Αναζήτηση αυτού του ιστολογίου

Τρίτη 6 Δεκεμβρίου 2022

Helicobacter pyhlori regulated microRNA map of human gastric cells

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Abstract

Background

Helicobacter pylori is an infection of concern for its chronic colonization leading to peptic ulcers and gastric cancer. In recent times, microRNAs have been extensively studied to understand their role in the pathogenesis of this bacteria in diverse contexts of gastric diseases. The current analysis reports the microRNA-mRNA interactions that are associated with effective survival and virulence of this pathogen.

Materials and Methods

We convened differentially regulated human microRNAs responsive to H. pylori infection (HP-hDEmiRs) at different multiplicity of infection and time points in human gastric cell lines through retrospective data mining of experimental studies. In view of the molecular disparity of clinical samples and animal models, data from tissue, serum/plasma, urine, and ascites were excluded. Further, we utilized diverse bioinformatics approaches to retrieve experimentally validated, high-confidence targets of the HP-hDEmiRs to analyze the microRNA-mRNA interactions that are relevant to H. pylori pathogenesis.

Results

A total of 39 HP-hDEmiRs that showed unidirectional expression of either overexpression or downregulation were identified to modulate 23 targets explicitly studied under this infection. We also identified 476 experimentally validated targets regulated by at least 4 of the HP-hDEmiRs. In addition to the pathways prior-associated with H. pylori infection, the microRNA-mRNA interactome analysis identified several cellular processes and pathways highly associated with cell cycle, cell division, migration, and carcinogenesis.

Conclusion

This study generated a platform to study the mechanisms utilized by this pathogen using microRNAs as surrogate.

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Switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e‐Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients

alexandrossfakianakis shared this article with you from Inoreader
Six months multicentre pilot open label single-arm study to evaluate patient experience, acceptability and satisfaction of switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e-Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients

AVA® is a new electromechanical injection device for self-injecting certolizumab pegol (CZP). Thirty four patients were included (28 women) RA 11, PsA 10 and axial axSpA 13. Patients reported >90% adherence assessed with AVA® injection log and the full dose of CZP was injected on all patients with AVA® device. No safety findings related to AVA® CZP administration were identified. AVA® device is an advantageous delivery option for CZP. This study provides further evidence to support that AVA® device is a valid method for switching CZP from syringe or pen with highly preference in patients with RA, PsA and axSpa.


Abstract

What Is Known and Objective

The study aimed to assess acceptability and patient experience of Certolizumab (CZP) self-injection with AVA® and clarify patient device preference after switching CZP from the syringe or auto-injection pen to AVA® in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients.

Method

A multicentre open-label, cross-sectional and prospective study among four Spanish hospitals was performed. Adult RA, PsA, axSpA patients treated for at least 6 months with the CZP syringe or pen were recruited. At the first visit, patients completed Pre-AVA® questionnaire. Patients were instructed on proper administration of CZP by AVA®. After 2 and 6 months of CZP self-injections using the AVA®, patient experience, adherence, preference and safety of each administration was assessed using post-AVA® questionnaire.

Results and Discussion

Thirty four patients were included (28 women). All patients self-administered CZP AVA® the full dose of CZP was injected. Patients reported >90% adherence to CZP AVA® assessed with the injection log. Pain at the injection site was reduced after switching to AVA®. Twenty nine patients preferred CZP AVA® and five patients preferred the CZP pen. No safety-related findings related to AVA® CZP administration were identified.

What Is New and Conclusion

The AVA® is an advantageous delivery option for CZP in patients with RA, PsA, axSpA.

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Myomucosal island flap in the reconstruction of oral cavity defects: Description of the surgical technique

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Abstract

Multiple options are available for the reconstruction of the defects of the oral cavity. Among these, the facial artery myomucosal island flap (FAMMIF) is a pedicled flap composed by cheek mucosa, submucosa, and part of the buccinator muscle. The FAMMIF is ideal for the reconstruction of small-to-moderate defects of the oral cavity and the oropharynx. This is due to low operating time, low morbidity, and good functional and aesthetic results. A step-by-step description of the flap harvesting is presented, with particular attention to flap design, identification of the vessels, harvesting of the myomucosal island, tunnel preparation for its passage in the neck and back to the oral cavity, and closure of the cheek donor site with the buccal fat pad.

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Traditional versus conservative endodontic access impact on fracture resistance of chairside CAD‐CAM lithium disilicate anterior crowns: An in vitro study

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Abstract

Purpose

To evaluate the effect of traditional and conservative endodontic access hole preparation on fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate maxillary right central incisor crowns.

Materials and Methods

Fifty-seven milled lithium disilicate maxillary right central incisor crowns were designed and fabricated with a chairside CAD-CAM system (Planmeca Romexis, Planmeca). The abutment preparation had a 1.0 mm incisal reduction and 1.0 mm chamfer finish. The restorations were bonded with resin cement to printed resin dies (n = 19 per group) and were treated and divided into three groups, 1) no endodontic access, 2) traditional triangular endodontic access, and 3) conservative ovoidal endodontic access. The endodontic access of the crowns was sealed with flowable resin composite. Restorations were subjected to 10,000 cycles of thermal cycling between 5° and 55°C. Then, restorations were loaded and exposed to compressive loading force, and the crack initiation (CI) and complete fracture (CF) were recorded. SEM micrographs of broken specimens on the printed dies were captured. ANOVA test and Bonferroni's correction were used for statistical comparison.

Results

The fracture resistance among the three groups varied. Crowns with no endodontic access displayed significantly (p < 0.001) higher resistance [CI: 1025 (121) N; CF 1134 (127) N], followed by crowns with conservative ovoidal endodontic access [CI: 924 (60) N; CF: 1000 (72) N. Crowns with traditional triangular endodontic access showed the significantly (p < 0.001) lowest fracture resistance [CI: 635 (82) N; CF: 709 (75) N].

Conclusion

The fracture resistance of chairside CAD-CAM lithium disilicate maxillary anterior crowns is influenced by the type of endodontic access provided. Conservative ovoidal endodontic access provides crowns with higher fracture resistance than traditional triangular endodontic access. Crowns with no endodontic access provided the highest resistance than other types of endodontic access.

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Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: a phase I, “windowofopportunity” study

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Abstract
Background
The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.
Methods
Patients received trotabresib 30 mg/day on days 1–4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity.
Results
Twenty patients received preoperative trotabresib and underwent resection with no delays or cancellations of surgery; 16 patients received maintenance trot abresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Sixmonth progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30.
Conclusions
Trotabresib penetrates the blood–brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concom itant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).
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