Analysis of Confidence Levels and Application Success Rates in Simulator-Based Dental Anesthesia Education Among Undergraduate Dental Students.

PURPOSE: We investigated the confidence levels of undergraduate dental students who used dental anesthesia simulators and patient reports of undergraduate dental students' confidence levels in delivering anesthesia injections, in comparison with undergraduate dental students who did not use dental anesthesia simulators. We also investigated application success rates. MATERIALS AND METHODS: The study was carried out in the dental anesthesia simulator laboratory and in the faculty clinics of the Faculty of Dentistry of Ankara University. One-hundred volunteer undergraduate dental students who had completed the third year of the 5-year undergraduate education program and who had not performed local anesthesia on a patient participated in the study. Seventy and 30 undergraduate dental students did and did not receive training on dental anesthesia simulators, respectively, before performing procedures on patients. Using a questionnaire, undergraduate dental students conducted a self-assessment of preparedness and confidence, educators assessed the application success rates, and patients evaluated the undergraduate dental students' confidence levels. RESULTS: Patients reported that the undergraduate dental students trained using the simulators were more confident. The self-reported confidence and success rates in providing anesthesia did not differ significantly as per the use of dental anesthesia simulators. CONCLUSIONS: Although use of simulators did not enhance self-reported confidence, patients reported that undergraduate dental students who used the simulators were more confident and reassuring. Use of simulators did not increase the undergraduate dental students' self-reported confidence or preparedness. However, we recommend using such simulators to overcome the ethical and moral issues associated with other teaching methods.

Analysis of Vitamin D Receptor Polymorphisms in Patients with Familial Multiple Sclerosis.

OBJECTIVE: Genetic and environmental factors are important in the development of the multiple sclerosis (MS). Vitamin D shows its effects on the immune system with the vitamin D receptor (VDR) in the nucleus. Single nucleotide polymorphisms (SNPs) in the VDR gene can lead to alterations in vitamin D functions and metabolism.Taq I, Apa I, Fok I and Bsm I polymorphisms and MS associations have been investigated in many studies. VDR gene polymorphism has not been previously studied in patients with familial MS. AIM: We aimed to investigate the relationship between familial MS patients present in Turkish population and VDR genotypes Taq I, Apa I and Fok I polymorphisms. METHODS: 29 patients with a family history of MS and 120 healthy control subjects were included in the present study. We studied present VDR genotypes Taq I, Apa I and Fok I polymorphisms. RESULTS: We observed a significant difference between controls and patient group only in Taq I polymorphism (p: 0.025). Homozygousity of G allele was not seen in the patients whereas in controls frequency of that genotype was p:0.208. When gender was considered males show significant difference for GG genotype. There were no significant association for the Apa I and Fok I polymorphisms. CONCLUSION: Although our findings suggest association between VDR Taq I polymorphism and the familial MS, additional studies are needed to establish detailed relationships.

Effects of Electroconvulsive Therapy on Some Inflammatory Factors in Patients With Treatment-Resistant Schizophrenia.

OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective option for several psychiatric conditions, including treatment-resistant schizophrenia. However, little is known about the molecular mechanism of action of ECT. The link between inflammatory system and schizophrenia is the focus of recent studies. However, the impact of ECT on inflammatory functioning in this disorder remains elusive. Whether ECT could modulate inflammatory factors in patients with schizophrenia was examined. METHODS: Plasma levels of interleukin-4 (IL-4), transforming growth factor-ß (TGF-ß), myeloperoxidase (MPO), and nuclear factor-κB (NF-κB) activation were analyzed in 20 schizophrenic patients, mainly with resistant to antipsychotic medication disorders, and in 20 sex- and age-matched healthy controls. Disease severity was evaluated using the Brief Psychiatric Rating Scale. All patients were followed with measurement of the inflammatory factors before and after ECT treatment and compared with the controls. RESULTS: Patients with schizophrenia had markedly raised NF-κB and but decreased TGF-ß levels compared with healthy controls. On the other hand, no significant differences were found for the levels of IL-4 and MPO levels. The clinical improvement during repeated ECT was accompanied by a gradual and significant increase in IL-4 and TGF-ß level, but MPO and NF-κB activation were left unaffected. Increases in TGF-ß were negatively correlated with the change in Brief Psychiatric Rating Scale scores after ECT. CONCLUSIONS: It is shown that ECT, while increasing the anti-inflammatory response such as the levels of IL-4 and TGF-ß, it did not affect the levels of MPO and NF-κB activation in this study.

Composition of the colon microbiota in the individuals with inflammatory bowel disease and colon cancer.

The human intestine is a habitat for microorganisms and, recently, the composition of the intestinal microbiota has been correlated with the etiology of diseases such as inflammations, sores, and tumors. Although many studies have been conducted to understand the composition of that microbiota, expanding these studies to more samples and different backgrounds will improve our knowledge. In this work, we showed the colon microbiota composition and diversity of healthy subjects, patients with inflammatory bowel disease (IBD), and colon cancer by metagenomic sequencing. Our results indicated that the relative abundance of prokaryotic and eukaryotic microbes differs between the healthy vs. tumor biopsies, tumor vs. IBD biopsies, and fresh vs. paraffin-embedded tumor biopsies. Fusobacterium, Escherichia-Shigella, and Streptococcus genera were relatively abundant in fresh tumor biopsies, while Pseudomonas was significantly elevated in IBD biopsies. Additionally, another opportunist pathogen Malasseziales was revealed as the most abundant fungal clade in IBD biopsies, especially in ulcerative colitis. We also found that, while the Basidiomycota:Ascomycota ratio was slightly lower in tumor biopsies compared to biopsies from healthy subjects, there was a significant increase in IBD biopsies. Our work will contribute to the known diversity of prokaryotic and eukaryotic microbes in the colon biopsies in patients with IBD and colon cancer.

Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus.

PURPOSE: The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). METHODS: The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. RESULTS: It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. CONCLUSIONS: Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM.

The association between vitamin D receptor polymorphisms and multiple sclerosis in a Turkish population.

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). Genetic and environmental factors are important in disease development. Many studies have investigated the relationship between MS and VDR polymorphisms. VDR gene polymorphism has not been previously studied in Turkish MS patients. We aimed to investigate the relationship between MS and VDR genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS: 167 MS patients and 146 healthy control subjects were included in the present study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121 females, 46 males) with MS and 146 healthy individuals (88 females, 58 males). The frequency of only the Fok I polymorphism differed significantly between the two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype distributions were not significantly different between MS patients and healthy controls (p = 0.626 and p = 0.990, respectively). Also there were no significant gender difference between patients and controls for Taq I and Apa I. CONCLUSION: In conclusion, we found a significant association between MS and the FokI polymorphism in our region of Turkey. However, the results may be different in other populations. More epidemiological and genetic studies are needed to explain the association between genetic factors and MS.

Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein.

Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East.

Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the Eastern Mediterranean region. The disease can be caused by mutations in either the cubilin (CUBN; MGA1; MIM# 602997) or the amnionless (AMN; MIM# 605799) gene. To explain the peculiar geographical distribution, we hypothesized that mutations in one of the genes would mainly be responsible for the disease in Scandinavia, and mutations in the other gene in the Mediterranean region. We studied 42 sibships and found all cases in Finland to be due to CUBN (three different mutations) and all cases in Norway to be due to AMN (two different mutations), while in Turkey, Israel, and Saudi Arabia, there were two different AMN mutations and three different CUBN mutations. Haplotype evidence excluded both CUBN and AMN conclusively in five families and tentatively in three families, suggesting the presence of at least one more gene locus that can cause MGA. We conclude that the Scandinavian cases are typical examples of enrichment by founder effects, while in the Mediterranean region high degrees of consanguinity expose rare mutations in both genes. We suggest that in both regions, physician awareness of this disease causes it to be more readily diagnosed than elsewhere; thus, it may well be more common worldwide than previously thought.

Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene.

PURPOSE: To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP). METHODS: Genomic DNA was isolated from blood samples obtained from 50 patients with Leber Congenital Amaurosis (LCA), 17 patients with the Enhanced S-Cone Syndrome (ESCS), and a patient with an atypical retinal degeneration that causes photoreceptor rosettes with blue cone opsin. The 5' upstream region (putative promoter), untranslated exon 1, coding exons 2 and 3, and exon-intron boundaries of the NRL gene were analyzed by direct sequencing of the PCR-amplified products. RESULTS: Complete sequencing of the NRL gene in DNA samples from this cohort of patients revealed only one nucleotide change. The C->G transversion at nucleotide 711 of NRL exon 3 was detected in one LCA patient; however, this change did not alter the amino acid (L237L). CONCLUSIONS: No potential disease causing mutation was identified in the NRL gene in patients with LCA, ESCS, or the atypical retinal degeneration. Together with previous studies, our results demonstrate that mutations in the NRL gene are not a major cause of retinopathy. To date, only missense changes have been reported in adRP patients, and sequence variations are rare. It is possible that the loss of NRL function in humans is associated with a more complex clinical phenotype due to its expression in pineal gland in addition to rod photoreceptors.

Early sign of atherosclerosis in slow coronary flow and relationship with angiotensin-converting enzyme I/D polymorphism.

Increase in carotid artery intima-media thickness (IMT) is an early sign of atherosclerosis. Slow coronary flow (SCF) is characterized by delay of opacification of coronary arteries in coronary angiography in the absence of any evident obstructive lesion, but its etiopathogenesis remains unclear. Genes that regulate the renin angiotensin system also play a role in developing cardiovascular system disorders. The presence of deletion (D) allele in angiotensin converting enzyme (ACE) gene polymorphism is associated with coronary artery disease. The aim of this study was to investigate the carotid artery IMT measurement, as an early sign of atherosclerosis, in patients with SCF and without SCF and also to assess the effect of the renin-angiotensin gene system on carotid IMT. Forty-four patients with angiographically proven SCF and 44 cases with normal coronary flow (NCF) pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases were determined by thrombolysis in myocardial infarction (TIMI) frame count method. Intima-media thickness was measured by recording ultrasonographic images of both the left and right common carotid artery with a 12-MHz linear array transducer. ACE I/D polymorphism and Angiotensin II tip 1 receptor (AT1R) A/C gene polymorphism were determined by polymerase chain reaction (PCR) amplification. Demographic characteristics and coronary artery disease risk factors of SCF and NCF groups were similar. Mean TIMI frame count and carotid IMT (mm) were significantly higher in the SCF group than controls (45.9 +/- 12 vs 23.3 +/- 3.7, P = 0.0001; 0.75 +/- 0.08 vs 0.69 +/- 0.06, P = 0.0001, respectively). Mean TIMI frame count was positively correlated with IMT of carotid artery in correlation analysis (r = 0.45, P = 0.0001). When analyzed in regard to ACE genotype in all subjects, IMT values were statistically different (0.78 +/- 0.06 for DD genotype, 0.72 +/- 0.05 for ID genotype, and 0.64 +/- 0.06 for II genotype, P = 0.0001). This difference remained significant in subgroup analyses for each genotype. No association could be observed between the AT1R A/C(1166) polymorphism and IMT of carotid artery measurement (P > 0.05). Lack of association was still observed with analysis carried out when genotype effect was assumed to be inherited as additive (CC versus AA versus AC) or dominant (AA versus AC+CC). Increased IMT in patients with SCF shows that subclinical atherosclerosis may play role in this phenomenon. This increase was most marked in the presence of D allele of ACE genotype, which is associated with vascular hypertrophy.

A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa (XLRP) is a clinically and genetically heterogeneous degenerative disease of the retina. At least five loci have been mapped for XLRP; of these, RP2 and RP3 account for 10%-20% and 70%-90% of genetically identifiable disease, respectively. However, mutations in the respective genes, RP2 and RPGR, were detected in only 10% and 20% of families with XLRP. Mutations in an alternatively spliced RPGR exon, ORF15, have recently been shown to account for 60% of XLRP in a European cohort of 47 families. We have performed, in a North American cohort of 234 families with RP, a comprehensive screen of the RP2 and RPGR (including ORF15) genes and their 5' upstream regions. Of these families, 91 (39%) show definitive X-linked inheritance, an additional 88 (38%) reveal a pattern consistent with X-linked disease, and the remaining 55 (23%) are simplex male patients with RP who had an early onset and/or severe disease. In agreement with the previous studies, we show that mutations in the RP2 gene and in the original 19 RPGR exons are detected in <10% and approximately 20% of XLRP probands, respectively. Our studies have revealed RPGR-ORF15 mutations in an additional 30% of 91 well-documented families with X-linked recessive inheritance and in 22% of the total 234 probands analyzed. We suggest that mutations in an as-yet-uncharacterized RPGR exon(s), intronic changes, or another gene in the region might be responsible for the disease in the remainder of this North American cohort. We also discuss the implications of our studies for genetic diagnosis, genotype-phenotype correlations, and gene-based therapy.