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

alexandrossfakianakis shared this article with you from Inoreader Interpretation of Mendelian randomization using a single measure of an exposure that varies over time via International Journal of Epidemiology - Advance Access 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. 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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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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