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Τρίτη 3 Μαΐου 2022

Verapamil down‐regulates iron uptake and up‐regulates divalent metal transporter 1 expression in H9C2 cardiomyocytes

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Abstract

Belgrade rats have a defect in divalent metal transport 1 (DMT1) with a reduced heart iron, indicating that DMT1 plays a physiological role in non-transferrin-bound iron (NTBI) uptake by cardiomyocytes. However, LVDCC (L-type voltage-dependent Ca2+ channel) blockers were recently demonstrated to significantly reduce NTBI uptake by cardiomyocytes, implying that LVDCC plays a dominant role in NTBI uptake by cardiomyocytes under iron-overloaded conditions. These findings led us to hypothesize that the LVDCC blocker-induced reduction in NTBI uptake might result not only from the inhibition of LVDCC-mediated NTBI uptake but also from the suppression of DMT1-mediated NTBI uptake. We therefore investigated the effects of the LVDCC blocker verapamil on NTBI uptake as well as DMT1 expression in H9C2 cells by the measurement of radio-labeled 55Fe(II), RT-PCR and western blot analysis. We demonstrated that verapamil induced a significant reduction in NTBI uptake by H9C2 cells, but also unexpectedly a remarkable increase rather than decrease in the expression of DMT1 mRNA and protein in H9C2 cells. Our findings imply that the verapamil-induced reduction in NTBI uptake by H9C2 cells is not associated with DMT1, and also indicate that verapamil stimulates rather than inhibits DMT1 expression and DMT1–mediated iron uptake by heart cells.

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HIV is associated with elevated FibroScan-AST (FAST) score

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Abstract
Background & Aims
Whether HIV infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-AST (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort.
Approach
Vibration controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women living with HIV (WLWH) and 381 women living without HIV (WLWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score.
Results
Median age of WLWH and WLWOH was 51 years and 48 years, respectively. Most (90%) WLWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WLWH compared to WLWOH, 6.3% vs 1.8% (p=0.001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (p=0.002) and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (p<0.001). In analysis limited to WLWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score.
Conclusions
Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons living with HIV are warranted.
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Relative Vaccine Effectiveness of a SARS-CoV-2 mRNA Vaccine Booster Dose Against the Omicron Variant

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Abstract
Background
The current SARS-CoV-2 vaccines may be less effective against the Omicron variant. With recent resurgence of SARS-CoV-2 cases, the role of booster doses of the vaccine needs to be highlighted.
Methods
Using a retrospective cohort study design emulating a target trial, we determined the relative effectiveness of a homologous booster dose of a SARS-CoV-2 mRNA vaccine compared with primary series alone in preventing infection, hospitalization, a nd intensive care unit (ICU) admission, and death in the Department of Veterans Affairs healthcare system in the US. Among infection-free survivors who received two doses of an mRNA vaccine prior to April 30, 2021, we identified those who received a booster between September 22 and December 25, 2021 and 1:1 matched individuals who did not receive a booster.
Results
Among 2,384,272 previously uninfected persons with two doses of an mRNA vaccine by April 30, 2021, we identified 462,950 booster recipients between September 22 and December 25, 2021 who were matched 1:1 with non-booster recipients. RVE (95% CI) was 19% (17-22%) for confirmed infection, 52% (46-57%) for hospitalization, and 83% (65-92%) for ICU admission or death. Recipients of the mRNA-1273 vaccine had a lower cumulative incidence of infections and hospitalizations compared with BNT-162b2 vaccine (log-rank p-value <0.001 for both comparisons).
Conclusion
While the RVE of SARS-CoV-2 mRNA booster vacci ne dose in preventing infection against the Omicron variant is low, the RVE is substantial in preventing hospitalization and high in preventing the most severe/critical disease.
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Investigating the efficacy of attentional bias modification on individuals with spider phobia through the emotional attention network test

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Abstract

Objectives

This study aimed to investigate the attention network function of spider phobics before and after attentional bias modification (ABM) through conduction of an emotional attention network test (eANT).

Methods

Scores from an eANT, an approach–avoidance task, and various scales were used to examine the training effect of a single ABM session among participants (30 individuals with spider phobia and 30 controls).

Results

At baseline, alertness scores in response to spider images were higher in the phobia group than in the control group ( = 51.81 vs. 30.35 ms). After ABM, this score decreased in the phobia group, indicating their lower susceptibility to distraction by images of spiders. However, ABM training did not considerably alleviate their fear of and avoidance behavior toward spiders.

Conclusion

This study elucidates the (1) vigilance–avoidance pattern among individuals with spider phobia when encountering spider-related stimuli and (2) change in underlying attentional mechanisms after ABM training.

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Incidence, etiology, risk factors and outcomes of pre‐engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation

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Abstract

Introduction

With increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT.

Materials and methods

This is a retrospective study of 284 patients who underwent first allo-HCT and 37 patients after the second allo-HCT at the National Research Center for Hematology in Moscow, Russia, from January 2018 till September 2021.

Results

Cumulative incidence of pre-engraftment BSI was 29.9% after the first allo-HCT and 35.1% after the second (p = 0,805). Median time to the first BSI was 9 days (range 0–61 days) after the first and 16 days (range 1–28 days) after the second allo-HCT (p = 0.014). A total of 113 pathogens were isolated during 94 BSI episodes after the first allo-HCT (gram-negative bacteria 52.2%; gram-positive bacteria 47.7%). Fourteen pathogens were isolated during 14 BSI episodes after the second allo-HCT (gram-negative bacteria 50.0%; gram-positive bacteria 50.0%). The only significant difference was found in the rate of carbapenem-resistant gram-negative bacteria, which was higher after the second allo-HCT compared to the first (57.1% vs. 13.6%; p = 0.048).

Mismatched unrelated donor (HR 3.01; 95% CI:1.62-5.60; p<0.0001) and haploidentical donor transplantations (HR 1.84; 95% CI:1.02-3.33; p = 0.042) were the only independent risk factors associated with the higher risk of pre-engraftment BSI.

Overall 30-day survival after all BSI episodes was 94.4%,. Survival was lower after BSI during the second allo-HCT compared to the first (71.4% vs. 97.9%; p<0,0001), particularly after BSI caused by carbapenem-resistant gram-negative bacteria (25.0% vs. 100.0%; p = 0.0023). Non-relapse mortality rate at day +60 was 4.0%, and the risk was highly associated with primary graft failure (HR 9.62; 95% CI: 1.33-71.43), second allo-HCT (HR 6.80; 95% CI: 1.36-34.48), and pre-engraftment BSI caused by carbapenem-resistant gram-negative bacteria (HR 32.11; 95% CI: 4.91-210.15).

Conclusions

Pre-engraftment BSI is still a common complication after allo-HCT, particularly after mismatched unrelated and haploidentical donor transplantations. BSI incidence was slightly higher after the second allo-HCT with significantly higher rate of carbapenem-resistant BSI. Although pre-engraftment BSI would generally follow benign clinical course, survival was dramatically lower during the second allo-HCT especially after carbapenem-resistant BSI.

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Clinical evaluation of the GSD NovaPrime® SARS-CoV-2 RTq-PCR assay

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Publication date: Available online 3 May 2022

Source: Diagnostic Microbiology and Infectious Disease

Author(s): Marie Tré-Hardy, Sébastien Piteüs, Ingrid Beukinga, Laurent Blairon

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Vocal fold fibroblasts promote angiogenesis in vocal fold leukoplakia by secreting pro-angiogenic factors

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Publication date: Available online 2 May 2022

Source: Auris Nasus Larynx

Author(s): Yinying Chu, Yi Fang, Haitao Wu, Jian Chen, Lei Cheng

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COVID-19: Τι είναι το πρωτεϊνικό εμβόλιο της Novavax

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Ιατροί της Θεραπευτικής Κλινικής της Ιατρικής Σχολής του ΕΚΠΑ συνοψίζουν τα στοιχεία που ξέρουμε για το πρωτεϊνικό εμβόλιο Novavax (Nuvaxovid) που έγινε πρόσφατα διαθέσιμο στη χώρα μας.

Τρόπος παρασκευής: Το NVX-CoV2373 είναι ένα εμβόλιο υπομονάδας που κατασκευάζεται από μια σταθεροποιημένη μορφή της πρωτεϊνικής ακίδας S του SARS-CoV-2 με τη χρήση τεχνολογίας νανοσωματιδίων. Τα συγκεκριμένα πρωτεϊνικά αντιγόνα που εμπεριέχονται στο εμβόλιο δεν μπορούν να αναπαραχθούν ή να προκαλέσουν COVID-19.

Το εμβόλιο περιέχει επίσης ένα ανοσοενισχυτικό ώστε να ενισχύσει την ανταπόκριση του ανοσοποιητικού συστήματος και τη δημιουργία ανοσιακής μνήμης. Μια εφάπαξ δόση εμβολίου περιέχει 5 μικρογραμμάρια (mcg) πρωτεΐνης και 50 mcg ανοσοενισχυτικού.

Τρόπος χορήγησης και αποθήκευσης: Το NVX-CoV2373 χορηγείται με ένεση σε υγρή μορφή και μπορεί να αποθηκευτεί και να διανεμηθεί σε συνήθεις θερμοκρασίες ψυγείου (1,7°C έως 7,5°C), χωρίς να απαιτείται βαθιά κατάψυξη. Το εμβόλιο χορηγείται ως δύο ενδομυϊκές ενέσεις σε απόσταση 21 ημερών (3 εβδομάδες).

Οι ανοσοκατεσταλμένοι ασθενείς μπορεί να έχουν μειωμένη ανοσολογική ανταπόκριση στον εμβολιασμό και γι΄ αυτό είναι υποψήφιοι για χορήγηση αναμνηστικής δόσης. Το εμβόλιο Novavax μπορεί να συνδυαστεί με άλλα εγκεκριμένα εμβόλια, αν και η διαδικασία συλλογής δεδομένων για την αποτελεσματικότητα αυτής της στρατηγικής είναι σε εξέλιξη.

Προκαταρκτικά δεδομένα έχουν δείξει ότι η χορήγηση του εμβολίου της Novavax μετά από μια δόση του εμβολίου της AstraZeneca οδηγεί στην παραγωγή υψηλών τίτλων εξουδετερωτικών αντισωμάτων και ιδιαίτερα ισχυρής Τ-ανοσιακής απόκρισης, η οποία υπερτερεί του συνδυασμού δύο δόσεων του εμβολίου της AstraZeneca. Αυτό είναι πολύ σημαντικό καθώς και τα δύο εμβόλια διατηρούνται στη ψύξη και όχι στην κατάψυξη και επομένως είναι ευκολότερη η ευρεία διάθεσή τους χωρίς την ανάγκη ειδικών υποδομών.

Κλινική αποτελεσματικότητα: Τα αποτελέσματα κλινικής μελέτης φάσης 3 PREVENT-19 στην οποία συμμετείχαν 29.960 ενήλικες εθελοντές άνω των 18 ετών στις Ηνωμένες Πολιτείες και το Μεξικό έδειξαν ότι το ερευνητικό εμβόλιο NVX-CoV2373 της Novavax είχε 90,4% αποτελεσματικότητα ως προς την πρόληψη της συμπτωματικής νόσου COVID-19. Ακόμα πιο σημαντικό είναι ότι το νέο εμβόλιο έδειξε 100% προστασία από COVID-19 μέτριας και σοβαρής βαρύτητας. Σε άτομα με υψηλό κίνδυνο εμφάνισης επιπλοκών από τη COVID-19 (άτομα 65 ετών και άνω, άτομα κάτω των 65 ετών με ορισμέ� �ες συννοσηρότητες ή με πιθανή τακτική έκθεση στον SARS-CoV-2), το εμβόλιο έδειξε 91% αποτελεσματικότητα ως προς την πρόληψη της συμπτωματικής νόσου COVID-19.

Δεν υπάρχουν διαθέσιμα σαφή στοιχεία για την αποτελεσματικότητα του εμβολίου ως προς το δυναμικό μετάδοσης του SARS-CoV-2. Οι συμμετέχοντες έλαβαν τυχαία με αναλογία 2:1 είτε το νέο εμβόλιο είτε το εικονικό φάρμακο σε δύο δόσεις με απόσταση 21 ημερών. Η κλινική δοκιμή ήταν διπλά τυφλή, δηλαδή ούτε οι ερευνητές ούτε οι συμμετέχοντες ήξεραν ποιος έλαβε το υποψήφιο εμβόλιο.

Η μελέτη PREVENT-19 σχεδιάστηκε για να αξιολογήσει εάν το NVX-CoV2373 μπορεί να αποτρέψει τη συμπτωματική νόσο COVID-19 επτά ή περισσότερες ημέρες μετά τη δεύτερη δόση σε σχέση με το εικονικό φάρμακο. Κατά την περίοδο πραγματοποίησης της μελέτης τα κυρίαρχα στελέχη σε αυτές τις χώρες ήταν το Άλφα, το Βήτα και το Δέλτα. Τα δεδομένα για την ακριβή αποτελεσματικότητα έναντι της Όμικρον συλλέγονται τώρα σε πραγματικό χρόνο. Κλινικές μελέτες βρίσκονται σε εξέλιξη για να συλλεχθούν δεδομένα ασφάλειας και ανοσογονικότητας για άτομα ηλικίας κάτω των 18 ετών.

Ασφάλεια: Τα δεδομένα ασφαλείας δείχνουν ότι το εμβόλιο Novavax είναι γενικά καλά ανεκτό. Ο ήπιος έως μέτριος πόνος και η ευαισθησία στο σημείο της ένεσης ήταν τα πιο κοινά εντοπισμένα συμπτώματα. Η κόπωση, ο πονοκέφαλος και ο μυϊκός πόνος που κράτησε λιγότερο από δύο ημέρες ήταν τα πιο συνηθισμένα συστηματικά συμπτώματα που εμφάνισαν οι εμβολιασθέντες.

Εγκυμοσύνη και Θηλασμός: Σύμφωνα με τον Παγκόσμιο Οργανισμό Υγείας, δεν υπάρχουν διαθέσιμα δεδομένα σχετικά με την ασφάλεια και την αποτελεσματικότητα της χρήσης του εμβολίου Novavax (NVX-CoV2373) σε εγκύους. Ωστόσο, με βάση προηγούμενα στοιχεία από άλλα εμβόλια που βασίζονται σε πρωτεΐνες κατά τη διάρκεια της εγκυμοσύνης, η αποτελεσματικότητα αναμένεται να είναι συγκρίσιμη με τις μη έγκυες γυναίκες παρόμοιας ηλικίας. Ο Παγκόσμιος Οργανισμός Υγείας συστήνει τη χορήγηση του εμβολίου COVID-19 σε εγκύους όταν τα οφέλη του εμβ ολιασμού υπερτερούν των πιθανών κινδύνων. Καθώς το εμβόλιο Novavax (NVX-CoV2373) δεν περιέχει ζωντανό ιό, είναι βιολογικά και κλινικά απίθανο να ενέχει κίνδυνο για το παιδί που θηλάζει.

Αντενδείξεις: Άτομα με ιστορικό αναφυλαξίας σε οποιοδήποτε συστατικό του εμβολίου δεν συστήνεται να το λάβουν. Τα άτομα με ενεργό λοίμωξη COVID-19 δε θα πρέπει να εμβολιάζονται μέχρι να αναρρώσουν και να έχουν ολοκληρώσει την περίοδο της καραντίνας.

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Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: results from eight european centres

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Publication date: Available online 2 May 2022

Source: Radiotherapy and Oncology

Author(s): Lone Hoffmann, Hanna Mortensen, Muhammad Shamshad, Maaike Berbee, Nicola Bizzocchi, Rebecca Bütof, Richard Canters, Gilles Defraene, Mai Lykkegaard Ehmsen, Francesca Fiorini, Karin Haustermans, Ryan Hulley, Erik W. Korevaar, Matthew Clarke, Sebastian Makocki, Christina T. Muijs, Luke Murray, Owen Nicholas, Marianne Nordsmark, Ganesh Radhakrishna

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HIP1R and Vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma

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Abstract
Background
IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression.
Methods
Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant.
Results
We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns high HIP1R and low vimentin levels w ere observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%.
Conclusions
We demonstrate that immunohistochemistry for HIP1R, vimentin and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.
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Angled ball and locator attachments for immediate loaded inclined implants used to retain maxillary overdentures: A cross over study of patient satisfaction and oral health related quality of life

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Abstract

Objectives

The aim of this was to compare the influence of two different angulated abutment designs on patient satisfaction, oral health-related quality of life, and prosthetic aspects of implant-supported maxillary overdentures.

Materials and Methods

For this cross-over study, 18 patients with completely edentulous maxillary ridges opposing implant-retained mandibular overdentures received 4 implants between the maxillary sinuses using computer-guided surgery. The anterior implants were installed at canine/lateral incisor areas and inclined 15° labially. The posterior implants were inserted just anterior to the maxillary sinuses and inclined 15o distally. Eight patients received maxillary overdentures retained by angled ball attachment (ball overdenture [BOD]) and angled locator attachment in random order. After 6 months, patients indicated satisfaction with their prosthesis using a visual analog scale (VAS), and oral health impact profile (OHIP-14). Moreover, postinsertion prosthodontic maintenance and complications were recorded for both attachments. Comparisons of patient satisfaction and prosthetic complications between groups were performed using the Wilcoxon matched-pairs test and the McNemar test, respectively.

Results

Locator overdenture (LOD) recorded significantly higher scores than the BOD group regarding all the VAS questions except for ease of cleaning (p < 0.007). LOD recorded significantly higher patient satisfaction regarding the pronunciation of sounds (p = 0.009), painful aching (p = 0.018), feeling tense (p = 0.011), unsatisfactory diet (p = 0.013), irritability with people (p = 0.005), and life in general (p = 0.004). The most common complications were matrix activation/renewal (n = 34). BOD showed a significantly higher incidence of attachment loosening (p = 0.002), and teeth fracture (p = 0.049) than LOD. LOD showed a significantly higher incidence of attachment wear and replacement than BOD (p <0.001). There was no difference between groups regarding soft tissue complications.

Conclusion

Within the limitations of this study, and in terms of improved patient-centered outcomes, angled locator attachments are recommended to retain maxillary implant overdentures opposed by implant retained mandibular overdentures at it was associated with increased patient satisfaction and oral health-related quality of life than angled ball attachments. However, locator attachment was associated with more postinsertion prosthodontic maintenance than ball attachment.

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The effect of (-)-epigallocatechin gallate as an adjunct to non-surgical periodontal treatment: a randomized clinical trial

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EGCG is proven to be of good effect to relieve periodontal inflammation, but it has not been applied as a local delivery medicine in patients with periodontitis widely. The aim of this clinical trial was to ev...
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