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.

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.

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.

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.

Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering.

Regeneration and functional recovery after peripheral nerve damage still remain a significant clinical problem. In this study, alginate/chitosan (alg/chit) hydrogel was used for the transplantation of olfactory ectomesenchymal stem cells (OE-MSCs) to promote peripheral nerve regeneration. The OE-MSCs were isolated from olfactory mucosa biopsies and evaluated by different cell surface markers and differentiation capacity. After creating sciatic nerve injury in a rat model, OE-MSCs were transplanted to the injured area with alg/chit hydrogel which was prepared and well-characterized. The prepared hydrogel had the porosity of 91.3 ± 1.27%, the swelling ratio of 379% after 240 min, weight loss percentages of 80 ± 5.56% after 14 days, and good blood compatibility. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4',6-diamidino-2-phenylindole, and LIVE/DEAD staining were done to assay the behavior of OE-MSCs on alg/chit hydrogel and the results confirmed that the hydrogel can provide a suitable substrate for cell survival. For functional analysis, alg/chit hydrogel with and without OE- MSCs was injected into a 3-mm sciatic nerve defect of Wistar rats. The results of the sciatic functional index, hot plate latency, electrophysiological assessment, weight-loss percentage of wet gastrocnemius muscle, and histopathological examination using hematoxylin-eosin and Luxol fast blue staining showed that utilizing alg/chit hydrogel with OE-MSCs to the sciatic nerve defect enhance regeneration compared to the control group and hydrogel without cells.

Protective mechanisms of melatonin against hydrogen-peroxide-induced toxicity in human bone-marrow-derived mesenchymal stem cells.

Many obstacles compromise the efficacy of bone marrow mesenchymal stem cells (BM-MSCs) by inducing apoptosis in the grafted BM-MSCs. The current study investigates the effect of melatonin on important mediators involved in survival of BM-MSCs in hydrogen peroxide (H2O2) apoptosis model. In brief, BM-MSCs were isolated, treated with melatonin, and then exposed to H2O2. Their viability was assessed by MTT assay and apoptotic fractions were evaluated through Annexin V, Hoechst staining, and ADP/ATP ratio. Oxidative stress biomarkers including ROS, total antioxidant power (TAP), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH), thiol molecules, and lipid peroxidation (LPO) levels were determined. Secretion of inflammatory cytokines (TNF-α and IL-6) were measured by ELISA assay. The protein expression of caspase-3, Bax, and Bcl-2, was also evaluated by Western blotting. Melatonin pretreatment significantly increased viability and decreased apoptotic fraction of H2O2-exposed BM-MSCs. Melatonin also decreased ROS generation, as well as increasing the activity of SOD and CAT enzymes and GSH content. Secretion of inflammatory cytokines in H2O2-exposed cells was also reduced by melatonin. Expression of caspase-3 and Bax proteins in H2O2-exposed cells was diminished by melatonin pretreatment. The findings suggest that melatonin may be an effective protective agent against H2O2-induced oxidative stress and apoptosis in MSC.

Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage. As chondrocytes are the only cell type forming the articular cartilage, their gradual loss is the main cause of OA. There is a substantial body of published research that suggests reactive oxygen species (ROS) are major causative factors for chondrocyte damage and OA development. Oxidative stress elicited by ROS is capable of oxidizing and subsequently disrupting cartilage homeostasis, promoting catabolism via induction of cell death and damaging numerous components of the joint. IL-1ß and TNF-α are crucial inflammatory factors that play pivotal roles in the pathogenesis of OA. In this process, the mitochondria are the major source of ROS production in cells, suggesting a role of mitochondrial dysfunction in this type of arthritis. This may also be promoted by inflammatory cytokines such as IL-1ß and TNF-α which contribute to chondrocyte death. In patients with OA, the expression of endoplasmic reticulum (ER) stress-associated molecules is positively correlated with cartilage degeneration. Melatonin and its metabolites are broad-spectrum antioxidants and free radical scavengers which regulate a variety of molecular pathways such as inflammation, proliferation, apoptosis, and metastasis in different pathophysiological situations. Herein, we review the effects of melatonin on OA, focusing on its ability to regulate apoptotic processes and ER and mitochondrial activity. We also evaluate likely protective effects of melatonin on OA pathogenesis.

Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney.

The risk of serious side-effects such as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in 5 groups, each containing 6 rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN, and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidney weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD, and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidney weight, renal ROS, and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.

A scientific paradigm for targeted nanophotothermolysis; the potential for nanosurgery of cancer.

The application of gold nanoparticles (AuNPs) in nanophotothermolysis as a great photosensitizer is expanding, and this subject is a challenging area for cancer therapy. Recent technological advances in nanoscale manufacturing and synthesis promise the development of highly beneficial and innovative methods for the targeting of cancer. However, there is an obstacle to conducting effective laser-based nanosurgery because AuNPs are activated by visible or near infrared wavelengths, and the penetration of a laser beam inside the body is limited by some absorbents, such as melanin, water, and blood molecules. Considering everything stated above, we have suggested the application of a folate-conjugated AuNP as an effective agent for targeted nanophotothermolysis and the application of an optical fiber to transport the laser light from the source to the target tissue inside the body. Thus, a new method of nanosurgery in which a surgeon is able to perform surgery at the cellular or even at the subcellular level may be possible.

The effects of folate-conjugated gold nanorods in combination with plasmonic photothermal therapy on mouth epidermal carcinoma cells.

The use of lasers has emerged to be highly promising for cancer therapy modalities, most commonly, the photothermal therapy method. Unfortunately, the most common disadvantage of laser therapy is its nonselectivity and requirement of high power density. The use of plasmonic nanoparticles as highly enhanced photoabsorbing agents has thus introduced a much more selective and efficient cancer therapy strategy. In this study, we aimed to demonstrate the selective targeting and destruction of mouth epidermal carcinoma cells (KB cells) using the photothermal therapy of folate-conjugated gold nanorods (F-GNRs). Considering the beneficial characteristics of GNRs and overexpression of the folate receptor by KB cells, we selected F-GNRs as a targeted photothermal therapy agent. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by flow cytometry using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. No cell damage or cytotoxicity from the individual treatment of laser light or F-GNRs was observed. However, a 56% cell lethality was achieved for KB cells using combined plasmonic photothermal therapy of 20 µM F-GNRs with seven pulses of laser light and 6-h incubation periods. Cell lethality strongly depends on the concentration of F-GNRs and the incubation period that is mainly due to the induction of apoptosis. This targeted damage is due to the F-GNRs present in the cancer cells strongly absorbing near-infrared laser light and rapidly converting it to heat. This new therapeutic avenue for cancer therapy merits further investigation using in vivo models for application in humans.

Photographic facial soft tissue analysis of healthy Iranian young adults: anthropometric and angular measurements.

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.

Evaluation of quality of life in patients with obstructive sleep apnea.

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.

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.

Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial study.

BACKGROUND: The role of vitamin D in Atopic Dermatitis (AD) is ambiguous and clinical trials are needed to assess the role of vitamin D in the treatment of AD. The aim of this clinical trial study to evaluate the effect of vitamin D supplementation on patients with AD. MATERIAL AND METHODS: sixty AD patients were included in a randomized, double-blind, placebo-controlled trial study. They were randomly divided into two groups and treated for 60 days: group vitamin D (n=30), and placebo group (n=30). The two groups were as follows: Group D, 1600 IU cholecalciferol (vitamin D) and second group placebo. The severity of AD was evaluated based on SCORAD (Scoring Atopic Dermatitis) and TIS (Three Item Severity score) value by the same trained physician before and after the trial. RESULTS: According to SCORAD and TIS value index in the vitamin D group showed significant improvement in patients with mild, moderate and severe AD (P<0.05) and in patients who the intake placebo, this improvement didn't showed (P>0.05). CONCLUSION: Results mention that supplementation with oral vitamin D dramatically improved disease severity in AD patients.

Severity of depression and anxiety in obstructive sleep apnea syndrome.

Obstructive sleep apnea (OSA) is a common sleep disorder which can result in mood problems. The aim of this study was to evaluate the severity of depression and anxiety symptoms as the most prevalent psychological disturbances present in different severity of OSA. We performed a cross-sectional study of 685 recently diagnosed sleep-disordered patients, over the age of 18, referred to Noor Sleep Lab from August 2008 to November 2010. The participants filled the Beck depression inventory-II (BDI-II) and the Beck anxiety inventory (BAI) to assess the depression and anxiety symptoms. We collected other characteristics of subjects such as age, sex, body mass index (BMI) and Epworth sleepiness scale (ESS). Apnea hypopnea index (AHI) was determined by an overnight polysomnography. Mean age of the participants was 47.63 years (SD 11.73). More than half of patient had some degrees of depression and anxiety. AHI showed no significant correlation with BDI (p = 0.105, r = -0.070) or BAI (p = 0.712, r = -0.016). Obesity was not either correlated with depression or anxiety (p = 0.18, r = 0.05). Nonetheless, ESS was weakly correlated with depression (p = 0.001, r = 0.148) and anxiety scores (p = 0.006, r = 0.120). BMI and ESS means were significantly higher in patients with severe OSA (p = 0.000). In comparison with men, the severity of depressive and anxiety symptoms was significantly higher in women (p = 0.000). In this cross-sectional study of patients with sleep problems, OSA was not associated with severity of depression and anxiety symptoms.

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.

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.

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.

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.