Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58) were administered hCG and Group B rLH (n = 56) in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures

Prevalence of Drug-Resistant HIV-1 Variants in Untreated Individuals in Europe: Implications for Clinical Management

BackgroundInfection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis penta increase-spacing 1>MethodsWe determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002 ResultsIn Europe, 1 of 10 antiretroviral-naive patients carried viruses with ⩾1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001 ConclusionsDrug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are update

Ανάπτυξη μοντέλου συμπλέγματος της πρωτεΐνης CF2 και DNA και στατιστική ανάλυση των αλληλουχιών δακτύλων ψευδαργύρου

The zinc finger is a small independently folded DNA recognition motif found in many eykaryotic proteins. In order to analyze them a database of 577 zinc fingers, from 106 different proteins has been constructed and a program for statistical analysis of aligned sequences written. We also designed a three dimensional model for the CF2-DNA interaction based on the structure of the Zif268-DNA complex (Pavletich and Pabo, 1991). The previous one represents an excellent working model for the interactions between the zinc fingers and the DNA. The chorion transcription factor CF2 was isolated as a potentional transcriptional regulator of a chorion gene of Drosophila melanogaster. It is a zinc finger protein which is present in the nuceli of follicle cells which produce the chorion. Localized CF2 is not detected in the early embryo but appears during later embryonic stages (Hsu et al., 1992). The model of the CF2-DNA complex was of general interest because it predicts the modularity of finger-DNA interactions other than the known hydrogen bonding has been reported at the Zif268-DNA structure. The binding site of the CF2 protein is A/T rich DNA (5-GATTATATA-3) instead of the G/C rich DNA (5-GCGTGGGCG-3) of the Zif268 protein. The results showed apart of the well characterized pattern observed in the Zif268 structure, that additional specific contacts may be formed with bases of the secondary DNA strand. From statstical analysis of the zinc finger sequences the particular role of each amino acid was noted and clusters of correlated residues at critical positions (DNA base contact positions) were observed. The results of the theoretical model of the complex CF2- DNA cmbined with statistical analysis will help to understand the mechanism of how zinc fingers, where the structure is unknown interact with the DNA.Oι δάκτυλοι ψευδαργύρου (zinc fingers) είναι μικρές περιοχές (domains) αποτελούμενες από περίπου 28 αμινοξέα, που αναγνωρίζουν επιλεκτικά συγκεκριμένες αλληλουχίες DNA. H παρούσα εργασία αναφέρεται i) στην δημιουργιά μοντέλου του συμπλέγματος τριών δακτύλων ψευδαργύρου της πρωτεΐνης CF2 (chorion factor-2) από δροσόφιλα με το DNA και ii) στη στατιστική ανάλυση 577 τέτοιων αλληλουχιών από 106 διαφορετικές πρωτεΐνες δακτύλων ψευδαργύρου. Tο μοντέλο του συμπλόκου της πρωτεΐνης CF2 με το DNA στηρίχτηκε αποκλειστικά στις συντεταγμένες της λυμένης δομής του συμλόκου Zif268 με το DNA (Pavletich and Pabo, 1991). H πρωτεΐνη Zif268 αποτελεί χαρακτηριστικό παράδειγμα των αλληλεπιδράσεων μεταξύ πρωτεϊνών δακτύλου ψευδαργύρου και του DNA. H πρωτεΐνη CF2 (chorion transcription factor) αποτελεί ρυθμιστικό παράγοντα γονιδίων στο χώριον (chorion) της δροσόφιλα (Drosophila melanogaster). O λόγος πραγματοποίησης του μοντέλου ήταν κυρίως για να ερευνηθεί αν τηρούνται οι ίδιοι κανόνες αλληλεπίδρασης με το DNA, όπως αυτοί περιγράφτηκαν σε γνωστές δομές πρωτεϊνών του είδους (Pavletich and Pabo, 1991). H αλληλουχία που αναγνωρίζεται από την πρωτεΐνη CF2 περιέχει κυρίως ζευγάρια βάσεων A/T (5-GATTATATA-3), σε αντίθεση με αυτή που αναγνωρίζεται από την πρωτεΐνη Zif268 που περιέχει κυρίως ζεύγη G/C (5-GCGTGGGCG-3) (Pavletich and Pabo, 1991). Tα αποτελέσματα έδειξαν ότι και στο μοντέλο του CF2 τα γενικά χαρακτηριστικά της αλληλεπίδρασης διατηρούνται όπως και στο μοντέλο του Zif268 (Pavletich and Pabo, 1991). Eπιπλέον όμως παρατηρήθηκαν και κάποια καινούργια στοιχεία, όπως η δυνατότητα αλληλεπίδρασης με βάσεις από το δευτερεύοντα κλώνο (secondary strand) του DNA, ή η δυνατότητα σχετικής τοποθέτησης των δακτύλων ψευδαργύρου, προς την κύρια αύλακα ανάλογα με το μήκος των πλευρικών αλυσίδων στις κρίσιμες θέσεις. Aπό την στατιστική ανάλυση των αλληλουχιών δακτύλων ψευδαργύρου προέκυψαν χρήσιμα συμπεράσματα για τον ρόλο που παίζει κάθε θέση στη διεργασία αναγνώρισης του DNA. Eπίσης βρέθηκαν ποιά συγκεκριμένα αμινοξέα και ποιοί συνδυασμοί τους απαντούν συχνώτερα στις κρίσιμες (αυτές δηλαδή που αλληλεπιδρούν με τις βάσεις του DNA) ή μη θέσεις ενός δακτύλου ψευδαργύρου. Σε συνδυασμό των αποτελεσμάτων από το θεωρητικό μοντέλο του CF2 και της στατιστικής ανάλυσης των δακτύλων ψευδαργύρου έχει προκύψει μια πιο ολοκληρωμέμη εικόνα, σε σχέση με αυτήν που υπήρχε ήδη για τον λειτουργικό και δομικό ρόλο κάθε αμινοξέος σ ένα δάκτυλο ψευδαργύρου

Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58) were administered hCG and Group B rLH (n = 56) in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures

Blood transcriptomes of anti-SARS-CoV2 antibody positive healthy individuals with prior asymptomatic versus clinical infection

The reasons behind the clinical variability of SARS-CoV-2 infection, ranging from asymptomatic infection to lethal disease, are still unclear. We performed genome-wide transcriptional whole-blood RNA sequencing, bioinformatics analysis and PCR validation to test the hypothesis that immune response-related gene signatures reflecting baseline may differ between healthy individuals, with an equally robust antibody response, who experienced an entirely asymptomatic (n=17) versus clinical SARS-CoV-2 infection (n=15) in the past months (mean of 14 weeks). Among 12.789 protein-coding genes analysed, we identified six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection relatively to those with clinical infection. All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that subtle differences at baseline expression of innate immunity-related genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study. © Copyright © 2021 Sfikakis, Verrou, Ampatziadis-Michailidis, Tsitsilonis, Paraskevis, Kastritis, Lianidou, Moutsatsou, Terpos, Trougakos, Chini, Manoloukos, Moulos, Pavlopoulos, Kollias, Hatzis and Dimopoulos

Transmission of drug-resistant HIV-1 in Europe remains limited to single classes

Background: The spread of drug-resistant HIV-1 might compromise the future success of current first-line regimens.status: publishe