Bridging Preclinical and Clinical Perspectives: New Insights on Melatonin’s Neuroprotective Effects in Neonatal Rats with Hypoxic-Ischemic Brain Injury and Discovering Prognostic Biomarkers in Patients with Traumatic Brain Injury

This thesis represents a comprehensive endeavor to bridge preclinical and clinical research, aiming to enhance our understanding and treatment approaches for brain injuries. It focuses on two specific areas: neonatal hypoxic-ischemic (HI) brain injury and traumatic brain injury (TBI). The thesis had a dual aim: first, to elucidate the neuroprotective mechanisms of melatonin in neonatal HI brain injury using a neonatal rat model of HI, and second, to identify prognostic biomarkers in patients with TBI. The thesis includes two main chapters. The first chapter, titled “Neonatal Hypoxic-Ischemic Brain Injury: Involvement of Notch1 Signaling Pathway and SIRT3 in the Neuroprotective Effect of Melatonin,” was conducted at the University of Urbino Carlo Bo, Italy. This study demonstrated how melatonin, a natural neurohormone, attenuated brain damage in neonatal HI by modulating the Notch1 signaling pathway and SIRT3. These findings offer new insights into the potential therapeutic role of melatonin in neonatal brain injuries. The second chapter, “Traumatic Brain Injury: Identification of Prognostic Biomarkers,” was conducted during my research at The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, Canada. This chapter includes two projects. The first project, “A Canadian Biobank and Database for Traumatic Brain Injury (CanTBI),” aimed to establish a comprehensive national database, linking regional biobanks and facilitating the translation of molecular biomarker research into clinical practice. The second project, “Prognostic Serum Protein Biomarkers in Children with Severe Traumatic Brain Injury,” discovered eight prognostic biomarkers. This discovery opens avenues for enhanced clinical monitoring and risk stratification in TBI patients, potentially guiding the development of novel treatment strategies. In summary, this thesis not only increases our understanding of brain injuries but also lays the foundation for future research in this field. It highlights the shared pathophysiological mechanisms in HI brain injury and TBI and proposes innovative diagnostic and therapeutic strategies.This thesis represents a comprehensive endeavor to bridge preclinical and clinical research, aiming to enhance our understanding and treatment approaches for brain injuries. It focuses on two specific areas: neonatal hypoxic-ischemic (HI) brain injury and traumatic brain injury (TBI). The thesis had a dual aim: first, to elucidate the neuroprotective mechanisms of melatonin in neonatal HI brain injury using a neonatal rat model of HI, and second, to identify prognostic biomarkers in patients with TBI. The thesis includes two main chapters. The first chapter, titled “Neonatal Hypoxic-Ischemic Brain Injury: Involvement of Notch1 Signaling Pathway and SIRT3 in the Neuroprotective Effect of Melatonin,” was conducted at the University of Urbino Carlo Bo, Italy. This study demonstrated how melatonin, a natural neurohormone, attenuated brain damage in neonatal HI by modulating the Notch1 signaling pathway and SIRT3. These findings offer new insights into the potential therapeutic role of melatonin in neonatal brain injuries. The second chapter, “Traumatic Brain Injury: Identification of Prognostic Biomarkers,” was conducted during my research at The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, Canada. This chapter includes two projects. The first project, “A Canadian Biobank and Database for Traumatic Brain Injury (CanTBI),” aimed to establish a comprehensive national database, linking regional biobanks and facilitating the translation of molecular biomarker research into clinical practice. The second project, “Prognostic Serum Protein Biomarkers in Children with Severe Traumatic Brain Injury,” discovered eight prognostic biomarkers. This discovery opens avenues for enhanced clinical monitoring and risk stratification in TBI patients, potentially guiding the development of novel treatment strategies. In summary, this thesis not only increases our understanding of brain injuries but also lays the foundation for future research in this field. It highlights the shared pathophysiological mechanisms in HI brain injury and TBI and proposes innovative diagnostic and therapeutic strategies

Study of Characteristics of Urban Public Open Spaces based on Social Interaction (Case study: Salavatabad’s 3-kilometer Route)

Urban public open spaces find their meaning with humans’ presence and activities, and more than physical role, they are important for creating social interactions among citizens. Public spaces of a city are affected by social- economic changes of their time with different appearances in the city. Space, identification of usages and advantages of these spaces are considered the first steps towards planning for such spaces. In this research, documentary method is first used to consider definitions and implications of urban open spaces and physical characteristics, activities and usages of such spaces, then following identifying people’s needs and expectations of these spaces, criteria and indices affecting public open spaces’ attraction from point of view of urban developers are taken into account. This study was carried out based on a descriptive- periodical survey. Results of this study indicate that though some superficial imitations and improper interventions have taken place  in Sanandaj’s public spaces leading to their severe fall of quality, given physical skeleton features and cultural, social and economic attributes of this city, we can add to its public  acceptability and improve social relationships in urban public spaces such as routes and roads to be able to modify and create attractive public open spaces to facilitate individuals relationships in them finally leading to more liveliness in urban life

Análisis numérico de diferentes geometrías en el análisis dinámico en la plataforma de gravedad.

On Gravity platform Dynamic Response is a support structure held in place by gravity. Given that the gravity platforms are supportedby the sea bed but not attached to the ground, the motion of them is known as a rocking fluctuation. During the fluctuations, theplatform maybe overturned if the angle is large. In this study, using Ansys Aqwa hydrodynamic software and analytical methods withregard to the performance, the dynamic interaction of platform’s geometry on hydrodynamic forces have been simulated. Theobjective of this study was to analyze the hydrodynamic parameters of the sea and rocking fluctuations of gravity platforms under theimpact of regular wave’s moment considering the soil mechanics and hydrodynamic features of the structure. In order to achievethe objective the hydrodynamic forces using numerical simulations and analytical methods for one column and three hollow columnsplatforms were analyzed. Finally, responses of the platform to irregular waves were studied using numerical simulation. The resultsshowed that with the increasing of the depth, the impact of wave’s force and moment on the base of platform are reduced throughexponential relationship. The reductions are due to the effective depth that is equal to half the wave length. The results suggestthat the response of the rocking motion of gravity platform shows significant changes in relation to height and wavelength. Based onthe curves fitted to the data of the fluctuation angle, sustainability of the platform in the rocking motion can be thoroughly andcompletely investigated

Cytotoxicity of Two Gypsophila Species to Human Breast Adenocarcinoma (MCF-7)

Introduction: Cancer is known as the second cause of death worldwide which results in serious problems in human life. It is developed by uncontrolled growth of a cell or a group of cells. Caryophyllaceae is a large family which has been reported to possess cytotoxic species and in the present study, the cytotoxic activity of two plants from this family has been evaluated. Methods and Results: Dried powder of Gypsophila bicolor (Freyn & Sint.) Grossh and Gypsophila ruscifolia Boiss. aerial parts were extracted with methanol 80% by maceration method (10 g). For fractionation, 30 g of the dried powder of both species was macerated with petroleum ether at room temperature. After 24 hours, the mixture was filtered and the plant residues were extracted with chloroform and methanol successively through the same process. Then they were concentrated using a rotary evaporator apparatus. The cytotoxic activity was evaluated against MCF-7 (human breast adenocarcinoma), A-549 (non-small cell lung carcinoma) and AGO-1522 (human fibroblast) cell lines using MTT assay. The chloroform fractions of both Gypsophila species showed cytotoxic effects against MCF-7 cells with IC50 value <100 μg/mL. None of the extracts or fractions demonstrated cytotoxicity to A-549 or AGO-1522 cells up to the tested concentrations. Conclusions: The selective toxicity of the chloroform fractions of the species only to the MCF-7 cell line suggested that Gypsophila bicolor and G. ruscifolia could be proper candidates for further studies in the field of cancer researches

A Dynamic Network Comparison Analysis of Crude Oil Trade: Evidence from Eastern Europe and Eurasia

This article characterizes a dynamic crude oil trade network of Eastern Europe and Eurasia using the network connectedness measure of Diebold and Yilmaz (2014, 2015) and asymmetric reaction of crude oil bilateral trade flow in response to the positive and negative changes of its key determinants using the nonlinear panel ARDL model. Results indicate the existence of large and time-varying spillovers with a considerable explanatory power among the crude oil trade flow volatility of Iran, Russia, US and Saudi Arabia in Eastern Europe and Eurasia crude oil trade network. The findings also show that crude oil trade flow of Eastern Europe and Eurasia experiences net volatility transmission to Iran, Russia and US respectively, whereas it is a net volatility receiver from Saudi Arabia. Also based on gravity models, the analysis confirms the existence of impact, reaction and adjustment asymmetry through different magnitude among network participants

Low-Dose Quetiapine in the Treatment of SSRI-Induced Bruxism and Mandibular Dystonia: Case Series

Objective: Selective serotonin reuptake inhibitors (SSRIs) have been the most widely used psychopharmacological agents prescribed for depression worldwide. Some adverse effects of SSRI drugs on central nervous system are insomnia and bruxism. These drugs also affect sleep. Quetiapine is used as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). It is a low- dose dibenzothiazepine with more potent 5-HT2 than D2 receptor-blocking properties that can be used to manage bruxism because of its antagonist effect on the 5-HT2 receptor. Cases: The cases were 5 patients who have recently been treated with SSRIs and presented with bruxism. Low- dose quetiapine (between 25 and 50 mg daily) was prescribed for the patients, and after a few days, they reported no bruxism and continued taking the medication. Conclusion: We found that quetiapine can improve bruxism and mandibular dystonia, which are side effects of SSRIs

The Effect of Production Sharing, Buyback, and Iranian Petroleum Contracts on the Optimal Production and Drilling Paths of Yadavaran Field: A Dynamic Optimization Approach

The purpose of this study is to compare the economic efficiency of Iran's petroleum contracts, buyback contracts, and production-sharing contracts. This study also determined the optimum path for production and drilling operations in the Yadavaran oil field which has special importance because it is a joint field with Iraq. It was estimated using real field data and the SQP algorithm by MATLAB software. First, the objective function, the constraints of each contract model, and the cost function are defined and expressed based on field data. For the objective function, the oil price is determined based on the reference price scenario and based on the forecast of the US Energy Information Administration (EIA). Cao et al (2009) 's cost function model is also modified by using historical field data (first development phase data) to be applied to the study field. The results show that the most efficient oil contract is the Iran petroleum contract, with a low floor for capital costs and no limit to the number of drilled wells. it was proved that the buyback contract with the ceiling of capital costs incompatible with the recovery coefficient has recorded the lowest efficiency. Also, the Iran petroleum contract can be a good alternative to the buyback contract, because it can well solve the problems of the buyback contract, especially for joint oil fields where the priority of the objective function of the maximum cumulative production over the objective function of the maximum present value of the total profit is more desirable

Evaluation of dentin penetration of three different endodontic sealers in the presence and absence of the smear layer

Introduction: A sealer’s ability to effectively and stably penetrate the dentinal tubules is an essential factor for selecting an effective root canal obturation material. Evaluation of the sealers’ penetration into the dentinal tubules provides valuable data in the endodontic treatment outcome.Aim: To compare the dentin penetration of AH Plus, Endoseal MTA, and Syntex endodontic sealers in the presence and absence of the smear layer.Materials and methods: Thirty single-rooted teeth were selected in the present in vitro study and randomly assigned to three experimental groups (n=10). Half of the samples were prepared by removing the smear layer in each group, and the remaining samples were prepared without removing the smear layer. Root canal preparation was carried out with the Perfect Rotary system up to file T3. The root canals were obturated with gutta-percha and AH Plus, Endoseal MTA, or Syntex endodontic sealers. The samples were incubated at 100% relative humidity at 37°C for one week. Each root was sectioned at 2-, 5-, and 8-mm distances from the apex, and sealer penetration depth at each section was determined under a scanning electron microscope (SEM). ANOVA was used to compare penetration depths.Results: There were significant differences in sealer penetration between the samples with and without smear layer removal in each group. The maximum and minimum sealer penetration was at the coronal and apical sections, respectively. The maximum sealer penetration depths in descending order were observed with AH Plus, Syntex, and Endoseal MTA sealers (p<0.05).Conclusions: Elimination of smear layer increased three sealers’ dentin penetration depth, with the deepest penetration for the AH Plus sealer in the coronal section without the smear layer

A Review of Wearing a Mask and How to Correctly Wear it in Shahroud City

Background: One of the most important issues since SARS-CoV-2 was identified was the growing information on how the virus was transmitted and how to protect against it. However, many key questions have not yet been fully answered. This study aimed to investigate the correct wearing of a mask in Shahroud city. Methods: This study was a descriptive cross-sectional one conducted on 800 people in Shahroud city in a two-month interval (Aug. 22, 2020, to October 30, 2020). Data were collected using a checklist including demographic information. After being collected, the data were entered into SPSS18 and analyzed using descriptive statistics. Results: The results indicated that out of 800 people taking part, 415 people (51.9%) were male and 385 ones (48.1%) were female. The mean participants’ age was 61.78 16±16.09; most participants in the study were born in the year 1972-1995 with 385 ones (48%). Also, concerning masks, it was found that the use of masks and the correct use of them accounted for 528 cases (66%) and 377 cases (47.1%), respectively. The most used mask was a surgical mask with 343 cases (42.9). Concerning the non-use of a mask, 132 people (16.5%) cited choking as the most important reason for not wearing a mask. Also, 681 people (85.1%) and 557 ones (69.6%) had chosen not to participate at weddings and parties, respectively. Conclusions: The results suggested that a greater percentage of participants in the study knew how to correctly wear a mask while not having a history of participating in ceremonies and parties, which is a very good issue. Keywords: Mask, Correct wearing, Shahrou