Clarithromycin Enhances the Antibacterial Activity and Wound Healing Capacity in Type 2 Diabetes Mellitus by Increasing LL-37 Load on Neutrophil Extracellular Traps

Background: Type 2 diabetes mellitus (T2D) is characterized by susceptibility to bacterial infections and impaired wound healing. Neutrophil extracellular traps (NETs) and the cathelicidin antimicrobial peptide LL-37 have been implicated both in defense against bacterial infections and in wound healing process. Recently, it was shown that macrolide antibiotic clarithromycin induces the release of LL-37-bearing NETs. In T2D there has not been identified any link between NETs and LL-37 and the effect of clarithromycin in neutrophils/NETs is unknown yet.Methods: Peripheral blood neutrophils were obtained from treatment-naive hyperglycemic T2D patients (naive), normoglycemic T2D patients under antidiabetic treatment (well-controlled) and healthy donors (controls). NET release and NET proteins were studied. Co-culture systems of NET structures with E. coli NCTC 9001 and primary skin fibroblasts were deployed to examine the in vitro antibacterial and fibrotic NET properties, respectively. The effect of clarithromycin was also investigated. Analysis was performed using immunofluorescence confocal microscopy, myeloperoxidase-DNA complex and LL-37 ELISA, immunoblotting and qRT-PCR.Results: NETs were characterized by the presence of LL-37, however they lacked antibacterial activity, in both groups of T2D patients. Clarithromycin significantly increased the externalization of LL-37 on NETs generated from well-controlled T2D neutrophils, thus restoring NET antibacterial capacity and promoting the wound healing process via fibroblast activation and differentiation.Conclusion: This study suggests that clarithromycin may add further advantage to well-controlled T2D patients, by enhancing their antibacterial defense and improving wound healing capacity of fibroblasts, through upregulation of LL-37 on NET structures

Anthimos Alexoudis: a scholar clergyman of the Late Ottoman era: life and work (authorial, archaeological, palaeographical et al.)

Hellenism, in the 19th century mainly, had the Church (Ecumenical Patriarchate) as its uniting factor, as proven in the present PhD thesis entitled “Anthimos Alexoudis: a scholar clergyman of the Late Ottoman era – Life and work", where the role of the Ecumenical Patriarchate on important issues regarding Hellenism of the late Ottoman Period is studied. Alexoudis, member of the Holy Synod and serving in Amasia and Velegrades Metropolises, was at the forefront of historic issues, such as the “Schism” and the drafting of the “National Regulations”, mainly from 1856 onwards. Alexoudis had a pivotal role in Greek education and Hellenism promotion policy in the provinces where he served. Specifically, his contribution to the education of the nation by establishing schools in the Ottoman Empire and the wider East region, as well as the staffing of the Church with educated clergymen, are thoroughly analyzed. Alexoudis also showed great interest in the Crypto-Christians of the Empire and, especially, in Spathia, while he was involved in the objectives of the Greek foreign policy, which, sometimes, were in opposition to the goals of the Church. Moreover, in the present dissertation we document and analyze Alexoudis’ writing and research activities, including collection and preservation of antiquities (we document information found in sources regarding donations of archaeological material to the Hellenic Philological Association of Constantinople and the Archaeological Society at Athens et al.), as well as preservation and study of paleographical sources (inscriptions on hard epigraphical materials and handwritten codices). The aforementioned are very important for the history of the Greek writing, the history of the Ottoman Hellenism and also the history of the Ecumenical Patriarchate. Alexoudis’ role is highlighted and investigated concerning the revelation and recognition of two of the most important purple vellum codices, “Codices Beratinus”, known as “purpureus Beratinus Φ” and “auropurpureus Anthymi”, codices of the 6th and 9th century respectively, which have been currently transferred and preserved in Tirana.Ο Ελληνισμός από τον 19o κυρίως αιώνα είχε ως συνεκτικό στοιχείο την Εκκλησία (Οικουμενικό Πατριαρχείο) κάτι που αποδεικνύεται και στην παρούσα διδακτορική διατριβή με τίτλο: “Άνθιμος Αλεξούδης: ένας λόγιος ιερωμένος της Ύστερης Οθωμανικής εποχής - Βίος και έργο”, όπου μελετάται ο ρόλος του Οικουμενικού Πατριαρχείου σε σημαντικά ζητήματα που αφορούν στον Ελληνισμό της ύστερης Οθωμανικής Περιόδου. Ο Αλεξούδης, ως μέλος της Ιεράς Συνόδου και υπηρετήσας στις Μητροπόλεις Βελεγράδων και Αμασείας, πρωταγωνίστησε σε ιστορικά ζητήματα, όπως στον “Όρο” του Σχίσματος, καθώς και στην σύνταξη των “Εθνικών Κανονισμών”, από το 1856 κυρίως κ.εξ., ενώ διαδραμάτισε σημαντικό ρόλο στην, εν γένει, πολιτική προώθησης της ελληνικής παιδείας και στην ανάδειξη της ελληνικότητας των επαρχιών όπου υπηρέτησε. Συγκεκριμένα, αναλύεται σχολαστικά η συμβολή του στην παιδεία του Γένους με την ίδρυση σχολείων στον χώρο της Οθωμανικής Αυτοκρατορίας και στην ευρύτερη Ανατολή, καθώς και στη στελέχωση, κυρίως, της Εκκλησίας με μορφωμένους ιερωμένους. Έντονο ενδιαφέρον επέδειξε και για τους κρυπτοχριστιανούς της Αυτοκρατορίας και ειδικότερα τους κρυπτοχριστιανούς στη Σπαθία, ενώ αναμείχθηκε και στις επιδιώξεις της ελληνικής εξωτερικής πολιτικής που έρχονταν σε αντίθεση, κάποτε, με τις επιδιώξεις της Εκκλησίας. Επίσης, καταγράφεται και αναλύεται η συγγραφική και ερευνητική του δραστηριότητα, που περιλαμβάνει συγκέντρωση και διάσωση αρχαιοτήτων (καταγράφουμε πληροφορίες εντοπιζόμενες στις πηγές που αφορούν σε δωρεές αρχαιολογικού υλικού προς τον Ελληνικό Φιλολογικό Σύλλογο της Κωνσταντινουπόλεως, στην Αρχαιολογική Εταιρεία στην Αθήνα κ.α.), αλλά και τη διάσωση και μελέτη παλαιογραφικών πηγών (επιγραφών σε σκληρά υλικά γραφής και χειρόγραφων κωδίκων). Η σημασία τους είναι μεγάλη για την ιστορία της ελληνικής γραφής, όπως και για την ιστορία του Οθωμανικού Ελληνισμού και την ιστορία του Οικουμενικού Θρόνου. Επισημαίνεται, κυρίως, και διερευνάται ο ρόλος του Αλεξούδη στον εντοπισμό και στην αποκάλυψη δύο από τους σπουδαιότερους στον κόσμο μεμβράνινους πορφυρούς κώδικες, τους “μπερατινούς κώδικες”, γνωστοί ως “purpureus Beratinus Φ” και “auropurpureus Anthymi”, κώδικες του 6ου και 9ου αιώνα, αντίστοιχα, που σήμερα έχουν μεταφερθεί και διασώζονται στα Τίρανα

HTR for Greek Historical Handwritten Documents

Offline handwritten text recognition (HTR) for historical documents aims for effective transcription by addressing challenges that originate from the low quality of manuscripts under study as well as from several particularities which are related to the historical period of writing. In this paper, the challenge in HTR is related to a focused goal of the transcription of Greek historical manuscripts that contain several particularities. To this end, in this paper, a convolutional recurrent neural network architecture is proposed that comprises octave convolution and recurrent units which use effective gated mechanisms. The proposed architecture has been evaluated on three newly created collections from Greek historical handwritten documents that will be made publicly available for research purposes as well as on standard datasets like IAM and RIMES. For evaluation we perform a concise study which shows that compared to state of the art architectures, the proposed one deals effectively with the challenging Greek historical manuscripts

Congenital Portosystemic Shunts in Dogs and Cats: Classification, Pathophysiology, Clinical Presentation and Diagnosis

Congenital portosystemic shunts (CPSS) are abnormal vascular communications between the portal and the systemic circulation, bypassing the hepatic parenchyma and resulting in liver hypoplasia and hepatic insufficiency. Such connections develop in utero and persist postnatally. CPSS are among the two most common congenital vascular anomalies of the liver in small animals, along with primary hypoplasia of the portal vein without portal hypertension (PHPV without PH). CPSS can be extrahepatic (ECPSS), most commonly diagnosed in small and toy breed dogs and cats, or intrahepatic (ICPSS), most commonly seen in large breed dogs. Single ECPSS is the most common type encountered in both dogs and cats. Clinical signs of CPSS are non-specific and may wax and wane, while laboratory findings can raise clinical suspicion for CPSS, but they are also not specific. Definitive diagnosis will be established by evaluation of liver function tests, such as determination of fasting plasma ammonia (FA) levels, and pre- and postprandial serum bile acids concentrations, and diagnostic imaging. The purpose of this article is to review the definition, classification, pathogenesis, clinical presentation, and diagnosis of CPSS in dogs and cats, highlighted by the authors’ clinical experience

A Three-Zone Scavenging Model for Large Two-Stroke Uniflow Marine Engines Using Results from CFD Scavenging Simulations

The introduction of modern aftertreatment systems in marine diesel engines call for accurate prediction of exhaust gas temperature, since it significantly affects the performance of the aftertreatment system. The scavenging process establishes the initial conditions for combustion, directly affecting exhaust gas temperature, fuel economy, and emissions. In this paper, a semi-empirical zero-dimensional three zone scavenging model applicable to two-stroke uniflow scavenged diesel engines is updated using the results of CFD (computational fluid dynamics) simulations. In this 0-D model, the engine cylinders are divided in three zones (thermodynamic control volumes) namely, the pure air zone, mixing zone, and pure exhaust gas zone. The entrainment of air and exhaust gas in the mixing zone is specified by time varying mixing coefficients. The mixing coefficients were updated using results from CFD simulations based on the geometry of a modern 50 cm bore large two-stroke marine diesel engine. This increased the model’s accuracy by taking into account 2-D fluid dynamics phenomena in the cylinder ports and exhaust valve. Thus, the effect of engine load, inlet port swirl angle and partial covering of inlet ports on engine scavenging were investigated. The three-zone model was then updated and the findings of CFD simulations were reflected accordingly in the updated mixing coefficients of the scavenging model

Association of clinical, laboratory and imaging biomarkers with the occurrence of acute myocardial infarction in patients without standard modifiable risk factors – rationale and design of the “Beyond-SMuRFs Study”

Abstract Background Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients. Methods The ‘‘Beyond-SMuRFs Study’’ is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023. Discussion The ‘‘Beyond-SmuRFs’’ study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients’ profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals. Trial Registration ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022