Dimethyl fumarate treatment in relapsing remitting MS changes the inflammatory CSF protein profile by a prominent decrease in T-helper 1 immunity.

BACKGROUND: Dimethyl fumarate (DMF) is a common treatment for multiple sclerosis (MS), but its mechanisms of action are not fully understood. Targeted proteomics offers insights into effects of DMF and biomarkers for treatment responses. OBJECTIVES: To assess influence of DMF on inflammation- and neuro-associated proteins in plasma and cerebrospinal fluid (CSF) in MS and to reveal biomarkers for predicting treatment responses. METHODS: Using the high-sensitivity and high-specificity method of proximity extension assay (PEA), we measured 182 inflammation- and neuro-associated proteins in paired plasma (n = 28) and CSF (n = 12) samples before and after one year of DMF treatment. Disease activity was evaluated through clinical examination and MRI. Statistical tests, network analysis, and regression models were used. RESULTS: Several proteins including T-helper 1 (Th1)-associated proteins (CXCL10, CXCL11, granzyme A, IL-12p70, lymphotoxin-alpha) were consistently decreased in CSF, while IL-7 was increased after one year of treatment. The changes in plasma protein levels did not follow the same pattern as in CSF. Logistic regression models identified potential biomarker candidates (including plexins and neurotrophins) for prediction of treatment response. CONCLUSIONS: DMF treatment induced prominent changes in CSF proteins, consistently reducing Th1-associated pro-inflammatory proteins. Neurodegeneration-related CSF proteins were able to predict treatment response. Protein biomarkers hold promise for personalized medicine.

Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis.

Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.

Effect of hydroalcoholic extract of whole pomegranate fruit on cariogenic bacteria and its clinical effect on dental plaque formation in 8-10-year-old children.

Background: This study aimed to assess the effect of hydroalcoholic extract of the whole pomegranate fruit on Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus) and its clinical effect on dental plaque formation in 8-10-year-old children. Materials and Methods: This study was conducted in two phases of in vitro and clinical trial. In the in vitro phase, the antibacterial effect of 50%-50% hydroalcoholic extract of whole pomegranate fruit on S. mutans and L. acidophilus was assessed by the disc diffusion test. In the double-blind cross-over clinical trial phase, 14 children between 8 and 10 years were randomly assigned to two groups of 38% pomegranate mouthwash and 0.12% chlorhexidine (CHX) after assessing their baseline dental plaque by oral hygiene index-simplified (OHI-S). The children were asked not to use any other plaque control measure during the study. Their OHI-S score was measured again after 5 and 14 days using disclosing tablets. Data were analyzed by t-test and paired t-test at 0.05 level of significance. Results: The hydroalcoholic extract of pomegranate showed a positive antibacterial effect on S. mutans and L. acidophilus. However, its inhibitory effect was significantly lower than that of 0.12% CHX (P < 0.05). None of the tested mouthwashes inhibited plaque formation, but pomegranate mouthwash and CHX decreased the OHI-S score by 34% and 36%, respectively (P < 0.05), with no significant difference between them (P > 0.05). Conclusion: The whole pomegranate fruit hydroalcoholic extract showed significant inhibitory effects on S. mutans and L. acidophilus. Furthermore, 38% pomegranate mouthwash had a comparable efficacy to CHX in the reduction of dental plaque.

Effect of Sucrosomial® Iron and Iron Drop Diluted with Natural Fruit Juice on Microhardness of Primary Enamel.

Objectives: Considering the high prevalence of consumption of iron drops, and the resultant reduction in microhardness of primary enamel, this in vitro study aimed to assess the effects of Sucrosomial® iron and iron drop diluted with natural fruit juice on microhardness of primary enamel. Materials and Methods: This in vitro, experimental study evaluated 45 extracted sound primary anterior teeth, that were randomly assigned to three groups (n=15) of Sideral, Irofant, and Irofant + natural apple juice. The titratable acidity and pH of solutions were measured. After measuring the baseline microhardness by a Vickers hardness tester, the teeth in the three groups were exposed to the respective iron drop solutions at 37°C for 5 minutes. They were then rinsed with distilled water, and their secondary microhardness was measured. Data were analyzed using the dependent Student t-test, ANOVA, and ANCOVA (alpha=0.05). Results: Irofant had the lowest pH and the highest titratable acidity among the tested solutions. A reduction in enamel microhardness occurred in all groups after exposure to iron drops (P=0.0001). The reduction in microhardness was significantly greater in Irofant group compared with Irofant + natural apple juice (P=0.0001). Also, the reduction in microhardness was significantly greater in Irofant + natural apple juice compared with Sideral iron drop group (P=0.0001). Conclusion: Sideral iron drop with Sucrosomial iron has minimal adverse effect on microhardness of primary enamel. Also, dilution of iron drops with natural apple juice can be suggested as an effective strategy to decrease their adverse effects on microhardness of primary enamel.

Detection of Microorganisms Using Graphene-Based Nanobiosensors.

Having an insight into graphene and graphene derivatives such as graphene oxide, reduced graphene oxide and graphene quantum dots is necessary since it can help scientists to detect possible properties and features that could be useful when using these carbon materials in preparation of a nanocomposites. In recent years, graphene and its derivatives have attracted a lot of attention and been extensively applied in biosensors due to fascinating properties, such as large surface area, optical and magnetic properties, and high elasticity for the detection of microorganisms as they can be modified with some other materials such as macromolecules, oxide metals and metals to improve the electrochemical behaviour of the biosensor. In this review paper, biosensor design strategies based on graphene and its derivatives (graphene-based nanocomposites in biosensors) are described. Then their application for the detection of microorganisms including prions, viroids, viral and bacterial cells as well as fungi, protozoa, microbial toxins and even microbial sources of antibiotics is reviewed.

Effect of Intranasal Sedation Using Ketamine and Midazolam on Behavior of 3-6 Year-Old Uncooperative Children in Dental Office: A Clinical Trial.

OBJECTIVES: The aim of the present study was to compare the effects of intranasal ketamine and midazolam on behavior of 3-6 year-old children during dental treatments. MATERIALS AND METHODS: In this randomized cross-over clinical trial, 17 uncooperative children requiring at least two dental treatments were selected and randomly received ketamine (0.5mg/kg) or midazolam (0.2mg/kg) prior to treatment. The other medication was used in the next visit. The children's behavioral pattern was determined according to the Houpt's scale regarding sleep, movement, crying and overall behavior. Physiological parameters were also measured at different time intervals. The data were subjected to Wilcoxon Signed Rank test and two-way repeated measures ANOVA. RESULTS: The frequency of crying decreased significantly following ketamine administration compared to midazolam (P=0.002); movement of children decreased with fewer incidence of treatment interruption (P=0.001) while their sleepiness increased (P=0.003). Despite higher success of sedation with ketamine compared to midazolam, no significant differences were found between the two regarding patients' overall behavior (P>0.05). The patients had higher heart rate and blood pressure with ketamine; however, no significant difference was found regarding respiratory rate and oxygen saturation (P>0.05). CONCLUSIONS: Ketamine (0.5mg/kg) led to fewer movements, less crying and more sleepiness compared to midazolam (0.2mg/kg). No significant differences were found between the two drugs regarding children's overall behavior and sedation efficiency. Both drugs demonstrated positive efficacy for sedation of children during dental treatments.

Effect of platelet-rich plasma concentrations on the proliferation of periodontal cells: An in vitro study.

OBJECTIVE: The purpose of this study was to evaluate the effect of different concentrations of platelet-rich plasma (PRP) on the proliferation of undifferentiated periodontal ligament (PDL) fibroblasts. MATERIALS AND METHODS: The undifferentiated PDL fibroblasts were obtained from two healthy human premolar teeth and cultured in Dulbecco's modified Eagle's medium. Cell wells were divided into five groups. Experimental groups received 0.1%, 5%, or 50% PRP; the positive and negative control groups were cultured in fetal bovine serum (FBS) 12% and in a medium without FBS 12%, respectively. The plates were incubated at 37°C for 1, 2, 3, 4, and 7 days. PDL cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay. Statistical analysis of the data was accomplished using repeated measure ANOVA and Tukey's test. P < 0.05 was considered statistically significant. RESULTS: The 5% PRP had the greatest effect on undifferentiated fibroblast proliferation, which was significant on the 3rd day. There was no significant difference between 0.1% PRP and positive control during the first 3 days. The group with 50% PRP presented significantly lower proliferation, compared to other experimental and control groups. CONCLUSIONS: It may be concluded that the growth-stimulating effect of PRP is dose dependent with the best results in low concentrations.

Comparison of oral and buccal midazolam for pediatric dental sedation: a randomized, cross-over, clinical trial for efficacy, acceptance and safety.

OBJECTIVE: Providing a safe and efficient dental treatment for a young patient is a challenge for the dentist and the child. The purpose of this study was to investigate the effectiveness, safety and acceptability of buccal midazolam in dental pediatric patients and to compare it with oral Midazolam. METHODS: Eighteen uncooperative healthy children aged 2.5-6 years were randomized to each of buccal midazolam (0.3mg/kg) or oral midazolam (0.5mg/kg) at the first visit, the alternative has been used at the second visit in a cross-over manner. The study took place at pediatric dentistry clinic of Shahed University, Tehran, from November 2011 to June 2012. The patients' vital signs and behavioral scores were recorded. The patient, the operator and the observer were blinded to the applied medication. Post operatively, patients' and parents' satisfaction were assessed by Visual Analogue Score and a questionnaire respectively. The P-value was set at 0.05 for significance level. FINDINGS: There were no significant differences in physiologic factors in the medication groups at time 0, 10, 20, 30 minutes and discharge. There was also no significant difference between the two groups in behavioral parameters. The majority of parents rated both sedative agents as "effective" or "very effective" and their children mostly were without anxiety or with minor anxiety. CONCLUSION: Buccal midazolam may be safely and efficiently used in sedation of pediatric dental patients.

Pomegranate juice (punica granatum): a new storage medium for avulsed teeth.

OBJECTIVE: There is evidence indicating that pomegranate juice contains many of the essential properties necessary to retain cell viability and cell proliferation. These properties indicate that pomegranate juice is a suitable storage medium for avulsed teeth. However, this idea has not yet been tested. In this study, the capacity of pomegranate juice (PJ) as a storage medium for retaining avulsed teeth was evaluated. MATERIALS AND METHODS: PDL fibroblasts were obtained from healthy human premolars and cultured in Dulbecco's Modified Eagle's Medium (DMEM). Cultured cells were subjected to different concentrations of pomegranate juice (PJ), 1% Hank's balanced salt solution (HBSS) and tap water for 1, 3, 6 and 24 hours. PDL cell viability was assessed by the neutral red uptake assay. RESULTS: The results indicated that 7.5% PJ was the most effective solution for maintaining PDL cell viability amongst all the experimental solution's and time intervals (P<0.05). The results also showed that 1% PJ was as effective as HBSS for maintaining PDL cell viability. The amount of cell viability increased with increasing concentration of PJ at all time intervals (P<0.001). This effect is suggestive of the proliferative potential of PJ solution. CONCLUSION: In conclusion, PJ can be recommended as a suitable transport medium for avulsed teeth.

Calcium enriched mixture cement for primary molars exhibiting root perforations and extensive root resorption: report of three cases.

In primary molars with root perforations of endodontic origin, tooth extraction and space maintainer are recommended. Calcium-enriched mixture (CEM) cement is a new biomaterial demonstrating favorable sealability/biocompatibility. This report presents a novel treatment modality for cases of primary molar teeth with root perforations associated with a periodontal lesion due to extensive inflammatory root resorption, whereby CEM was used as a perforation repair/pulpotomy biomaterial. Three cases of primary molar root perforations due to inflammatory resorption were selected; all cases were associated with furcal lesions of endodontic origin. Pulp chambers were accessed/irrigated with NaOCl; the root canal orifices were filled with CEM and restored with stainless steel crowns. Clinical/radiographic examinations up to 17 months revealed that all teeth were functional and free of signs/symptoms of infection and all had complete bone healing. Further trials are suggested to confirm CEM use for management of root perforations in primary molars exhibiting root perforation.

Comparison of various concentrations of tricalcium phosphate nanoparticles on mechanical properties and remineralization of fissure sealants.

OBJECTIVE: The aim of this study was to investigate the mechanical properties (flexural strength, micro-shear bond strength) and remineralizing potential of fissure sealants by adding various concentrations of ß-tricalcium phosphate nanoparticles. MATERIALS AND METHODS: This in-vitro study consisted of five experimental groups containing prepared nano-fisssure sealants (1-5 wt.% ß-TCP nanoparticles) and two control groups containing a prepared and a commercial fissure sealant. Flexural/micro-shear bond strength values were measured using Zwick test machine. Cavities on sixty healthy premolar teeth were filled with the fissure sealants containing 0-5 wt.% of nano ß-TCP. The samples were assessed for remineralization under scanning electron microscopy (SEM) and EDAX. Kolmogorov-Smirnov test, One-way ANOVA and Tukey's Post Hoc analysis/HSD were used to analyze the data. RESULTS: There was no significant difference between the flexural strengths/elastic modulus of the 0-5 wt.% nano ß-TCP groups (p>0.05). The average flexural strength/elastic modulus of the prepared fissure sealant group (0%) was significantly higher than the commercial fissure sealant group (Clinpro) (p<0.05). There was no significant difference between micro-shear bond strengths of the experimental groups (1-5 wt.%), and between the commercial and the prepared (0%) fissure sealant groups (p>0.05). Examining the samples under SEM showed a significant increase in thickness of the intermediate layer with increasing concentrations of ß-TCP nanoparticles (p<0.05). CONCLUSION: Addition of 1-5 wt.% ß-TCP nanoparticles to the fissure sealants significantly increased the remineralization potential without affecting the mechanical properties.