The use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review

alexandrossfakianakis shared this article with you from Inoreader The use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review via International Endodontic Journal Abstract Background Current treatment of immature necrotic permanent teeth with a periapical lesion is regenerative endodontics, which is based on tissue engineering under the triade of stem cells, scaffolds and bioactive molecules. Objectives This Umbrella Review was aimed to evaluate the success of scaffold and regenerative materials used for the treatment of these teeth, in terms of apical closure, tooth length increase, widening of root canal walls, tissue vitality and periapical lesion repair. Methods An extensive literature research was carried out in the Medline, ISI Web of Science, and Scopus databases for relevant systematic reviews matching the keyword search strategy. Based on inclusion and exclusion criteria, reviewers independently rated the quality of each study to determine their level of evidence. Methodological quality assessment of each article was obtained using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool, and risk of bias was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool. Results After removing duplicates, 155 articles were found; from which 133 were excluded for being non-relevant and 15 other due to exclusion criteria. One more was discarded after methodological quality evaluation, for a total of 6 articles remaining. The most common scaffold used was the blood clot, others used were poly lactic-co-glycolic acid (PLGA) and platelet-rich fibrin matrix (PRFM). The most common regeneration material used was Mineral Trioxide Aggregate (MTA), followed by Biodentine. An increase in tooth length and widening of root canal walls were reported in all selected studies with different proportions, as well as periapical lesion repair. ROBIS analysis showed that only one article had low bias, two were classified as unclear bias, while the remaining three had high risk of bias. Discussion An exhaustive literature search was carried out applying language filters, high-quality indexed journals, year of publication, which ensures the best quality articles were included. Blood clot was the most used scaffold as is the most easy to place inside the canal and does not require to extract blood from the patient. The use of MTA and Biodentine as sealing materials has been associated with thickening of canal walls, apical closure and reduced signs and symptoms of apical periodontitis. However, most of the included reviews assessed were case reports and only in a few of them were clinical trials included. There is also a lack of risk of bias analysis in most reviews. Conclusion The blood clot is the most common scaffold used for inducing regeneration during the treatment of immature necrotic teeth. Tooth length increase and widening of root canal walls are the most common criteria used in the studies as success indicators. MTA and Biodentine did not show differences in the results analysed. Quality assessment and bias risk evaluation showed that it is necessary to design better studies with rigorous methodology to recommend a trustable and predictable protocol for the treatment of immature necrotic permanent teeth with periapical lesions. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Effects of concentration of sodium hypochlorite as an endodontic irrigant on the mechanical and structural properties of root dentine: A laboratory study via International Endodontic Journal 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. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader 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 via Journal of Human Nutrition and Dietetics 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. This article is protected by copyright. All rights reserved. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader The deciphering of the immune cells and marker signature in COVID‐19 pathogenesis: An update via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial via Neuro-Oncology Advance Access 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. View on Web

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Current trends in carotid body tumors: Comprehensive review

alexandrossfakianakis shared this article with you from Inoreader Current trends in carotid body tumors: Comprehensive review via Head & Neck 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. View on Web

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Cell‐to‐cell transmission of HIV‐1 from provirus‐activated cells to resting naïve and memory human primary CD4 T cells is highly efficient and requires CD4 and F‐actin but not chemokine receptors

alexandrossfakianakis shared this article with you from Inoreader Cell‐to‐cell transmission of HIV‐1 from provirus‐activated cells to resting naïve and memory human primary CD4 T cells is highly efficient and requires CD4 and F‐actin but not chemokine receptors via Journal of Medical Virology Abstract Latently infected cells harboring replication-competent proviruses represent a major barrier to HIV-1 cure. One major effort to purge these cells has focused on developing the "shock and kill" approach for forcing provirus reactivation to induce cell killing by viral cytopathic effects, host immune responses, or both. We conducted kinetic and mechanistic studies of HIV-1 protein expression, virion production, and cell-to-cell virus transmission during provirus reactivation. Provirus-activated ACH-2 cells stimulated with romidepsin (RMD) or PMA produced Nef early, and then Env and Gag in parallel with the appearance of virions. Env on the surface of provirus-activated cells and cellular F-actin were critical in the formation of virological synapses to mediate cell-to-cell transmission of HIV-1 from provirus-activated cells to uninfected cells. This HIV-1 cell-to-cell transmission was substantially more efficient than transmission seen via cell-free virus spread and required F-actin remodeling and CD4, but not chemokine receptors. Resting human primary CD4+ T cells including naïve and memory subpopulations and, especially the memory CD4+ T cells, were highly susceptible to HIV-1 infection via cell-to-cell transmission. Cell-to-cell transmission of HIV-1 from provirus-activated cells was profoundly decreased by protease inhibitors (PIs) and neutralizing antibodies (nAbs) that recognize the CD4-binding site (CD4bs) such as VRC01, but not by reverse transcriptase (RT) inhibitor Emtricitabine (FTC). Therefore, our results suggest that PIs with potent blocking abilities should be used in clinical application of the "shock and kill" approach, most likely in combination with CD4bs nAbs, to prevent new HIV-1 infections. This article is protected by copyright. All rights reserved. View on Web

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Latent class analysis to characterize neonatal risk for neurodevelopmental differences

alexandrossfakianakis shared this article with you from Inoreader Latent class analysis to characterize neonatal risk for neurodevelopmental differences via Journal of Child Psychology and Psychiatry 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Ferulic Acid Mitigates Diabetic Cardiomyopathy via Modulation of Metabolic Abnormalities in Cardiac tissues of Diabetic Rats via Fundamental & Clinical Pharmacology 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. View on Web

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Empagliflozin has favourable effect on frontal plane QRS‐T angle in diabetic patients with cardiovascular disease

alexandrossfakianakis shared this article with you from Inoreader Empagliflozin has favourable effect on frontal plane QRS‐T angle in diabetic patients with cardiovascular disease via Journal of Clinical Pharmacy and Therapeutics Empagliflozin treatment is associated with a significant decrease in the frontal plane QRS-T angle (fQRST) in patients with diabetes mellitus (DM). However, despite similar antihyperglycemic effect with empagliflozin treatment in patients with and without cardiovascular disease (CVD), the significant decrease in fQRST angle was observed only in patients with CVD and no significant decrease was observed in fQRST angle in patients without CVD. Therefore, as a sign of ventricular repolarization heterogeneity that can be easily measured from a standard 12-lead electrocardiography (ECG), fQRST angle may be a useful ECG parameter in the monitoring of cardiovascular effects of empagliflozin in type 2 DM patients with CVD. Abstract What is Known and Objective Empagliflozin treatment is significantly associated with lower risk of cardiovascular events in patients with diabetes mellitus (DM) independent of its antihyperglycemic effect. However, little is known regarding the impact of empagliflozin on electrocardiography (ECG) parameters. This study aimed to investigate whether empagliflozin has favourable effect on frontal plane QRS-T (fQRST) angle, which is an ECG sign of ventricular repolarization heterogeneity, in patients with type 2 DM. Methods We prospectively enrolled 111 patients with known diagnosis of type 2 DM who newly prescribed empagliflozin on top of their standard anti-diabetic therapy. Patients were divided into two groups according to presence or absence of cardiovascular disease (CVD) at baseline and followed-up for 6 months. The impact of empagliflozin treatment on fQRST angle was investigated and patient groups were compared regarding the pre- and post-treatment fQRST angle. Results and Discussion Among 111 patients, 32 (28.8%) had CVD and 79 (71.2%) had no CVD. Empagliflozin treatment lead a significant decrease in the mean fQRST angle throughout the study period and mean fQRST angle was significantly lower at 3- and 6-month follow-up visits compared to baseline values (62° ± 17.4° vs. 57.2° ± 14.8° vs. 50.5° ± 13.6°, p < 0.001 for all dual comparisons). However, despite similar antihyperglycemic effect with empagliflozin treatment in patients with and without CVD, the significant decrease in the mean fQRST angle was observed only in patients with CVD and no significant decrease was observed in the mean fQRST angle in patients without CVD. What is New and Conclusion Empagliflozin leads a significant narrowing in the fQRST angle in type 2 DM patients with known CVD. View on Web

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