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Abstract Background The objective of the study was to prepare and assess novel remineralizing oral films loaded with fluorapatite powder and composed of a combination of hydroxyethyl cellulose (HC) and cellulose nanofibers (CF). Methods Three concentrations of the prepared nano-fluorapatite were tried and tested after loading in the cellulose blends and films were prepared using solvent cast technique. Along with SEM, measurements of thickness of film, bending tolerance, time of disintegration, surface pH and release of ions were made. The produced film’s ability to remineralize demineralized teeth in vitro was investigated. Results The findings showed that the films’ thicknesses were uniform, their folding endurance exceeded 300, and their disintegration times exceeded 24 h. High amounts of fluoride and calcium ions were released, and nearly neutral pH values were observed. The distribution of fluorapatite powder particles was uniform, as demonstrated by SEM. The Vickers microhardness (VHN) of enamel and morphological analysis results showed that in comparison with the demineralized specimens, there was a substantial microhardness value increase following 15 and 30 days remineralization. Conclusions Newly developed prepared films are a successful method for remineralizing early-stage demineralized tooth lesions.

Abstract Natural-based materials represent green choices for biomedical applications. In this study, resin pulp capping restoration enclosing strengthening silica and bioactive portlandite nanofillers were prepared from industrial wastes. Silica nanoparticles were isolated from rice husk by heat treatment, followed by dissolution/precipitation treatment. Portlandite nanoparticles were prepared by calcination of carbonated lime waste followed by ultrasonic treatment. Both were characterized using x-ray diffraction, energy dispersive x-ray, and transmission electron microscopy. For preparing pulp capping restoration, silica (after silanization) and/or portlandite nanoparticles were mixed with 40/60 weight ratio of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate. Groups A, B, and C enclosing 50 wt.% silica, 25 wt.% silica + 25 wt.% portlandite, and 50 wt.% portlandite, respectively, were prepared. All groups underwent microhardness, compressive strength, calcium release, pH, and apatite forming ability inspection in comparison to mineral trioxide aggregate (MTA) positive control. In comparison to MTA, all experimental groups showed significantly higher compressive strength, group B showed comparable microhardness, and group C showed significantly higher calcium release. Groups B and C showed prominent hydroxyapatite formation. Thus, the preparation of economic, silica-fortified, bioactive pulp capping material from under-utilized agricultural residues (rice husk) and zero-value industrial waste (carbonated lime from sugar industry) could be achieved.

Abstract In this research, Mg–3Zn–xSi (x = 0, 0.1, 0.3, and 0.6 wt%) biodegradable alloys were produced by simple stir casting method, their microstructure and phase changes were evaluated using X-ray diffraction (XRD), optical microscope (OM) and scanning electron microscope coupled with energy dispersive x-ray analysis (SEM–EDS). Potentiodynamic polarization was conducted to measure the alloys’ corrosion behavior in simulated body fluid (SBF). Tensile strength test and in-vitro biocompatibility evaluation regarding MTT cytotoxicity, ALP osseointegration assay and MG-63 cell growth pattern were conducted. Electrochemical investigations showed that Mg–3Zn alloys enclosing Si attained degradation rates suitable for structural support until bone healing, while the Mg–3Zn alloy without Si had a corrosion rate of 0.128 mm/year which is much lower than the required value. None of the inspected alloys exhibited a significant cytotoxic effect, meanwhile, Mg–Zn base alloy and the alloy with 0.3 wt% Si demonstrated the highest ALP level. The optimum cell growth pattern was demonstrated for Mg–Zn base alloy and the alloy with 0.1 wt% Si. Evidence of calcium phosphate precipitation was observed in the four investigated Mg–3Zn alloys. Therefore, based on the fore mentioned results, Mg–3Zn–xSi alloys were suggested as viable biodegradable materials due to their compatible degradation rates, proved cytocompatibility, high cell viability and excellent osseointegration potential.

Abstract Introduction Dental erosion has a great effect on oral health, when diagnosed it is irreversible, this sets the importance of different preventive measures being investigated against dental erosion. Aim This in vitro study aims to evaluate the effectiveness of silver diamine fluoride and Potassium iodide (SDF-KI) in comparison to casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) varnish, sodium fluoride (NaF) varnish, silver diamine fluoride (SDF) alone and deionized water as a control group in the prevention of dental erosion in primary teeth and assessing its staining effect. Materials and methods Forty deciduous teeth enamel specimens were randomly allocated into the five study groups. Tested materials were applied. An erosive challenge was done by immersing the specimens in a citric acid-containing soft drink with pH 2.85, for 5 min, 4 times/day, for 5 days. Changes in surface microhardness, mineral loss, and color change were evaluated besides recording of the surface topography and surface roughness for selected specimens. Results The highest decrease in surface microhardness was recorded in the control group (−85.21 ± 10.60%), with a statistically significant difference (p = 0.002). SDF-KI group (−61.49 ± 21.08%) showed no statistically significant difference when compared to CPP-ACPF, NaF, and SDF groups. For calcium and phosphorous loss, control group was statistically significantly higher compared to the treatment groups (p = 0.003) and (p

Carfilzomib (CFZ) is a proteasome inhibitor approved for relapsed/refractory multiple myeloma (MM) but its clinical use is limited by cardiovascular toxicity. The mechanisms of CFZ-induced cardiovascular toxicity are not fully understood but endothelial dysfunction may be a common denominator. Here, we first characterized the direct toxic effects of CFZ on endothelial cells (HUVECs and EA.hy926 cells) and tested whether SGLT2 inhibitors, known to have cardioprotective effects, can protect against CFZ-induced toxicity. To determine the chemotherapeutic effect of CFZ in the presence of SGLT2 inhibitors, MM and lymphoma cells were treated with CFZ with or without canagliflozin. CFZ decreased cell viability and induced apoptotic cell death in endothelial cells in a concentration-dependent manner. CFZ also upregulated ICAM-1 and VCAM-1 and downregulated VEGFR-2. These effects were associated with the activation of Akt and MAPK pathways, inhibition of p70s6k, and downregulation of AMPK. Canagliflozin, but not empagliflozin or dapagliflozin, protected endothelial cells from CFZ-induced apoptosis. Mechanistically, canagliflozin abrogated CFZ-induced JNK activation and AMPK inhibition. AICAR (an AMPK activator) protected from CFZ-induced apoptosis, and compound C (an AMPK inhibitor) abrogated the protective effect of canagliflozin, strongly suggesting that AMPK mediates these effects. Canagliflozin did not interfere with the anticancer effect of CFZ in cancer cells. In conclusion, our findings demonstrate for the first time the direct toxic effects of CFZ in endothelial cells and the associated signaling changes. Canagliflozin abrogated the apoptotic effects of CFZ in endothelial cells in an AMPK-dependent mechanism, without interfering with its cytotoxicity in cancer cells.

Abstract Tau accumulation is clearly linked to pathogenesis in Alzheimer’s disease and other Tauopathies. However, processes leading to Tau fibrillization and reasons for its pathogenicity remain largely elusive. Mical emerged as a novel interacting protein of human Tau expressed in Drosophila brains. Mical is characterized by the presence of a flavoprotein monooxygenase domain that generates redox potential with which it can oxidize target proteins. In the well-established Drosophila Tauopathy model, we use genetic interactions to show that Mical alters Tau interactions with microtubules and the Actin cytoskeleton and greatly affects Tau aggregation propensity and Tau-associated toxicity and dysfunction. Exploration of the mechanism was pursued using a Mical inhibitor, a mutation in Mical that selectively disrupts its monooxygenase domain, Tau transgenes mutated at cysteine residues targeted by Mical and mass spectrometry analysis to quantify cysteine oxidation. The collective evidence strongly indicates that Mical’s redox activity mediates the effects on Tau via oxidation of Cys322. Importantly, we also validate results from the fly model in human Tauopathy samples by showing that MICAL1 is up-regulated in patient brains and co-localizes with Tau in Pick bodies. Our work provides mechanistic insights into the role of the Tau cysteine residues as redox-switches regulating the process of Tau self-assembly into inclusions in vivo, its function as a cytoskeletal protein and its effect on neuronal toxicity and dysfunction.

Abstract Background Enormous improvements in dental materials’ manufacturing for the aim of producing durable dental materials without compromising the aesthetic properties were developed. One of the approaches that fulfill this aim is the use of reinforcing glass fibers as fillers into dental materials, typically resin polymers, in order to obtain glass fiber-reinforced composites. Glass fiber-reinforced composite offered many advantages to the dental materials though some limitations were recorded in many literature. Methods In this review, a study of the glass fibers’ types, factors affecting the properties and the properties of glass fibers reinforced materials was carried out; in addition, research papers that experimentally studied their applications in dentistry were presented. Conclusion The success of glass fibers reinforced composites in dentistry depends on glass fibers’ composition, orientation, distribution, amount, length and adhesion; these factors once employed according to the required clinical situation would provide the essential reinforcement to the dental restorations and appliances.

Introduction: The number of reportings on sexual abuse (SA), sexual violence (SV) cases covered in the media has risen a significant amount with most cases involving women and children. The aim of the study is to explore the questions: Are people aware of sexual abuse and sexual violence in the media? What are the predictors of awareness of sexual abuse and sexual violence? Does the awareness of sexual abuse and sexual violence in the media affect the actions of the individuals?Methods: A representative survey of the German-speaking resident population (2020) on physical and mental well-being was used. The participants (N = 2,503: females = 50.9%) were between the ages of 14 and 97 (M = 49.81). The German version of the Adverse Childhood Experiences Questionnaire, The General Habitual Well-Being Questionnaire and questions about own experiences of sexual harassment on the internet, experiences of domestic sexual abuse and different socio-economic variables were used. The outcome variables regarding the awareness of SA and SV in the media, different types of scandals (church, pedophile, USA), #MeToo-debate and the change in actions were used. Frequency analyses and binary regressions were conducted.Results: One thousand five hundred and fifty-five (62.6%) respondents answered yes to being aware of SA and SV in the media. The results show that females, aging, number of children in household, Protestant and Catholic religion, school graduation, own experience(s) of sexual harassment on the internet, own experience(s) of SA in childhood, and Adverse Childhood Experiences have a significant higher association to the awareness of SA and SV in the media. German nationality and Muslim religion have a significant lower association. The variables that most commonly affected the awareness of SA and SV, scandals, debate and the individual actions were age, own experiences of sexual harassment on the internet and the Protestant religion.Conclusion: Advertising more support centers, hotlines and linking this information to sexual abuse cases covered in the media should be considered. Media bystander interventions could be helpful to train people to react appropriately. Further investigation that considers the different types of media and its influence on the awareness of SA and SV is needed.

The present investigation aimed to prepare and evaluate an innovated re-mineralizing oral films made from a blend of hydroxyethyl-cellulose (HEC) and cellulose nanofibers (CNF), loaded with nepheline fluorapatite glass powder. Evaluation of film thickness, folding endurance, disintegration time, surface pH, ions release, together with SEM were carried out. In vitro re-mineralizing effect of the prepared film on demineralized teeth was examined. Results revealed the uniformity in thickness of films, folding endurance more than 300, and the disintegration times more than 24 hrs. The pH values were nearly neutral and high concentrations of calcium and fluoride ions were released. SEM showed a uniformity of glass powder particles distribution. Results of enamel micro-hardness (VHN) and ultra-morphology revealed that there was a significant increase in mean VHN after the remineralization for 15 and 30 days compared to the demineralized specimens. The innovative prepared films are effective approach for remineralization of early demineralized tooth lesions.

Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a representative single isoform. However, the six human tau isoforms present overlapping but distinct distributions in the brain and are differentially involved in particular tauopathies. These observations support the notion that tau isoforms possess distinct functional properties important for both physiology and pathology. To address this hypothesis, the six human brain tau isoforms were expressed singly in the Drosophila brain and their effects in an established battery of assays measuring neuronal dysfunction, vulnerability to oxidative stress and life span were systematically assessed comparatively. The results reveal isoform-specific effects clearly not attributed to differences in expression levels but correlated with the number of microtubule-binding repeats and the accumulation of a particular isoform in support of the functional differentiation of these tau isoforms. Delineation of isoform-specific effects is essential to understand the apparent differential involvement of each tau isoform in tauopathies and their contribution to neuronal dysfunction and toxicity.

Background Atherosclerotic renovascular disease (ARVD) is defined as renal artery stenosis with an occlusion of 60% or more. It is an established cause of resistant hypertension and renal insufficiency. ARVD is evaluated using renal artery duplex ultrasound, which measures the degree of renal artery stenosis and renal resistance index. Treatment with renal artery balloon angioplasty and stents has been shown to improve blood pressure and renal function in some patients. Aim of the studyThis was a prospective study evaluating the early effects of renal artery angioplasty and stenting in patients with ARVD as regards the blood pressure and renal function. MethodsDuring March 2009 to September 2011, 37 patients (21 men and 16 women) with ARVD (unilateral or bilateral), resistant hypertension, and renal impairment were selected and divided into two groups: group A (25 patients) comprised patients who underwent renal artery balloon angioplasty and stenting (intervention group) and group B (12 patients) comprised those who were kept on medical treatment as controls and followed up without intervention. Results Two weeks after intervention, eight patients (32%) stopped one medication, seven patients (28%) stopped two medications (i.e. one antihypertensive medication only), and five patients (20%) stopped all medications, whereas the blood pressure did not change in five patients (20%). The average mean systolic blood pressure of group A was 140 mmHg and the average serum creatinine level was 2.1. As regards group B, the average mean systolic blood pressure was 170 mmHg for patients who were on three antihypertensive medications, and the average serum creatinine level was 2.4. Conclusion The main effect of renal artery revascularization in ARVD is on blood pressure control in patients with resistant hypertension, with minimal influence on the renal function.

BackgroundLenalidomide is an immunomodulatory drug used to treat multiple myeloma that requires renal dosing adjustment based on Cockcroft-Gault (CG). Various equations to estimate kidney function exist and pose a potential issue with lenalidomide dosing.ObjectiveThe objective of this analysis was to evaluate the impact of estimating kidney function in newly diagnosed multiple myeloma patients with CG, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and their potential impact on lenalidomide dosing.MethodsData from 1121 multiple myeloma patients at the time of diagnosis acquired from the Mayo Clinic were used to calculate creatinine clearance (CrCl) using Cockcroft-Gault with actual body weight (CGABW), ideal body weight (CGIBW), or adjusted body weight (CGAdjBW); MDRD; and CKD-EPI for each subject. Discordances in dosing were then analyzed, and lenalidomide exposure was calculated for each subject to assess impact on pharmacokinetics of lenalidomide for patients who received discordant doses.ResultsOverall, approximately 16% of patients received a discordant dose when using MDRD or CKD-EPI instead of CGABW. The most common dose discordance was the decrease of a full dose of lenalidomide 25 mg when using CGABW down to 10 mg and when using MDRD or CKD-EPI with 53.8% to 55.6% of all discordances in this category. When assessing different body weights, the most common discordance was a decrease from 25 to 10 mg when using CGIBW instead of CGABW; the same trend was observed when using CGAdjBW instead as well. Patients were also at risk of over- or underexposure based on area under the concentration versus time curve (AUC) for discordant dosing.Conclusion and relevanceA significant proportion of patients are at risk of under- or overdose of lenalidomide if CKD-EPI or MDRD are used instead of CGABW. Physicians should use CGABW when estimating renal function to dose lenalidomide.

What is known and objectiveTenofovir exposure is increased in non-pregnant adults when tenofovir disoproxil fumarate is coadministered with lopinavir/ritonavir. In pregnant women, tenofovir exposure is decreased. Our objective is to describe the effect of lopinavir/ritonavir on tenofovir pharmacokinetics during pregnancy.MethodsData were collected through the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network P1026s protocol. This was a nonrandomized, open-label, parallel-group and multicentre phase-IV prospective study in pregnant women with HIV. Intensive steady-state 24-h pharmacokinetic profiles were collected during the third trimester of pregnancy and postpartum. Tenofovir was measured in plasma using validated liquid chromatography-mass spectrometry method (quantification limit: 10 ng/ml). Statistical tests compared paired and between group pharmacokinetic data.Results and discussionIn women not receiving lopinavir/ritonavir (n = 28), tenofovir AUC0-24 was 27% lower (2.2 mcg·h/ml vs 2.8 mcg·h/ml, p = 0.002) and oral clearance was 27% higher (61 L/h vs 48 L/h, p = 0.001) during the third trimester compared to paired postpartum data. In women receiving lopinavir/ritonavir (n = 10), tenofovir AUC0-24 and oral clearance were not different antepartum compared to postpartum. Women with and women without concomitant lopinavir/ritonavir displayed no significant differences in postpartum tenofovir pharmacokinetics.What is new and conclusionTenofovir exposure during the third trimester was reduced compared to postpartum in pregnant women not receiving lopinavir/ritonavir, but not in pregnant women also receiving lopinavir/ritonavir. Our findings suggest that pregnancy confounds the expected decrease in tenofovir exposure with concomitant lopinavir/ritonavir in non-pregnant adults. These findings illustrate the need for drug-drug interaction studies in pregnant women as drug disposition differs significantly in pregnant women compared to non-pregnant adults.

Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

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