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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Nutrition Education: Optimizing Preparation and Recovery for Benign Esophageal Surgery

alexandrossfakianakis shared this article with you from Inoreader Nutrition Education: Optimizing Preparation and Recovery for Benign Esophageal Surgery via Journal of Human Nutrition and Dietetics Abstract Background Patients requiring upper gastrointestinal surgery for benign esophageal conditions are at nutrition risk before and after surgery. There is a dearth of published evidence guiding clinicians on effective collaboration with patients to mitigate perioperative nutritional challenges. We conducted a qualitative study to explore patients' perioperative food, nutrition, and educational experiences to guide future care. Methods Adult patients who had undergone elective, benign esophageal surgery were invited to participate in semi-structured interviews within 3 weeks of hospital discharge. Interviews were transcribed and analyzed with a reflexive form of inductive thematic analysis in addition to synthesized member checking. Results Interviews with 12 patients identified three major themes. First, nutrition education fosters a better surgical recovery experience: patients expressed a desire to be prepared for their upcoming surgery a nd engage in the recovery process with informed food choices. Most patients preferred preoperative education given limited capacity for learning during hospital admission. Second, patients have priorities for nutrition information: patients expressed that educational material should be printed, comprehensive, practical, include familiar foods, and focus on managing postoperative physical symptoms. Third, food impacts social and emotional experiences of surgery: resumption of a normal diet was a sign of recovery that enabled social reintegration. Identified themes resonated with Knowles' six-core principles of andragogy. Conclusions Patients with benign esophageal conditions perceived nutrition education to be a vital aspect of surgical preparation and recovery. Re-designing perioperative education with patient input has the potential to improve outcomes and experiences. 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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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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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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Toll‐like receptor‐1, ‐2, and ‐6 genotypes in relation to salivary human beta‐defensin‐1, ‐2, ‐3 and human neutrophilic peptide‐1

alexandrossfakianakis shared this article with you from Inoreader Toll‐like receptor‐1, ‐2, and ‐6 genotypes in relation to salivary human beta‐defensin‐1, ‐2, ‐3 and human neutrophilic peptide‐1 via Journal of Clinical Periodontology 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. This article is protected by copyright. All rights reserved. View on Web

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Critical roles for CCR2 and the therapeutic potential of cenicriviroc in periodontitis: a pre‐clinical study

alexandrossfakianakis shared this article with you from Inoreader Critical roles for CCR2 and the therapeutic potential of cenicriviroc in periodontitis: a pre‐clinical study via Journal of Clinical Periodontology Abstract Aim CCR2 plays important roles in many inflammatory and bone metabolic diseases, but its specific role in periodontitis is unknown. In the present study, we aimed to explore the role of CCR2 in the progression of periodontitis and evaluate the effect of cenicriviroc (CVC) on periodontitis. Methods The expression of CCR2 was studied in patients with periodontitis and in ligation-induced murine model of periodontitis. The role of CCR2 in promoting inflammation and bone resorption in periodontitis was evaluated in Ccr2 −/− mice and wild-type mice. The effect of CVC in the prevention and treatment of periodontitis was evaluated by systemic and local medication. Micro-CT, Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time qPCR, ELISA, and flow cytometric were used for histomorphology, molecular biology and cytology analysis respectively. Results In this study, we demonstrated that CCR2 was highly expressed in human and murine periodontitis and that CCR2 deficiency was associated with decreased inflammation, alveolar bone resorption, osteoclast number, monocyte and macrophage infiltration. Prevention and treatment with CVC significantly reduced the severity of periodontitis, regardless of whether it was administered systemically or locally. Conclusion CCR2 plays an important role in the development and progression of periodontitis and CVC is a potential drug for the prevention and treatment of periodontitis. View on Web

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A randomized multi‐center study on the effectiveness of non‐surgical periodontal therapy in general practice

alexandrossfakianakis shared this article with you from Inoreader A randomized multi‐center study on the effectiveness of non‐surgical periodontal therapy in general practice via Journal of Clinical Periodontology Abstract Aim To evaluate the effectiveness of two non-surgical treatment protocols for periodontitis patients in general dental practice. Material and methods Ninety-five dental hygienists (59 dental clinics) were randomly assigned to one of two treatment protocols: (i) establishment of adequate self-performed oral hygiene prior to a single session of ultrasonic instrumentation (guided periodontal infection control, GPIC) or (ii) conventional non-surgical therapy (CNST) including patient education and scaling and root planing integrated in multiple sessions. Residual pockets at 3 months were retreated in both groups. The primary outcome was pocket closure (probing pocket depth ≤4 mm) at 6 months. Multilevel models were utilized. Results Based on data from 615 patients, no significant differences with regard to clinical outcomes were observed between treatment protocols. Treatment-related costs (i.e. chair time, number of sessions) were significantly lower for GPIC than CNST. Smoking and age significantly affected treatment outcomes. Conclusion No significant differences between the two approaches were observed in regard to clinical outcomes. GPIC was more time-effective. Patient education should include information on the detrimental effects of smoking. View on Web

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