Intra and inter-regional functional connectivity of the human brain due to Task-Evoked fMRI Data classification through CNN & LSTM.

BACKGROUND AND PURPOSE: Olfaction is an early marker of neurodegenerative disease. Standard olfactory function is essential due to the importance of olfaction in human life. The psychophysical evaluation assesses the olfactory function commonly. It is patient-reported, and results rely on the patient's answers and collaboration. However, methodological difficulties attributed to the psychophysical evaluation of olfactory-related cerebral areas led to limited assessment of olfactory function in the human brain. MATERIALS AND METHODS: The current study utilized clustering approaches to assess olfactory function in fMRI data and used brain activity to parcellate the brain with homogeneous properties. Deep neural network architecture based on ResNet convolutional neural networks (CNN) and Long Short-Term Model (LSTM) designed to classify healthy with olfactory disorders subjects. RESULTS: The fMRI result obtained by k-means unsupervised machine learning model was within the expected outcome and similar to those found with the conn toolbox in detecting active areas. There was no significant difference between the means of subjects and every subject. Proposing a CRNN deep learning model to classify fMRI data in two different healthy and with olfactory disorders groups leads to an accuracy score of 97 %. CONCLUSIONS: The K-means unsupervised algorithm can detect the active regions in the brain and analyze olfactory function. Classification results prove the CNN-LSTM architecture using ResNet provides the best accuracy score in olfactory fMRI data. It is the first attempt conducted on olfactory fMRI data in detail until now.

The brain functional connectivity alterations in traumatic patients with olfactory disorder after low-level laser therapy demonstrated by fMRI.

BACKGROUND: Low-level laser therapy (LLLT) has been clinically accepted to accelerate the nerve regeneration process after a nerve injury or transection. We aimed to investigate the neuronal basis and the influence of LLLT on brain functional networks in traumatic patients with olfactory dysfunction. METHODS: Twenty-four Patients with traumatic anosmia/hyposmia were exposed to pleasant olfactory stimuli during a block-designed fMRI session. After a 10-week period, patients as control group and patients who had completed the sessions of LLLT were invited for follow-up testing using the same fMRI protocol. Two-sample t-tests were conducted to explore group differences in activation responding to odorants (p-FDR-corrected <0.05). Differences of functional connectivity were compared between the two groups and the topological features of the olfactory network were calculated. Correlation analysis was performed between graph parameters and TDI score. RESULTS: Compared to controls, laser-treated patients showed increased activation in the cingulate, rectus gyrus, and some parts of the frontal gyrus. Shorter pathlength (p = 0.047) and increased local efficiency (p = 0.043) within the olfactory network, as well as decreased inter-network connectivity within the whole brain were observed in patients after laser surgery. Moreover, higher clustering and local efficiency were related to higher TDI score, as manifested in increased sensitivity to identify odors. CONCLUSIONS: The results support that low-level laser induces neural reorganization process and make new connections in the olfactory structures. Furthermore, the connectivity parameters may serve as potential biomarkers for traumatic anosmia or hyposmia by revealing the underlying neural mechanisms of LLLT.

A TGF-α and TGF-ß1 Poloxamer-based micelle/hydrogel composite: A promising novel candidate for the treatment of anosmia.

Anosmia is the inability to smell or loss of the sense of smell. It can reduce your ability to detect the smell of smoke, gas leaks, or spoiled food, as well as hinder the quality of life related to social interactions and feelings of well-being. In the current study, a drug delivery composite was designed to cure anosmia and its efficiency in delivering transforming growth factor alpha (TGF-α) and transforming growth factor beta 1 (TGF-ß1) to the nasal cavity was evaluated. Bovine serum albumin (BSA) was used as a model protein for encapsulation into Poloxamers 407 micelles. For the optimization of the BSA-micelle formulation, a two-parameter five-level central composite design (CCD) was applied. The BSA-micelle was optimized with a particle size of 41 nm, drug loading of 8%, and encapsulation efficiency of 74%. Further, the BSA-micelle was characterized by FESEM, TEM, and FTIR. The analysis of release profile suggested high-paced free BSA release compared to the gradual and prolonged release of BSA-micelle/hydrogel and BSA-micelles. The cytotoxicity assay demonstrated the safety of TGF-α and TGF-ß1-micelles/hydrogel. Moreover, it was observed that TGF-α and TGF-ß1 within the hydrogels promote cellular viability and human olfactory ectomesenchymal stem cell OE-MSCs proliferation. In conclusion, According to the results of our study, the TGF-α and TGF-ß1-micelle/hydrogel-based delivery system provides a suitable alternative for anosmia treatment.

Determinants of gold nanoparticle interactions with Proteins: Off-Target effect study.

Photothermal therapy is one of the promising approaches toward cancer treatment. To date, several compounds have been developed for this application, among which nanoparticles are attracting ever-increasing attention. One of the obstacles in developing efficient photothermal nanoparticle agents is their off-target effect which is mainly mediated via non-specific interactions with proteins. Such interaction not only reduces the bioavailability of the agent but also will cause protein aggregation that can be lethal. So, gaining knowledge on the mechanisms mediating such interactions will facilitate development of more effective agents. Our last studies showed the mechanism of action of two modified gold nanoparticles, folic acid functionalized gold nanoparticles (FA-AuNPs) and gold shelled Fe3O4 nanoparticles (AuFeNPs), as photothermal agents. In the current work, we focus on the interaction of these two NPs with human serum albumin (HSA) and human hemoglobin (Hb) as model proteins. The complex formation between NPs and proteins was investigated by fluorescence spectroscopy, dynamic light scattering and circular dichroism. Our data distinguishes the very distinct mode of interaction of charged and neutral NPs with proteins. While the interaction of neutral AuFeNP to proteins is protein dependent, charged nanoparticles FA-AuNP interact indistinguishably with all proteins via electrostatic interactions. Moreover, complexes obtained from FA-AuNPs with proteins are more stable than that of AuFeNP. However, the secondary structure content of proteins in the presence of NPs indicates the insignificant effect of NPs on the secondary structure of these proteins. Our data propose that the charge functionalization of the NPs is an effective way for modulating the interaction of nanoparticles with proteins.

Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments.

The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.

A study of depression, partnership and sexual satisfaction in patients with post-traumatic olfactory disorders.

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.

Simulation and In Vitro Experimental Studies on Targeted Photothermal Therapy of Cancer using Folate-PEG-Gold Nanorods.

BACKGROUND: Selective targeting of malignant cells is the ultimate goal of anticancer studies around the world. There are some modalities for cancer therapy devastating tumor size and growth rate, meanwhile attacking normal cells. Utilizing appropriate ligands, like folate, allow the delivery of therapeutic molecules to cancer cells selectively. There are a variety of photosensitizers, like gold nanorods (GNRs), capable of absorbing the energy of light and converting it to heat, evidently build a photothermal procedure for cancer therapy. OBJECTIVE: To develop a one-step approach for calculating the temperature distribution by solving the heat transfer equation with multiple heat sources originating from NIR laser-exposed GNRs. MATERIAL AND METHODS: In this experimental study, we simulated NIR laser heating process in a single cancer cell, with and without incubation with folate conjugated PEG-GNRs. This simulation was based on a real TEM image from an experiment with the same setup. An in vitro experiment based on aforesaid scenario was performed to validate the simulated model in practice. RESULTS: According to the simplifications due to computational resource limits, the resulting outcome of simulation showed significant compatibility to the supporting experiment. Both simulation and experimental studies showed a similar trend for heating and cooling of the cells incubated with GNRs and irradiated by NIR laser (5 min, 1.8 W/cm2). It was observed that temperature of the cells in microplate reached 53.6 °C when irradiated by laser. CONCLUSION: This new method can be of great application in developing a planning technique for treating tumors utilizing GNP-mediated thermal therapy.

From Transcriptome to Behavior: Intranasal Injection of Late Passage Human Olfactory Stem Cells Displays Potential in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which is caused by the loss of dopaminergic (DAergic) neurons. Thus, cell replacement therapy (CRT) might be regarded as an alternative therapy to effectively treat motor functional defects in PD patients. Human olfactory ectomesenchymal stem cells (OE-MSCs) are a novel type of mesenchymal stem cells (MSCs) with a strong tendency to differentiate into DAergic neurons. However, there are various barriers to successful CRT including the proliferation capacity of stem cells at higher passage numbers as well as the route of stem cell delivery. In this regard, we aimed to explore the efficacy of late passage OE-MSC administration through the intranasal (IN) route in PD rat models. Herein, the proliferation capacity of OE-MSCs was compared at early and late passage numbers; then, the results were validated via RNA sequencing analysis. Subsequently, the efficacy of IN injection of late passage OE-MSC in PD models was evaluated. The results manifested the absence of noticeable differences in proliferation capacity and signaling pathways in OE-MSCs at early and late passage numbers. Moreover, it was found that the IN administration of OE-MSCs with a high passage number substantially increased the levels of DAergic markers and improved the motor function in rat models of PD. Overall, our findings suggested that OE-MSCs with a high passage number are a promising CRT candidate due to their fundamental potential to provide a large number of cells with an enormous proliferation capacity. Moreover, they exhibit the high efficiency of IN administration as a noninvasive route of late-passage OE-MSC delivery for CRT, particularly for PD.

Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease.

One of the complex neurodegenerative disorders is Parkinson disease (PD). PD is mainly caused by dopaminergic (DAergic) neuron degeneration in the midbrain. The loss of DAergic neurons is considered as a key reason of motor functional defects in PD patients. Cell replacement strategies are considered as an alternative remedy to effectively address neurodegeneration in PD. In this report, we evaluated the restorative effect of human olfactory ecto-mesenchymal stem cells (OE-MSCs) in rat models of PD. Accordingly, human OE-MSCs were isolated and phenotypically characterized by flow cytometry and immunocytochemistry. Next, the undifferentiated OE-MSCs were unilaterally transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rat models, followed by molecular and histological analyzes as well as assessment of motor skills. Our results displayed that the grafting of OE-MSCs increased the expression of DAergic markers namely dopamine transporter (DAT), tyrosine hydroxylase (TH), nuclear receptor related-1 (Nurr1) in a 6-OHDA model compared with that of control, detected by immunohistochemical staining and western blot. Moreover, noticeable improvements in motor coordination, muscle activity and locomotor performance were observed in 6-OHDA model of PD following OE-MSCs transplantation. Taken together, our finding indicates that undifferentiated OE-MSCs might be counted as an appropriate source for cell replacement therapy particularly aimed at PD.

Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment.

Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models.

Promoting motor functions in a spinal cord injury model of rats using transplantation of differentiated human olfactory stem cells: A step towards future therapy.

Human olfactory ecto-mesenchymal stem cells (hOE-MSCs) derived from the human olfactory mucosa (OM) can be easily isolated and expanded in cultures while their immense plasticity is maintained. To mitigate ethical concerns, the hOE-MSCs can be also transplanted across allogeneic barriers, making them desirable cells for clinical applications. The main purpose of this study was to evaluate the effects of administering the hOE-MSCs on a spinal cord injury (SCI) model of rats. These cells were accordingly isolated and cultured, and then treated in the neurobasal medium containing serum-free Dulbecco's Modified Essential Medium (DMEM) and Ham's F-12 Medium (DMEM/F12) with 2% B27 for two days. Afterwards, the pre-induced cells were incubated in N2B27 with basic fibroblast growth factor (bFGF), fibroblast growth factor 8b (FGF8b), sonic hedgehog (SHH), and ascorbic acid (vitamin C) for six days. The efficacy of the induced cells was additionally evaluated using immunocytochemistry (ICC) and real-time polymerase chain reaction (RT-PCR). The differentiated cells were similarly transplanted into the SC contusions. Functional recovery was further conducted on a weekly basis for eight consecutive weeks. Moreover, cell integration was assessed via conventional histology and ICC, whose results revealed the expression of choline acetyltransferase (ChAT) marker at the induction stage. According to the RT-PCR findings, the highest expression level of insulin gene-enhancer protein (islet-1), oligodendrocyte transcription factor (Olig2), and homeobox protein HB9 was observed at the induction stage. The number of engraftment cells also rose (approximately by 2.5 % ± 0.1) in the motor neuron-like cells derived from the hOE-MSCs-grafted group compared with the OE-MSCs-grafted one. The functional analysis correspondingly revealed that locomotor and sensory scores considerably improved in the rats in the treatment group. These findings suggested that motor neuron-like cells derived from the hOE-MSCs could be utilized as an alternative cell-based therapeutic strategy for SCI.

Cultural Adaptation of the Iranian Version of the "Sniffin' Sticks" Olfactory Test.

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.

Situation Analysis of Ear and Hearing Care Program in Islamic Republic of Iran: System's Challenges and Proper Interventions.

Background: More than 6.8% of the world's population suffer from disabling hearing impairment. Hearing impairment can cause lifelong or even life-threatening problems and has a significant impact on the health and quality of life. This study aimed to analyze the current situation of the ear and hearing care (EHC) in the frame of Iran health system. Methods: This situation analysis was performed over a 5-year period (2013-2017) using the Strengths, Weaknesses, Opportunities, and Threats analysis method. First, after formation of the steering committee, all relevant published and unpublished articles and reports were reviewed and analyzed. In the next step, focused group discussion sessions (FGDs) were held with the participation of the experts, stakeholders, and Steering Committee members. Through the scissor-and-sort technique, the relevant data were highlighted and main categories evolved. Results: The main challenges included inadequate health literacy, weak intrasectoral and intersectoral cooperation, the inadequacy of policy responses, nonintegration of the EHC in the primary health care system, poor standard processes, and resources of EHC, and lack of EHC surveillance system. The 6 major interventions and strategies extracted as identifying the capacities of both the public and private sectors, reinforcement of intersectoral cooperation and intersectoral collaboration, standardizing the processes and integrating of EHC services in the PHC, reorganizing the referral system, promoting hearing health literacy, and minimizing hearing loss risk factors. Conclusion: Implementing the proposed interventions and strategies is essential to improve the situation of Iran EHC management system during the next 5 years.

Control of cellular adhesiveness in hyaluronic acid-based hydrogel through varying degrees of phenol moiety cross-linking.

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.

Global study of variability in olfactory sensitivity.

Variability in human olfactory sensitivity has been attributed to individual-level factors such as genetics, age, sex, medical history of infections and trauma, neurogenerative diseases, and emotional disorders. Scarce evidence exists on the cross-cultural variation in olfactory sensitivity. Hence, we performed 2 studies to estimate the variability in olfactory threshold as a function of location and environment. Study 1 involved 11 laboratories from 4 continents (N = 802). In each location, in a designated laboratory, approximately 80 subjects underwent olfactory sensitivity testing with custom-made tests with eucalyptol and phenylethanol (PEA) odors. Tests were based on the Threshold subtest of the Sniffin' Sticks battery. In Study 2, we compared olfactory sensitivity and suprathreshold perception of PEA and eucalyptol in 2 Chinese (N = 160) and 2 Indian (N = 92) populations-one based in their native country and the other in Germany. Both studies present large-scale evidence that olfactory sensitivity varies as a function of geographical location and suggest that environmental factors play an important role in shaping olfactory sensitivity and suprathreshold olfactory perception. We delineate further steps necessary to identify specific factors underlying uncovered variability and the relationship between olfactory sensitivity and suprathreshold odor perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran.

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.

A multimodal MR-compatible olfactometer with real-time controlling capability.

Design of an MR-compatible and computer-controlled odour stimuli system is essential in the studies of human olfactory function. Olfactometers are used to deliver odours to the subjects in an objective manner. We present a portable, computer-controlled eight channels olfactometer able to stimulate olfaction by employing liquid odorant stimuli. We used a high-pressure pump to generate medical grade airflow. After passing through solenoid valve-controlled odour reservoirs, odorant stimulus is conveyed to the nasal mask. The odour delivery delay of the device was measured using photo-ionisation detectors. To assess the application of the designed olfactometer, an fMRI experiment was done with 9 healthy subjects. Two odour stimuli (Vanillin and Rose) were presented to each subject in an alternating block design task of odour and non-odour conditions. The response time of each subject was gathered using the response box. Group analysis revealed a significant BOLD signal change in some regions of olfactory and trigeminal networks including the orbitofrontal cortex, insula, inferior frontal gyrus, hippocampus, cingulate gyrus and piriform cortex. The odour delivery delay measured by photo-ionisation detector was 190 ms, and the subjects' response showed 205 ms for the Vanillin and 243 ms for the Rose odour stimuli. Our portable MR-compatible olfactometer as a stimulation device is capable of creating adequate stimulation suitable for olfactory fMRI experiments.

Validity and Reliability of Persian Smell Identification Test.

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.

Iranian centers of excellence in medical sciences: A qualitative study to analyze the current state and design of a future roadmap.

Background: Due to the law for the fifth development plan and Iran's 20- year economic perspective, Centers of Excellence (COEs) were expected to upgrade the level of research and education besides improving infrastructures in Iran. This study is aimed to analyze the current state of national centers of excellence and designing a future roadmap. Methods: In this qualitative study, data was gathered by reviewing relevant national & international literature and upstream documents, interview with experts, and focused group discussions with stakeholders. Finally, a roadmap was prepared for approval. Results: Lack of common understanding of the COEs definition, lack of clear professional orientation for each center, lack of mandate and commitment in using COEs in the health system and community health promotion, weakness in enticing elites, and unresponsive to basic needs of the country were five major challenges COEs encountered. The consensus prospective vision for centers of excellence was developed based on the establishment and management of special institutions of thought and technology in centers of excellence to advise health policymakers and provide the highest level of the regional and global position. Conclusion: Despite over a decade of development of medical COEs, their goals have not been reached yet. Enactment of designed roadmap and its subprojects in the Supreme Council of Centers is the primary steps for functional improvement of COEs.

Fabrication of chitosan/agarose scaffolds containing extracellular matrix for tissue engineering applications.

One of the most effective approaches for treatment of cartilage involves the use of porous three-dimensional scaffolds, which are useful for improving not only cellular adhesion but also mechanical properties of the treated tissues. In this study, we manufactured a composite scaffold with optimum properties to imitate nasal cartilage attributes. Cartilage extracellular matrix (ECM) was used in order to improve the cellular properties of the scaffolds; while, chitosan and agarose were main materials that are used to boost the mechanical and rheological properties of the scaffolds. Furthermore, we explored the effect of the various weight ratios of chitosan, agarose, and ECM on the mechanical and biomedical properties of the composite scaffolds using the Taguchi method. The resulting composites display a range of advantages, including good mechanical strength, porous morphology, partial crystallinity, high swelling ratio, controlled biodegradability rate, and rheological characteristics. Additionally, we performed the cytotoxicity tests to confirm the improvement of the structure and better cell attachments on the scaffolds. Our findings illustrate that the presence of the ECM in chitosan/agarose structure improves the biomedical characteristics of the final scaffold. In addition, we were able to control the mechanical properties and microstructure of the scaffolds by optimizing the polymers' concentration and their resulting interactions. These results present a novel scaffold with simultaneously enhanced mechanical and cellular attributes comparing to the scaffolds without ECM for nasal cartilage tissue engineering applications.