 [5-7] versus 6 [5-7]; p < 0.001), and Charlson Comorbidity Indices (median score 0 in both cohorts; p < 0.001). The POST patients had a longer LOS (1 [1-2] versus 1 [1-1] days; p < 0.001). There were no differences in the number who had ED visits within 30 days (9% versus 8%; p = 0.435), hospital re-admission (4% versus 2%; p = 0.165), an index hospitalization SSI (0.2% for both cohorts; p = 0.69), an SSI within 30 days (4% versus 2%; p = 0.165), index hospitalization IAA rate (0.3% versus 0.1%; p = 0.190), 30-day IAA (2% versus 1%; p = 0.71), index hospitalization interventions (0.5% versus 0.1%; p = 0.137) or 30-day secondary interventions (2% versus 1%; p = 0.155). Conclusions:Post-operative antibiotic use after appendectomy for simple appendicitis is not associated with better post-operative clinical outcomes at index hospitalization or at 30 days after discharge