The effect of progesterone on the anesthetic and analgesic requirements for ovariohysterectomy in the dog

Η παρούσα μελέτη διερεύνησε την επίδραση της συγκέντρωσης της προγεστερόνης, είτε ενδογενούς κατά τον ωοθηκικό κύκλο και την κυοφορία, είτε εξωγενούς, καθώς και του ενεργού μεταβολίτη της αλλοπρεγνανολόνη, στις απαιτήσεις σε αναισθητικά και αναλγητικά φάρμακα και στην ένταση του μετεγχειρητικού πόνου για τη διεξαγωγή ωοθηκυστερεκτομής στον σκύλο. Περιελήφθησαν 150 υγιείς, θηλυκοί σκύλοι, οι οποίο προσκομίστηκαν στην Κλινική Ζώων Συντροφιάς του ΑΠΘ για ωοθηκυστερεκτομή και οι οποίοι κατανεμήθηκαν σε 6 ομάδες με βάση το στάδιο του ωοθηκικού κύκλου και την ενδεχόμενη ορμονική αγωγή που έλαβαν. Συγκεκριμένα, σχηματίστηκαν 6 ομάδες από ζώα στο στάδιο του ανοίστρου (ομάδα Α), ζώα σε άνοιστρο που έλαβαν προγεστερόνη ενδομυϊκώς (Απ), ζώα στο στάδιο του διοίστρου (Δ), ζώα σε δίοιστρο που έλαβαν υποδορίως αγλεπριστόνη (Δα), ζώα σε δίοιστρο που έλαβαν κάψουλες τριλοστάνης (Δτ) και ζώα σε κυοφορία 28-42 ημερών (Ε). Σε κάθε ζώο καταγράφηκαν οι απαιτήσεις σε προποφόλη για εγκατάσταση της γενικής αναισθησίας, οι απαιτήσεις σε ισοφλουράνιο για διατήρηση, οι απαιτήσεις σε επιπλέον αναλγητικά φάρμακα είτε διεγχειρητικά είτε μετεγχειρητικά και έγιναν μετεγχειρητικές εκτιμήσεις πόνου. Επίσης έγιναν αιμοληψίες σε συγκεκριμένες χρονικές στιγμές για ορμονολογικές αναλύσεις. Μετά τη στατιστική επεξεργασία των αποτελεσμάτων δε βρέθηκε στατιστικώς σημαντική διαφορά στις απαιτήσεις σε αναισθητικά ή σε αναλγητικά φάρμακα μεταξύ των ομάδων, ούτε στατιστικώς σημαντική συσχέτιση μεταξύ των απαιτήσεων αυτών και των συγκεντρώσεων στο αίμα της προγεστερόνης ή της αλλοπρεγνανολόνης, εκτός από 2 συσχετίσεις εντός συγκεκριμένων ομάδων. Συμπεραίνεται ότι οι συγκεντρώσεις προγεστερόνης ή αλλοπρεγνανολόνης στο αίμα δεν επηρεάζουν τις απαιτήσεις σε αναισθητικά ή αναλγητικά φάρμακα για τη διεξαγωγή ωοθηκυστερεκτομής στο σκύλο ή ότι ενδεχόμενη τέτοια επιρροή επικαλύπτεται από τη χορήγηση προαναισθητικής αγωγής και αναλγητικών φαρμάκων.The objective of the current study was to investigate the effect of serum progesterone concentration, either endogenous, during the ovarian cycle and pregnancy, or exogenous, when administered during anestrus, and of its active metabolite allopregnanolone, on anesthetic and analgesic requirements, as well as post-operative pain intensity, for the performance of ovariohysterectomy in dogs. One hundred and fifty healthy female dogs, which were admitted to our clinic for elective ovariohysterectomy, were included in the present study. They were allocated to 6 groups according to the stage of the ovarian cycle and the corresponding serum progesterone co ncentration. The six groups consisted of dogs in anestrus (group A), in anestrus which received intramuscular progesterone injections prior to surgery (group Ap), dogs in diestrus (group D), in diestrus which received subcutaneous aglepristone injections prior to surgery (group Da), in diestrus which received oral trilostane prior to surgery (group Dt) and dogs in pregnancy of duration of 28-42 days (group P). Serum progesterone concentrations were measured in all dogs before and after any hormonal treatment and serum allopregnanolone concentrations were measured in selected dogs from all groups. The required dose of propofol for induction of anesthesia and the required isoflurane concentration for maintenance of anesthesia and the need for intraoperative fentanyl administration and extra postoperative pethidine analgesia were recorded. After statistical analysis, there were no significant differences between groups, regarding their anesthetic or analgesic requirements, that could be attributed to serum progesterone and/or allopregnanolone concentration. However, moderate correlations within certain groups were noted. Serum progesterone or allopregnanolone concentrations do not seem to have an effect on anesthetic and analgesic requirements for ovariohysterectomy in the dog or any potential effect is weak enough to be masked by the action of anesthetic premedication and/or analgesic and/or anaesthetic drugs used

Donor-Recipient Body Surface Area Mismatch and the Outcome of Liver Transplantation in the UK

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area (BSA) ratio or BSA index (BSAi) with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low BSAi cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the BSAi and compared to complications, graft and recipient survival. Results: The BSAi ranged from 0.491 to 1.691 with a median of 0.988. The BSAi > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with BSAi ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or BSAi > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants

Pharmacological Properties of DOV 315,090, an ocinaplon metabolite

metabolit

Allen's Interval Algebra Makes the Difference

Allen's Interval Algebra constitutes a framework for reasoning about temporal information in a qualitative manner. In particular, it uses intervals, i.e., pairs of endpoints, on the timeline to represent entities corresponding to actions, events, or tasks, and binary relations such as precedes and overlaps to encode the possible configurations between those entities. Allen's calculus has found its way in many academic and industrial applications that involve, most commonly, planning and scheduling, temporal databases, and healthcare. In this paper, we present a novel encoding of Interval Algebra using answer-set programming (ASP) extended by difference constraints, i.e., the fragment abbreviated as ASP(DL), and demonstrate its performance via a preliminary experimental evaluation. Although our ASP encoding is presented in the case of Allen's calculus for the sake of clarity, we suggest that analogous encodings can be devised for other point-based calculi, too.Comment: Part of DECLARE 19 proceeding

Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer

Abstract Background Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required. Methods In this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-naïve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings. Results Plasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3–2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12. Conclusions The measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment

Chemically and thermally stable silica nanowires with a β-sheet peptide core for bionanotechnology

Background: A series of amyloidogenic peptides based on the sequence KFFEAAAKKFFE template the silica precursor, tetraethyl orthosilicate to form silica-nanowires containing a cross-β peptide core. Results: Investigation of the stability of these fibres reveals that the silica layers protect the silica-nanowires allowing them to maintain their shape and physical and chemical properties after incubation with organic solvents such as 2-propanol, ethanol, and acetonitrile, as well as in a strong acidic solution at pH 1.5. Furthermore, these nanowires were thermally stable in an aqueous solution when heated up to 70 °C, and upon autoclaving. They also preserved their conformation following incubation up to 4 weeks under these harsh conditions, and showed exceptionally high physical stability up to 1000 °C after ageing for 12 months. We show that they maintain their β-sheet peptide core even after harsh treatment by confirming the β-sheet content using Fourier transform infrared spectra. The silica nanowires show significantly higher chemical and thermal stability compared to the unsiliconised fibrils. Conclusions: The notable chemical and thermal stability of these silica nanowires points to their potential for use in microelectromechanics processes or fabrication for nanotechnological devices

The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia

Background - Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation. To dissect the contribution of systemic inflammation and anti-angiogenic factors in preeclampsia, we investigated the relationships between the circulating markers of neutrophil activation and anti-angiogenic factors in severe preeclampsia or systemic inflammatory state during pregnancy. Methods and results - Serum sEng, sFlt-1, placenta growth factor, interleukin-6 (IL-6), calprotectin, and plasma a-defensins concentrations were measured by ELISA in 88 women of similar gestational age stratified as: severe preeclampsia (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL, n = 27). Neutrophil activation occurred in sPE and SIR, as a-defensins and calprotectin concentrations were two-fold higher in both groups compared to CRL (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P < 0.001) were ˜20-fold higher in sPE compared to CRL, but were not elevated in SIR. In women with sPE, anti-angiogenic factors were not correlated with markers of neutrophil activation (a-defensins, calprotectin) or inflammation (IL-6). Conclusions - Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia