In vitro effect of fiber reinforcement on fracture resistance of incisal edge composite restorations

Objective: Introduction of fiber-reinforced composites (FRC) greatly enhanced the restoration of fractured anterior teeth. The purpose of this study was to assess the effect of fiber reinforcement on fracture resistance of incisal edge composite restorations of variable thicknesses.Methods: Forty extracted sound human maxillary incisors were divided into four groups of 10. Incisal reduction was done by 3mm in groups 1 and 3 and by 4mm in groups 2 and 4. Incisal edge was restored with hybrid composite in groups 1 and 2 and hybrid composite reinforced by two Ribbond fibers in the palatal surface in groups 3 and 4. All specimens were mounted in acrylic blocks, stored in saline solution and thermocycled. The teeth were then subjected to static load by universal testing machine until fracture. The load was applied at 135° angle relative to the tooth surface to an area2mm apical tothe incisal edge at a crosshead speed of 1mm/min. Data were analyzed using Tukey’s test and p≤0.05 was considered significant.Results: The mean fracture resistance was 436 (242) N, 492 (195) N, 992 (275) N and 1080 (236) N in groups 1 to 4, respectively and the difference in this regard among the 4 groups was statistically significant (p=0.000). The mean fracture resistance in group 3 (fiber-reinforced, 3mm thickness) was higher than that in group 1 (no fiber, 3mm thickness). This value in group 4 (fiber-reinforced, 4 mm thickness) was also higher than in group 2 (no fiber, 4mm thickness). The highest fracture resistance was seen in group 4.Thickness of composite had no significant effect on fracture resistance (p=0.347).Conclusion: Application of two Ribbond fibers can significantly increase the fracture resistance of incisal edge composite restorations

The Effect of Placenta Growth Factor Knockdown on hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 Expressions in MKN-45- derived Gastric Cancer Stem-like Cells

Background: Placental growth factor is involved in human gastric cancer initiation and progression through stimulating the proliferation, angiogenesis, invasion and metastasis of cancerous cells. Previous studies indicate that the expression profiles of hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 change in MKN-45- derived gastric cancer stem-like cells. Therefore, this study aims to investigate the effect of PlGF knockdown on hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 expressions in MKN-45-derived gastric cancer stem-like cells. Methods: We used a non-adhesive culture system to derive the cancer stem-like cells from MKN-45 cells. PlGF gene silencing was performed by PlGF-specific siRNA. The transcript of PlGF and miRNAs were measured by real-time RT-PCR. We conducted bioinformatics analyses with the online software programs TargetScan, miRanda, miRWalk, PicTar, and the Database for Annotation, Visualization, and Integrated Discovery tools to predict miRNAs’ targets and their signaling pathways. Results: hsa-let-7b-3p had a 2.28-fold up-regulation, whereas we observed downregulation of hsa-mir-451b (25%), hsa-mir-4290 (34%), and hsa-mir-22-3p (9%). Bioinformatics analysis results indicated that the miRNA target genes TGF-β, MAPK, and Wnt, and hedgehog signaling pathways contributed to cancer initiation and progression by influencing different cellular behaviors. Conclusion: We suggest that PlGF signaling may influence miRNA expression profiles in MKN-45-derived cancer stem-like cells, which can influence the expressions of different genes and signaling pathways. However, more empirical studies should determine the exact effect of PlGF knockdown on the expression of miRNA targets in cancer stem-like cells to locate their actual gene targets

Molecular analysis of the clavulanic acid regulatory gene isolated from an Iranian strain of Streptomyces clavuligerus, PTCC 1709

Objective: The clavulanic acid regulatory gene (claR) is in the clavulanic acid biosynthetic gene cluster that encodes ClaR. This protein is a putative regulator of the late steps of clavulanic acid biosynthesis. The aim of this research is the molecular cloning of claR, isolated from the Iranian strain of Streptomyces clavuligerus (S. clavuligerus). Materials and Methods: In this experimental study, two different strains of S. clavuligerus were used (PTCC 1705 and DSM 738), of which there is no claR sequence record for strain PTCC 1705 in all three main gene banks. The specific designed primers were subjected to a few base modifications for introduction of the recognition sites of BamHI and ClaI. The claR gene was amplified by polymerase chain reaction (PCR) using DNA isolated from S. clavuligerus PTCC 1705. Nested-PCR, restriction fragment length polymorphism (PCR-RFLP), and sequencing were used for molecular analysis of the claR gene. The confirmed claR was subjected to double digestion with BamHI and ClaI. The cut claR was ligated into a pBluescript (pBs) vector and transformed into E. coli. Results: The entire sequence of the isolated claR (Iranian strain) was identified. The presence of the recombinant vector in the transformed colonies was confirmed by the colony-PCR procedure. The correct structure of the recombinant vector, isolated from the transformed E. coli, was confirmed using gel electrophoresis, PCR, and double digestion with restriction enzymes. Conclusion: The constructed recombinant cassette, named pZSclaR, can be regarded as an appropriate tool for site directed mutagenesis and sub-cloning. At this time, claR has been cloned accompanied with its precisely selected promoter so it could be used in expression vectors. Hence the ClaR is known as a putative regulatory protein. The overproduced protein could also be used for other related investigations, such as a mobility shift assa

Effects of resveratrol, exercises and their combination on Farnesoid X receptor, Liver X receptor and Sirtuin 1 gene expression and apoptosis in the liver of elderly rats with nonalcoholic fatty liver

Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. This study aims to consider effects of resveratrol, exercise and their combination on Farnesoid X receptor (Fxr), the liver X receptor (Lxr) and Sirtuin 1 (Sirt 1) genes expression in the liver of elderly rats with NAFLD. Methods Rats with NAFLD were randomly divided into seven groups including patient, saline, resveratrol (RSV), interval exercise, continuous exercise, interval exercise + RSV and continuous exercise + RSV. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the liver tissue were measured using specific ELISA kits. A TUNEL assay kit was used for the assessment of hepatic cells apoptosis. Lipid profiles were considered by measuring the serum triglyceride, cholesterol, LDL, and HDL. Expression of Sirt1, Lxr and Fxr genes was considered using RT-PCR. Results Resveratrol administration alone or combined with exercise training significantly improved the expression of Sirt1, Lxr and Fxr genes (p < 0.05) in the hepatic tissue of rats with NAFLD, while levels of AST, ALT, ALP enzymes, as well as apoptotic cells were significantly decreased (p < 0.05). Discussion Although resveratrol alone improves the expression of Sirt1, Lxr and Fxr, as well as liver function, combined therapy with exercise training is more effective to improve NAFLD

A 21-year-old Man with Delayed Puberty

Abstract Delayed puberty is defined clinically by the absence or incomplete development of secondary sexual characteristics bounded by an age at which 95 percent of children of that sex and culture have initiated sexual maturation. The upper 95th percentile in the United States for age for boys is 14 (an increase in testicular size being the first sign) and for girls is 12 (breast development being the first sign). Delayed puberty pathophysiologically is classified according to the circulating levels of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in to two groups of high serum LH/FSH and low or normal serum LH/FSH concentrations which are related to primary hypogonadism and hypothalamic dysfunction respectively. Patient Presentation. A 21 year old boy presented with severe respiratory distress syndrome due to pneumonia and generalized edema. Laboratory studies showed pancytopenia which made clinicians work up for hematologic disorders, leading to bone marrow aspiration and biopsy which was consistent with megaloblastic anemia resulting from vit B12 deficiency. Another manifestation of this patient was delayed puberty which had been ignored over these years. Evaluation of delayed puberty revealed a low serum LH/FSH concentration. Accompaniment of delayed puberty resulting from hypothalamic origin with edema and hypoalbuminemia made clinicians work up for a malabsorption syndrome. Therefore upper endoscopy and colonoscopy were done and duodenal biopsies were consistent with celiac sprue. The unusual symptom of this patient was vit B12 deficiency which is rare in celiac disease. Conclusion. Neglected celiac sprue can be accompanied by vit B12 deficiency probably because of involvement of more distal parts of small intestine over the time

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites

Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant CYP2D6 alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1).Materials and Methods: Using TaqMan® assays common alleles of CYP2D6 (∗1, ∗2, ∗4, ∗5, ∗6, ∗10, ∗17, and ∗41) and gene duplication were identified in 134 breast cancer patients. Based on CYP2D6 genotypes patients with an activity score 1 (n = 15) and 0–0.5 (n = 2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/day, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology.Results: At baseline, (Z)-endoxifen plasma concentrations (33 ± 15.5, 28.1 ± 14, 26.6 ± 23.4, 14.3 ± 8.6, and 10.7 ± 5.5 nmol/l for EM/EM, EM/IM, EM/PM, IM/IM and PM/PM, respectively) and the metabolic ratio (Z)-Endoxifen/N-desmethyltamoxifen (0.0558 ± 0.02, 0.0396 ± 0.0111, 0.0332 ± 0.0222, 0.0149 ± 0.0026, and 0.0169 ± 0.0177 for EM/EM, EM/IM, EM/PM, IM/IM, and PM/PM, respectively) correlated with CYP2D6 genotype (Kruskal–Wallis p = 0.013 and p &lt; 0.0001, respectively). Dose escalation to 30 and 40 mg/day in patients with a CYP2D6 activity score of 1 (n = 15) and 0–0.5 (n = 2) resulted in a significant increase in (Z)-endoxifen plasma levels (22.17 ± 24.42, 34.43 ± 26.54, and 35.77 ± 28.89 nmol/l at baseline, after 4 and 8 months, respectively, Friedman p = 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. No severe side effects were recorded during dose escalation.Conclusion: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen

The evaluation of a virtual education system based on the DeLone and McLean model: A path analysis [version 2; referees: 3 approved]

Background: The Internet has dramatically influenced the introduction of virtual education. Virtual education is a term that involves online education and e-learning. This study was conducted to evaluate a virtual education system based on the DeLone and McLean model. Methods: This descriptive analytical study was conducted using the census method on all the students of the Nursing and Midwifery Department of Alborz University of Medical Sciences who had taken at least one online course in 2016-2017. Data were collected using a researcher-made questionnaire based on the DeLone and McLean model in six domains and then analyzed in SPSS-16 and LISREL-8.8 using the path analysis. Results: The goodness of fit indices (GFI) of the model represent the desirability and good fit of the model, and the rational nature of the adjusted relationships between the variables based on a conceptual model (GFI = 0.98; RMSEA = 0.014).The results showed that system quality has the greatest impact on the net benefits of the system through both direct and indirect paths (β=0.52), service quality through the indirect path (β=0.03) and user satisfaction through the direct path (β=0.73). Conclusions: According to the results, system quality has the greatest overall impact on the net benefits of the system, both directly and indirectly by affecting user satisfaction and the intention to use. System quality should therefore be further emphasized, to use these systems more efficiently

Study of type and frequency of Alfa-thalassemia mutations in a cohort of 3,823 patients from Isfahan Province, Iran

Introduction: Alpha-thalassemia (α-thalassemia) is caused by a range of mutations in the α-globin gene resulting in the complete reduction or absence of α-globin chain production. Material and methods: This study assessed the presence of α-thalassemia in 3,823 patients referred to Al-Zahra Hospital, Isfahan, Iran during a 10-year period (from 2012 to 2022). These patients experienced anaemia for more than ten years but had not the full indication for β-thalassemia or iron deficiency. Results: Based on the present assessment, 3,483 cases out of 3,823 suspicious cases had an α-Thalassemia-involved mutation (91.1%). According to the results, the most common detected mutation in the α-thalassemia carriers of Isfahan province was –α3.7 with a frequency of 81.58% (3,119 individuals), followed by α5nt (–TGAGG) (3.71% in total or 39.01% between 364 patients), polyadenylation signal mutations (polyA2) (14.28% between 364 patients), αcodon 19 (GCG4GC–, a2) (11.53%), –α3.7/–α3.7 (11.53%), –α20.5 (7.69%), Hb Constant Spring [Hb CS, a142, Stop →Gln; HBA2: c.427T4C] (5.7%), α4.2 (5.49) and – –MED (4.67%). Conclusion: The results of this investigation may be valuable for designing a program for carrier screening, premarital genetic counselling, and prenatal diagnosis in the Isfahan province

The expression analysis of IL-6, IL-18, IL-21, IL-23, and TGF-β mRNA in the nasal mucosa of patients with Allergic rhinitis

Background: The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/ TH2 balance in Allergic rhinitis (AR). Objective: This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-beta in nasal biopsies in AR patients and evaluate its correlation with the severity of AR. Material and method: The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moder- ate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-beta was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured. Result: The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-beta declined in the M/S PAR group rather than the AR-group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR-groups. Conclusion: We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients \u3e 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P\u3c0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended