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Masoumeh Falah,1 Mohammad Farhadi,1 Seyed Kamran Kamrava,1 Saeid Mahmoudian,1 Ahmad Daneshi,1 Maryam Balali,1 Alimohamad Asghari,2 Massoud Houshmand1,3 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Skull Base Research Center, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran Background: The prominent role of mitochondria in the generation of reactive oxygen species, cell death, and energy production contributes to the importance of this organelle in the intracellular mechanism underlying the progression of the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial DNA (mtDNA) gene expression and coding region variation have frequently been reported as being associated with the development of presbycusis. The mtDNA control region regulates gene expression and replication of the genome of this organelle. To comprehensively understand of the role of mitochondria in the progression of presbycusis, we compared variations in the mtDNA control region between subjects with presbycusis and controls.Methods: A total of 58 presbycusis patients and 220 control subjects were enrolled in the study after examination by the otolaryngologist and audiology tests. Variations in the mtDNA control region were investigated by polymerase chain reaction and Sanger sequencing.Results: A total of 113 sequence variants were observed in mtDNA, and variants were detected in 100% of patients, with 84% located in hypervariable regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and 15,954 A>C, were significantly different between presbycusis and control subjects.Conclusion: The statistically significant difference in the frequencies of four nucleotide variants in the mtDNA control region of presbycusis patients and controls is in agreement with previous experimental evidence and supports the role of mitochondria in the intracellular mechanism underlying presbycusis development. Moreover, these variants have potential as diagnostic markers for individuals at a high risk of developing presbycusis. The data also suggest the possible presence of changes in the mtDNA control region in presbycusis, which could alter regulatory factor binding sites and influence mtDNA gene expression and copy number. Keywords: age-related hearing impairment, presbycusis, mtDNA control region, audiology

Masoumeh Falah,1,2 Massoud Houshmand,3 Mohammad Najafi,2 Maryam Balali,1 Saeid Mahmoudian,1 Alimohamad Asghari,4 Hessamaldin Emamdjomeh,1 Mohammad Farhadi1 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Skull base research center, Iran University of Medical Sciences, Tehran, Iran Objectives: Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined.Methods: Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction.Results: Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant (P=0.007). Mitochondrial DNA copy number was also significantly associated with degree of hearing impairment (P=0.025) and audiogram configuration (P=0.022).Conclusion: The findings of this study suggest that lower mitochondrial DNA copy number is responsible for presbycusis through alteration of mitochondrial function. Moreover, the significant association of mitochondrial DNA copy number in peripheral blood samples with the degree of hearing impairment and audiogram configuration has potential for use as a standard test for presbycusis, providing the possibility of the development of an easy-to-use biomarker for the early detection of this condition. Keywords: age-related hearing impairment, presbycusis, biomarker, mtDNA

Masoumeh Falah,1,2 Mohammad Najafi,2 Massoud Houshmand,3 Mohammad Farhadi1 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran Abstract: Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. Keywords: age-related hearing impairment (ARHI), presbycusis, biomarker, treatment

Maryam Balali,1,2 Behnam Kamalidehghan,3 Mohammad Farhadi,2 Fatemeh Ahmadipour,4 Mahmoud Dehghani Ashkezari,1 Mohsen Rezaei Hemami,2 Hossein Arabzadeh,2 Masoumeh Falah,2 Goh Yong Meng,5 Massoud Houshmand3 1Department of Biology, Islamic Azad University, Ashkezar Branch, Ashkezar, 2Department and Research Centre of ENT and Head & Neck Surgery, Iran University of Medical Sciences, Tehran, Iran; 3Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; 4Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, 5Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Mitochondrial DNA mutations play an important role in causing sensorineural hearing loss. The purpose of this study was to determine the association of the mitochondrial genes RNR1, MT-TL1, and ND1 as well as the nuclear genes GJB2 and GJB6 with audiological examinations in nonfamilial Iranians with cochlear implants, using polymerase chain reaction, DNA sequencing, and RNA secondary structure analysis. We found that there were no novel mutations in the mitochondrial gene 12S rRNA (MT-RNR1) in patients with and without GJB2 mutation (GJB2+ and GJB2-, respectively), but a total of six polymorphisms were found. No mutations were observed in tRNALeu(UUR) (MT-TL1). Furthermore, eight polymorphisms were found in the mitochondrial ND1 gene. Additionally, no mutations were observed in the nuclear GJB6 gene in patients in the GJB2- and GJB2+ groups. The speech intelligibility rating and category of auditory perception tests were statistically assessed in patients in the GJB2- and GJB2+ groups. The results indicated that there was a significant difference (P

Lymphocyte CD4+count, a standard laboratory test for staging of HIV infection, is expensive and unavailable in resource-restricted countries. Total lymphocyte count (TLC) and hemoglobin (Hb) are recommended as simple & inexpensive surrogates. The aim of this study was to assess the correlation, sensitivity and predictive power of these parameters as substitutes for CD4 count. One hundred HIV patients enrolled in this analytic descriptive study in Ahvaz, a city in the South of Iran, from 2005 to 2006. They were tested for CD4 count, TLC, Hb, and hematocrit (Hct). The cutoffs were determined as: 200 cells/µL, 1200 cells/µL, 12 g/dl and 30%, respectively. We used Sys Max SE 9500 for CBC and Flow cytometry for CD4 count. The correlation coefficient established correlation between values. Sensitivity, specificity and positive predictive values were calculated. 2 females (%2) and 98 males (%98) of the mean age of 32±5 years were studied. 87 cases (%87) were IV drug users, the majority having a history of imprisonment. The mean CD4 count, TLC, Hb and Hct were 279±225, 2102±1250, 10.7±2.4 and 30.4±9.0, respectively. A strong correlation was observed between CD4 count and TLC (R = 0.645, P = 0.001), but no correlation was seen between CD4 count and Hb or Hct (R= 0.451, P=0.056 and R= 0.375, P=0.816 respectively). This study shows that TLC is a suitable surrogate marker for CD4 count. Hb and Hct are of limited value in predicting CD4 counts and should not be substituted for CD4counts.

Photovoltaic panels' performance is degraded when their temperature rises above 25 °C. Various cooling methods are proposed to deal with this issue. In this study pin fin cooling is introduced as a simple and cost-effective passive cooling technique to cool a 10 (W) monocrystalline photovoltaic module. Indoor experimental tests have been conducted to investigate the module's thermal and electrical performance. Based on the radiation intensity, module's tilt angle, pin fin numbers, and pin fin arrangements, four categories are defined and extensively studied. The obtained results reveal that adding pin fins can reduce the module's temperature up to nearly 10 °C. More interestingly, by inclining the bare photovoltaic module from a horizontal state to a 45-degree inclination angle the module's average temperature is reduced by 6 °C. This temperature reduction is about 15 °C if the PV module is inclined by 45 degrees and also attached by 100 pin fins. Based on the experimental findings, the change in the pin fins' arrangement did not show a sensible change in either thermal or electrical performance of the photovoltaic device. [ABSTRACT FROM AUTHOR]

A novel double network (DN) hydrogel nanocomposite with good compressive strength has been prepared by using Carboxymethyl Cellulose-g-Acrylic acid-Iron Oxides Nanoparticles (CMC-g-AA-IONs) as the primary network and polyacrylamide as the secondary network. The structure of the synthesized DN hydrogel nanocomposite was investigated by Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), and mechanical strength measurement. The synthesized DN hydrogel showed high mechanical strength (σ of 0.238 MPa), despite the water content of 90%. Its biocompatibility effect on sensitive nerve cells was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) test. The results showed that the DN hydrogel nanocomposite has no cytotoxicity on these cells and did not cause any disturbance or inhibit their growth and proliferation. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study investigated vestibular function outcomes after cochlear implantation in patients with inner-ear anomalies. Methods: Twenty-two patients with bilateral symmetric inner-ear anomalies and 28 patients with normal inner ears were included. All were congenitally or progressively deaf persons implanted unilaterally during the previous 15 years. Vestibular system function was assessed by vestibular-evoked myogenic potential and bithermal caloric tests. Results: The vestibular-evoked myogenic potential abnormality rate in implanted ears with an inner-ear anomaly was 81.8 per cent, compared with 39.3 per cent in implanted ears with normal anatomy. In the non-implanted sides, the rate was 45.5 per cent (10 out of 22 cases) in the inner-ear anomaly patients compared with 17.9 per cent in patients with normal inner-ear structure. The respective abnormal caloric test rates in inner-ear anomaly versus normal anatomy patients were 81.8 per cent and 17.9 per cent (implanted ears), 77.3 per cent and 14.3 per cent (non-implanted sides). Conclusion: Inner-ear anomaly and implantation were both associated with more vestibular-evoked myogenic potential abnormalities; when occurring together, these factors showed a synergistic effect. Caloric test abnormality is mainly dependent on the presence of an inner-ear anomaly, but implantation is not associated with caloric abnormality. [ABSTRACT FROM AUTHOR]