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Background: The heterogeneity of nasal features across different racial and ethnic groups is evident. This large-scale multicenter study was performed to evaluate the dorsal keystone area and its relation to superficial nasal anatomy through computed tomography (CT) scans., Methods: Six populations were included: South Caucasian, Middle Eastern, Black South African, Eastern Asian, Mestizo, and Eastern European. Each center obtained CT scans performed between January of 2020 and December of 2022 from patients presenting a nasal hump and from an age- and sex-matched control group. Osteocartilaginous measurements in relation to ethmoidal point and to rhinion, as well as their relation to superficial nasal anatomy, were collected from nasal CT scans in midsagittal view. These were compared between populations and, in each center, between patient groups (nasal hump versus no nasal hump)., Results: The study population included 600 patients (254 with nasal hump) with a mean age of 33.98 years (range, 18 to 59 years); 55.6% were women. Average distances from the ethmoidal point were 10.1 ± 3.5 mm to the rhinion and 1.68 ± 0.23 mm to the beginning point of the nasal hump. In 96% of cases, the ethmoidal point was cranial or no more than 5 mm caudal to the beginning of the nasal hump. S-shaped nasal bones were associated with nasal hump, but angulation (kyphion angle) did not correlate with nasal hump height., Conclusions: In most patients, the nasal hump has no ethmoid bone underneath it, and the apex is located over the septal cartilage. The ethmoidal point is a reliable landmark and should be considered when evaluating established and new preservation and structural rhinoplasty approaches., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Topical delivery to paranasal sinuses through sustained-release stents is one of the new horizons in treating chronic rhinosinusitis (CRS). This study aims to introduce and evaluate sustained co-release of encapsulated ciprofloxacin (CIP) and dexamethasone (DEX) in polyvinyl alcohol-based carriers within the maxillary sinus of rabbit animals. DEX and CIP were loaded in a tyramine-substituted polyvinyl alcohol microparticle (PVATyr MP). The mechanical stability, degradability, and sustained-release patterns of both drugs as well as cellular cytocompatibility were assessed in vitro. The PVATyr MPs were then injected into the maxillary sinus of rabbits and they were monitored weekly for 21 days. Nasal endoscopy, MRI imaging, and tissue microscopy were used to follow the changes and compared them with the control condition. Also, the concentrations of drugs were evaluated in the maxillary sinus and blood samples over the study period. Produced PVA-based MPs possessed a relatively narrow particle size distribution (CV 7.7%) with proper physical stability until 30 days of incubation. The uniform-sized PVATyr MPs and their surrounding hydrogel showed sustained-release profiles for DEX and CIP for up to 32 days in vitro. The injected drugs-loaded hydrogel showed complete clearance from the maxillary sinus of rabbits within 28 days. The concentrations of DEX and CIP in mucosal remained within the therapeutic window when measured on days 7, 14, and 21, which were well above the plasma concentrations without any pathological changes in endoscopy, MRI imaging, and histological examinations. DEX/CIP loaded PVATyr MPs provided an effective, controlled, and safe sustained-drug delivery in both in vitro and in vivo analyses at therapeutic concentrations with minimal systemic absorption, suggesting a promising treatment approach for CRS., (© 2024. The Author(s).)

Background : Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods : In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4 + T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results : The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups ( p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP ( p <0.05) and control ( p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control ( p <0.001) and CRSwNP ( p <0.05) groups. Conclusions : Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including "positive regulation of intracellular signal transduction", "arachidonic acid metabolic process", "spermatogenesis" and "negative regulation of cellular protein metabolic process". Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies., (© 2024. The Author(s).)

Background: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders., Methods: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set., Results: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients., Conclusion: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies., (© 2023. Fondazione Società Italiana di Neurologia.)

Chronic tympanic membrane (TM) perforation is a consequence of trauma or chronic otitis media, and these chronic TM perforations often lead to conduction hearing loss. This study focuses on the development of a patch using a combination of chitosan (CS) and polyvinyl alcohol (PVA) as graft material for repairing chronic tympanic membrane (TM) perforations. Aligned nanofibers were created using a specially designed collector (SDC) through the electrospinning method. The scanning electron microscopy (SEM) analysis revealed that the CS/PVA ratio of (15:85) resulted in uniform and bead-free nanofibers. The aligned nanofibers had a diameter of 131.11 ± 28 nm, indicating that the influence of the electrostatic field introduced by the SDC affected not only the nanofiber alignment but also the nanofiber diameter. The nanofiber angles demonstrated effective alignment. This patch is infused with thyme essential oil (TEO) for antibacterial properties. The results showed that its antibacterial property for Pseudomonas aeruginosa bacteria was enhanced in such a way that the diameter of the antibacterial halo increased from zero to 25 mm. Cell viability assays showed >80 % viability. A preclinical case study on six patients demonstrated the biocompatibility and promising potential of the fabricated patch for eardrum repair., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent studies have established the possible role of microbiota in developing various diseases. In this regard, attention has shifted to the evaluation of microbiota changes in the paranasal sinuses and its relationship to chronic rhinosinusitis (CRS), especially CRS with nasal polyposis (CRSwNP). This study aimed to examine the bacterial communities of the sphenoidal sinus in Iranian patients with and without CRS. The investigation included 36 subjects, including 18 patients with CRSwNP who underwent Functional Endoscopic Sinus Surgery (FESS) and 18 non-CRS patients who underwent Endoscopic Endonasal Approach (EEA) for pituitary adenoma. The surgeries were performed under general anesthesia, and the sphenoidal sinus was sampled using sterile rayon-tipped swabs coated with a sheet. TaqMan quantitative real-time polymerase chain reaction (qPCR) method (the 16S rDNA gene from bacteria) was used for detection of bacterial communities in different samples. Staphylococcus haemolyticus and Pseudomonas aeruginosa were significantly more prevalent in CRS patients than non-CRS patients (P value ≤ 0.05). However, no significant difference in the frequency of Corynebacterium spp. and Staphylococcus aureus was observed between the two groups, and no Streptococcus pneumoniae or Haemophilus influenza species were isolated from any of the samples. The current study's findings indicated a significant difference in the frequency of certain bacterial species in patients with CRS vs. non-CRS patients. By establishing a link between microbial burden and CRS, it is possible to develop effective treatments or even prevent disorders in this body area., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to evaluate cytocompatibility of hyaluronic acid (HA) and gelatin (Gela) conjugation with phenolic groups (Phs) via enzyme-mediated crosslinking. Phenolic moieties were substituted on the backbone of HA (HA-Ph) and Gela (Gela-Ph) and subsequently were subjected for horseradish peroxidase crosslinking in the presence of H 2 O 2 as an electron donor to create a stable hybrid microenvironment for cellular behavior and cartilage tissue engineering., Results: Successful synthesis of biopolymers confirmed by NRM and UV-Vis spectrophotometry. The physical characteristic of hydrogels including mechanical properties and water contact angle of hydrogels enhanced with addition of Gela-Ph in HA-based hydrogel. The Gela-Ph showed longest gelation time and highest degradation rate. The cellular studies showed cells did not attach to HA-Ph hydrogel. While, proper cell attachment and proliferation observed on blend hydrogel surface compared with the neat hydrogels which interpret by the existence of cell-adhesive motifs of utilized Gela-Ph in this hydrogel. The encapsulated cells in HA-Ph hydrogel were spheroid and just maintained their viability. Hydrogels containing Gela-Ph, the cells were spindle shape with high degrees of cytoplasmic extension. Overall, the results suggest that hybrid biomimetic hydrogel can provide a superior biological microenvironment for chondrocytes in 3D cartilage tissue engineering., (© 2022. The Author(s).)

Background: Chordoma is a locally aggressive bone tumor with a high capability of recurrence. Because chordoma often occurs at critical locations next to neurovascular structures, there is an urgent need to introduce validated biomarkers. T-box transcription factor T (TBXT; OMIM: 601397) plays an important role in the pathogenesis and survival of chordoma cells., Methods: Herein, we aimed to show whether rs2305089 polymorphism is correlated with chordoma in the Iranian population. In order to detect rs2305089, tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used. In total, 19 chordoma patients and 108 normal healthy individuals were recruited and screened using T-ARMS-PCR. The results were subsequently validated by Sanger sequencing., Results: The genotype distributions and allele frequencies were significantly different among the patient and healthy groups (p-value <0.05). The A allele of rs2305089 showed a significant positive association with chordoma risk (p-value <0.05). DNA sequencing verified the T-ARMS-PCR results as well. This study demonstrated the association between TBXT rs2305089 and chordoma in an Iranian population using a simple, accurate, and cost-effective T-ARMS-PCR assay., Conclusions: Our results were in line with those of previous studies showing that TBXT rs2305089 is associated with chordoma development. We also developed an efficient T-ARMS-PCR assay to determine the genotype of rs2305089., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background :Psychophysical tests are typically used for clinical assessment of human smelling function. Given that olfactory identification is linked to the regional culture, the main aim of this study was to provide the comprehensive "sniffin' sticks" olfactory test, culturally adapted on the Iranian population as well as to examine the discriminatory power of this test between normal people and patients with olfactory disorder. Methods : This cross-sectional study consisted of 3 steps. A total of 200 healthy people were recruited to determine odor familiarity (using Likert- scale) for the first step. In the second step, based on the original sniffin' sticks test and odor familiarity, 16 odor items were selected. Odor modification was performed and the identification part of the sniffin' sticks test was created. Then, 99 patients with olfactory disorders and 214 healthy participants were tested using the Iranian sniffin' sticks test (Ir-SST). After 2 to 4 weeks, participants were reexamined and test reliability was evaluated by using a Pearson correlation coefficient test. Results : The Ir-SST showed that scores of patients with smell loss were significantly lower than normosmic participants (13.6 ± 5.24 vs 34.3 ± 3.41, P < 0.001). The sensitivity (95.2%) and specificity (93.5%) of the test were also found to be high. Test-retest reliability was as follows: composite score: r = 0.8; odor identification: r = 0.83; odor threshold: r = 0.77; and odor discrimination test: r = 0.56; P < 0.001. Conclusion : The results suggest that the Ir-SST can be effectively adapted to the Iranian population. The current study validates that the sniffin' sticks olfactory test is applicable as a useful screening tool for comprehensive assessment of olfactory function in an Iranian population., (© 2021 Iran University of Medical Sciences.)

Non-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that "mRNA processing" and "spindle organization" biological processes are important in NFAPs invasiveness. Specifically, our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology., (© 2021. The Author(s).)

Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case-control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin' Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p < 0.001). The SSSW score was lower in the patient group than in controls (p < 0.01), although the ECS score was not significantly different between patients and controls. Also, there was no significant difference in the severity of trauma between marital satisfaction and sexual satisfaction. However, the analysis showed a statistically significant difference in depression scores in connection with the head trauma severity. In the PTOD group, depression was increased and sexual satisfaction declined. Understanding the association of olfactory dysfunction with depression and sexuality allows patients and doctors to deal with less notable consequences of this disorder., (© 2021. The Author(s).)

Current hyaluronic acid-based hydrogels often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective biomedical and tissue engineering applications. Provision of the cell-adhesive surface is an important requirement to improve its biocompatibility. An aqueous solution of hyaluronic acid possessing phenolic hydroxyl (HA-Ph) moieties is gellable via a horseradish peroxidase (HRP)-catalyzed oxidative cross-linking reaction. This study evaluates the effect of different degrees of cross-linked Ph moieties on cellular adhesiveness and proliferation on the resultant enzymatically cross-linked HA-Ph hydrogels. Mechanical characterization demonstrated that the compression force of engineered hydrogels could be tuned in the range of 0.05-35 N by changing conjugated Ph moieties in the precursor formulation. The water contact angle and water content show hydrophobicity of hydrogels increased with increasing content of cross-linked Ph groups. The seeded mouse embryo fibroblast-like cell line and human cervical cancer cell line, on the HA-Ph hydrogel, proved cell attachment and spreading with a high content of cross-linked Ph groups. The HA-Ph with a higher degree of Ph moieties shows the maximum degree of cell adhesion, spreading, and proliferation which presents this hydrogel as a suitable biomaterial for biomedical and tissue engineering applications., (© 2020 Wiley Periodicals LLC.)

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury., Competing Interests: I wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. I confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. I further confirm that the order of authors listed in the manuscript has been approved by all of authors. I confirm that the authors have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing I confirm that we have followed the regulations of our institutions concerning intellectual property., (© 2021 The Authors.)

One of the most effective approaches for treatment of chronic rhinosinusitis is the use of hydrogel scaffolds with the sustained release of a given required drug. With this in mind, first, we synthesized and characterized poly (lactide-co-glycolide) (PLGA) micro and nano particles loaded with dexamethasone (DEX). We observed a 7-day release of DEX from nanoparticles, while the microparticles showed a 22-day release profile. Due to their slower rate of release, the PLGA microparticles loaded with DEX (PLGADEX microparticles) were specifically chosen for this study. As a second step, chitosan/polyvinylpyrrolidone (PVP) based hydrogels were prepared in various weight ratios and the PLGADEX microparticles were optimized in their structure based on variable gelation times. The morphological studies showed PLGADEX microparticles homogenously dispersed in the hydrogels. Moreover, the effect of weight ratio in the presence and absence of optimum percentage of PLGADEX microparticles was studied. The resultant hydrogels demonstrated a range of advantages, including good mechanical strength, porous morphology, amorphous structure, high swelling ratio, controlled biodegradability rate, and antibacterial activity. Additionally, a cytotoxicity analysis confirmed that the hydrogel scaffolds do not have adverse effects on the cells; our release studies in the hydrogel with the highest PVP content also showed 80% release after 30 days. Based on these results we were able to predict and control some of the mechanical properties, including the microstructure of the scaffolds, as well as the drug release, by optimizing the polymers - microparticle concentration, plus their resulting interactions. This optimized hydrogel can become part of a suitable alternative for treatment of allergic rhinitis and chronic sinusitis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neurodegenerative diseases (NDDs) are increasing serious menaces to human health in the recent years. Despite exhibiting different clinical phenotypes and selective neuronal loss, there are certain common features in these disorders, suggesting the presence of commonly dysregulated pathways. Identifying causal genes and dysregulated pathways can be helpful in providing effective treatment in these diseases. Interestingly, in spite of the considerable researches on NDDs, to the best of our knowledge, no dysregulated genes and/or pathways were reported in common across all the major NDDs so far. In this study, for the first time, we have applied the three-way interaction model, as an approach to unravel sophisticated gene interactions, to trace switch genes and significant pathways that are involved in six major NDDs. Subsequently, a gene regulatory network was constructed to investigate the regulatory communication of statistically significant triplets. Finally, KEGG pathway enrichment analysis was applied to find possible common pathways. Because of the central role of neuroinflammation and immune system responses in both pathogenic and protective mechanisms in the NDDs, we focused on immune genes in this study. Our results suggest that "cytokine-cytokine receptor interaction" pathway is enriched in all of the studied NDDs, while "osteoclast differentiation" and "natural killer cell mediated cytotoxicity" pathways are enriched in five of the NDDs each. The results of this study indicate that three pathways that include "osteoclast differentiation", "natural killer cell mediated cytotoxicity" and "cytokine-cytokine receptor interaction" are common in five, five and six NDDs, respectively. Additionally, our analysis showed that Rps27a as a switch gene, together with the gene pair {Il-18, Cx3cl1} form a statistically significant and biologically relevant triplet in the major NDDs. More specifically, we suggested that Cx3cl1 might act as a potential upstream regulator of Il-18 in microglia activation, and in turn, might be controlled with Rps27a in triggering NDDs., Competing Interests: The authors have declared that no competing interests exist.

Background: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined., Objective: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19., Methods: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients., Results: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07)., Conclusions: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.

Background: The occurrence of anosmia/hyposmia during novel Coronavirus disease 2019 (COVID-19) may indicate a relationship between coincidence of olfactory dysfunction and coronavirus disease 2019 (COVID-19). This study aimed to assess the frequency of self-reported anosmia/hyposmia during COVID-19 epidemic in Iran. Methods: This population-based cross sectional study was performed through an online questionnaire from March 12 to 17, 2020. Cases from all provinces of Iran voluntarily participated in this study. Patients completed a 33-item patient-reported online questionnaire, including smell and taste dysfunction and their comorbidities, along with their basic characteristics and past medical histories. The inclusion criteria were self-reported anosmia/hyposmia during the past 4 weeks, from the start of COVID-19 epidemic in Iran. Results: A total of 10 069 participants aged 32.5±8.6 (7-78) years took part in this study, of them 71.13% women and 81.68% nonsmokers completed the online questionnaire. The correlation between the number of olfactory disorders and reported COVID-19 patients in all provinces up to March 17, 2020 was highly significant (Spearman correlation coefficient = 0.87, P< 0.001). A sudden onset of olfactory dysfunction was reported in 76.24% of the participations and persistent anosmia in 60.90% from the start of COVID19 epidemic. In addition, 80.38% of participants reported concomitant olfactory and gustatory dysfunctions. Conclusion: An outbreak of olfactory dysfunction occurred in Iran during the COVID-19 epidemic. The exact mechanisms by which anosmia/hyposmia occurred in patients with COVID-19 call for further investigations., (© 2020 Iran University of Medical Sciences.)

Introduction: Smell Identification Tests (SIT) are routinely utilized for the clinical evaluation of olfactory function. Since Iran consists of various ethnic subgroups, the reliability and validity of this test as a national SIT are required to be evaluated across the country., Materials and Methods: This cross-sectional study evaluated the cultural adaptation of SIT administered to 420 healthy volunteers from 6 various ethnic subgroups (i.e., Fars, Turk, Kurd, Lor, Baluch, and Arab) living in 7 cities (one city for each subgroup, and Tehran [capital of Iran] with mixed ethnicities). The SIT consists of pens pre-filled with 24 odorants. The correct identification response rate was evaluated in all and each subgroup. The test was performed twice on 60 participants with a 2-week interval to assess its reliability. The SIT was further administered to 150 cases with documented abnormal olfactory function to evaluate its validity., Results: The correct identification response rate was estimated at 70% for all odorants in all and each subgroup. The mean odor identification score was 21.41±1.37 (score range: 17- 24) with no significant difference among various subgroups. Moreover, the test-retest correlation coefficient was obtained at 0.77. The mean odor identification score in patients with olfactory impairment was 10.69±3.76, which was significantly different from that in healthy participants (P<0.001). The best cut-point for the beginning of olfactory impairment was 17.5 (95% CI: 9-100, Sensitivity=99, Specificity=81). Females obtained higher scores of odor identification, compared to males (P=0.025)., Conclusion: The results indicated the reliability and validity of the SIT, which can be used nationally for the assessment of olfactory function in various ethnic subgroups across the country.

Mesenchymal stromal cells (MSCs) have potent immunomodulatory abilities to regulate most of the immune cells. Not only the tissue origin of MSCs can affect their functions, but also their microenvironment can strongly influence their biology, particularly through toll-like receptors (TLR)/ligands interaction. In the present study, we compared MSCs derived from two different sources, i.e. human olfactory ecto-mesenchymal stem cells (OE-MSCs) and adipose tissue (AT-MSCs), in terms of their immunosuppressive effects before and after TLR3 and TLR4 stimulation through low-level and short-term TLR-priming protocol. After isolation and characterization of OE-MSCs and AT-MSCs, flow cytometry analyses were used to assess the expression of TLR3, TLR4 by MSCs. Secretion and expression levels of immune-related genes were analyzed using ELISA and RT-qPCR techniques. Based on the results, the proliferation potential of OE-MSCs was significantly higher than that of AT-MSCs. The gene expression and also protein levels of both TLR3 and TLR4 were significantly higher in OE-MSCs, compared to AT-MSCs. Among the examined cytokines and chemokines, OE-MSCs exhibited significantly higher levels of CCL5, IL-8, and TGF-β production, in comparison with AT-MSCs. However, IL-6 secretion by AT-MSCs was considerably more than that by OE-MSCs. OE-MSCs were only affected by the TLR4 ligand, and IL-8 and IL-6 production levels increased after LPS treatment. However, only IL-8 significantly increased after adding LPS or Poly (I:C) to the AT-MSC media. According to the obtained data, OE-MSCs exhibited a higher proliferative potential and greater expression levels of TLR3 and TLR4 genes, compared to AT-MSCs. However, unlike AT-MSCs, the expression of TLR3 by OE-MSCs was nonfunctional. Finally, based on our findings, OE-MSCs have a stronger secretion of immunosuppressive cytokines both before and after LPS or PIC treatment, compared to AT-MSCs.

Objective: Meningiomas comprise 6-15 % of cerebellopontine angle (CPA) tumors. Surgical treatment is a real challenge because this area is occupied by several critical neurovascular elements. Currently, surgery is the first choice of treatment, however several factors may be present that necessitate choosing the alternative treatments such as Gamma Knife Stereotactic Radiosurgery (GKS)., Patients and Methods: Ninety-three patients with CPA meningioma who were treated by GKS for a period of 8 years, were retrospectively reviewed. Factors affecting clinical and radiological improvement were analyzed., Results: The median tumor volume was 6 cm 3 . The mean values for maximal and marginal dose were 20.2 and 13.6 Gy, respectively. The mean follow-up time was 31.5 months. Tumor control (lack of progression) was achieved in 96.8% of the patients and 55.9% of the patients showed tumor regression on follow-up MRI. The actuarial 3-year progression-free survival (PFS) rate was 96%. Clinical improvement was seen in 49.5% of the patients while 11.8% experienced worsening or new-onset symptoms. Adverse radiation effects were seen in 4.3% of the patients. A worse symptomatic outcome, male sex, a lower tumor coverage, and marginal doses <13.5 Gy were associated with worse radiologic outcomes. Worse radiologic outcomes and higher tumor volumes, especially tumor volumes ≥8.5 cc, were associated with worse symptomatic outcomes. The male sex was associated with a lower PFS., Conclusion: Gamma Knife radiosurgery, either primarily or post- operatively, offers a decent long-term tumor control in CPA meningioma, and is associated with an acceptable complication profile, especially in tumors with lower volumes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Processing odor information by the olfactory system depends greatly on the odor concentration. In order to use an odorant in a smell identification test (SIT), the minimum identification concentration (MIC) needs to be determined., Materials and Methods: This study was conducted in 60 healthy native individuals aged 20 to 60 years, selected from patients' companions in a tertiary hospital. In the first step, 25 odorants were presented to evaluate familiarity among the subjects. Then, the MICs for the eligible odorants were measured using the ascending method of limits., Results: Out of 25 odorants, only one (cacao) was distinguished by less than 70% of the subjects, and was therefore removed from the list. The MICs of the remaining 24 odorants ranged from 6.87±2.74% for menthol to 27.62±18.98% for cantaloupe. There was significant correlation between age and the MIC only for coffee (P=0.02, r=-0.300). There was a significant difference in MIC between men and women only for hazelnut (P=0.03)., Conclusion: We present the MICs of 24 culturally-familiar odorants in a sample of the Persian population in a SIT.

Background: This study aimed to determine the prevalence of hearing impairment (HI) by age and gender in a population aged 5 yr and older residing in Tehran, Iran., Methods: In this cross-sectional study, 140 clusters each including 10 households from Tehran, Iran were sampled between 2012 and 2013 using cluster random sampling. Trained audiologists examined the participants during face-to-face interviews. The hearing of the participants was evaluated before the removal of wax or other foreign bodies. In this study, HI was categorized as mild (grade 1, 26-40 db), moderate (grade 2, 41-60 db), severe (grade 3, 61-80 db), and deaf (grade 5, 81 db or more). All participants signed informed consent forms. The SATA software was used for data analysis., Results: Of 6521 individuals, 4370 (67%) were interviewed. The prevalence of HI (auditory threshold of 0.5, 1, 2, 4 KHz and more than 25 db in the better ear) was 14.27 (11.53-17.91) of whom 9.52 (7.07-11.98) had grade 1, 4.04 (3.02-5.06) had grade 2, 0.67 (0.33-1.02) had grade 3 HI and 0.48 (0.16-0.8) were deaf. About 5.19% of the participants had disabling hearing impairment. All HI grades increased significantly with age but no significant difference was observed between men and women., Conclusion: The considerable prevalence of HI in Iran in comparison with other developing countries, with regards to the trend of aging in the population, seems concerning. The results of the study could be used as a treatment and research guideline for future works in the area of policymaking and plan to decrease these disorders., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interest.

Introduction: The Questionnaire for Olfactory Dysfunction (QOD) is a self-reporting olfactory-related quality of life questionnaire. The aim of this study was to determine the reliability and validity of the Persian version of this questionnaire., Materials and Methods: One hundred and thirteen patients with olfactory problems were enrolled in this study. The English version of the QOD was first translated into Persian. The reliability was then tested by determining the Cronbach alpha coefficient to assess internal consistency. The QOD was reviewed by a panel of experts, followed by calculating the content validity index to determine the content validity., Results: Based on the reliability analysis, the total Cronbach alpha was 0.88. The items in the "life quality" and "parosmia" domains had a good internal consistency in total, as well as in both genders and in different age subgroups. For the "sincerity" domain, however, low internal consistency was revealed (Cronbach alpha = 0.25). When questions related to the sincerity domain were omitted, the Cronbach alpha reached 0.89. The overall scale validity index for clarity and relevance were 0.88 and 0.87, respectively., Conclusion: The Persian version of the QOD seems to be a reliable and valid tool for the assessment of quality of life in patients with olfactory dysfunction. The "sincerity" domain cannot be used separately or should be substantially modified in order to be applicable to the Iranian population. However, there is no need to change the whole format of the questionnaire.

Background: Excessive bleeding is an unwanted complication of trans-sphenoidal resection of pituitary adenoma due to increases in intracranial pressure (ICP) and hemodynamic instability. Dexmedetomidine (Dex) anα2-agonists is the drug of choice in intensive care units (ICU) and cardiac surgeries to control abrupt changes in hemodynamic. Severe cardiovascular responses occur during trans-sphenoidal resection (TSR) of the pituitary adenoma despite adequate depth of anesthesia. The aim of this paper was to determine the effect of Dexmedetomidine on bleeding as primary outcome, and surgeon's satisfaction and hemodynamic stability as secondary outcomes in patients undergoing trans-sphenoidal resection of pituitary adenoma., Methods: Total numbers of 60 patients between 18-65 years old and candidate for elective trans-sphenoidal resection of pituitary adenoma were randomLy allocated to two groups; Dexmedetomidine infusion (0.6µg/kg/hour) or normal saline infusion. Mean arterial pressure (MAP), heart rate (HR), dose of hypnotics and narcotics during surgery, bleeding, and surgeon's satisfaction were recorded., Results: Propofol maintenance dose (µg/kg/min) and total Fentanyl use (µg) were significantly lower in Dex group compare to control group (P=0.01 and 0.003, respectively). Total bleeding amount during operation in Dex group was significantly lower than control group (P=0.012). Surgeon's satisfaction was significantly higher in Dex group at the end of surgery. MAP and heart rate throughout surgery were significantly lower in Dex group compare to control group (P=0.001)., Conclusions: Dexmedetomidine infusion (0.6µg/kg/hour) could reduce bleeding and provide surgeon's satisfaction during trans-sphenoidal resection of pituitary adenoma.

Objectives: The outcomes of Gamma Knife radiosurgery (GKRS) for cavernous sinus meningioma (CSM) are presented, and factors possibly affecting outcome are investigated., Methods: The medical records and imaging and procedural reports of 166 patients with CSM were retrospectively reviewed. Demographic data, procedural data, symptomatic improvement, radiological regression, and progression-free survival (PFS) rates were evaluated., Results: There were 124 women and 42 men; including 44 postoperative and 122 primary GKRS cases. Mean follow-up was 32.4 months. Mean marginal dose was 13 Gy. Symptomatic improvement was seen in 40.4%, while neurologic deterioration occurred in 9.6%; 50% remained symptomatically stable. Radiological regression was noted in 57.2%; the tumor remained stable in 35.5%, and 7.2% of the patients experienced tumor progression. The actuarial 5- and 10-year PFS rates were 90.1% (±3.3) and 75.8% (±8.8), respectively. History of previous surgery or radiotherapy were associated with lower symptomatic improvement. Higher tumor coverage and isodose lines were accompanied with better radiological prognosis. However, a history of conventional radiotherapy, presence of facial sensory deficits at presentation, a higher tumor volume, and tumor extension to the suprasellar compartment affected the radiologic outcome negatively., Conclusion: This study revealed a high efficacy and safety for GKRS in both postoperative and primary GKRS patients. Achievability of a good profile of tumor coverage and isodose lines at radiosurgical planning predict a better outcome., (© 2017 S. Karger AG, Basel.)

Introduction: Vitamin D has been suggested to play a considerable role in the function of the immune system in various infectious, inflammatory, and autoimmune conditions. Otitis media with effusion (OME), defined as the presence of non-purulent fluid within the middle ear without signs or symptoms of suppurative otitis media, has a number of inflammatory predisposing factors. This study was designed to explore the association between vitamin D deficiency and OME., Materials and Methods: In this cross-sectional study, 74 children aged 2-7 years with an obstructive indication for adenotonsillectomy were included. Patients were divided into two groups based on the need for ventilation tube insertion for OME. Thirty-two children were enrolled in the OME group and 42 in the control group. The mean vitamin D level was compared between the two groups., Results: Mean vitamin D concentration in all patients was 11.96±5.85 ng/ml (9.79±4.36 ng/ml in the OME group and 13.61±6.33 ng/ml in the control group; P=0.003). There was also a significant difference in levels of vitamin D in patients referred in winter (9.0±2.94 ng/ml) compared with the summer (19.85±4.21 ng/ml; P=0.001). Data analyzed based on the season in which the patients were referred showed no significant difference between the OME and the control group., Conclusion: Although our results showed lower serum levels of vitamin D in OME patients, the difference was not significant when seasons were taken into consideration. Therefore, the season is an important confounding factor in any research related to vitamin D due to the effect of sun-induced vitamin D.

Background: Nose is used as a corridor in endoscopic endonasal transsphenoidal approach (EETSA) for pituitary adenoma. Thus, it may affect the nasal airway patency, function and sinonasal-related quality of life. The aim of this study is to objectively and subjectively evaluate these effects., Methods: In this prospective study, 43 patients with pituitary adenoma who were candidates for EETSA from March 2012 to October 2013 were enrolled. The patients were evaluated preoperatively using acoustic rhinometry and rhinomanometry (with/without the use of decongestant drops) and asked to complete the 22-Item Sinonasal Outcome Test (SNOT-22) questionnaire. The tests were repeated at one and three months postoperatively. The preoperative data were compared with the first and second postoperative ones using paired-sample t-test., Results: Without the use of decongestant drops, the total airway resistance increased significantly (p=0.016), and the nasal airflow decreased significantly (p=0.031) in the first postoperative evaluation. However, in the 3rd postoperative month, the difference was not significant. With the use of decongestant drops, the objective parameters showed no significant changes compared to preoperative data even at the first evaluation. The SNOT- 22 scores also did not differ significantly in 1st and 3rd postoperative months. The first postoperative SNOT-22 showed a strong correlation with the second minimal cross-sectional area on simultaneous evaluation, and with the preoperative total airway resistance., Conclusion: EETSA has a transient adverse effect on the nasal patency that quickly improves, making it a safe approach for the sinonasal system. Rhinomanometry is the most sensitive test for detecting these nasal functional changes objectively.

To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal trans-sphenoidal approach (EETSA), the data of 106 eligible patients were included from February 2011 to December 2014. The scores of Sinonasal Outcome Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12 months postoperatively. Nine most related sinonasal questions were evaluated separately (9Q). There were no significant inter-group differences in the mean SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all postoperative assessments. Within each group, a significant improvement of SNOT-22 and 9Q scores were noted after 12 months of surgery compared to preoperative data. In the NSF group, comparison of the pre- and first postoperative evaluation revealed a significant deterioration in 9Q score (p = 0.007) and "sense of taste/smell" (p < 0.001) which both returned to baseline in the 3rd month. Patients who used nasal paper mask for more than 100 "hour-days" showed a better SNOT-22 scores at 1st (p = 0.04) and 3rd (p < 0.001) months after surgery. Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed significantly higher scores of SNOT-22 in all postoperative assessments compared to the others. Although nasal symptoms deteriorated at first postoperative month (compare to preoperative data) in the NSF group, no negative impacts on the sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas could be assumed as a risk factor for poorer sinonasal QOL in EETSA.

Importance: Because large dorsal reduction may weaken the keystone area, later notching of this area should be prevented while reducing large humps during septorhinoplasty., Objective: To determine whether a triangular-shaped flap of upper lateral cartilages (ULCs) that we designed can prevent secondary deformity of the nasal dorsum in the keystone area following large hump reduction., Design, Setting, and Participants: In this retrospective study, medical records as well as preoperative and postoperative photographs of septorhinoplasty cases in which triangular flaps had been used between April 1, 2012, and March 3, 2013, were reviewed. Data analysis was conducted from March 3 to May 10, 2014. Demographic data, amount of hump reduction, and any irregularity of the dorsum in the keystone area mentioned in the medical record or identified in postoperative profile view photographs were assessed. The study was conducted in a research center, and the operations were performed in a private setting. Patients had been scheduled for septorhinoplasty with flap reconstruction if more than 3 mm of dorsal hump reduction was planned and their skin was not thin. Of 41 identified patients, 3 could not be monitored for 1 year; 38 patients were included in the analysis., Exposures: Open septorhinoplasty had been performed, and more than 3 mm of dorsum had been removed in all patients whose data were analyzed. During stepwise resection of the nasal dorsum, a triangular-shaped remnant of the most cephalomedial part of the ULC was maintained intact on each side over the keystone area., Main Outcomes and Measures: Irregularity of the nasal dorsum over the keystone area in postoperative profile view photographs., Results: More than 3 mm of hump reduction had been made in all 38 patients. No irregularities were observed in the postoperative photographs or had been found on digital examination of the keystone area after at least 12 months of follow-up., Conclusion and Relevance: Maintaining a remnant of the ULC over the keystone area in the form of a triangular-shaped flap on each side is a simple, reliable, and durable way to prevent notching of the keystone area during lowering of the nasal dorsum in large noses with sufficient skin thickness., Level of Evidence: 4.

Background: SCORE, OST and ORAI risk assessment tools could reduce the cost burden of BMD tests by selecting the high risk patients to osteoporosis. In this study we compared the ability of these risk assessment measures to assess probability of the osteoporosis among post-menopausal women., Methods: 211 post-menopausal women aged 45-88 years enrolled into the study. All of the patients underwent BMD test and divided into two groups according to T-Score level. 43 patients (20.4%) had T-Score ≤-2.5 (osteoporotic) (group-1) and 168 (70.6%) patients had T-Score of > -2.5 (non-osteoporotic). Among 168 nonosteoporotic cases, 88 had -2.5≤T-Score≤-2 in at least one bony area. These 88 cases in addition to the 43 cases with -2.5≤T-Score considered as high risk group to osteoporosis (group 2). Afterward, SCORE, OST and ORAI risk scores were calculated and sensitivity, specificity, likelihood ratio, accuracy index and area under the curve of each tool were determined in both groups and then compared with each other., Results: SCORE had the highest sensitivity compared with others in both groups (95% and 88.2% respectively). Moreover, it had the highest diagnostic odds ratio and negative predictive value between the three methods. OST had the highest likelihood ratio and specificity in both groups (71.4% and 75.4%). There was significant difference between the sensitivity and specificity of the tests (p= 0.004 and 0.027)., Conclusion: OST with the highest specificity and positive LR had a special role in determining the osteoporotic patients and SCORE with the highest sensitivity and negative predictive value had an exceptional role in exclusion of the non- osteoporotic individuals. However, considering the area under the curve, there was no significant difference among these three methods in determining osteoporosis.

Background: Soft tissue profile can be widely different in various populations. Furthermore, this profile can be also continues to change throughout life. However, there are few studies that quantitatively evaluate the soft tissue profile in Iranian population. In order to determine normal reference values of facial parts in our populations, we aimed to measure standards for facial soft tissue parameters in Iranian young population., Methods: The study samples included 155 medical students at the Firouzgar hospital in winter 2011. The soft tissue facial profiles were digitally analyzed using linear measurements and angles made with standardized photographic records, taken in a natural head position, to determine the average soft tissue facial profile for males and females., Results: There was a statistically significant difference between males and females in 21 of our 26 measurements. The most prominent differences between the genders were observed in the measurements taken from the face region. Minimum frontal breadth and supraorbital breadth were larger in males than in females. Except for middle face height measurement, other horizontal and vertical measurements for the face were larger in males than in females, indicating wider and higher faces in men than in women. Some measurements of facial angles are discrepant between the two genders., Conclusion: Due to the specific features of Iranian facial soft tissue values and also observable differences in facial measurements and angles between men and women, the Iranian standard values on facial measurements and angles should be given more attention, especially by plastic and cosmetic surgeons.

Acquired non-traumatic transethmoidal encephaloceles are very infrequent lesions that are generally caused by a tumor or hydrocephalus. As far as we know, there is no reported case of encephalocele after CSF diversion in the literature. We present a 25-year-old woman with hydrocephalus due to aquiductal stenosis who was treated with endoscopic third ventriculostomy. Nine months later, she had developed rhinorrhea and on imaging she had a transethmoidal encephalocele. She underwent endonasal endoscopic repair of the defect and removal of herniated parenchyma. CSF diversion to parasellar cisterns is not a known iatrogenic cause of basal encephalocele and is not noted elsewhere as a complication of third ventriculostomy. However, as third ventriculostomy is performed usually for intracranial hypertension treatment and intracranial hypertension itself is a known but rare cause of lacunar skull defect and encephalocele, this co-incidence may occur.

Background: University of Pennsylvania Smell Identification Test (UPSIT) is one of the most common smell identification tests to assess olfactory function., Objectives: The study was conducted to assess the accuracy of University of Pennsylvania Smell Identification Test (UPSIT) in Iranian population., Materials and Methods: University of Pennsylvania Smell Identification Test was performed on 30 (50%) female and 30 (50%) male, who were healthy adult volunteers. The total mean score as well as mean scores according to the gender were assessed and compared to the UPSIT classification. Odors considered valid and accurate if its correct identification ability rate was more than 70% among study population., Results: The test score was 25.04 ± 4.92 in female and 23.29 ± 4.23 in male volunteers that all were considered as microsmia according to UPSIT. Sixteen odorants were correctly identified by about 70% of the volunteers and the remains 24 odorants were identified by less than 70%; 7, 5 and 12 odors was identified by60%-70%, 50%-60% and less than 50% of the volunteers, respectively., Conclusions: According to the results of the study, documented that even less than half of the odors (16 out of 40) were identified correctly by the volunteers, which indicating that the UPSIT is not a suitable test to evaluate olfactory function in Iranian population due to the high amount of unfamiliar smells that should be replaced with more familiar ones.

Rathke cleft cyst (RCC) is an uncommon albeit benign sellar lesion with an incidence rate of between 2 to 33%. RCCs are usually asymptomatic except in the large cases whit suprasellar extension. We herein describe a unique case of RCC, which presented with severe visual loss owing to massive herniation of the optic chiasm and third ventricle down into the sphenoid sinus through a small 8 x 8 mm foramen after transnasal endoscopic surgical fenestration and marsupialization of the cyst. We describe a reconstruction method via endonasal transsphenoidal approach in this case and suggest prophylactic reconstruction of the sellar floor in sellar lesions with equal or more voluminous suprasellar extensions that are susceptible to such massive herniation and secondary empty sella syndrome.

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Proposing a strategy for sellar reconstruction in endoscopic transsphenoidal transsellar approachfor pituitary adenoma., Methods: 240 patients with pituitary adenoma underwent pure endoscopic endonasal transsphenoidal surgery.Intra-operative CSF leaks were classified as grade 0, no observable leak; grade 1, CSF dripping through anarachnoid membrane defect of less than 1 mm; and grade 2, CSF flowing through an arachnoid defect of morethan 1 mm. Sellar reconstruction was performed according to our staging system; in stage I, the defect was coveredwith oxidized cellulose and sphenoid sinus filled up with Gelfoam. In stage II, a layer of fat was appliedon the defect and fascia lata placed epidurally. In stage III, one or two layers of fascia were used with addingsurgical glue and/or lumbar drainage. Mucosa of sphenoid sinuses was kept intact as much as possible and approximatedat the end of procedure., Result: intra-operative CSF leaks grade 0, 1 and 2 resulted in 133(55.4%), 78 (32.5%) and 29(12.1%) patients,respectively. Stage I of reconstruction was used in 126 patients (52.5%) with no intra-operative CSF leak orsever prolapse of arachnoid membrane. Stage II was performed in 80 patients (33.3%) with either leak grade 1(73 patients) or grade 0 with severe prolapse of the suprasellar components induced in the sella (2 cases) or inwhom extra-pseudocapsular dissection performed (5 cases). Stage III was performed in 34 cases (14.2%) witheither CSF leak grade 2 (29 patients) or grade 1 with simultaneous severe destruction or removal of sellar floorlaterally, superiorly or inferiorly (5 patients) which made it impossible to place the fascia underlay to the bone.A minimum of 18 months follow-up showed development of 2 CSF leaks (0.8%), one pneumocephalus (0.4%)and 2 meningitis (0.8%) cases., Conclusion: Given the low postoperative CSF leak rate, we demonstrated that our adopted sellar reconstructionstrategy focusing mostly on the adopted intra-operative CSF leak grading system is safe and useful forovercoming devastating complications like postoperative CSF leaks.

Background: The quality of life (QOL) is an important indicator for disease-severity classification and outcome measurement in obtaining treatment sinonasal diseases. The sinonasal outcome test 22 (SNOT 22) questionnaire has been introduced as the best specific sinonasal instrument for QOL measurement., Objectives: To prepare a valid and reliable Persian language version of SNOT 22 questionnaire., Patients and Methods: After forward and backward translation of the original version of SNOT 22 questionnaire from English to Persian, a group of patients with nasal septal deviation who need septal surgery and another group of healthy volunteers answered the Persian version of the questionnaire. The responsiveness rate, validity (Pearson correlations and differential validity) and reliability (internal consistency and test-retest reliability) of the 22 items of the questionnaire was calculated. P value < 0.05 was considered significant., Results: Thirty adults with nasal septal deviation need surgical correction and 30 healthy volunteers were included (mean age 30.4 ± 7.1 vs. 33 ± 6.7, P value = 0.148). The questionnaire was introduced to subjects two times with a two-week-period gap. Total responsiveness rate for 22 items was more than 97%. The total Cronbach's Alfa coefficient was 0.898 (ranging 0.890-0.903). The Pearson correlations were 0.85 and 0.96 for patients and healthy volunteers, respectively. The mean total score were 25.6 ± 13.3 (range 6-52) and 7.6 ± 9.1 (range 0-45) in patients and healthy volunteers, respectively (P < 0.0001). The subscales scores were also significantly different between two groups., Conclusions: The Persian version of SNOT 22 questionnaire is a valid and reliable instrument for accessing sinonasal diseases in Persian-speaking people.

Obstructive sleep apnea (OSA) is a common sleep disorder affecting quality of life. The aim of this study was to evaluate the perception of Quality of Life (QOL) in patients with OSA by means of World Health Organization Quality of Life (WHOQOL-BREF) instrument. This study was conducted on adult patients with sleep problems referred to Noor Sleep Lab for an overnight sleep study. Subjects were assessed for QOL using WHOQOL-BREF questionnaire. The Epworth sleepiness scale (ESS) was also employed to assess excessive daytime sleepiness (EDS). Baseline characteristics, ESS, and measured QOL are reported and their correlations with QOL were examined. Out of 502 patients included in the study, 62.7 % had moderate to severe OSA. The mean score of QOL in physical domain was significantly lower compared with normative population data. While AHI did not show any correlation with quality of life, mean O(2) was weakly correlated with physical domain. Among the baseline characteristics, BMI and ESS were negatively correlated with physical and mental domains. Findings of this study show the impairment in quality of life related to physical functioning in patients with obstructive sleep apnea. Our study further supports the lack of association between AHI and QOL.

Objective: New cochlear implant (CI) designs and developments in implantation techniques have revolutionized the management of hearing loss. However, cochlear implantation still has some disadvantages, such as its potential to initiate an inflammatory response that may lead to further hair cell damage. Recent topics of investigation have been the effect of glucocorticoids on inflammatory tissue response reduction, glucocorticoid dosage levels, and drug-delivery methods. In the present study, dexamethasone delivery via a drug-eluting CI was evaluated histologically through assessing inflammatory cell infiltration., Methods and Materials: Thirty healthy, adult male guinea pigs were included and randomly assigned to one of three surgical groups that underwent cochleostomy of the basal turn. The experimental group (Group 1) of 12 animals were implanted with a dexamethasone-loaded silicone elastomer shaped like a CI electrode. The primary control group (Group 2) of 12 animals were implanted with a simple CI (non-eluting). A second control group (Group 3) of six animals underwent cochleostomy only. Inflammatory responses were compared between groups by evaluating inflammatory cell infiltration in inner-ear specimens at days 3 and 13., Results: The Mann‐Whitney test revealed reduction in most of the inflammatory indices in Group 1 compared with Group 2. This was significant for fibrocyte, macrophage, and giant cell infiltration at day 3 as well as lymphocyte, macrophage infiltration, and capillary formation at day 13., Conclusion: This study showed some attenuation in inflammatory response following insertion of a dexamethasone-eluting CI, suggesting that it could be a route for local drug delivery into the cochlea.

A wide range of population, 4% to 30%, suffers from tinnitus that is defined as perception of sound without apparent acoustic stimulus. We conducted the present study to determine the prevalence of tinnitus in Iranian population; Tehran province. This cross-sectional study was conducted from January 2009 to December 2009, recruiting 3207 individuals (age range, 7-98) who were residing in Tehran province, Iran. Participants were asked to fill two questionnaires; the validated Persian version of Tinnitus Questionnaire (TQ) and another one that was specifically designed for this study. Prevalence of tinnitus and its association factors were evaluated. 3207 participants enrolled into our study comprising 1429 (44.7%) male and 1765 (55.3%) female with mean age of 55.01±17.85. Of total of 3207 participants, 146 (4.6%) had tinnitus consisting of 80 male (54.8%) and 66 (45.2%) female participants. It showed a rising trend with increasing age that was especially significant after the sixth decade of life (P=0.001). The analysis showed mean TQ global score of 35.96±25.52 that was significantly different between male and female participants (P=0.051) and had no significant correlation with increasing age (Spearman's r=0.1, P=0.10). The tinnitus intensity was moderate to very severe in 95 (56.1%) of the participants. Its severity level was not significantly different between men and women (P=0.09). Tinnitus intensity had no significant association with increasing age (Spearman's r=0.1, P=0.31). Patients with higher TQ global score had higher tinnitus intensities (P=0.001). The annoyance level was significantly different between men and women (P=0.04) and its impact on the participants daily routine functions were significantly higher in men (P=0.003). Given the results of the study, demonstrating that prevalence of tinnitus in Iranian population (Tehran province) was lower than the other countries and had a direct correlation with increasing age only after the sixth decade. TQ global score had significant correlation with tinnitus intensity, annoyance and impact on the participants' daily routine functions. However, none of the above had correlation with increasing age. Tinnitus TQ global score and intensity were not different between men and women; however annoyance of tinnitus and its impact on participants' daily routine functions were significantly higher in men.

Objectives: We conducted a study to determine and compare the efficacy of pathology and photodynamic studies in establishing diagnosis of malignant dermal and mucosal lesions., Methods and Patients: This descriptive cross-sectional study was performed on 40 patients suspected of SCC (squamous cell carcinoma). First, in PDD (photodynamic diagnosis) photosensitizing agent was applied to the lesion, and after 4-5h the fluorescence spectrum was detected by laser radiation. Based on fluorescence intensity, normal area was differentiated from malignant area. Also, biopsy samples from these suspected areas were sent to pathology simultaneously. Data were analyzed with SPSS v.16. The distribution of nominal variables was compared using the Chi-square test. Diagnostic index for photodynamic diagnosis were calculated. A two-sided p-value<0.05 was considered to be statistically significant., Results: In 27 cases (90%), results of pathology and photodynamic studies similarly showed malignancy. In 8 cases (80%), results of pathology and photodynamic studies similarly showed non-malignant lesion. But in five cases (12.5%) the results of pathology and photodynamic studies were not the same. This difference was not statistically significant showed by the Chi-square test analysis (p-value>0.05). A sensitivity of 90%, specificity of 80%, accuracy of 87.5%, positive predictive value (PPV) of 93%, negative predictive value (NPV) of 72%, positive likelihood ratio (PLR) of 4.5, negative likelihood ratio(NLR) of 0.125 were found in diagnosing SCC for photodynamic studies., Conclusion: Photodynamic diagnosis is a useful non-invasive initial step in the diagnostic work-up of patients with suspected malignant lesions (SCC). In this work we have studied 40 SCC suspicious patients using PDD method and successfully carried out 27 cases as malignant all of which were matching with pathologic results. This outcome can prove both accuracy and reliability of PDD method for detecting SCC lesions on head and neck regions. Also PDD can fully demarcate the lesion peripheries less invasively as well as preserving much more time and effort. Although PDD method is a bit more expensive that biopsy and pathology but great advantages can easily cover this issue. We recommend PDD as a useful easy technique to visualize and detect the extension of the tumor preoperatively., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Tympanic membrane (TM) perforation is still one of the most common otology complications. New designs of biomaterials, and lately tissue-engineered composites and grafts, have thoroughly revolutionized the management of TM perforation. In this study, we examined a biologically modified collagen-immobilized polydimethyl siloxane patch to repair TM perforation. In vitro potential of the aforementioned patch as a scaffold to support fibroblast cell growth and adhesion was assessed. An in vivo assay of the patch for initiating repair of TM perforations also was investigated. In vitro assay showed that the patch has significantly increased cell adhesion and growth in comparison with unmodified ones (p < 0.05). In vivo study also showed an overall closure rate of TM perforation of 70% and an average gain of 15.75 ± 4.29 dB in air-bone gap. This study shows that the preliminary in vivo evaluation of a modified siloxane patch in humans had promising results and is comparable to existing biomaterial patches., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: The Ministry of Health and Medical Education of Iran, and similar institutions in many other countries, advises physicians to use current guidelines for the diagnosis and treatment of acute otitis media (AOM). However, there has been no evaluation of the effectiveness of such guidelines or whether physicians in Iran adhere to them. Thus, as laryngologists are the most important group of people who interact with patients with AOM, the aim of this study was to evaluate the attitude of laryngologists to the established guidelines., Materials and Methods: A total of 120 anonymous surveys were mailed to 120 otolaryngologists in Tehran, Iran, to evaluate the patterns of diagnosis and treatment of AOM used by these physicians. The survey included questions regarding the otolaryngologists' age, gender, place of work, and attitude towards diagnosis and treatment of AOM., Results: Sixty-two completed surveys were received, for a response rate of 51%. There was no significant difference between respondents to these surveys according to sex, age, practice setting, graduation year, or the number of patients with AOM seen each month., Conclusion: Our study adds new insights to the previous literature on the use of guidelines in the management of AOM. We can now assess the impact of guidelines on the usual practice of physicians in evidenced-based management of AOM.

Objective. To evaluate the changes in nasal dimensions of healthy Iranian volunteered for cosmetic rhinoplasty after surgery using acoustic rhinometry. Methods. Pre- and postoperative nasal dimension of 36 cases undergoing cosmetic rhinoplasty were compared using acoustic rhinometry (AR), and the measured variables were distance to first and second constriction (d1, d2), first and second minimal cross-sectional area (MCA1, 2), and volume. Results. Mean age (SD) of cases were 24.63 (4.4) years. Septoplasty was performed in 12 cases (33.3%). After surgery, bilateral d1 and both MCA2 decreased significantly, while significant increase was observed in MCA1 postoperatively using decongestant. Cases with septoplasty experienced more increase in MCA1 and less constriction in MCA2 postoperatively. In cases with rhinoplasty alone, they received benefit from double osteotomy in MCA1. In either group of rhinoplasty with and without septoplasty, placing a strut was beneficial for patients. Discussion. The cross-sectional area of the nose is a major factor in the determination of airflow. Cosmetic rhinoplasty may generate a mix effect on nose function. Performing osteotomy may better help patients to save nasal patency, septoplasty is beneficial even in mildly deviated septums, and placing a strut may be beneficial in most of the cases.