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Κυριακή 17 Ιουλίου 2022

Effects of concentration of sodium hypochlorite as an endodontic irrigant on the mechanical and structural properties of root dentine: A laboratory study

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Abstract

Aim

The use of high-concentration sodium hypochlorite (NaOCl) as an endodontic irrigant remains controversial because of its potential impact on the fracture strength of endodontically-treated teeth. This study evaluated the effects of using different NaOCl concentrations, with 2-min-ethylenediaminetetraacetic acid (EDTA) as the final active irrigant, on the biomechanical and structural properties of root dentine.

Methodology

A new test method, which is more clinically relevant, was utilized to calculate the fracture strength of root dentine. Bovine incisors were used to obtain root dentine discs. The root canals were enlarged to mean diameter of 2.90 mm with a taper of 0.06. The resulting discs were divided into 5 groups (n=20) and treated with different concentrations of NaOCl (5.25%, 2.5%, and 1.3%) for 30 min plus 17% EDTA for 2 min. The discs were then loaded to fracture by a steel rod with the same taper through the central hole. The fractured specimens were examined by scanning electron microscopy to evaluate changes in the dimensions of the remaining intertubular dentine and the tubular radius. Micro-hardness was also measured with a Knoop diamond indenter along a radius to determine the depth of dentine eroded by the irrigation. Results were analyzed by one-way ANOVA and the Tukey test. The level of significance was set at α = 0.05.

Results

The damage by NaOCl increased with its concentration. 5.25% NaOCl greatly reduced the fracture strength of root dentine from 172.10±30.13 MPa to 114.58±26.74 MPa. The corresponding reduction in micro-hardness at the root canal wall was 34.1%. The damages reached a depth of up to 400 μm (p < 0.05). Structural changes involved degradation of the intratubular wall leading to enlarged dentinal tubules and the loss of intertubular dentine. Changes in the microstructural parameters showed positive linear relationships with the fracture strength.

Conclusions

With the adjunctive use of EDTA, NaOCl caused destruction to the intratubular surface near the root canal and, consequently, reduced the root dentine's mechanical strength. The higher the concentration of NaOCl, the greater the effect. Therefore, endodontists should avoid using overly high concentration of NaOCl for irrigation to prevent potential root fracture in endodontically-treated teeth.

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Response to a novel, weight self‐awareness plan used in a multi‐component lifestyle intervention programme to reduce breast cancer risk factors in older women – secondary analysis from The ActWELL trial

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Abstract

Background

The ActWELL RCT assessed the effectiveness of a weight management programme delivered by volunteer lifestyle coaches (LC) in women attending breast clinics. The intervention focused on caloric intake and physical activity, utilising behavioural change techniques including a weight awareness plan (WAP). The current work is a secondary analysis of the ActWELL data and aims to examine the response to the weight self-awareness plan (used as part of the intervention programme).

Methodology

The LCs invited participants (n=279) to undertake an implementation intention discussion to formulate a self-weighing (SW) plan. Bodyweight scales were offered, and recording books provided. The PA intervention focused on a walking plan assessed by accelerometers. The LCs contacted participants by telephone monthly and provided personalised feedback. Mann-Whitney tests and chi-squared analysis were used to examine the effect of SW on weight change. A qualitative evaluation utilising semi-structured interviews was also undertaken.

Results

Most participants (96.4%) agreed to set a weekly SW goal and 76 (27%) requested scales. At 12 months, 226 (81%) returned for follow up. The median (IQR) weight change for those who self- reported at least one weight (n=211) was -2.3kg (-5.0, 0.0) compared to -1.2kg (-5.0, 0.03) in those who did not (n=14). Participants who reported weights on >8 occasions (39%) were significantly more likely (p=0.012) to achieve 5% weight loss compared to those who weighed less often. Low numbers of accelerometers were returned which did not allow for significance testing. Qualitative data (n=24) indicated that many participants found the WAP helpful and motivating.

Principal Conclusion

Greater adherence to the WAP initiated by volunteer coaches is associated with achieving 5% weight loss.

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The deciphering of the immune cells and marker signature in COVID‐19 pathogenesis: An update

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Abstract

The precise interaction between the immune system and severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is critical to deciphering the pathogenesis of Coronavirus disease 2019 (COVID-19) and is also vital for developing novel therapeutic tools, including monoclonal antibodies, antivirals drugs, and vaccines. Viral infections need innate and adaptive immune reactions since the various immune components like neutrophils, macrophages, CD4+ T, CD8+ T, and B lymphocytes play different roles in various infections. Consequently, the characterization of innate and adaptive immune reactions toward SARS-CoV-2 is crucial to defining the pathogenicity of COVID-19. In this study, we explain what is currently understood concerning the conventional immune reactions to SARS-CoV-2 infection to shed light on the protective and pathogenic role of immune response in this case. Also, in particular, we investigate the in-depth roles of other i mmune mediators, including neutrophil elastase, serum amyloid A, and Syndecan, in the immunopathogenesis of COVID-19.

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Interpretation of Mendelian randomization using a single measure of an exposure that varies over time

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Abstract
BackgroundMendelian randomization (MR) is a powerful tool through which the causal effects of modifiable exposures on outcomes can be estimated from observational data. Most exposures vary throughout the life course, but MR is commonly applied to one measurement of an exposure (e.g. weight measured once between ages 40 and 60 years). It has been argued that MR provides biased causal effect estimates when applied to one measure of an exposure that varies over time.
Methods
We propose an approach that emphasizes the liability that causes the entire exposure trajectory. We demonstrate this approach using simulations and an applied example.
Results
We show that rather than estimating the direct or total causal effect of changing the exposure value at a given time, MR estimates the causal effect of changing the underlying liability for the exposure, scaled to the effect of the liability on the exposure at that time. As such, results from MR conducted at different time points are expected to differ (unless the effect of the liability on exposure is constant over time), as we illustrate by estimating the effect of body mass index measured at different ages on systolic blood pressure.
Conclusion
Univariable MR results should not be interpreted as time-point-specific direct or total causal effects, but as the effect of changing the liability for the exposure. Estimates of how the effects of a genetic variant on an exposure vary over time, together with biological knowledge that provides evidence regarding likely effective exposure periods, are required to interpret time-point-specific causal effects.
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Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial

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Abstract
Background
Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor EGFR gene amplification (EGFR-amp). Preclinical and early phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.
Methods
In this phase III trial, adults with centrally confirmed, EGFR-amp, newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy (CE) was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a Hazard Ratio (HR) ≤0.75 for survival (OS) at a 2.5% one-sided significance level (i.e., traditional two-sided p ≤0.05) by log-rank testing.
Results
There were 639 randomized patients (median age 60, range 22-84; 62% men). Pre-specified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82-1.26, one-sided p= 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% CI 0.70-1.01, p=0.029), particularly among those with EGFRvIII mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56-0.93, p=0.002 one sided) or MGMT unmethylated (HR 0.77, 95% CI 0.61-0.97; p=0.012 one-sided) tumors but without an OS improvement. CE occurred in 94% of depatux-m treated patients (61% grade 3-4), causing 12% to discontinue.
Conclusions
Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.
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Current trends in carotid body tumors: Comprehensive review

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Abstract

Background

Carotid body tumor (CBT) is a rare neoplasm that has been increasingly studied during the last decades; nevertheless, it continues to be a topic of controversy. This review aims to provide an update on the general features of CBT and particularly review different treatment strategies and primary outcomes.

Methods

Data for this literature review were identified by PubMed, Scopus, and Medline. 93 articles from the initial search were included, as well as 28 relevant studies utilizing the snowballing method; totaling 121 articles about CBT.

Results

Main features such as anatomy, embryology, genetics, clinical presentation, and diagnosis of CBT are presented, followed by evidence of different treatment strategies such as radiotherapy, preoperative embolization, vascular resection, and vascular reconstruction. Main complications are also discussed.

Conclusion

This review summarizes the most critical aspects regarding CBT. Future studies should compare different treatments to attain the best surgical results with lower morbidity rates.

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Latent class analysis to characterize neonatal risk for neurodevelopmental differences

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Background

Neonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age.

Methods

Neonates who received neonatal care at an academic public hospital during an almost 10-year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population.

Results

The best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent-rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains.

Conclusions

The current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person-centered, as opposed to variable-centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person-centered approach.

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Ferulic Acid Mitigates Diabetic Cardiomyopathy via Modulation of Metabolic Abnormalities in Cardiac tissues of Diabetic Rats

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Abstract

Background

Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetic (T2D) rat model was elucidated in this study.

Methods

T2D rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5 weeks of treatment and their blood and hearts were collected.

Results

Induction of T2D depleted the levels of reduced glutathione, glycogen, HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase and 5'Nucleotidase. It simultaneously triggered marked increase in levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, ACE, ATPase, Glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase and lipase. T2D induction further revealed obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favourable comparison with the standard drug, metformin. Additionally, T2D induction led to depletion of 40, 75, and 33% of fatty acids, fatty esters, and steroids, respectively with concomitant generation of eicosenoic acid, gamolenic acid and vitamin E. Ferulic acid tre atment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-Octadecenoic acid, (Z)-, cis-11-Eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene.

Conclusion

These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy.

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Toll‐like receptor‐1, ‐2, and ‐6 genotypes in relation to salivary human beta‐defensin‐1, ‐2, ‐3 and human neutrophilic peptide‐1

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Abstract

Aim

To examine whether functional gene polymorphisms of toll-like receptor (TLR)1, TLR2, and TLR6 are related to the salivary concentrations of human beta-defensins (hBDs)-1, -2, -3, and human neutrophilic peptide (HNP)-1.

Materials and methods

Polymorphisms of TLR1 (rs5743618), TLR2 (rs5743708), and TLR6 (rs5743810) were genotyped by PCR-based pyrosequencing from the salivary samples of 230 adults. Salivary hBD-1, -2, -3, and HNP-1 concentrations were measured using ELISA. General and periodontal health examination, including panoramic radiography, were available for all participants.

Results

The genotype frequencies for wild types and variant types were as follows: 66.5% and 33.5% for TLR1, 95.5% and 4.5% for TLR2, and 25.1% and 74.9% for TLR6, respectively. The TLR2 heterozygote variant group exhibited higher salivary hBD-2 concentrations than the TLR2 wild type group (p=0.038). On the contrary, elevated hBD-2 concentrations were detected in the TLR6 wild type group compared to the TLR6 heterozygote & homozygote variant group (p=0.028). The associations between TLR6 genotypes and salivary hBD-2 concentrations remained significant after adjusting them for periodontal status, age, and smoking.

Conclusion

hBD-2 concentrations in saliva are related to TLR2 and TLR6 polymorphisms, but only the TLR6 genotype seems to exhibit an independent association with the salivary hBD-2 concentrations.

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Anterior implant restorations with a convex emergence profile increase the frequency of recession: 12‐month results of a randomized controlled clinical trial

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Abstract

Objectives

To test whether or not the emergence profile (CONVEX or CONCAVE) of implant-supported crowns influences the mucosal margin stability up to 12 months post insertion of the final restoration.

Materials and methods

Forty-seven patients with a single implant in the anterior region were randomly allocated to one of three groups:1) CONVEX (n=15), implant provisional and an implant-supported crown both with a convex profile; 2) CONCAVE (n=16), implant provisional and an implant-supported crown both with a concave profile; 3) CONTROL (n=16), no provisional (healing abutment only) and an implant-supported crown. All patients were recalled at baseline, 6 and 12 months. The stability of mucosal margin along with clinical, aesthetic, profilometric outcomes as well as time and costs were evaluated. To predict the presence of recession multivariable logistic regressions were performed and linear models using generalized estimation equations (GEE) were conducted for the different outcomes.

Results

Forty-four patients were available at 12 months post-loading. The frequency of mucosal recession amounted to 64.3% in group CONVEX, 14.3% in group CONCAVE and 31.4% in group CONTROL. Regression models revealed that a CONVEX profile was significantly associated with the presence of recessions (OR:12.6, CI:95%: 1.82-88.48, p=0.01) compared to the CONCAVE profile. Pink aesthetic scores amounted to 5.9 in group CONVEX, 6.2 in group CONCAVE and 5.4 in group CONTROL, with no significant differences between the groups (p=0.756). Groups CONVEX and CONCAVE increased the appointments and costs compared to the CONTROL group.

Conclusion

The use of implant-supported provisionals with a CONCAVE emergence profile results in a greater stability of the mucosal margin compared to a CONVEX profile up to 12 months of loading. This is accompanied, however, by increased time and costs compared to the absence of a provisional and may not necessarily enhance the aesthetic outcomes.

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