Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τετάρτη 22 Ιουνίου 2022

CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3

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Publication date: Available online 22 June 2022

Source: Experimental Cell Research

Author(s): Zhan Qu, Ke-Da Yang, Bai-Hua Luo, Fan Zhang

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Drugs‐associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip

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Drugs-associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip

We performed a retrospective disproportionality analysis exploiting FAERS database and unveiled drugs associated with Red man syndrome. Further, a novel in silico technique of PHARMIP was used followed by molecular docking to signify the role of Carbonic anhydrase II and MRGPRX2 in causing the event. Corroborating the drugs causing the adverse event with the genes revealed Oritavancin to have the highest affinity. This indicated the potentiality of this drug to cause Red man syndrome.


Abstract

What is known and objective

Red man syndrome (RMS) is a non-IgE-mediated anaphylactoid adverse event frequently witnessed after a rapid infusion of vancomycin. This study aims to unravel drugs and associated off-label targets that induce RMS by exploiting FDA Adverse Event Reporting System (FAERS) and Pharmacovigilance/Pharmacogenomics Insilico Pipeline (PHARMIP).

Methods

The case/non-case retrospective observational study was conducted in the FAERS database. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) data mining algorithms were used to evaluate the strength of the signal. The off-label targets of the drugs with potential signals were obtained using online servers by applying a similarity ensemble approach and a reverse pharmacophore database, which was further validated by molecular docking studies.

Results and discussion

Oritavancin exhibited a strong positive signal (PRR:1185.20 and ROR:1256), which suggests a higher risk for causing RMS. The literature search revealed the involvement of the MRGPRX2 gene in the development of RMS. PHARMIP study unearthed Carbonic anhydrase II (CA2) as the common off-label target among the drugs causing RMS. The results obtained from molecular docking studies reinforced the findings as mentioned earlier, wherein the highest docking score was disinterred for oritavancin (−9.4 for MRGPRX2 and − 8.7 for CA2).

What is new and conclusion

Many antibiotics and other classes of medications have been discovered in the quest for drugs that may induce RMS, although a causal relationship could not be established. The implication of MRGPX2 and CA2 in the initial stages of pathogenesis necessitates the development of inhibitors that could be used as potential therapeutic agents against RMS.

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Assessing masticatory performance with a color mixing‐ability test using smartphone camera images

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Abstract

Background

Color-mixing ability tests are frequently used to assess masticatory performance but the image acquisition process may be cumbersome and technique sensitive.

Objectives

To evaluate the reliability of smartphone camera images in assessing masticatory performance using a color-mixing ability test.

Methods

Participants were recruited into three groups of dental state (n=20 each): fully dentate, removable partial denture wearers and complete denture wearers. After performing a color-mixing ability test, images of the gum specimens (Hue-Check Gum©) were captured with two smartphones and compared with the images obtained from a flat-bed scanner by two examiners. The images were analyzed with a subjective- (SA) and an opto-electronical assessment (VoH). Inter- and intra-rater reliability were tested. ANOVA models with repeated measures were used for statistical analysis (⍺=0.05).

Results

All three image acquisition techniques were able to distinguish masticatory performance between different dental states. For SA, intra-rater reliability was slight to moderate and inter-rater reliability was substantial to almost perfect. For VoH, intra-rater reliability with the smartphones were significantly different between two examiners, but the inter-rater assessment was reliable. The opto-electronic analysis with smartphone images underestimated the masticatory performance significantly when compared to the flat-bed scanner analysis. Seven-day ageing of the specimens did not significantly affect the results.

Conclusions

The assessment of masticatory performance with the Hue-Check Gum© is a reliable method. The use of smartphones may occasionally underestimate masticatory performance; image acquisition with a flatbed scanner remains the gold standard. A centralized analysis of the photographed wafer may foster the reliability of the diagnosis.

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Effects of anterior bite planes fabricated from acrylic resin and thermoplastic material on masticatory muscle responses and maximum bite force in children with a deep bite: a 6‐month randomized controlled trial

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Abstract

Background

Anterior bite planes are bite-raising appliances used for deep bite correction. However, muscle responses to anterior bite planes of different hardnesses may vary.

Objectives

To prospectively evaluate masticatory muscle activity, muscle balance, and maximum bite force (MBF) responses to anterior bite planes fabricated from acrylic resin (ABP) or bi-laminate thermoplastic (TBP) over 6 months in children with a deep bite.

Methods

Sixty-six children were randomly assigned to the ABP, TBP, or untreated control groups. Masticatory muscle activity, activity index (AC), and percentage overlapping coefficient (POC) were assessed by surface electromyography; MBF, using a custom-made bite force sensor. Data were collected before, immediately after appliance insertion, and after 2 weeks and 1, 3, and 6 months of treatment. Within- and between-group differences were analyzed using one-way ANOVA/Kruskal-Wallis and Mann Whitney U-tests (α=0.05); Friedman's tests were used to assess within-group differences over time (α=0.08).

Results

At rest, no dependent variables changed throughout the study. At maximum clenching, masticatory muscle activity immediately dropped significantly but returned to baseline values and was equal to the control group at 1-3 months. The ABP group had significantly lower masseter activity and AC than the TBP group after insertion. Neither POC nor MBF were significantly different within or between groups.

Conclusion

Masticatory muscle activity reduced after anterior bite plane insertion but returned to baseline after 1-3 months. Masseter activity decreased significantly more in the ABP group than TBP group. Neither appliance significantly affected POC or MBF.

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Shared Decision-Making Concerning Anal Cancer Screening in Persons with HIV

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Abstract
Background
Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with HIV (PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening.
Methods
Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse-probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias.
Results
Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least one anal cytology test. First-time cytology aHS IL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve (AUC) of 0.63 (95% CI%: 0.60-0.65).
Conclusion
PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factors profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening.
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Pelvic Floor Rehabilitation After Rectal Cancer Surgery: A Multicenter Randomized Clinical Trial (FORCE Trial)

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imageObjective: To investigate the effects of PFR after LAR compared to usual care without PFR. Summary of background data: Functional complaints, including fecal incontinence, often occur after LAR for rectal cancer. Controversy exists about the effectiveness of PFR in improving such postoperative functional outcomes. Methods: This was a multicenter, randomized controlled trial involving 17 Dutch centers. Patients after LAR for rectal cancer were randomly assigned (1:1) to usual care or PFR and stratified by sex and administration of neoadjuvant therapy. Selection was not based on severity of complaints at baseline. Baseline measurements were taken 3 months after surgery without temporary stoma construction or 6 weeks after stoma closure. The primary outcome measure was the change in Wexner incontinence scores 3 months after randomization. Secondary outcomes were fecal incontinence-related quality of life, colorectal-specific quality of life, and the LARS scores. Results: Between October 2017 and March 2020, 128 patients were enrolled and 106 randomly assigned (PFR n = 51, control n = 55); 95 patients (PFR n = 44, control n = 51) were assessable for final analysis. PFR did not lead to larger changes in Wexner incontinence scores in nonselected patients after LAR compared to usual care [PFR: –2.3, 95% confidence interval (CI) –3.3 to –1.4, control: –1.3, 95% CI –2.2 to –0.4, P = 0.13]. However, PFR was associated with less urgency at follow-up (odds ratio 0.22, 95% CI 0.06–0.86). Patients without near-complete incontinence reported larger Wexner score improvements after PFR (PFR: –2.1, 95% CI –3.1 to –1.1, control: –0.7, 95% CI –1.6 to 0.2, P = 0.045). For patients with at least moderate incontinence PFR resulted in relevant improvements in all fecal incontinence-related quality of life domains, while the control group deteriorated. These improvements were even larger when patients with near-complete incontinence were excluded. No serious adverse PFR-related events occurred. Conclusion: No benefit was found of PFR in all patients but several subgroups were identified that did benefit from PFR, such as patients with urgency or with at least moderate incontinence and no near-complete incontinence. A selective referral policy (65%–85% of all patients) is suggested to improve postoperative functional outcomes for patients after LAR for rectal cancer. Trial Registration: Netherlands Trial Registration, NTR5469, registered on 3 September 2015.
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