Polymer Mixtures for Experimental Self-Limited Dental Burs Development-A Preliminary Approach (Part 1).

Alternative techniques have been investigated for effectiveness in caries removal because conventional metallic dental burs can lead to an excessive loss of sound tissue. The aim of the present study is to realize a preliminary approach in obtaining effective polymer mixtures for polymeric bur development, capable of removing primary dental caries using combinations of polymers to ensure the requirements for such instruments, but also a greater compatibility with the teeth structure. This study assessed the main mechanical properties, water sorption, solubility and microscopic structure of four new polymer mixture recipes to provide essential features in obtaining experimental self-limited dental burs. Two mixtures have in their composition polymer mixtures of Bis-phenol A diglycidyl ether dimethacrylate/Triethylene glycol dimethacrylate/Urethane dimethacrylates (R1, R2), and two other mixtures have Bis-phenol A diglycidyl ether dimethacrylate/Polymethyl methacrylate/Methyl methacrylates (R3, R4). The incorporation of nanoparticles into the polymer matrix has become essential due to the need of polymer biocompatibility increasing along with teeth surface remineralization, so that the powder charge was added to four recipes, such as 5% glass with BaF2 and 0.5% graphene with silver particles. All data sets were analyzed using the One-Way ANOVA test. R3, R4 showed higher compressive strength and diametrical compression values; these values increased when glass and graphene were added. Moreover, the addition of glass particles lead to an increase in flexural strength. Regarding the sorption, sample R3 had the most significant differences between day 69 and the rest of the investigation days, while the solubility varied at different intervals. From the mechanical evaluation, we could conclude that the Bis-GMA/PMMA/MMA mixtures fit the mechanical characteristics supported by polymer burs, following future studies regarding their use on the affected dentin.

An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated disorder of the CNS manifested by recurrent attacks of neurological symptoms (related to focal inflammation) and gradual disability accrual (related to progressive neurodegeneration and neuroinflammation). Sphingosine-1-phosphate-receptor (S1PR) modulators are a class of oral disease-modifying therapies (DMTs) for relapsing MS. The first S1PR modulator developed and approved for MS was fingolimod, followed by siponimod, ozanimod, and ponesimod. All are S1P analogues with different S1PR-subtype selectivity. They restrain the S1P-dependent lymphocyte egress from lymph nodes by binding the lymphocytic S1P-subtype-1-receptor. Depending on their pharmacodynamics and pharmacokinetics, they can also interfere with other biological functions. AREAS COVERED: Our narrative review covers the PubMed English literature on S1PR modulators in MS until August 2022. We discuss their pharmacology, efficacy, safety profile, and risk management recommendations based on the results of phase II and III clinical trials. We briefly address their impact on the risk of infections and vaccines efficacy. EXPERT OPINION: S1PR modulators decrease relapse rate and may modestly delay disease progression in people with relapsing MS. Aside their established benefit, their place and timing within the long-term DMT strategy in MS, as well as their immunological effects in the new and evolving context of the post-COVID-19 pandemic and vaccination campaigns warrant further study.

Serum Uric Acid Levels in Parkinson's Disease: A Cross-Sectional Electronic Medical Record Database Study from a Tertiary Referral Centre in Romania.

Background and Objectives: Parkinson's disease (PD) is a prevalent neurodegenerative condition responsible for progressive motor and non-motor symptoms. Currently, no prophylactic or disease-modifying interventions are available. Uric acid (UA) is a potent endogenous antioxidant, resulting from purine metabolism. It is responsible for about half of the antioxidant capacity of the plasma. Increasing evidence suggests that lower serum UA levels are associated with an increased risk of developing PD and with faster disease progression. Materials and Methods: We conducted an electronic medical record database study to investigate the associations between UA levels and different characteristics of PD. Results: Out of 274 datasets from distinct patients with PD, 49 complied with the predefined inclusion and exclusion criteria. Lower UA levels were significantly associated with the severity of parkinsonism according to the Hoehn and Yahr stage (rs = 0.488, p = 0.002), with the motor complications of long-term dopaminergic treatment (r = 0.333, p = 0.027), and with the presence of neurocognitive impairment (r = 0.346, p = 0.021). Conclusions: Oxidative stress is considered a key player in the etiopathogenesis of PD, therefore the involvement of lower UA levels in the development and progression of PD is plausible. Data on the potential therapeutic roles of elevating serum UA (e.g., by precursor administration or diet manipulation) are scarce, but considering the accumulating epidemiological evidence, the topic warrants further research.

Preparation and In Vitro Characterization of Gels Based on Bromelain, Whey and Quince Extract.

The growing interest in the appearance and color of teeth has led to the emergence of a wide range of teeth whitening methods, both in dental offices and in patients' homes. Concerns about the possible side effects or toxic effects of peroxide-based whitening gels leads to the identification of alternative whitening methods, based on natural compounds with mild action on tooth enamel and remineralizing effect. In this context, this study describes the preparation and in vitro analysis of whitening gels based on natural active agents-bromelain, quince and whey-using organic (polyacrylate, polyethylene glycol) and/or inorganic (silicate) excipients. Five natural products gels were prepared, containing bromelain extract, quince extract and whey, in various proportions. Two supplementary gels, one containing Lubrizol and another containing SiO2, were prepared. All gels were submitted for multiple in vitro analysis such as: SDS-PAGE analysis, UV-vis and FTIR spectroscopy, SEM microscopy, antibacterial activity on Streptococcus mutans ATCC 25175, Porphyromonas gingivalis ATCC 33277, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. The quince extract sample was the only one which completely discolored the blue dye on SDS-PAGE analysis. On the UV-vis spectra, the 303 nm band is assigned to an in situ modified form of bromelain. SEM images of gels containing SiO2 particles show evident marks of these particles, while the rest of the gels containing Lubrizol or whey are more uniform. Regarding antibacterial tests, the SiO2 gel samples did not show inhibition in any strains, but the other tested samples varied in the size of the inhibition diameter depending on the amicrobial strain tested; the protease activity of bromelain modulates the composition of the added whey proteins. Bromelain added as a nanoencapsulated assembly better preserves its integrity. The prepared gels showed antibacterial properties.

Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson's Disease.

Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut-brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson's disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

Parkinson's disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17-51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75-189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.

CACNA1B gene variants in adult-onset isolated focal dystonia.

BACKGROUND: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. METHODS: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). RESULTS: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. CONCLUSION: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.

Non-Motor Manifestations in Idiopathic Dystonia with Focal Onset - A Pilot Study.

Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project - GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cut-offs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cut-off for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.

On the Apparent Redox Reactivity of "Oxygen-Enriched Water".

Molecular oxygen-enriched water (OxEW) is advocated in popular media as useful for various health issues, presumably due to involvement of a purported antioxidant activity and to such notions as "active oxygen." To our knowledge, there are no explicit reports in the scientific literature where such redox reactivity would be described and explained. Reported here are data showing that a commercial preparation of OxEW does display a measurable, albeit very small, antioxidant activity as monitored by reaction with a standard reagent, DPPH. Moreover, OxEW also displays an apparent pro-oxidant reactivity, against caffeic acid. This does not correlate with any UV-vis-detectable contents of chemical substances in the water, nor can it be explained by typical chemical impurities (e.g., hydrogen peroxide or molecular hydrogen) that would arise upon enrichment with molecular oxygen of pure water by the two most common procedures: purging with gaseous O2 or electrolysis. Instead, this apparent redox reactivity is revealed to be due to differences in pH and in chemical content - and the differences in turn are most likely due to the trace amounts of inorganic ions/elements in the OxEW; importantly, electrolysis, which is often employed as a means to generate O2 in OxEW preparation, is also found to enhance the redox effect of OxEW-like preparations. Thus, in line with expectations, the herein-reported data show that there are no long-lived reactive oxygen species, no activated oxygen, and no extra reducing agents in OxEW - but that an apparent weak redox reactivity can still be measured and assigned to simple side effects of the electrolysis procedure presumably performed in order to enrich the sample in oxygen.

Toothpaste Composition Effect on Enamel Chromatic and Morphological Characteristics: In Vitro Analysis.

The aim of this in vitro study was to assess the effect of toothpastes, with different compositions, on optical and morphological features of sound and demineralized enamel. We selected twenty-five teeth, recently extracted for orthodontic purposes, for this in vitro study. The teeth were caries free, without stains, fissures, filling or hypoplasia observed at inspection under standard conditions. Teeth were brushed (for 2-3 min, twice a day, for 21 days), with five different toothpastes (four commercially available and an experimental one) containing fluoride and hydroxyapatite. After that, teeth were demineralized with 37% orthophosforic acid (Ultra Etch®, Ultradent Products Inc., South Jordan, UT, USA) for 60 s. We repeated the brushing protocol for another 21 days on demineralized enamel. Enamel vestibular surfaces were examined using a spectrophotometer (Vita EasyShade -Vita Zahnfabrik, Bad Sackingen, Germany) and a Scanning Electron Microscope (Inspect S®, FEI Company, Hillsboro, OR, USA). Differences were statistically significant for colour parameters L* and ΔE*. SEM evaluation reveals demineralized enamel mineral gain after brushing with selected toothpastes. Toothpastes with specific ingredients can represent a balance between aesthetic and mineralization, and an oral hygiene correct algorithm is able to preserve enamel characteristics during ortodontic treatement with fixed appliances.

Preparation and Characterization of Natural Bleaching Gels Used in Cosmetic Dentistry.

The novelty of this study consists of the formulation and characterization of three experimental bleaching gels with hydroxylapatite oxides and fluorine (G28®, G29®, G30®) based on natural fruit extracts compared to the commercial Opalescence 15% (GC, Ultradent, South Jordan, UT, USA). Studies have been conducted on the effect that the experimental bleaching gels have on the color and morphology of different restorative materials (Nanofill®-Schulzer, P.L. Superior Dental Materials GmbH, Hamburg, Germany, and experimental nanocomposites (P11®, P31®, P61®)), immersed in coffee and artificial saliva (for 10 days and 30 days). The study also includes a cytotoxicity test on the gels and nanocomposites after bleaching, with ISO 109993-5 protocols on human dental follicle stem cells. UV-VIS spectroscopy, computerized measurement, and fluorescence spectrometry were used in order to observe the color changes, while the microstructure of the surface was investigated by Scanning Electron Microscopy (SEM). All of the samples immersed in coffee showed the highest color shift in comparison to the baseline. The color difference ΔE values obtained using the two methods (UV-Vis, computerized based on digital images) both after coloring and bleaching, respectively, were different for all four types of nanocomposites stored in the coffee, while no difference was observed in those stored in artificial saliva. The studied experimental gels and nanocomposites had a low cytotoxic effect on cell cultures after bleaching.

Siponimod for the treatment of secondary progressive multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic central nervous system immune-mediated disease with an important inflammatory component associated with focal demyelination and widespread neurodegeneration. In most cases, the clinical presentation is relapsing-remitting, followed by a secondary progressive phase, characterized by disability accrual unrelated to relapses. In a minority, the phenotype is progressive from the beginning. Major therapeutic achievements have been made concerning the relapsing phase but modifying the evolution of progressive MS remains an unmet need. Areas covered: This review covers siponimod (BAF312), a new sphingosine 1-phosphate receptor modulator, and its role in the treatment of secondary progressive MS. The authors reviewed PubMed English literature using the keywords 'siponimod' or 'BAF312' and 'multiple sclerosis.' They also present the pharmacological profile of siponimod, as well as clinical efficacy and safety, with emphasis on the recently published results of a Phase III trial. Phase II data in relapsing MS are also summarized. Expert opinion: Siponimod may reduce the activity of the disease and has a modest effect on the gradual disability accrual. If approved, it may become one of the few available therapy options for secondary progressive MS.

Recent developments in interferon-based therapies for multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic and disabling immune-mediated disease of the central nervous system. Beta-interferons are the first approved and still the most widely used first-line disease-modifying treatment in MS. AREAS COVERED: Here we focus on recent developments in pharmacology and delivery systems of beta-interferons, and discuss their place within current state of the art therapeutic approaches. We briefly review the clinical trials for classical and PEGylated formulations, emphasizing effectiveness, safety concerns, and tolerability. The mechanisms of action of IFN-ß in view of MS pathogenesis are also debated EXPERT OPINION: Though only modestly efficient in reducing the annualized relapse rate, beta-interferons remain a valid first-line option due to their good long-term safety profile and cost-efficacy. Moreover, they are endogenous class II cytokines essential for mounting an effective antiviral response, and they may interact with putative MS triggering factors such as Epstein-Barr virus infection and human endogenous retroviruses. Recent improvements in formulations, delivery devices and drug regimens tackle the tolerability and adherence issues frequently seen with these drugs, and scientific advances may offer means for a better selection of patients. Although a well-established immunomodulatory treatment, beta-interferons have not said their last word in the management of MS.

Oxidative Stress and the Microbiota-Gut-Brain Axis.

The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.

Acute Bilateral Phrenic Neuropathy: from Diabetes Mellitus to Focal Guillain-Barré Syndrome.

Bilateral phrenic neuropathy is a rare cause of acute ventilatory failure posing both diagnostic and therapeutic difficulties. We report the case of a 55-years-old diabetic male presenting with acute onset orthopnea. Clinical and radioscopic evaluations suggested bilateral diaphragmatic paralysis, electroneuromyographic studies revealed bilateral acute phrenic neuropathy, and cerebrospinal fluid examination found albuminocytologic dissociation. The administration of high-dose intravenous immunoglobulin was followed by prompt improvement. During the next months the symptoms continued to regress. There were no recurrences. We consider the patient had a spatially limited form of acute inflammatory demyelinating polyradiculoneuropathy. The case underlies the importance of considering an immune mediated etiology in patients with acute bilateral phrenic neuropathy. To the best of our knowledge no similar case has been reported.

Development of new radiopaque glass fiber posts.

The aim of this study was to analyze the radiopacity and filler content of three experimental glass fiber posts (EGFP) in comparison with other glass/carbon fibers and metal posts from the dental market. Three EGFP were obtained by pultrusion of glass fibers in a polymer matrix based on 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)-phenyl]propane (bis-GMA) and triethyleneglycol dimethacrylate (TEGDMA) monomers. Using intraoral sensor disks 27 posts, as well as mesiodistal sections of human molar and aluminum step wedges were radiographed for evaluation of radiopacity. The percentage compositions of fillers by weight and volume were investigated by combustion analysis. Two EGFP showed radiopacity higher than enamel. The commercial endodontic posts showed radiopacity as follows: higher than enamel, between enamel and dentin, and lower than dentin. The results showed statistically significant differences (p b 0.05)when evaluatedwith one-way ANOVA statistical analysis. According to combustion analyses, the filler content of the tested posts ranges between 58.84wt.% and 86.02wt.%. The filler content of the tested EGFP ranged between 68.91 wt.% and 79.04 wt.%. EGFP could be an alternative to commercial glass fiber posts. Futureglass fiber posts are recommended to present higher radiopacity than dentin and perhaps ideally similar to or higher than that of enamel, for improved clinical detection. The posts with a lower radiopacity than dentin should be considered insufficiently radiopaque. The radiopacity of some glass fiber posts is not greatly influenced by the amount of filler.

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

Assessing the biocompatibility of a dental composite product.

OBJECTIVE: The purpose of the study was to assess the biocompatibility of a composite material considering the reaction caused at the implant site during 21 days by daily observing the subjects' behavior as well as by macroscopic examination and histological examination upon expiry of the testing period. MATERIALS AND METHODS: We performed the tolerance test by implant of the composite material Dualcim. The implant test was made on two species of lab animals, Guinea pigs and Wistar rats in two versions: subcutaneous implant and intramuscular÷perimuscular implant. RESULTS: After a 21 days period, when the implant was in direct contact with the tissue, no change of the shape and consistency, color or surface of the implant occurred. Around the implants, the biocompatibility was kept under physiological limits. CONCLUSIONS: The product, in the structure and shape presented, could be easily placed under good conditions, both at the level of the subcutaneous tissue and at inter-muscular level. In case of both species and in all subjects, the histological exam proved a favorable development of the relationship between the implant body and the placing site.

Influence of inorganic filler content on the radiopacity of dental resin cements.

Digital radiography was used to measure the radiopacity of 18 resin cements to determine the influence of inorganic filler content on radiopacity. Four disk specimens (n=4) of each light-curing cement were digitally radiographed alongside an aluminum step wedge using an intraoral sensor (XIOS Plus, Sirona, Germany), and their mean gray value measured. Percentage of filler by weight was determined using an analytical combustion furnace. Data were statistically analyzed using one-way ANOVA and Tukey's test (α=0.05). All materials were more radiopaque than dentin and 12 materials were more radiopaque than enamel. Filler percentage ranged between 17.36 to 53.56 vol% and radiopacity between 1.02 to 3.40 mm Al. There were no statistically significant differences in inorganic filler percentage and radiopacity among the different shades of the same material (p>0.05), but the highest radiopacity was measured for the material which contained a higher percentage of filler.