Αρχειοθήκη ιστολογίου

Πέμπτη 18 Αυγούστου 2022

MicroRNA‐22 suppresses NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokine production by targeting the HIF‐1α and NLRP3 in Human dental pulp fibroblasts

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Abstract

Aim

To investigate the synergetic regulatory effect of miR-22 on HIF-1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis.

Methodology

Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR-22-3p, NLRP3 and HIF-1α in human dental pulp tissues (HDPTs). The miR-22 mimics and inhibitor or plasmid of NLRP3 or HIF-1α were used to upregulate or downregulate miR-22 or NLRP3 or HIF-1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF-1α, NLRP3, caspase-1, IL-1β and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1β and IL-18 was analyzed by ELISA. The significance of the differences between the experimental and control groups was determined by one-way analysis of variance, P<0.05 indicated statistical significance.

Results

A decrease in miR-22 and an increase in HIF-1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p<0.05). In the normal HDPTs, miR-22-3p was extensively expressed in dental pulp cells. HIF-1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR-22-3p, HIF-1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF-1α were direct targets of miR-22 in HDPFs. The miR-22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p<0.05). In contrast, the miR-22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p<0.05).

Conclusion

MiR-22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF-1α. These results provide a novel function and mechanism of miR-22-HIF-1α-NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.

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Humoral response to heterologous prime‐booster vaccination in heart transplant recipients aged 18 to 70 years primed with a viral vector SARS‐CoV‐2 vaccine

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Abstract

Background

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster).

Methods

Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay.

Results

A total of 80 heart transplant patients (mean age 49±13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28–33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p<0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p<0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine based-regimen (p = 0.007).

Conclusion

Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

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Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients

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Abstract

Background

Development of cytomegalovirus (CMV) and BK polyoma virus (BKV) infection following kidney transplantation have been associated with allograft dysfunction and allograft loss. Reduction in immunosuppression is a mainstay of management yet has been associated with increased risk of rejection. According to international consensus guidelines, one approach to management of these viral infections is to discontinue the antimetabolite. Little is known surrounding long-term outcomes in these patients, and it remains unclear if consideration should be given to resuming the antimetabolite as variable re-escalation strategies have been reported. The objective was to describe episodes of rejection and identify risk factors for rejection following antimetabolite withdrawal after CMV or BKV DNAemia in kidney transplant recipients.

Methods

This single-center, retrospective review evaluated adult kidney transplant recipients with a serum CMV or BKV DNA PCR ≥ 500 copies/mL who underwent antimetabolite discontinuation. The primary outcome assessed was the incidence of biopsy-proven acute rejection (BPAR).

Results

159 patients were included. Overall, 14 patients (8.8%) experienced BPAR at a median of 1.6 years after antimetabolite discontinuation. Compared to CMV, discontinuation after BKV DNAemia was associated with a higher incidence of BPAR. Characteristics observed more frequently in patients with BPAR included younger age, female sex, higher initial viral load, and development of de novo donor-specific antibody (DSA).

Conclusion

These findings suggest that antimetabolite discontinuation after CMV or BKV DNAemia in kidney transplant recipients is a reasonable and safe approach. Further prospective studies investigating optimal immunosuppression management following CMV or BKV DNAemia in kidney transplant recipients are warranted.

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Τετάρτη 17 Αυγούστου 2022

Evolution and transmission of cefiderocol-resistant Acinetobacter baumannii during an outbreak in the burn intensive care unit

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Abstract
We report 11 critically-ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and inter-patient transmission of cefiderocol-resistant A. baumannii between patients. Resistant isolates harbored disrupted pirA and piuA gen es that were not disrupted among susceptible isolates.
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Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE

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Publication date: Available online 17 August 2022

Source: Annals of Diagnostic Pathology

Author(s): Elizabeth Arslanian, Kamaljeet Singh, Katrine Hansen, M. Ruhul Quddus

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Onkolytische Virotherapie bei Kopf-Hals-Karzinomen

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Laryngorhinootologie
DOI: 10.1055/a-1901-9214

Ziel Onkolytische Viren (OV) infizieren und töten Krebszellen und lösen eine antitumorale Immunantwort aus. Durch ihr Potenzial, die Immunresistenz von Tumoren zu durchbrechen, könnten OV eine zukünftige zusätzliche Behandlungsoption bei Patient*innen mit fortgeschrittenen Kopf-Hals-Karzinomen (HNC) sein. Wirkungsweise und Modifikationen der OV zur Behandlung von HNC werden erläutert, ebenso die Risiken bei der Anwendung. Ergebnisse präklinischer und klinischer Studien werden vorgestellt. Methoden Präklinische und klinische Studien zu OV und HNC wurden in der PubMed-Literaturdatenbank und internationalen Studienregistern analysiert. Untersuchungen zum onkolytischen Herpes-Simplex-Virus (HSV), Adenovirus, Vacciniavirus und Reovirus wurden ausgewählt. Ergebnisse In jüngsten präklinischen Studien wurde eine verstärkte Infektion und Abtötung von Tumorzellen durch OV mit Kapsid- und Genommodifikationen beschrieben. Die meisten klinischen Studien waren Phase-I/II-Studien. In Phase-III-Studien wurden nach Behandlung mit onkolytischem HSV, Adenoviren und Reoviren eine partielle Tumorregression und ein verlängertes Überleben beobachtet. In den meisten Studien wurden OV mit Radiochemotherapie oder Immuntherapie kombiniert. Schlussfolgerung In den vorliegenden Studien war die OV-Therapie zur Behandlung von Patient*innen mit HNC sicher, oft gut verträglich und zeigte vielversprechende Ergebnisse in Hinsicht auf Ansprechen und Überleben, insbesondere in Kombination mit einer Radiochemotherapie oder Checkpoint-Inhibitoren.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Tension pneumocephalus: case report and review

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This report presents a case of traumatic tension pneumocephalus associated with an anterior and posterior table frontal sinus fracture in a patient with pneumosinus dilatans and osteogenesis imperfecta. (Source: International Journal of Oral and Maxillofacial Surgery)
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Τρίτη 16 Αυγούστου 2022

Effect of cut‐out rescan procedures on the accuracy of an intraoral scanner used for digitizing an ear model: An in vitro study

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Abstract

Purpose

The purpose of this study was to evaluate the impact of the rescanning of mesh holes of different diameters on the accuracy of an intraoral scanner (IOS) used to digitize an ear model.

Materials and methods

An ear model was digitized using an intraoral scanner (Medit i500) to obtain a reference mesh. A baseline experimental scan was created by editing a duplicate of the reference mesh using the cut-out tool of the IOS software. Three equal groups were created based on the diameter of the cut-out areas: 2-mm (G1), 5mm (G2), and 8-mm (G3) (n = 15). The cut-out areas were rescanned and a total of 45 digital files were exported. The discrepancy between the reference and the experimental digital scans was measured using the root mean square calculation (RMS). The data were analyzed by a Kruskal–Wallis test followed by a post hoc Dunn's test with Bonferroni correction.

Results

The trueness values ranged from 19.53 to 27.13 μm. There were significant differences in the RMS error values among the groups tested (p<.001) and post hoc multiple comparisons showed significant differences between the G1 and G2 groups (p = .04), G1 and G3 groups (p<.001), and G2 and G3 groups (p = .004). Overall, the precision values ranged from 4.93 to 7.73 μm and significant differences in the RMS values were only found between the G1 and G2 groups (p = .014).

Conclusions

Mesh hole rescanning affected the scanning accuracy (trueness and precision) of the IOS tested. The larger the diameter of the mesh holes, the less the trueness of the IOS tested. The precision values seemed to be less affected compared with the trueness by the cut-out and rescanning procedures.

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Survival rates, patient satisfaction, and prosthetic complications of implant fixed complete dental prostheses: A 12‐month prospective study

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Abstract

Purpose

To determine the survival rate, incidence of prosthetic complications and patient satisfaction of implant fixed complete dental prostheses (IFCDPs) after a mean observation period of 1.4 years.

Materials and Methods

Twenty-eight (28) eligible participants were recruited according to specific inclusion and exclusion criteria. The definitive metal-acrylic resin IFCDPs consisted of titanium bars veneered with acrylic resin and acrylic denture teeth. Prosthodontic complications, divided into major and minor, were monitored. Parameters such as gender, jaw location, bruxism, and occlusal scheme were evaluated. Moreover, a questionnaire was administered throughout the study to assess patient satisfaction. Poisson regression as well as repeated measures ANOVA were used for statistical analysis.

Results

Fourteen (14) males and 14 females were enrolled and followed-up at 3, 6, and 12 months. All IFCDPs survived (100% survival rate). The most frequent minor complication was the loss of material used to close the screw access hole (20% out of total complications). The most frequent major complication was chipping of the acrylic denture teeth (77.14% out of total complications). Gender (P = 0.008) and bruxism (P = 0.030) were significant predictors for the total major complications (major wear and major chipping) while occlusal scheme was a significant predictor for major chipping events (P = 0.030).

Conclusions

While IFCDPs demonstrated high prosthetic survival rates, they also exhibited a high number of chipping events of the acrylic veneering material, especially in males, bruxers, and individuals with canine guidance occlusion. However, the occurrence of these prosthetic complications did not negatively affect patient satisfaction.

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Influence of geometric dimensions on early failures of adhesively retained composite resin core build‐ups

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Abstract

Objective

To determine the influence of the geometric dimensions of core build-ups on early core build-up failure, that is, loss before definitive prosthesis cementation.

Materials and Methods

Adhesive core build-ups of exclusively vital teeth in 114 participants were evaluated (n materials: 40 Rebilda DC, 38 Multicore Flow, 36 Clearfil DC Core; n teeth: 8 incisors, 54 premolars, 52 molars). Impressions of the abutment teeth were made (1) after removal of insufficient restorations/caries and (2) after core build-up and preparation for a fixed prosthesis. Digitized model surfaces of both situations were aligned (Geomagic Design X) and core build-up volume (V CBU), remaining hard tissue volume (V Abut), and size of the adhesive surface (A adh) were assessed. The derived measure d CBU = V CBU/A adh can be interpreted as mean arithmetic core build-up thickness. Associations between participant or core build-up design characteristics and the occurrence of early failures were statistically evaluated (SPSS v27, α = 0.05).

Results

A total of six (5.3%) core build-up failures were registered. Higher participant age, greater core build-up volume V CBU and greater arithmetic uniform thickness d CBU were associated with a greater incidence of failure in bivariate and univariate, however, not in multivariate statistics.

Conclusions

Core build-up volume and thickness were associated with early success or failure.

Clinical Significance

In the case of voluminous/thick core build-ups in relation to the adhesive surface, additional measures, such as the preparation of retentive elements to increase the bonding area, might be considered to reduce the risk of early core build-up failure.

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