â-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population

ABSTRACT â-thalassemia (â-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic pituitary -gonadal axis in patients with â-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with â-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into â-thal major (51 males and 62 females) and â-thal intermedia phenotypes (16 males and 6 females). Male patients with â-thal major were subdivided into three groups a) eugonadal (35%, Tanners stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanners stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanners stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with â-thal major were subdivided into: a) eugonadal (32%, Tanners stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanners stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanners stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with â-thal intermedia were subdivided into eugonadal (75% of males -33% of females) and hypogonadal (25% of males -67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, â-thal patients could be eugonadal or develop early or late onset HH. â-thal intermedia patients have a more favorable profile than â-thal major individuals. Current gonadal status of â-thal patients cannot be predicted by means of history, clinical or laboratory parameters

Unpublished Mediterranean and Black Sea records of marine alien, cryptogenic, and neonative species

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12,649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia).peer-reviewe

Synthesis of phosphinic pseudopeptidic inhibitors of Zn-metalloproteases

Several studies have demonstrated that the synthesis of phosphinic peptides is a very effective approach to develop highly potent inhibitors of zinc-metalloproteases. In the last decades, a large number of phosphinic peptides have been prepared using Fmoc solid phase synthetic methodology. The development of these peptides is based on the synthesis of Fmoc-protected phosphinic pseudodipeptidic building blocks which are designed to be compatible with the Fmoc solid phase methodology. The application of these building blocks in the synthesis of pseudopeptides demands suitable protection of the hydroxyphosphinyl moiety, since there is no satisfactory method in the literature where the hydroxyphosphinyl moiety can be unprotected during the synthesis of phosphinic peptides. This study concerns: The investigation of the protection of the hydroxyphosphinyl moiety of the phosphinic derivative Z-PheΨ[PO(OH)CH2]Gly-OEt. The protective groups that have been used are methyl, isopropyl, benzyl, 9-fluorenyl, tert-butyl, diphenylmethyl and 1-adamantyl. These esters were submitted to acidic (TFA/CH2Cl2 of various concentrations) and alkaline (NaOH/MeOH 0.4 M) deprotection conditions as well as to hydrogenolysis (Η2, Pd/C 10% or HCOONH4, Pd/C 10%). Collective tables concerning the behaviour of these esters towards deprotection conditions are presented. The effect of steric hindrance as well as the contribution of neighboring groups in the hydrolysis rate of phosphinic esters and C-terminal ethylesters in suitably selected β-carboxyphosphinic derivatives was studied using acidic and alkaline deprotection conditions. These effects led to the conclusion that intramolecular five-membered mixed anhydride type intermediates are responsible for the increase in cleavage rate in both acidic and alkaline deprotection. This hypothesis was supported by the absence of such an intramolecular assisting effect in the case of α-carboxyphosphinic methylesters in similar conditions. Finally, from the reactivity study of Z-aminoprotected phosphinic pseudodipeptides towards hydrogenolysis, where the hydroxyphosphinyl moiety is protected with the 1-adamantyl group, it is derived that a combined assisting effect of β-carboxyl group and α-amino group might take place in the unexpected removal of the adamantyl group. The study of the chemical features of phosphinic pseudodipeptides, in addition to new bibliographical data led to the development of a synthetic methodology affording phosphinic pseudodipeptidic building blocks in high yields. This method consists of an Fmoc-protection of the aminophosphinic acid, a Michael-type addition of the activated aminophosphinic derivative in a benzyl acrylate, a hydroxyphospinyl protection step by 1-adamantyl group and a selective removal of the benzyl group in catalytic hydrogenolysis conditions. The key reaction of this methodology is the Michael type addition reaction, which is carried out in mild conditions (TMSCl, DIPEA, 0ΟC). These conditions do not affect the Fmoc group. Using this strategy four pseudodipeptic building blocks were prepared in overall yield ~80%, achieving like this a profound improvement as compared to an already reported method. The applicability of phosphinic pseudopeptides in Ζn metalloproteases as potent inhibitors led to the development of potent and selective inhibitors of stromelysin 3, a member of the matrixin family which seems to be involved in the metastasis of cancer. The synthesis of the inhibitors was based in structural criteria derived from previous studies in structure-activity relations as well as in bibliographical data for the preferences of the enzymes in the Ρ1, Ρ1΄ and Ρ2΄ of their substrates. The general structure of these inhibitors is ΖΗΝC(R1)(R2)Ψ[PO(OH)CH2]CH(R3)CONHCH(R4)CONH2. This study led to the conclusion that Trp is well tolerated in P2 position. In addition, better results were achieved by using 3-phenylpropyl group as R2 side chain. When R1 = H and R2 = CH2(mBrPh) a compound was resulted which inhibits potently stromelysin 3 (Κi < 1 nM) and displayed a significant selectivity factor as compared to six other members of the matrixin family. These results led to useful conclusions concerning the size of S1΄ cavity of matrixins which is the main differentiation factor of these enzymes towards their substrates. The synthesis of phosphinic pseudodipeptides bearing in their Ρ1 position the aminophosphinic analogue of Asp and Glu aminoacids is a subject which hasn’t been dealed with success yet. This fact is due to the failure of the Michael addition of a partially or fully protected aminophosphinic analogue of aspartic acid to an acrylic derivative. The key reaction for the solution of this problem is the selective transformation of the phenyl group of a phenylalanine or an homophenylalanine to a carboxyl group via an Sharpless type oxidation step (RuCl3/NaIO4/CH3CN/H2O) in the phosphinic pseudodipeptides Boc-PheΨ[PO(OAd)CH2]Ala-OEt and Boc-hPheΨ[PO(OAd)CH2]Ala-OEt respectively. Using this methodology phosphinic pseudodipeptidic analogues of H-Asp-Ala-OH and H-Glu-Ala-OH, suitably protected for the synthetic demands of peptide development in solid phase, were prepared. The above methodology was applied to the synthesis of potent inhibitors of aminopeptidase A which act selectively towards other peptidases involved in the regulaion of the cardiovascular system. The need for the presence of a glutamic acid side chain in P1 position, a hydrophobic group in Ρ1΄ position and an aminoacid bearing a small side chain in Ρ2΄ position are highlighted in this study. These results were derived from the systematic study of these positions by applying specific differentiations in the side chains of P1, Ρ1΄ and Ρ2΄ positions as well as the C-terminal group of the putative inhibitor. This investigation led to the most potent and selective, inhibitor of aminopeptidase A, the pseudotripeptide H-GluΨ[PO(OH)CH2]LeuAla-OH, which is extremely selective towards APA as compared to neutral endopeptidase (NEP), aminopeptidase N (APN) and angiotensin converting enzyme (ACE), three petidases which are directly involved in the regulation of the cardiovascular system

A comprehensive methodological framework for improving security and efficiency of port container logistics

As ports have become key logistics nodes in global chains, port management of container operations has been experiencing radical changes. Moreover, the ramifications of the associated policy-making expand well beyond their own boundaries. The challenging managerial environment is further exacerbated by security concerns and regulations that have gained increased importance during the past years. In this work, we present a System Dynamics simulation-based methodological framework for the modelling and analysis of strategic decision-making for port containers management tackling the issues of security and efficiency. More specifically, we investigate the implications of alternative inspection policies on port system performance, while taking into account the interdependencies of the inspection process with the capacity planning of port operations. Finally, we demonstrate the applicability of the developed methodology on a major port of Greece.capacity planning, container operations, port logistics management, security, system dynamics, supply chain management, SCM, efficiency, port management, simulation, modelling, strategic decision making, inspection policies, Greece,

A comprehensive methodological framework for improving security and efficiency of port container logistics

As ports have become key logistics nodes in global chains, port management of container operations has been experiencing radical changes. Moreover, the ramifications of the associated policy-making expand well beyond their own boundaries. The challenging managerial environment is further exacerbated by security concerns and regulations that have gained increased importance during the past years. In this work, we present a System Dynamics simulation-based methodological framework for the modelling and analysis of strategic decision-making for port containers management tackling the issues of security and efficiency. More specifically, we investigate the implications of alternative inspection policies on port system performance, while taking into account the interdependencies of the inspection process with the capacity planning of port operations. Finally, we demonstrate the applicability of the developed methodology on a major port of Greece.capacity planning; container operations; port logistics management; security; system dynamics; supply chain management; SCM; efficiency; port management; simulation; modelling; strategic decision making; inspection policies; Greece.