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Walking constitutes a fundamental activity and pedestrians play a vital role in the vitality of urban spaces. This research endeavor aims to conduct a comparative analysis of walkability between Tehran's Takhti and Marzdaran neighborhoods while validating the findings and comparing specialized models. The assessment of data and the comparative examination of the two neighborhoods were carried out utilizing three quantitative models: WalkScore, Smartraq, and SpaceSyntax. Statistical analysis was conducted using SPSS LISREL software. The research methodology employed was descriptive, analytical, and survey-based, representing an applied approach. The statistical population encompassed 250 residents from both neighborhoods. The analysis of pedestrian circulation models revealed that the Takhti neighborhood attained a WalkScore rating of 93.07%, achieved a connectivity index of 1.76 in the Space Syntax model, and exhibited three positive Z-scores in the Smartraq model. Conversely, the Marzdaran neighborhood obtained a WalkScore rating of 77.86%, recorded a connectivity index of 1.69 in the Space Syntax model, and displayed three negative Z-scores in the Smartraq model. By evaluating these outcomes and subjecting them to statistical analyses, encompassing the examination of performance, physical, social, and environmental criteria, it becomes evident that the Takhti neighborhood, with an average score of 3.52, exhibits a superior capability for walkability compared to the Marzdaran neighborhood, which achieved an average score of 2.40. These results reinforce the quantitative model findings regarding walkability in the Takhti neighborhood. Introduction The absence of pedestrian presence in local areas and the subsequent decline in neighborhood walkability have adverse effects on security, safety, and social interactions. These issues are further compounded by environmental concerns like air and noise pollution, public health implications, anonymity of neighborhood spaces, a lack of community belonging, and the resulting physical fatigue. Therefore, obtaining a comprehensive understanding of the current situation is vital for informed decision-making. To address these challenges, it is crucial for urban designers and planners to evaluate and measure the walkability of neighborhoods. This enables them to transform the urban environment, creating a pedestrian-friendly atmosphere that enhances the quality of walking in cities today. This research aims to assess and analyze the local walkability in two neighborhoods in Tehran, employing the WalkScore, Smartraq, and space syntax methods. By comparing the outcomes of these approaches, the study provides a comprehensive analysis of the walkability status within the selected neighborhoods. Furthermore, the research employs statistical analysis to validate the findings obtained from these models. This rigorous examination ensures the reliability and accuracy of the results. Ultimately, the study will propose recommendations that not only highlight the advantages and limitations of the utilized models but also present a neighborhood pattern that prioritizes pedestrian needs and activities. Literature Review By conducting a thorough literature review of previous studies and research pertaining to walkability, with a specific focus on measurement and assessment, it becomes apparent that there are noticeable deficiencies and erroneous approaches in the domestic research landscape. These shortcomings are particularly evident when it comes to result validation. While international research has diligently addressed methodological challenges, there is a dearth of investigation into the validation of these methods using questionnaire data in distinct localities. The necessity of undertaking this research lies in the imperative to introduce effective models for evaluating the state of local walkability. Additionally, it is crucial to validate the outcomes generated by these models and establish comparative analyses to discern their respective strengths and weaknesses. This rigorous examination is integral to unearthing the merits and limitations of each model, thus contributing to the advancement of knowledge in the field. Methodology This study adopts an applied research approach with a combined framework that incorporates both survey-based statistical analysis and descriptive-analytical data analysis methods. The research procedure, data collection, and analysis can be classified into two categories: quantitative and qualitative. Quantitative measures, assessment tools, and statistical techniques were employed to analyze the collected data, while a qualitative approach employing comparative techniques was utilized to compare two specific neighborhoods. Multiple methods were utilized to assess and comparatively analyze the walkability status of the studied neighborhoods. These methods include WalkScore, Smartraq, and space syntax models, each focusing on different dimensions of walkability. The analysis for WalkScore and Smartraq was performed using ArcGIS software, and a customized Python algorithm was developed and executed for the WalkScore method. For space syntax analysis, DepthMap software was employed. In the following section, statistical analysis was carried out to validate the outcomes derived from these models. This serves two purposes: enhancing the credibility of the models and confirming the reliability of the results in practical applications. This research falls under the comparative research category. The statistical population comprised residents residing in the Takhti and Marzdaran neighborhoods, with a randomly selected sample of 250 individuals. Results Based on the analysis conducted using the space syntax method, the findings reveal that the Takhti neighborhood exhibits a higher level of walkability quality compared to the Marzdaran neighborhood. This conclusion is supported by the evaluation of two critical indicators related to walkability in space syntax: connectivity and integration. Table 1 Indicator Neighborhood Max Min Average Integration Takhti 3.21 0.84 1.75 Marzdaran 3.48 0.87 1.69 Connectivity Takhti 30 1 3.5 Marzdaran 21 1 4.5 Intensity Takhti 1.2 0.32 0.69 Marzdaran 1.25 0.42 0.79 Mean Depth Takhti 7.82 2.79 4.47 Marzdaran 6.31 2.33 3.9n The findings derived from the WalkScore method indicate that the residential blocks located within the Takhti neighborhood consistently exhibit significantly higher average scores in comparison to those situated within the Marzdaran neighborhood. These scores were formulated based on the proximity of each residential block to local amenities, encapsulating an essential aspect of neighborhood livability. Table2 Neighborhood Total Units St.diversion Interval Walkscore Point Average Walkscore point Min Max Takhti 3070 0.16 85.87 98.92 93.07 Marzdaran 2742 0.73 43.75 97.91 77.86 The application of a method known as Smartraq brought to light notable disparities between the Takhti and Marzdaran neighborhoods in terms of intersection density, residential block density, and land use mix index. The findings indicate that the Takhti neighborhood exhibits a substantially higher magnitude in these metrics in comparison to its counterpart, the Marzdaran neighborhood. Table 3 Neighborhood Area (m2) intersections Nodes intersection index (per m2) households Residential Units Area (m2) Residential density Commercial land use area (m2) Office land use area(m2) Residential land use area (m2) land use mix indices Takhti 665946 419 307 6.29 7008 471821 0.018 140553 45604 371821 0.348 Marzdaran 1609772 311 293 1.93 10948 937252 0.011 62697 40771 937252 0.223 This research endeavors to employ rigorous statistical analyses in order to systematically investigate and substantiate the walkability attributes of the two focal neighborhoods, while simultaneously corroborating the results obtained from three distinct walkability models. Notably, regression analysis has effectively demonstrated that the aforementioned components decisively account for approximately 75% of the walkability variance discernible within the Takhti and Marzdaran neighborhoods. The outcomes derived from regression analyses and the comparison of mean values derived from the perceptions of neighborhood residents pertaining to walkability indices convincingly illustrate that the Takhti neighborhood, boasting an average score of 3.52, exhibits a considerably higher level of walkability in comparison to the Marzdaran neighborhood, whose average rating stands at a modest 2.40. Table 4 Indicates Neighborhood Statistics n Mean Median Mode s.d Var Functional Takhti 125 3.8 3.75 3.5 0.54 0.29 Marzdaran 125 2.20 2.32 2.3 0.43 0.48 Physical Takhti 125 3.71 3.5 3.61 0.52 0.27 Marzdaran 125 2.53 2.12 2.75 0.62 0.39 Social Takhti 125 4.12 4 4 0.54 0.32 Marzdaran 125 2.64 2.37 2.25 0.68 0.46 Environment Takhti 125 2.46 2.25 2.25 0.83 0.69 Marzdaran 125 2.24 2.3 2.5 0.68 0.38 Total Takhti 125 3.52 3.15 3.26 0.91 0.99 Marzdaran 125 2.40 2.90 2.75 0.663 0.441 Conclusion In conclusion, the synthesis of findings arising from the WalkScore, Smartraq, and Spaces syntax methods has yielded valuable insights into the strengths and limitations of each approach within the assessment framework. Based on the comprehensive analysis, it can be deduced that all three models have demonstrated efficacy, with their outcomes exhibiting notable congruity. However, none of these methods in isolation can be deemed adequate for a holistic evaluation of neighborhood walkability. Therefore, it is advisable to combine these methodologies to achieve a more comprehensive assessment of pedestrian environments. Unanimously, all three models concur on the walkability of the Takhti neighborhood, renowned for its historical character, intricate urban fabric, diverse land uses, and abundant amenities. Notably, this neighborhood excels across various indicators of walkability, encompassing ease of access to facilities, a mix of land uses, safety measures, population density, residential density, intersection density, continuity of networks, and street connectivity. As corroborated by the models, Takhti emerges as a notably pedestrian-friendly environment, diligently addressing the diverse needs of pedestrians, in stark contrast to the recently developed Marzdaran neighborhood. Acknowledgments The authors express their sincere gratitude to all individuals who have played a role in the conception and execution of this scholarly article.

Machine Learning (ML) is considered a promising tool to aid and accelerate diagnosis in various medical areas, including neuroimaging. However, its success is set back by the lack of large-scale public datasets. Indeed, medical institutions possess a large amount of data; however, open-sourcing is prevented by the legal requirements to protect the patient's privacy. Federated Learning (FL) is a viable alternative that can overcome this issue. This work proposes training an ML model for Alzheimer's Disease (AD) detection based on structural MRI (sMRI) data in a federated setting. We implement two aggregation algorithms, Federated Averaging (FedAvg) and Secure Aggregation (SecAgg), and compare their performance with the centralized ML model training. We simulate heterogeneous environments and explore the impact of demographical (sex, age, and diagnosis) and imbalanced data distributions. The simulated heterogeneous environments allow us to observe these statistical differences' effect on the ML models trained using FL and highlight the importance of studying such differences when training ML models for AD detection. Moreover, as part of the evaluation, we demonstrate the increased privacy guarantees of FL with SecAgg via simulated membership inference attacks.

Abstract We evaluate stability of spectral results at different heart rates, acquisition modes, and cardiac phases in first-generation clinical dual-source photon-counting CT (PCCT). A cardiac motion simulator with a coronary stenosis mimicking a 50% eccentric calcium plaque was scanned at five different heart rates (0, 60–100 bpm) with the three available cardiac scan modes (high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, retrospectively ECG-gated spiral). Subsequently, full width half max (FWHM) of the stenosis, Dice score (DSC) for the stenosed region, and eccentricity of the non-stenosed region were calculated for virtual monoenergetic images (VMI) at 50, 70, and 150 keV and iodine density maps at both diastole and systole. FWHM averaged differences of − 0.20, − 0.28, and − 0.15 mm relative to static FWHM at VMI 150 keV across acquisition parameters for high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, and retrospectively ECG-gated spiral scans, respectively. Additionally, there was no effect of heart rate and acquisition mode on FWHM at diastole (p-values

The goal of the present study is to prepare a room temperature cured hydrophobic and self-cleaning nano-coating for power line insulators. As a result, the installed insulators operating in power lines can be coated without being removed from the circuit and without the need to cut off power. For this purpose, hydrophobic silica nanoparticles were synthesized by sol-gel method using TEOS and HMDS. The synthesized hydrophobic silica nanoparticles were characterized by XRD, FTIR, SEM, and TEM analyses to investigate phase formation, particle size, and morphology. Then the surface of the insulator was cleaned and sprayed by Ultimeg binder solution, an air-dried insulating coating, as the base coating. Then the hydrophobic nano-silica powder was sprayed on the binder coated surface and left to be air-cured at room temperature. After drying the coating, the contact angle was measured to be 149o. Pull-off test was used to check the adhesion strength of the hydrophobic coating to the base insulator. To evaluate the effect of environmental factors, UV resistance and fog-salt corrosion tests were conducted. The results showed that 150 hours of UV radiation, equivalent to 9 months of placing the samples in normal conditions, did not have any significant effect on reducing the hydrophobicity of the applied coatings.

The tourism industry is inherently complex and a key player in sustainable development. This paper intends to discuss the path towards building a sustainable smart tourism ecosystem model by delving deep into the pivotal topics with interesting speculations on smart cities' perspectives that lay a broader foundation of smart tourism destinations. First, it discusses the interconnections and foundation of smart tourism ecosystems by proposing a general conceptual model describing traditional tourism transformation through ICTs. Second, by explicating each building block of smart tourism ecosystems and using systems methodology (systems thinking method and qualitative modeling in a frame of system dynamics) to break down the complex system of smart tourism's roles and components. Such methods are widely utilized in different fields of study to facilitate the decision-making process by furnishing a holistic view of the problem. For that matter, Causal Loop Diagramming (CLDs) was used as one of the powerful tools of systems thinking to depict smart tourism ecosystems. The proposed causal loop diagram considers sustainability as one of the main concerns and trying to shed some light on intricate networks of businesses, socio-economic, and environmental subsystems in smart tourism destinations that are performing distinctively yet interdependent. This study is an ongoing process employing System Dynamics (SD) methodology for model testing and validation.

Abstract Background Artificial intelligence (AI) in diagnostic radiology is undergoing rapid development. Its potential utility to improve diagnostic performance for cardiopulmonary events is widely recognized, but the accuracy and precision have yet to be demonstrated in the context of current screening modalities. Here, we present findings on the performance of an AI convolutional neural network (CNN) prototype (AI-RAD Companion, Siemens Healthineers) that automatically detects pulmonary nodules and quantifies coronary artery calcium volume (CACV) on low-dose chest CT (LDCT), and compare results to expert radiologists. We also correlate AI findings with adverse cardiopulmonary outcomes in a retrospective cohort of 117 patients who underwent LDCT. Methods A total of 117 patients were enrolled in this study. Two CNNs were used to identify lung nodules and CACV on LDCT scans. All subjects were used for lung nodule analysis, and 96 subjects met the criteria for coronary artery calcium volume analysis. Interobserver concordance was measured using ICC and Cohen’s kappa. Multivariate logistic regression and partial least squares regression were used for outcomes analysis. Results Agreement of the AI findings with experts was excellent (CACV ICC = 0.904, lung nodules Cohen’s kappa = 0.846) with high sensitivity and specificity (CACV: sensitivity = .929, specificity = .960; lung nodules: sensitivity = 1, specificity = 0.708). The AI findings improved the prediction of major cardiopulmonary outcomes at 1-year follow-up including major adverse cardiac events and lung cancer (AUCMACE = 0.911, AUCLung Cancer = 0.942). Conclusion We conclude the AI prototype rapidly and accurately identifies significant risk factors for cardiopulmonary disease on standard screening low-dose chest CT. This information can be used to improve diagnostic ability, facilitate intervention, improve morbidity and mortality, and decrease healthcare costs. There is also potential application in countries with limited numbers of cardiothoracic radiologists.

Recently, there has been a significant surge of interest in Self-Attention Networks (SANs) based on the Transformer architecture. This can be attributed to their notable ability for parallelization and their impressive performance across various Natural Language Processing applications. On the other hand, the utilization of large-scale, multi-purpose language models trained through self-supervision is progressively more prevalent, for tasks like speech recognition. In this context, the pre-trained model, which has been trained on extensive speech data, can be fine-tuned for particular downstream tasks like speaker verification. These massive models typically rely on SANs as their foundational architecture. Therefore, studying the potential capabilities and training challenges of such models is of utmost importance for the future generation of speaker verification systems. In this direction, we propose a speaker embedding extractor based on SANs to obtain a discriminative speaker representation given non-fixed length speech utterances. With the advancements suggested in this work, we could achieve up to 41% relative performance improvement in terms of EER compared to the naive SAN which was proposed in our previous work. Moreover, we empirically show the training instability in such architectures in terms of rank collapse and further investigate the potential solutions to alleviate this shortcoming.

Background: Determination of the total number and size of all pulmonary metastases on chest CT is time-consuming and as such has been understudied as an independent metric for disease assessment. A novel artificial intelligence (AI) model may allow for automated detection, size determination, and quantification of the number of pulmonary metastases on chest CT. Objective: To investigate the utility of a novel AI program applied to initial staging chest CT in breast cancer patients in risk assessment of mortality and survival. Methods: Retrospective imaging data from a cohort of 226 subjects with breast cancer was assessed by the novel AI program and the results validated by blinded readers. Mean clinical follow-up was 2.5 years for outcomes including cancer-related death and development of extrapulmonary metastatic disease. AI measurements including total number of pulmonary metastases and maximum nodule size were assessed by Cox-proportional hazard modeling and adjusted survival. Results: 752 lung nodules were identified by the AI program, 689 of which were identified in 168 subjects having confirmed lung metastases (Lmet+) and 63 were identified in 58 subjects without confirmed lung metastases (Lmet-). When compared to the reader assessment, AI had a per-patient sensitivity, specificity, PPV and NPV of 0.952, 0.639, 0.878, and 0.830. Mortality in the Lmet + group was four times greater compared to the Lmet-group (p = 0.002). In a multivariate analysis, total lung nodule count by AI had a high correlation with overall mortality (OR 1.11 (range 1.07–1.15), p < 0.001) with an AUC of 0.811 (R2 = 0.226, p < 0.0001). When total lung nodule count and maximum nodule diameter were combined there was an AUC of 0.826 (R2 = 0.243, p < 0.001). Conclusion: Automated AI-based detection of lung metastases in breast cancer patients at initial staging chest CT performed well at identifying pulmonary metastases and demonstrated strong correlation between the total number and maximum size of lung metastases with future mortality. Clinical impact: As a component of precision medicine, AI-based measurements at the time of initial staging may improve prediction of which breast cancer patients will have negative future outcomes.

Abstract Background Structured reports have been shown to improve communication between radiologists and providers. However, some radiologists are concerned about resultant decreased workflow efficiency. We tested a machine learning-based algorithm designed to convert unstructured computed tomography pulmonary angiography (CTPA) reports into structured reports. Methods A self-supervised convolutional neural network-based algorithm was trained on a dataset of 475 manually structured CTPA reports. Labels for individual statements included “pulmonary arteries,” “lungs and airways,” “pleura,” “mediastinum and lymph nodes,” “cardiovascular,” “soft tissues and bones,” “upper abdomen,” and “lines/tubes.” The algorithm was applied to a test set of 400 unstructured CTPA reports, generating a predicted label for each statement, which was evaluated by two independent observers. Per-statement accuracy was calculated based on strict criteria (algorithm label counted as correct if the statement unequivocally contained content only related to that particular label) and a modified criteria, accounting for problematic statements, including typographical errors, statements that did not fit well into the classification scheme, statements containing content for multiple labels, etc. Results Of the 4,157 statements, 3,806 (91.6%) and 3,986 (95.9%) were correctly labeled by the algorithm using strict and modified criteria, respectively, while 274 (6.6%) were problematic for the manual observers to label, the majority of which (n = 173) were due to more than one section being included in one statement. Conclusion This algorithm showed high accuracy in converting free-text findings into structured reports, which could improve communication between radiologists and clinicians without loss of productivity and provide more structured data for research/data mining applications.

The COVID-19 pandemic has emerged as a serious global health crisis, with the predominant morbidity and mortality linked to pulmonary involvement. Point-of-Care ultrasound (POCUS) scanning, becoming one of the primary determinative methods for its diagnosis and staging, requires, however, close contact of healthcare workers with patients, therefore increasing the risk of infection. This work thus proposes an autonomous robotic solution that enables POCUS scanning of COVID-19 patients’ lungs for diagnosis and staging. An algorithm was developed for approximating the optimal position of an ultrasound probe on a patient from prior CT scans to reach predefined lung infiltrates. In the absence of prior CT scans, a deep learning method was developed for predicting 3D landmark positions of a human ribcage given a torso surface model. The landmarks, combined with the surface model, are subsequently used for estimating optimal ultrasound probe position on the patient for imaging infiltrates. These algorithms, combined with a force–displacement profile collection methodology, enabled the system to successfully image all points of interest in a simulated experimental setup with an average accuracy of 20.6 ± 14.7 mm using prior CT scans, and 19.8 ± 16.9 mm using only ribcage landmark estimation. A study on a full torso ultrasound phantom showed that autonomously acquired ultrasound images were 100% interpretable when using force feedback with prior CT and 88% with landmark estimation, compared to 75 and 58% without force feedback, respectively. This demonstrates the preliminary feasibility of the system, and its potential for offering a solution to help mitigate the spread of COVID-19 in vulnerable environments.

The next wave of communication and applications will rely on new services provided by the Internet of Things which is becoming an important aspect in human and machines future. IoT services are a key solution for providing smart environments in homes, buildings, and cities. In the era of massive number of connected things and objects with high growth rate, several challenges have been raised, such as management, aggregation, and storage for big produced data. To address some of these issues, cloud computing emerged to the IoT as Cloud of Things (CoT), which provides virtually unlimited cloud services to enhance the large-scale IoT platforms. There are several factors to be considered in the design and implementation of a CoT platform. One of the most important and challenging problems is the heterogeneity of different objects. This problem can be addressed by deploying a suitable “middleware” which sits between things and applications as a reliable platform for communication among things with different interfaces, operating systems, and architectures. The main aim of this paper is to study the middleware technologies for CoT. Toward this end, we first present the main features and characteristics of middlewares. Next, we study different architecture styles and service domains. Then, we present several middlewares that are suitable for CoT-based platforms and finally, a list of current challenges and issues in the design of CoT-based middlewares is discussed. Keywords: CoT, IoT, Middleware, Fog computing, Cloud

Background: Caffeine is a kind of methylxanthine whose consumption can promote the cognitive and executive functions of the human brain. Objectives: In this study, we seek to investigate the effect of drinking coffee on the period of the eye movement fixation component. Materials and Methods: The research was of the quasi-experimental type. 60 subjects were randomly divided into two groups of thirty. The subjects in one group drank coffee before the experiment was conducted. The other group, which is the control group, did not. Both groups would then read a text, and the eye movement tracking device would record the fixation periods of the subjects’ eyes while reading. Results: The results of the independent t-test comparing the mean fixation time in the two groups demonstrated that the difference was significant at the 0.001 level, where the group that drank coffee before studying had significantly less fixation time than the control group. Additionally, Cohen’s d index of 4.29 determined that the difference lies in the maximum effect size range. Conclusion: It can be concluded that drinking a cup of coffee before studying can lead to decrease in eye movement fixation period and increase in information encoding and processing speed.

Recent years have witnessed a growing interest in enhancing pedestrian access in urban areas. This paper uses a combination of methodologies to assess the quality of pedestrian pathways in Shahrak-e-Gharb District, Tehran. The walk-ability of diverse pathway configurations is first analyzed by using the Space Syntax methodology. As a result, a set of streets are selected for further investigation. Then, pedestrian discomfort levels are determined for the selected pathways by comparing the sidewalk pavement width with movement characteristics. Then, by using the Systematic Pedestrian and Cycling Environmental Scan (SPACES) methodology, the walk-ability of these pathways is assessed based on their physical characteristics. The selected pathways are finally rated on the basis of all these methodologies. The characteristics of the top-ranking street, Dadman Boulevard, could accordingly be referred to as a set of optimal properties for a walk-able pathway.

Restricted Boltzmann Machines (RBMs) have shown success in both the front-end and backend of speaker verification systems. In this paper, we propose applying RBMs to the front-end for the tasks of speaker clustering and speaker tracking in TV broadcast shows. RBMs are trained to transform utterances into a vector based representation. Because of the lack of data for a test speaker, we propose RBM adaptation to a global model. First, the global model—which is referred to as universal RBM—is trained with all the available background data. Then an adapted RBM model is trained with the data of each test speaker. The visible to hidden weight matrices of the adapted models are concatenated along with the bias vectors and are whitened to generate the vector representation of speakers. These vectors, referred to as RBM vectors, were shown to preserve speaker-specific information and are used in the tasks of speaker clustering and speaker tracking. The evaluation was performed on the audio recordings of Catalan TV Broadcast shows. The experimental results show that our proposed speaker clustering system gained up to 12% relative improvement, in terms of Equal Impurity (EI), over the baseline system. On the other hand, in the task of speaker tracking, our system has a relative improvement of 11% and 7% compared to the baseline system using cosine and Probabilistic Linear Discriminant Analysis (PLDA) scoring, respectively.

Background and aims. Current chemical methods may not efficiently disinfect dental stone casts. The aim of this study was to investigate if microwave irradiation is effective for disinfection of stone casts. Materials and methods. In this laboratory study, three groups (n = 162) of prepared spherical stone beads as carriers with a diameter of 10 mm were inoculated by separately soaking in three broth culture media, each containing a study microorganism—Pseudomonas aeruginosa, Staphylococcus aureus or Candida albicans. Six inoculated carriers were used for every test, including irradiation in a household microwave oven at 300, 450, 600 or 900 W energy level, or soaking in 0.03%, 0.06%, 0.12%, 0.25% or 0.50% concentration of sodium hypochlorite solution, at 1, 2, or 3-minute test times. Positive and negative control groups were considered for each test. All treated carriers were then individually transferred to nutrient broth culture medium and one milliliter from each tube was cultured in nutrient agar media over night. Colony forming unit per milliliter (CFU/mL) was counted, and multi-factor ANOVA was used to analyze data (α = 0.05). Results. Microwave irradiation at 600 W resulted in high-level disinfection in 3 minutes. Immersion of the stone casts in hypochlorite solution at 0.06% concentration resulted in disinfection after 2 minutes. Conclusion. According to the results, high level disinfection of the stone casts can be achieved by microwave irradiation at 600 W in 3 minutes, similar to a validated chemical method.

Trigeminocardiac reflex (TCR) is currently defined as a sudden bradycardia and decrease in mean arterial blood pressure by 20% during the manipulation of the branches of trigeminal nerve. TCR, especially during the last decade has been mostly studied in the course of neurosurgical procedures which are supposed to elicit the central subtype of TCR. Previously the well-known oculocardiac reflex was also considered as a subtype of TCR. Recently, surgeons dealing with the other branches of the fifth cranial nerve have become more interested in this reflex. Some noteworthy points have been published discussing new aspects of the trigeminocardiac reflex (TCR) in simple oral surgical procedures. Arakeri et al. have reviewed the similarities and differences between TCR, vasovagal response (VVR), and syncope. They have also explained a new possible pathway for the reflex during the simple extraction of upper first molars. The present paper aims to briefly discuss these recently presented points. Although the discussed concepts are noteworthy and consistent our preliminary results of our yet to be published studies, it seemed timely for us to discuss some possible shortcomings that may affect the results of such assessments.

Purpose. Patients undergoing craniotomies necessitating preparation of the temporal muscle (TM) may experience postoperative functional impairment of the temporomandibular joint. This topic has not been thoroughly discussed in the literature so far. In the present study, the authors propose a questionnaire as an evaluation tool to assess to what degree different TM preparation techniques correlate with postoperative temporomandibular joint dysfunction. Materials and Methods. Between 2004 and 2006, 286 patients underwent either pterional or temporal craniotomies in the department of craniotomies at the University of Münster in Germany. Intraoperatively the TM was prepared either interfascial, submuscular, or subfascial. A patient-based questionnaire was designed and validated (Kendalls-τ = +1) in order to evaluate the patients’ postoperative temporomandibular functional outcome. Based on strict inclusion/exclusion criteria, 69 patients were eligible for the application of the questionnaire in this preliminary study. Results. Seventeen percent of the patients complained of either temporomandibular joint pain (3%) or restricted mouth opening (13%) postoperatively in a follow-up period between 3 and 12 months. In 92% postoperative complaints were reported within the first 3 months and in 58% of the patients with complaints the pain eased off. In 34% a therapy was required for the pain to be controlled. In one patient (8%) a postoperative arthroscopy has been necessary. Of the patients who experienced postoperative complaints, 67% had undergone temporal and 33% pterional craniotomy. In the group where postoperatively there were issues of temporomandibular pain/dysfunction, 42% had had the TM dissected, in 25% incised, and in 8% transected. For 25% of the patients, the type of intraoperative manipulation remained unknown. Conclusion. For postoperative quality control, the questionnaire showed to be a suitable evaluation tool. Concerning the different preparation techniques, subfascial preparation of the TM tends to result in less postoperative complaints and is thus recommended.

Abstract Background Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties. Results Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more potent than L-Tat9 while the addition of biotin resulted in a prodrug that was 2850 times more potent than L-Tat9. Flow cytometry and confocal microscopy studies suggest that variations in intracellular uptake and intracellular localization, as well as synergistic inhibitory effects of SQV and Tat peptides, contributed to the unexpected and substantial differences in antiviral activity. Conclusion Our results demonstrate that highly potent nanoscale multi-drug conjugates with low non-specific toxicity can be produced by combining moieties with anti-HIV agents for different targets onto macromolecules having improved delivery properties.

We consider a disordered topological insulator thin film placed on the top of a ferromagnetic insulator with a perpendicular exchange field M and subjected to a perpendicular electric field. The presence of ferromagnetic insulator causes that bottom surface states of the topological insulator thin film become spin polarized and the electric field provides a potential difference V between the two surface states, resulting in breaking of time-reversal and inversion symmetry in the system. Using Kubo formalism and employing the first Born approximation as well as the self-consistent Born approximation, we calculate the spin Hall conductivity. We find that for small values of V, a large spin conductivity can be generated through large values of M away from the charge neutrality point. But for large values of V, the spin conductivity can be promoted even with small values of M around the charge neutrality point. The effect of vertex corrections and the stability of the obtained large spin conductivity against disorders are also examined., (© 2022. The Author(s).)

Introduction: The current prevalence of the metabolically healthy obesity is about 3%. Genetic and nutrition are influencers of such phenotypes. The main goal of this study was to assess the interaction between Dietary Total Antioxidant Capacity (DTAC) and the genotypes of MC4R and Insulin resistance in metabolically healthy/unhealthy overweight and obese women in Iran., Material and Methods: This cross-sectional study was conducted on 237 overweight-obese women with a mean age of 36. The value of Dietary total antioxidant capacity (DTAC) was calculated using the following indices: Total reactive antioxidant potential (TRAP), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP). The Metabolic health status was evaluated using the Karelis criteria. Melanocortin 4 receptor single nucleotide polymorphisms were determined by the restriction fragment length polymorphism (PCR-RFLP) method. Also, insulin resistance was evaluated through homeostasis model assessment (HOMA)., Result: Our data noted that 72.96% of participants presented Unhealthy Metabolically and 26.94% Healthy Metabolically including 33.5% of the total had T/T genotype, 23.8% had the C/T genotype, and 42.5% had the C/C genotype ( P  = .05). A linear regression model test showed that the probability of metabolically healthy obesity was significantly higher in patients with the T/C genotype. The test value was statistically significant (95% CI: 0.000-0.001; P  = .056, β = 0). No statistically significant relation was observed between study parameters and DTAC values. HOMA-Index was higher in all unhealthy subjects significantly., Conclusions: The findings indicated that there are significant associations between genotypes of rs1333048 SNP and DTAC. The C/C genotype subjects with higher DTAC had a better lipid profile and were metabolically healthier., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: The increasing trend of obesity prevalence is a serious health warning for people worldwide. Evaluation of anthropometric measures is essential for explaining individual's health status. Studies have investigated the effect of diet on inflammation. Empirical Dietary Inflammatory Pattern (EDIP) was recently developed to empirically create a score for overall inflammatory potential of diet. This study aimed to investigate the relationship between EDIP with anthropometric measures in women with overweight and obesity., Methods: In a cross-sectional study, the EDIP score was calculated for 301 participants from their food frequency questionnaire, who referred to health centers in Tehran, Iran in 2018. Anthropometric measures was assessed through multi-frequency bioelectrical impedance analyzer., Results: 49% (95% CI: 40.8 - 57.2) had positive EDIP score. A significant relationship was found between EDIP quartiles with weight ( P =0.004), BMI ( P =0.012), FM ( P =0.013), WC ( P =0.003) and WHR ( P =0.031). Those individuals in the lowest group of EDIP score had significantly lower weight, Body Mass Index, Fat Mass, Waist Circumference and Waist to Hip Ratio, compared to those with highest inflammation score., Conclusion: A significant relationship was found between EDIP with anthropometric measures in women with overweight and obesity, supporting the hypothesis that an anti-inflammatory diet is associated with decreasing trend of weight, Body Mass Index, Fat Mass, Waist Circumference and Waist to Hip Ratio., Competing Interests: Conflict of interest No conflict of interest was declared., (Copyright © 2022 Badrooj et al. Published by Tehran University of Medical Sciences.)

Background: Recent studies have shown that dietary carbohydrate quantity and quality as well as genetic variants may contribute to determining the metabolic rate and general and central obesity. This study aimed to examine interactions between melanocortin 4 receptor gene (MC4R) rs17782313 and dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) on body mass index (BMI), waist circumferences (WC), basal metabolic rate (BMR), and BMR/kg in overweight/obese women., Methods: A total of 282 Iranian women (BMI ≥ 25) aged 18-56 years were enrolled in this cross-sectional study. All participants were assessed for blood parameters, body composition, BMR, and dietary intake. Dietary carbohydrate intake, GI, and GL were determined using a valid, reliable 147-item food frequency questionnaire. MC4R rs17782313 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method., Results: After adjustment for age and energy intake, significant interactions were observed between carbohydrate intake and MC4R rs17782313 in terms of BMI (P Interaction = 0.007), WC (P Interaction = 0.02), and BMR/kg (P Interaction = 0.003) in this way that higher carbohydrate intake, compared with lower intake, was associated with an increase in BMI and WC for individuals with C allele carriers (TC + CC genotypes), while related to an increase in BMR/kg for those carrying the TT genotype. No significant interaction was found between MC4R rs17782313 and GI and GL on BMI, WC, BMR/kg, and BMR., Conclusions: Interactions between the MC4R rs17782313 and carbohydrate intake probably can have an effect on BMI, WC, and BMR/kg in overweight/obese women., (© 2022. The Author(s).)

Background: Although various dietary patterns have been indicated to be associated with the resting metabolic rate [RMR], limited data are available in this field. This study was therefore focused on the association between dietary patterns and resting metabolic rate among participants with overweight and obesity., Methods: This cross-sectional study was conducted on 304 women with overweight or obesity (BMI ≥ 25 kg/m 2 ), aged 18-50. Anthropometric assessments, physical activity and biochemical measurements were assessed. RMR was also measured by means of indirect calorimetry. Dietary intake of participants was evaluated by 147-item semi-quantitative food frequency questionnaire [FFQ]., Results: There was a significant association between higher adherence to the healthy dietary pattern [HDP] and RMR (P = 0.05), intakes of protein (P = 0.003), minerals (P = 0.001) as well as fat free mass [FFM] (P = 0.002), bone mineral content (P = 0.001), skeletal muscle mass (P = 0.001), soft lean mass (P = 0.002) and visceral fat area (P = 0.05). Also, there was a considerable association between higher adherence to the unhealthy dietary pattern [UHDP] and fasting blood sugar [FBS] (P = 0.05). Using multinomial logistic regression has been shown that the medium adherence to the HDP was marginally significant with decreased resting metabolic rate [Dec. RMR] group in crude model (OR: 0.54; 95% CI: 0.28-1.05, P = 0.07). After controlling for various confounders such as age, FFM, physical activity, and energy intake, the association between Dec. RMR group and the lowest quartile of the HDP (OR: 0.36; 95% CI: 0.14-0.91, P = 0.03) became significant as well as the association between Dec. RMR group and medium adherence to the HDP (OR: 0.42; 95% CI: 0.18-0.97, P = 0.04). The medium adherence to the UHDP in crude model was also significant with increased resting metabolic rate [Inc. RMR] group (OR: 2.59; 95% CI: 1.01-6.65, P = 0.04)., Conclusions: Our study showed that there are significant associations between dietary patterns and RMR status., (© 2022. The Author(s).)

Resting metabolic rate (RMR) accounts for most daily energy expenditure. The low carbohydrate diet (LCD) attenuates decreases in RMR. This study aims to investigate the relationship between an LCD and RMR status among overweight and obese women. We enrolled 291 overweight and obese women in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, visceral fat, and insulin level were assessed. RMR was measured using indirect calorimetry. LCD score (LCDS) was measured using a validated semi-quantitative food frequency questionnaire. Analysis of variance, independent sample t-test, and Multinomial logistic regression tests were used. Results showed no relationship between LCDS and deviation of normal RMR (DNR) even after adjust for confounders (increased [Inc.] RMR: odds ratio [OR], 0.97; 95% confidence interval [CI], 0.92-1.01; p = 0.20; decreased [Dec.] RMR: OR, 0.97; 95% CI, 0.94-1.00; p = 0.14). Some components of LCDS had no significant association with DNR, such as carbohydrate and Dec. RMR in adjusted model (OR, 1.62; 95% CI, 0.98-1.37; p = 0.08) and monounsaturated fatty acids and Dec. RMR in adjusted model (OR, 0.48; 95% CI, 0.21-1.10, p = 0.08). However, refined grains had a significant association with Inc. RMR in crude model (OR, 0.87; 95% CI, 0.77-0.99, p = 0.04). There is no association between LCDS and RMR status., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests., (Copyright © 2022. The Korean Society of Clinical Nutrition.)

Background: Previous studies showed the possible association between obesity, dietary pattern, and depressive symptoms. Due to the lack of enough data to confirm the association of obesity and depression in the Middle East, here, we aimed to explore the possible mediatory role of adipokines Galectin-3, transforming growth factor-beta (TGF-β), and endothelial plasminogen activator inhibitor (PAI-1) in the association between low carbohydrate diet (LCD) and depressive symptoms., Methods: A total of 256 women aged 17-56 years old were grouped based on their LCD score. Depression anxiety stress scales-21 (DASS-21) self-administered questionnaire was used to evaluate the three negative emotional states of stress, depressive symptoms, and anxiety. Body composition and dietary intake were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Galectin-3, TGF-β, and PAI-1., Results: No significant difference was observed regarding Galectin-3, TGF-β, and PAI-1 levels between the groups with dissimilar adherence to LCD or the groups with different levels of depressive symptoms (P>0.05). However, there was a negative association between LCD score as a covariant and depressive symptoms as an independent variable (P = 0.02) and remarkably, a regression model linear analysis using Galectin-3, TGF-β, and PAI-1 as confounding variables indicated the mediatory role of these adipokines in this association (P>0.05). In other words, adipokines eliminated the significance of the relationship between adherence to LCD and depressive symptoms., Conclusion: It seems that higher adherence to LCD is probably associated with a lower prevalence of depressive symptoms in obese adults through the mediatory role of adipokines., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313, may be associated with incidence of obesity and the risk of cardiovascular diseases (CVDs). Moreover, inflammation caused by the diet has been shown to have, potentially, unfavorable effects on CVD risk. This study used a linear regression model to investigate the interactions between the dietary inflammatory index (DII) and MC4R gene variants on markers of CVD., Methods: This comparative cross-sectional study was conducted on 266 Iranian women with overweight and obesity. A food frequency questionnaire (FFQ) with 147 items was used to assess dietary intakes. Individuals were categorized into three groups based on rs17782313 genotype. Participants were also divided into four groups based on DII score., Results: Higher quartiles of DII were associated with lower levels of high density lipoproteins (HDL) (p = 0.01) and higher levels of triglycerides (TG) (p = 0.04). There was a significant difference between genotypes for insulin (p < 0.001), HOMA index (p < 0.001), total body mineral content (p = 0.03), and bone mineral content (BMC) (p = 0.04). Our findings also showed significant interactions between DII score and rs17782313 polymorphism on total cholesterol, total body mineral content, BMC, soft lean mass (SLM), fat free mass (FFM) (p = 0.03), skeletal muscle mass (SMM), and basal metabolic rate (BMR)., Conclusion: Higher DII scores were associated with lower HDL levels and higher TG levels, respectively; whilst significant differences were observed between the genotypes of rs17782313 for insulin and HOMA index, total body mineral content, and BMC. These results highlight that dietary compositions, gene variants, and their interaction, should be considered in CVD risk assessment., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The high prevalence of vitamin D deficiency may be due to both genetic and environment factors. The aim of this study was to demonstrate that vitamin D deficiency may be due to variants of vitamin D binding protein ( DBP) among otherwise healthy Iranian adults. Methods: This cross-sectional study was conducted on 265 healthy adults in Tehran. Anthropometric and biochemical parameters were assessed. Dietary vitamin D intake was assessed with a Food Frequency Questionnaire (FFQ), and participant DBP genotypes were determined by polymerase chain reactions - restriction fragment length polymorphism. Results: Significant associations were found between vitamin D status and low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and fasting blood sugar (P < 0.001), after adjustment for confounder factors. This study demonstrated that "rs7041" gene was associated with vitamin D deficiency (OR = 0.63, β ± SE = -0.46 ± 0.14, P < 0.0001). After considering the "GG" genotype of the "rs7041" polymorphism as a reference, the prevalence of vitamin D deficiency was found to be higher in the individuals with "TT" genotype from the "rs7041" polymorphism. Conclusion: It was found that the prevalence of vitamin D deficiency was higher in individuals with T allele carriers in the "rs7041" polymorphism.

Objectives: Obesity plays an important role in the development of chronic diseases like cardiovascular diseases and diabetes. The possible underlying mechanism for this connection is that adipose tissue secretes an array of chemical messenger adipokines proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). This study aimed to investigate the linkage between adipocytokines and insulin with the cardiovascular disease risk, with particular reference to the adipokines galectin-3, plasminogen activator inhibitor-1, and interleukin-1-beta, C-reactive protein, and monocyte chemoattractant protein., Result: Two patterns were identified. The first pattern was galectin-3, plasminogen activator inhibitor-1 and interleukin-1-beta and the second one was C-reactive protein, insulin and monocyte chemoattractant protein-1. The second pattern was strongly associated with the higher scores for resting metabolic rate, diastolic blood pressure, homeostasis model insulin resistance index, lipid profile (except low density lipoprotein, total cholesterol), and body composition parameters (except fat free mass index and waist hip ratio), while negatively associated with age and high density lipoprotein level (all p < 0.05). The first pattern was, however, significantly associated with body fat mass, obesity degree percentage, waist circumference, fat mass index, and waist hip ratio (p < 0.05 for all). This is a retrospective study. Ethics approval (IR.TUMS.VCR.REC.1395.1597).

The attachment of PEG to biopharmaceuticals has been applied for enhancement of bioavailability and improved stability. The PEG polymer is highly hydrated; thus effective attachment to inaccessible sites could be hindered. We have devised a scheme to address this issue by introducing a considerable distance between PEG and protein by addition of a linear peptide, appended to long chained reactive linkers. Second, the position of PEG conjugation directly affects biological activity. Accordingly, a disulfide bond could be considered as an ideal choice for site directed PEGylation; but reactivity of both thiol moieties to bridging reagent is critical for maintenance of protein structure. In our design, a forked structure with two arms provides essential flexibility to account for dissociation of reduced cysteines. An efficient yield for disulfide PEGylation of IFN-β1b was attained and specificity, biophysical characterization, biological activity, and pharmacokinetics were surveyed.

Stability of the microtubule protein (MTP) network required for its physiological functions is disrupted in the course of neurodegenerative disorders. Thus, the design of novel therapeutic approaches for microtubule stabilization is a focus of intensive study. Dynamin-related protein-1 (Drp1) is a guanosine triphosphatase (GTPase), which plays a prevailing role in mitochondrial fission. Several isoforms of Drp1 have been identified, of which one of these isoforms (Drp1-x01) has been previously described with MTP stabilizing activity. Here, we synthesized peptide LIQ, an 11-amino-acid peptide derived from the Drp1-x01 isoform, and reported that LIQ could induce tubulin assembly in vitro . Using a Stern-Volmer plot and continuous variation method, we proposed one binding site on tubulin for this peptide. Interestingly, FRET experiment and docking studies showed that LIQ binds the taxol-binding site on β-tubulin. Furthermore, circular dichroism (CD) spectroscopy and 8-anilino-1-naphthalenesulfonic acid (ANS) assay provided data on tubulin structural changes upon LIQ binding that result in formation of more stable tubulin dimers. Flow cytometry analysis and fluorescence microscopy displayed that cellular internalization of 5-FAM-labeled LIQ is attributed to a mechanism that mostly involves endocytosis. In addition, LIQ promoted polymerization of tubulin and stabilized MTP in primary astroglia cells and also protected these cells against zinc toxicity. This excellent feature of cellular neuroprotection by LIQ provides a promising therapeutic approach for neurodegenerative diseases.

Despite the attention given to the treatment of multiple sclerosis (MS), still no certain cure is available. The main purpose of MS drugs is acting against neuroinflammation which underlies the pathology of MS. Neuroinflammation is associated with endoplasmic reticulum (ER) stress that mediates neural apoptosis. In the present study, we hypothesized that the tetrapeptide N-acetyl-ser-asp-lys-pro (Ac-SDKP) with the previously described anti-fibrotic effects might have anti-inflammatory, anti-oxidative and anti-ER stress roles in the hippocampus. We used myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE), a widely-accepted animal model of MS, in C57BL/6 mice. The protein levels of ER stress-related molecules including caspase-12, C/EBP homologous protein (CHOP), and protein disulfide isomerase (PDI) in the hippocampus were examined by immunoblotting. Hence, reactive oxygen species (ROS) production, lipid peroxidation and antioxidant capacity of the hippocampus were studied. Moreover, hippocampal morphology changes, leukocytes infiltration, and the levels of IL-6 and IL-1β pro-inflammatory cytokines were evaluated. Our results displayed that Ac-SDKP down regulates caspase-12 and CHOP expression in the hippocampus-resident oligodendrocytes of EAE mice. Further, treatment with Ac-SDKP decreased oxidative stress markers and caspase-3 activation in the hippocampus of EAE mice. According to our findings, Ac-SDKP showed beneficial effects against ER stress and oxidative stress in addition to inflammation in the hippocampus of EAE mice. The present study provides the basis for further research on the therapeutic applications of Ac-SDKP to reduce ER stress and oxidative stress-induced apoptosis in neurodegenerative disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The previous studies have revealed that there is a link between dietary glycemic index and lipid profile in overweight and obesity. The aim of study was to investigate whether the glycemic index is associated with liver enzymes., Method: Anthropometric and biochemical parameters were measured in 265 participants. Dietary glycemic index (GI) was assessed by using a validated food-frequency questionnaire. With adjusting confounder variable, Binary logistic regression was also used to predict the relationship between liver enzymes and quartile of intake., Results: There was a significant difference between low and high GI diet for BMR (P = 0.01), FFM (P = 0.03), TG (P = 0.02), HDL (P = 0.002). The association between HDL and glycemic index remained significant after adjustment of sex and age (P = 0.03). Using the regression model following adjustment revealed that for each 1% increase in the degree of the GI, there was 11% elevation in liver enzyme abnormalities. In both groups of men and women, enzyme abnormalities positively correlated with GI, while only men showed remarkable correlation in all models (crude model: β = 0.07, OR = 1.07, CI = 0.98to 1.16). Additionally, an increase in the degree of GI caused an elevation in enzyme abnormalities by 7%. With adjusting sex, age, BMI, and Physical activity, a significance correlation was found between GI and Enzyme abnormalities (p-value = 0.03, OR = 1.115)., Conclusion: Our study indicated that high glycemic index diet led to the elevated levels of the liver enzymes, while being significant only in men., (Copyright © 2019. Published by Elsevier Ltd.)

Testosterone is a nuclear androgen receptor ligand that controls multiple pathways in brain. In addition to the active biosynthesis of steroids in classic steroidogenic organs such as gonads, adrenals and placenta, testosterone also produced in astrocyte cells of brain. Testosterone and its level must be regulated in brain; because, it directly and indirectly affects memory and several key behavioral characteristics. The significance of sound waves on key enzymes that regulate levels of testosterone in brain has not been investigated. The aim of our study was to examine physical stress of such as sound on induction behavioral changes in animal models. According to the current study, sound waves with 528 Hz frequency in 100 dB intensity induce testosterone production in brain by enhancing StAR and SF-1 and reducing P450 aromatase gene expression. Frequency of 528 Hz also reduces total concentration of reactive oxidative species in brain tissue. Prolonged exposure to this sound wave showed reduction of anxiety related behaviors in rats. The results reveal that reduced anxiety is related to increased concentration of testosterone in brain. This study may lead to ascertain a possible therapy in which sounds may be utilized to reduce anxiety in individual.

Objective: No studies have examined the contribution of major dietary patterns to MUH phenotypes in obese and overweight people based on Karelis criteria. This study was conducted to evaluate the association of major dietary patterns with MUHOW/O and MHOW/O phenotypes., Methods: This cross-sectional study was conducted on 290 overweight and obese women aged 18-50 (BMI≥25 kg/m 2 ). Anthropometric measurements were assessed in all participants. The MH phenotype was defined according to the Karelis criteria. Major dietary patterns were determined using factor analysis of 21 foods groups using a valid and reliable FFQ containing 147 items. Participants' body composition was assessed by BIA. Serum HDL, LDL, TG, insulin, and hs-CRP levels were quantified by ELISA., Results: By the use of factor analysis, 3 major dietary patterns were extracted: healthy dietary pattern (HDP), western dietary pattern (WDP) and unhealthy dietary pattern (UNHDP). Binary logistic analysis showed that participants in the in the upper category of WDP had greater odds of MUH phenotype (OR = 2.33, 95%CI = 1.11-4.91, P = 0.02), after confounder factor control. Individuals with high adherence to the UNHDP score had high odds of MUH phenotype (OR = 1.75, 95%CI = 0.98-3.10, P = 0.05), after adjustment for BMI, age, and total EI, compared to those with low adherence. A positive relation was observed between WDP and levels of hs-CRP, HOMA-IR (OR = 1.94, 95%CI = 0.91-4.10, P = 0.05 and OR = 2.53, 95%CI = 1.26-5.11, P = 0.009) as well as a positive association between UHDP and plasma level of LDL (OR = 1.90, 95%CI = 1.04-3.47, P = 0.03), but an inverse association between HDP and hs-CRP level (OR = 0.56, 95%CI = 0.29-0.92, P = 0.03)., Conclusions: The present evidence indicates various significant associations among major dietary patterns and MUHOW/O phenotypes., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Multiple adult health problems are associated with adolescent stress. As the brain discriminates physical and psychological stressors by activation of different neural networks, we hypothesized that behavioral and physiological performance would be modulated differently based on the nature of the stressors. Thus, we studied the comparative effects of adolescent repeated physical and psychological stresses on adult cognitive performance, pro-oxidant-antioxidant balance (PAB) and heart rate in female rats. The aim was to differentiate disparate potency of chronic psychological and physical stresses leading to long-term behavioral and physiological alterations. Twenty-one female rats were divided randomly into three groups of seven rats each; control, physical, and psychological stress. Experimental rats were exposed to the stressors for five consecutive days (10 min daily) via a two-communication box. After verifying stress induction by serum corticosterone measurement, the rats were returned to their home cage for 6 weeks, until adulthood, elevated plus maze (EPM), forced swimming test (FST), Y-maze, object recognition task (ORT), and passive avoidance test (PAT) were used as five different behavioral tests to evaluate cognitive performance of each group. Serum PAB and heart rate were measured to assess long-term stress-induced physiological disorders. The results showed exposure to adolescent psychological stress resulted in a larger set of significant changes (in behavioral variation, oxidative stress, and elevated heart rate) 6 weeks post-stress compared to adolescent physical stress. Hence, mental health care in adolescence and therapies targeting PAB and heart rate could be prevention and treatment approaches to confront persistent adolescent stress-induced disorders. Lay summaryThe aim of our study on female laboratory rats was to differentiate disparate potency of chronic psychological and physical stresses in adolescence leading to long-term behavioral and physiological alterations. The results suggest that psychological stresses result in a greater extent of changes compared to physical stress. Adolescent chronic psychological stress may reveal itself in the form of certain behavioral and physiological variations in adulthood. Therefore, mental health care in adolescence could be a valuable prevention approach to confront a variety of adult stress-induced disorders.

Background: Recent studies have shown that depression is inversely correlated with high protein and low fat intake and positively correlated with vitamin D-binding protein (VDBP). Therefore, the aim of this study was to examine the interaction between protein/fat dietary patterns and VDBP genotypes with regard to the risk of depression in apparently healthy adults who have not been diagnosed with any chronic disease., Methods: In this study, 265 individuals (126 males and 139 females) aged 18-55 years were recruited from the communities of central and west Tehran based on convenience sampling. Body composition was measured with a body composition analyzer and depression symptoms were categorized as normal, moderate depression, or severe depression using the Depression Anxiety Stress Scales 21 (DASS-21) questionnaire. Dietary patterns were determined by a semiquantitative food frequency questionnaire to assess typical food intake during the 12-month period. Blood samples were collected from and biochemical measurements performed on all participants. An analysis of two polymorphisms (rs7041 and rs4588) in the GC gene, which encodes VDBP, was performed by polymerase chain reaction-restriction fragment length polymorphism., Results: A statistically significant association was found between depression and diet (p = 0.03) after having categorized the participants into three groups: a high-protein/low-fat (HP/LF) group, a moderate-protein/moderate-fat (MP/MF) group, and a low-protein/high-fat (LP/HF) group. Moreover, the findings demonstrated that depression was related to both the rs7041 and the rs4588 polymorphism (p = 0.05 and p = 0.02, respectively). We next used multinomial logistic modeling to investigate the risk of depression. A significant interaction was observed between HP/LF diet and the rs7041 polymorphism in the moderate- and severe-depression groups (β = -0.30, p = 0.05, and β = -0.48, p = 0.01, respectively)., Conclusion: This study showed that an HP/LF diet interacts with the rs7041 polymorphism, with T allele carriers having a greater prevalence of moderate and severe depression., (© 2018 S. Karger AG, Basel.)

Background: Bleeding during surgery can lead to serious complications. Methods and drugs to control bleeding are always important both for the surgeon and anesthesiologist, especially in endoscopic procedures. A lot of efforts are made to optimize the surgical conditions for functional endoscopic sinus surgery. Induced hypotension is widely advocated to prevent bleeding and consequently to improve the quality of an operation . Amongst the pharmacological agents, dexmedetomidine is the most recently introduced drug to provide hypotensive anesthesia during functional endoscopic sinus surgery., Objectives: The current study aimed at investigating the effects of intravenous infusion of dexmedetomidine on bleeding, nausea, awakening time, and other intravenous anesthetic doses during functional endoscopic sinus surgery., Methods: Sixty patients aged 16 to 60 years with American society of anesthesiologists (ASA) class I or II in Imam Khomeini hospital of Ahvaz, Iran, who were the candidate for the elective functional endoscopic sinus surgery were enrolled in the current double-blind clinical trial. They were randomly divided into 2 groups: group D (receiving dexmedetomidine), and group N (receiving normal saline). Sampling was based on the block randomization method. In group D, a 1-μg/kg dexmedetomidine was injected during 10 minutes just before the induction. Then, 0.5 µg/ kg/ hour infusion was started. Both groups had the same induction and maintenance method as well as the drugs administered for general anesthesia induction. For maintenance, the patients received O 2 50%: N 2 O 50% and 100 μg/kg/minute of propofol and 0.2 μg/kg/minute of remifentanil. In group N, instead of dexmedetomidine in bolus and maintenance, normal saline was used with the same volume. Mean arterial pressure was maintained between 65 to 75 mmHg. The incidence of bleeding, nausea and vomiting after surgery, the amount of maintenance drugs, and awakening time were recorded in a checklist., Results: The intravenous use of dexmedetomidine significantly reduced the amount of bleeding (P < 0.0001); in addition, the need for opioids (P < 0.0001) and intravenous anesthetics significantly decreased (P = 0.001). Awakening time was significantly longer (P = 0.001), but its effect on postoperative nausea and vomiting was not significant (P = 0.052)., Conclusions: The current study showed that although propofol and remifentanil compounds can control hemodynamic state, but intravenous infusion of dexmedetomidine during the functional endoscopic sinus surgery reduced the amount of bleeding more significantly. It also reduced the dosage of maintenance drugs.

Ethnopharmacological Relevance: Cyperus rotundus L. (Cyperaceae), commonly known as purple nutsedge or nut grass is one of the most invasive and endemic weeds in tropical, subtropical and temperate regions. This plant has been extensively used in traditional medicine for anti-arthritic, antidiarrheal and antiplatelet properties as well as treatment for several CNS disorders such as epilepsy, depression and inflammatory disorders. Inflammation is evidently occurring in pathologically susceptible regions of the Alzheimer's disease (AD) brain as well as other disorders. Many cellular processes are responsible in chronic inflammation. Microtubule-based inflammatory cell chemotaxis is a well-recognized process that influences production of cytokines and phagocytosis. The effect of α-Cyperone, one of main ingredients of Cyperus rotundus on microtubule assembly and dynamics has not been examined and is the purpose of this investigation., Materials and Methods: Microtubules and tubulin were extracted in order to explore their interaction with α-Cyperone by utilization of turbidimetric examinations, intrinsic fluorescence and circular dichroism spectroscopy (CD) studies. The molecular docking analysis was executed in order to facilitate a more detail and stronger evidence of this interaction. The BINding ANAlyzer (BINANA) algorithm was used to evaluate and further substantiate the binding site of α-Cyperone., Results: It was demonstrated that α-Cyperone had a pronounced influence on the tubulin structure, decreased polymerization rate and reduced concentration of polymerized tubulin in vitro. The CD deconvolution analysis concluded that significant conformational changes occurred, demonstrated by a drastic increase in content of β-strands upon binding of α-Cyperone. The fluorescence spectroscopy revealed that a static type of quenching mechanism is responsible for binding of α-Cyperone to tubulin. Upon characterization of various biophysical parameters, it was further deduced that ligand binding was spontaneous and a single site of binding was confirmed. Transmission electron microscopy revealed that upon binding of α-Cyperone to microtubule the number and complexity of fibers were noticeably decreased. The computational analysis of docking suggested that α-Cyperone binds preferably to β-tubulin at a distinct location with close proximity to the GTP binding and hydrolysis site. The ligand interaction with β-tubulin is mostly hydrophobic and occurs at amino acid residues that are exclusively on random coil. The BINANA 1.2.0 algorithm which counts and tallies close molecular interaction by performing defined set of simulations revealed that amino acid residues Arg 48 and Val 62 have registered the highest scores and are possibly crucial in ligand-protein interaction., Conclusion: α-Cyperone binds and interacts with tubulin and is capable of distinctly destabilizing microtubule polymerization. The effect of this interaction could result in reduction of inflammation which would be highly beneficial for treatment of inflammatory diseases such as AD., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Tau protein consists of six different isoforms and each one has particular physiological roles. In order to analyze the specific function of each single isoforms, large quantity of highly purified tau isoforms is essential. Many studies have been done to purify tau isoforms by heat treatment, followed by perchloric acid and glycerol precipitation. We found out that 1N/4R tau is soluble in glycerol, that is why mentioned methods do not work for purifying this isoform. In this study, large amounts of active and highly purified (97%) 1N/4R tau protein has been prepared by utilization of trichloroacetic acid as precipitating agent., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the current study, the design, synthetic feasibility and biochemical characterization of biodegradable peptidic PEG-based nanocarriers are described. The components were selected to influence the body elimination pathway upon nanocarrier biodegradation. Two prototypical nanocarriers were prepared using non-PEGylated and PEGylated peptidic cores [CH(3)CO-(Lys-betaAla-betaAla)(X)-Cys-CONH(2) (X=2, 4)]. A homodimeric nanocarrier with 4 copies of fluorescein-PEG5kDa was synthesized by linking two PEGylated peptidic cores (X=2) using a disulfide bond. A dual labeled heterodimeric nanocarrier with 2 copies of fluorescein-PEG5kDa and 4 copies of Texas Red was also synthesized. Optimum conditions for linking imaging agents, PEG, or a peptidic core to a peptidic core were determined. Significantly higher yields (69% versus 30%) of the PEGylated peptidic core were obtained by using 2 copies of beta-alanine as a spacer along with increasing DMSO concentrations, which resulted in reduced steric hindrance. Stoichiometric addition of the components was also demonstrated and found to be important for reducing polydispersity. Nanocarrier biodegradation was evaluated in simulated intracellular and extracellular/blood environments using 3 mm and 10 microm glutathione in buffer, respectively. The nanocarrier was 9-fold more stable in the extracellular environment. The results suggest selective intracellular degradation of the nanocarrier into components with known body elimination pathways.

Cell-penetrating peptides (CPPs) can enter many types of cells and have become useful tools for introducing a variety of cargo such as exogenous peptides, proteins, and nucleic acids into cultured cells in vitro. Tat CPPs derived from the HIV-1 Tat protein are the most widely used among the arginine-rich CPPs. Even though CPPs hold considerable promise for drug delivery, poor biological stability and high in vivo clearance may limit their effectiveness for delivering cargo. Therefore, we utilize a retro-inverso form of a Tat peptide, R.I.-CKTat9, which is proteolytically stable. In the current study, the cellular entry mechanism of this arginine-rich CPP is investigated. Fluorescently labeled R.I.-CKTat9 entered HeLa cells in a concentration- and energy-dependent manner demonstrating both diffuse and punctate (vesicular) appearance inside the cells. The labeled R.I.-CKTat9 colocalized with labeled transferrin in the punctate structure, suggesting that the peptide enters HeLa cells by clathrin-dependent endocytosis. Incubation of cells with an isotonic/high K(+) buffer (KPBS) or an NH(4)Cl solution abolished the diffuse but not the punctate fluorescence, suggesting that membrane potential plays a critical role. This result also suggests that the flux originates from the endosome, not the extracellular space, and relies on the acidity of the endosome. Impairment of clathrin-mediated endocytosis by RNAi with clathrin heavy chain function and endocytosis inhibitors greatly reduced or completely abolished both diffuse and punctate fluorescence, further supporting a single route of endocytosis and subsequent endosomal escape. Since cells in the mitotic (M) phase shut down endocytosis but maintain plasma membrane potential, this property was used to further confirm the endocytic mechanism. Direct measurement of plasma membrane potential confirmed its persistence in M phase arrested HeLa cells. Consistent with our working hypothesis, these cells did not show any vesicular nor diffuse fluorescence of labeled R.I.-CKTat9, providing compelling evidence for the sequential steps of endocytosis and endosomal escape. Binding of labeled R.I.-CKTat9 to the surface of HeLa cells at 0 degrees C was reduced under the mildly acidic conditions of early endosomes, suggesting an acidity-dependent endosomal escape mechanism. Overall, these results indicate that both endocytosis and membrane potential are required for R.I.-CKTat9 entry into HeLa cells and suggest that translocation occurs at the endosomal membrane.

Curing HIV-1 infection has remained elusive because of low and fluctuating drug levels arising from poor absorption, the development of viral reservoirs and sanctuary sites, toxicity, and patient nonadherence. The present study addresses the issue of insufficient drug exposure in macrophages. Viral reservoir sites such as macrophages are believed to be responsible for the viral rebound effect observed upon the discontinuation of anti-HIV drug therapy. In our proposed model, a drug can be covalently attached to a nanocarrier in order to facilitate the delivery of therapeutic agents to the site(s) of infection. As an initial step, we propose the covalent attachment of several copies of N-formyl-Met-Leu-Phe (fMLF), a known chemo-attractant for macrophages. In this article, one or more copies of fMLF were conjugated to multifunctional commercially available or novel, peptide-based PEG nanocarriers in which the structure was varied by appending PEGs with average molecular weights of 5, 20, and 40 kDa. U937 cell-specific binding and cellular uptake were analyzed. The results of uptake studies indicate that (i) uptake is energy dependent and mediated by a fMLF receptor, (ii) appending only 2 copies of the targeting ligand to the multifunctional nanocarrier appears sufficient for binding in vitro, and (iii) of the three configurations studied, the nanocarrier with a molecular weight of about 20 kDa, corresponding to a size of 20-60 nm, demonstrated the highest uptake. The results of the current studies demonstrate the feasibility of targeting macrophages and the suitability of using these synthetically versatile peptide--backbone PEG nanocarriers. The convenience, flexibility and possible limitations of this nanocarrier approach are discussed.

Purpose: To assess in vivo macrophage targeting potential of PEG-fMLF nanocarriers and to investigate their biodistribution, peritoneal macrophage uptake, and pharmacokinetics., Methods: Multiple copies of fMLF were conjugated to purchased and novel (branched, peptide-based) PEG nanocarriers. Peritoneal macrophage uptake was evaluated in mice 4 hours after IP administration of fluorescence-labeled PEG-fMLF nanocarriers. Pharmacokinetics and biodistribution were determined in rats after IV administration of tritiated PEG-fMLF nanocarriers., Results: Attachment of one, two, or four fMLF copies increased uptake in macrophages by 3.8-, 11.3-, and 23.6-fold compared to PEG without fMLF. Pharmacokinetic properties and tissue distribution also differed between nanocarriers with and without fMLF. Attachment of fMLF residues increased the t(1/2) of PEG(5K) by threefold but decreased the t(1/2) of PEG(20K) by 40%. Attachment of fMLF increased accumulation of nanocarriers into macrophages of liver, kidneys and spleen. However, on a molar basis, penetration was equivalent suggesting nanocarrier size and targeting moieties are important determinants., Conclusions: These results demonstrate the feasibility for targeting macrophages, a primary HIV reservoir site. However, these studies also suggest that balancing peripheral tissue penetration (a size-dependent phenomenon) versus target cell uptake specificity remains a challenge to overcome.

Background: Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties., Results: Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more potent than L-Tat9 while the addition of biotin resulted in a prodrug that was 2850 times more potent than L-Tat9. Flow cytometry and confocal microscopy studies suggest that variations in intracellular uptake and intracellular localization, as well as synergistic inhibitory effects of SQV and Tat peptides, contributed to the unexpected and substantial differences in antiviral activity., Conclusion: Our results demonstrate that highly potent nanoscale multi-drug conjugates with low non-specific toxicity can be produced by combining moieties with anti-HIV agents for different targets onto macromolecules having improved delivery properties.