Mutation analysis of connexin 26 gene and del (GJB6-D13S1830) in patients with hereditary deafness from two provinces in Iran

Mutations in the connexin 26 (Cx26) gene at the DFNB1 locus on chromosome 13q12 are associated with autosomal recessive non-syndromic hearing loss (ARNSHL). There are many known mutations in this gene that cause hearing loss. A single frameshift, at position 35 (35delG) accounts for 50% of mutations in the Caucasian population with carrier frequencies of 1.5-2.5%. In this study we investigated the prevalence of Cx26 gene mutations by directly sequencing the coding exon of this gene belonging to ARNSHL individuals from 53 families in Qom and Markazi provinces of Iran. Seven different Cx26 variants were identified. Five Cx26 mutations including 35delG, 233delC, 176del16, W24X, L90P were found in 10 of 53 families (18.87%). One olymorphism V153I was also found. One variant A171T with unknown effects was also detected. Six of the 53 families were observed to have GJB2 mutations in both alleles (11.32%). The most common mutation was 35delG. Three out of 10 families (30%) with GJB2 variants contained 35delG mutation in both alleles and the frequency of 35delG allele was 0.50 among 10 out of 53 families. Also screening for the 342-kb GJB6 deletion mutant did not reveal any large deletion among families studied. Thus, in the two provinces, contribution of GJB2 (Gap Junction Protein Beta 2) mutations to familial deafness appears to be less significant. This necessitates further assessment of the other known genes regions as well as a search for new genetic factors in hereditary deafness in the Iranian population

Contribution of GJB2 mutations and Four common DFNB loci in autosomal recessive non-syndromic hearing impairment in Markazi and Qom provinces of Iran

This study aimed to investigate the contribution of four common DFNB ("DFN" for deafness and "B" for autosomal resessive locus) loci and GJB2 gene mutations (exon 2) in hearing impairment in individuals living in Markazi and Qom provinces of Iran. Forty consanguineous Iranian families with at least three affected individuals in family or pedigree who suffer from an autosomal recessive non-syndromic congenital hearing impairment were the subjects of this study. Blood samples were taken from both hearing and non-hearing individuals, DNA was extracted and amplified by using specific primers for the coding region of GJB2 gene (exon 2). The PCR product of GJB2 gene was then sequenced. Also short tandem repeat (STR) markers amplified by using specific primers for loci DFNB2, DFNB3, DFNB4 and DFNB21. At least 2 microsatellite markers (STR) for each DFNB locus exceeding to 4-6 markers for the linked families were used. The amplified markers were analyzed by conventional Polyacrylamide Gel Electrophoresis followed by silver staining. Six families were homozygous or compound heterozygous for GJB2 mutations and were excluded from further studies. Linkage analysis was carried out for the remaining 34 families by genotyping the flanked STR markers of DFNB2, DFNB3, DFNB4 and DFNB21 loci. Six families showed linkage; including one family to DFNB2, two families to DFNB3 and three families to DFNB4 locus while no family showed linkage to DFNB21 locus. Undoubtedly, the best understanding of the genetic basis of hearing loss in Iranian population will be achieved by performing similar experiments in other provinces and also by analyzing more loci

The effect of HLADRB1 subtypes, on clinical diseases activity index in rheumatoid arthritis patients referred to rheumatology clinic of Shahrekord University of Medical Sciences

زمینه و هدف: بیماری آرتریت روماتویید (RA)، شایع ترین بیماری التهابی مفاصل است و در صورت عدم درمان مناسب می تواند منجر به ناتوانی قابل توجه فرد بیمار گردد. عوامل متعدد ژنتیکی، محیطی و ایمونولوژیک، در پاتوژنز این بیماری نقش دارند. هدف این مطالعه بررسی اثرات ژن HLA-DRB1 بر روی شاخص فعالیت بالینی بیماری (CDAI) در بیماران مبتلا به آرتریت روماتوئید و نیز تعیین فراوانی نسبی آلل های HLA-DRB1 در این بیماری می باشد. روش بررسی: در این مطالعه توصیفی تحلیلی تعداد 64 نفر از بیماران مبتلا به RA مراجعه کرده به کلینیک روماتولوژی بیمارستان هاجر شهرکرد به روش نمونه گیری در دسترس بر اساس معیار های کالج روماتولوژی آمریکا (ACR) سال 1987 و با نظر تشخیصی روماتولوژیست انتخاب گردیدند. پس از آن همه بیماران برای تعیین CDAIاولیه مورد معاینات بالینی قرار گرفتند. پس از استخراج DNA بیماران، با استفاده از روش فنل کلروفورم انواع زیر گروه های ژن HLA-DRB1 با استفاده از کیت های تخصصی و بر اساس متد SSP-PCR تعیین گردید. معاینه دوم بیماران 6 ماه بعد انجام شد و با تکمیل چک لیست مربوط به هر بیمار تجزیه و تحلیل داده ها با استفاده از تست های آماری کای اسکوئر و تی تست گروه های زوجی انجام شد. یافته ها: شایعترین HLA-DRB1 موجود در بیماران مورد مطالعه نوع 04* با فراوانی نسبی 3/31 درصد بود. در بیماران دارای 15*، 01*،04*HLA-DRB1، شاخص فعالیت بالینی شان بعد از 6 ماه واضحاً کاهش پیدا کرده (05/0>P)، ولی در سایر گروه های بیمار این نتایج دیده نشد (05/

Pernicious anemia following COVID-19 vaccination: A report of two cases

Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm COVID-19 vaccine. Some side effects of this vaccine were reported previously, including pain at the vaccination site, fatigue, lethargy, headache, and tenderness, which were more prevalent among individuals <49 years old. Herein, we reported two patients aged 45 and 51 years old. Both patients have different signs and symptoms after receiving the second dose of the vaccine. None had a history of chronic disease. On examination and following labs and other diagnostic investigations, we found megaloblastic anemia due to atrophic gastritis and low intrinsic factor. These cases showed an autoimmune side effect of the Sinopharm COVID-19 vaccine that was previously reported with an exact mechanism but other features called Covid Arm, Guillain-Barré syndrome, and thrombocytopenia. The mechanism of this reaction is unclear yet

Digoxin Inhibits Retinoblastoma through Suppressing a Non-canonical TGFβ Signaling Pathway.

Aims: Retinoblastoma is a childhood ocular tumor rapidly developing from the immature cells of the retina due to loss of functional retinoblastoma protein. Digoxin, a cardiac glycoside, has been reported to be effective in inducing apoptosis, cell cycle arrest, and cytotoxic effects on human cancers. In this regard, the present study aims to investigate whether digoxin could suppress retinoblastoma cancer through the regulation of transforming growth factor-β (TGF-β) signaling pathway. Methodology: The effects of digoxin on Y-79 cells, retinoblastoma cancer cell line, were investigated using MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazoli-umbromide) and BrdU (bromodeoxyuridine) assays to measure cellular cytotoxicity effects and cell apoptosis, respectively. Also, a qPCR assay was employed to analyze the mRNA expression levels of TGFβ signaling pathway including C-MYC, P21, P15, TGFβRI, TGFβRII, and SMAD2, 3, and 4 genes. Results: The results of the cell function assays revealed that digoxin inhibited the cell viability and proliferation of Y-79 cells. In addition, it was found that digoxin significantly suppressed C-MYC expression and enhanced the expression of P21, P15, SMAD2 and SMAD4 genes in a dose-and time-dependent manner. However, the obtained results could not detect any significant effect of digoxin on TGFβRI, TGFβRII and SMAD3 genes. Conclusion: Taken together, the findings of the present study suggest that digoxin could be a potential therapeutic agent in the treatment of retinoblastoma by regulating the cell cycle genes via a non-canonical TGF-β signaling pathway

Shear Bond Strength of an Etch-and-rinse Adhesive to Er:YAG Laser- and/or Phosphoric Acid-treated Dentin

Background and aims. Er:YAG laser irradiation has been claimed to improve the adhesive properties of dentin; therefore, it has been proposed as an alternative to acid etching. The aim of this in vitro study was to investigate the shear bond strength of an etch-and-rinse adhesive system to dentin surfaces following Er:YAG laser and/or phosphoric acid etching. Materials and methods. The roots of 75 sound maxillary premolars were sectioned below the CEJ and the crowns were embedded in auto-polymerizing acrylic resin with the buccal surfaces facing up. The buccal surfaces were ground using a diamond bur and polished until the dentin was exposed; the samples were randomly divided into five groups (n=15) according to the surface treatment: (1) acid etching; (2) laser etching; (3) laser etching followed by acid etching; (4) acid etching followed by laser etching and (5) no acid etching and no laser etching (control group). Composite resin rods (Point 4, Kerr Co) were bonded to treated dentin surfaces with an etch-and-rise adhesive system (Optibond FL, Kerr Co) and light-cured. After storage for two weeks at 37°C and 100% humidity and then thermocycling, bond strength was measured with a Zwick Universal Testing Machine at a crosshead speed of 1 mm/min. Data was analyzed using parametric and non-parametric tests (P<0.05). Results. Mean shear bond strength for acid etching (20.1±1.8 MPa) and acid+laser (15.6±3.5 MPa) groups were significantly higher than those for laser+acid (15.6±3.5 MPa), laser etching (14.1±3.4 MPa) and control (8.1±2.1 MPa) groups. However, there were no significant differences between acid etching and acid+laser groups, and between laser+acid and laser groups. Conclusion. When the cavity is prepared by bur, it is not necessary to etch the dentin surface by Er:YAG laser following acid etching and acid etching after laser etching

The Study of Antibiotic Resistance Pattern and the Frequency of Extended-Spectrum Beta-Lactamases (ESBL) in Pseudomonas aeruginosa Strains Isolated from Medical Centers in Arak City, Iran

Background and Objectives: Pseudomonas aeruginosa is one of important causes of nosocomial infections that is an important medical problem in developed and developing countries. Resistance of this gram-negative organism towards various antibiotics, particularly beta-lactam and carbapenem has been reported increasingly. This study was done aiming at determining antibiotic resistance pattern and the frequency of extended-spectrum beta-lactamase in clinically isolated P. aeruginosa strains.Methods: In this cross-sectional study, 108 P. aeruginosa strains were collected from medical centers of Arak city. Antibiotic susceptibility of the isolated strains to antibiotics, such as, ceftazidime, imipenem, meropenem, ciprofloxacin, amikacin, and gentamicin was determined using disk diffusion method (Kirby-Bauer). Identification of ESBL producing strains was performed by combined disk method. Also, MIC test was done on 36 isolates with four antibiotics including imipenem, ceftazidime, cefipime, and ciprofloxacin.Results: Among the 108 isolates of P. aeruginosa, resistances to ceftazidime (33.3%), imipenem (22.2%), meropenem (24%), amikacin (20.3%), ciprofloxacin (15.7%) and gentamicin (19.4%) were obtained. In the MIC test, the rates of resistance to antibiotic were respectively reported 15, 20, 10, and 15%. Thirty-two strains out of 36 ceftazidime resistant strains (88.8%), were detected ESBL-positive. Conclusion: The results of this study are indicative of a high level resistance against different antibiotics of among P. aeruginosa isolates. Therefore, it is necessary to use a more appropriate treatment protocols

The effect of re-bonding using surface sealant or adhesive system on microleakage of class V resin composite restorations

Background: Microleakage is still one of the defects of resin composites that can lead to treatment failure; and re-bonding technique is one of the effective ways to reduce it. This study evaluated the effect of re-bonding with a surface sealant or a dentin adhesive on microleakage in class V microhybrid, nanohybrid, and packable composite restorations. Materials and Methods: In this in vitro study, class V cavities with occlusal margins in enamel and cervical margins in dentin/cementum were prepared on the buccal and lingual surfaces of 54 extracted premolars. The prepared teeth were randomly assigned to three groups (3 group′s Χ 18 teeth each), with each group being restored with microhybrid (Point 4); nanohybrid (Herculite XRV Ultra), and packable (Packable Premise) resin composite. Following finishing and polishing procedures, each group was randomly subdivided in to three subgroups (n = 12). The margins of two groups were both etched and re-bonded with surface sealant (Optiguard) or dentin adhesive (Opti Bond Solo Plus) and control group received no treatment. Specimens were thermocycled 1500 cycles, immersed in a methylene blue, sectioned, evaluated for microleakage using a stereomicroscope at a x 20 and scored on a scale of 0-3. Data were analyzed with Kruskal - Wallis, Mann - Whitney, and Wilcoxon tests (α = 0.05). Results: There were no significant differences among the three resin composites tested, and also no significant differences among subgroups with the same surface treatment. Only the microhybrid and packable composite restorations sealed with Optiguard had significantly lower microleakage compared to the control subgroups at the occlusal margin. There were no significant differences between occlusal and cervical margins regarding the microleakage scores when compared to the control subgroups of microhybrid and packable composite restorations. Conclusion: The re-bonding technique could be considered as an advisable procedure in order to minimize microleakage and its effect might be material-dependent

Accessing Genetic and Environmental Factors of Hearing Loss in 354 Families in Gom and Markazi Provinces

Objective: Hearing loss (HL) is the most prevalent sensorineural defect in human. Mild to severly Profound HL occurs in about l.0 per 1000 births. Many previous studies have shown that about 50% of deafness is due to genetic factor and 50% is due to environmental and etiologically unknown. In this study, we are searching the causes of deafness at these families and introduce strategies for diagnosis and prevention. Materials & Methods: Questionaires were distributed in deaf schools, hearing loss and rehabilitation centers in Qom and Markazi provinces collecting done after filling by the parents. The criterias such as age, sex, number of deaf individuals in families their close relatives, the marriage type of the parents and etiology of disease (if it is genetic or environmental) were extracted from questionnaires and were analysed by SPSS software. Results: Three hundred and fifty four (354) Questionnaires contained complete information from hearing loss families were collected. Age mean of proband individuals is 16.1±8.1. Sex distribution of 48.4% and 51.6% girls and boys, respectively. Parents were 59.3% and 36.7% of consanguineous and unfamilial marriage, respectively. The marriage type of were not determined in 4%. Mean of deaf individuals among these families was 1.8±1.4.By assessing the filled questionnaires and pedigrees. The deafness etiology in the studies population was categorized as genetic cause (70.9 %), environment factor (9%) and unknown etiology (20.1%). Conclusion: Genetic factor with and autosomal recessive inheritance pattern was the most common cause of hearing loss due to the high prevalence of consanguineous marriage which resulted and increased genetic causes in more than 50%. Multiplicity of offspring also shawn an increased in frequency of hearing loss in families that have deaf with genetic background of this disorder. In this study, environmental and unknown factors are second cause of HL. We may interestingly reduce frequency of HL in Iran with discouraging consanguineous marriage, health education, population regeneration control also genetic counseling especially for high risk families

Identification of a De Novo 3bp Deletion in CRYBA1/A3 Gene in Autosomal Dominant Congenital Cataract

Autosomal dominant congenital cataract (ADCC) is the most common form of inherited cataracts and accounts for one-third of congenital cataracts. Heterozygous null mutations in the crystallin genes are the major cause of the ADCC. This study aims to detect the mutational spectrum of four crystallin genes, CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD in an Iranian family. Genomic DNA was isolated from whole blood cells from theproband and other family members. The coding regions and flanking intronicsequences of crystalline genes were analyzed by Sanger sequencing in aproband with ADCC. The identified mutation was further evaluated in available family members. To predict the potential protein partners of CRYBA1/A3, we also used an in-silico analysis. A de novo heterozygous deletion (c.272-274delGAG, p.G91del) in exon 4 of CRYBA1/A3 gene, leading to a deletion of Glycine at codon 91 was found. This genetic variation did not change the reading frame of CRYBA1 protein. In conclusion, we identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling