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Abstract Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: “Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature”. Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of “a globally coordinated diagnostic and research pipeline”. To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient’s diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.

Abstract Background The utilization of complementary and alternative medicine (CAM) is experiencing a global surge, accompanied by the adoption of national CAM policies in numerous countries. Traditional Persian medicine (TPM) is highly used as CAM in Iran, and the ongoing scientific evaluation of its interventions and the implementation of evidence-based medicine (EBM) encounters various barriers. Therefore, comprehending the characteristics and interactions of stakeholders is pivotal in advancing EBM within TPM policies. In this study, we utilized both classical stakeholder analysis and social network analysis to identify key stakeholders and potential communication patterns, thereby promoting EBM in TPM policy-making. Methods A cross-sectional nationwide stakeholder analysis was conducted in 2023 using snowball sampling. The interviews were carried out using a customized version of the six building blocks of health. Data were collected through semi-structured interviews. Stakeholders were assessed based on five factors (power, interest, influence, position, and competency). The connections and structure of the network were analyzed using degree, betweenness, closeness centrality, and modularity index to detect clusters of smaller networks. Results Among twenty-three identified stakeholders, the Ministry of Health and Medical Education (MOHME) and the Public were the most powerful and influential. The Iranian Academy of Medical Sciences was the most competent stakeholder. Social network analysis revealed a low density of connections among stakeholders. Pharmaceutical companies were identified as key connectors in the network, while the Public, supreme governmental bodies, and guilds acted as gatekeepers or brokers. The MOHME and Maraji were found to be high-ranking stakeholders based on four different centrality measures. Conclusion This study identifies powerful stakeholders in the network and emphasizes the need to engage uninterested yet significant stakeholders. Recommendations include improving competence through education, strengthening international relations, and fostering stronger relationships. Engaging key connectors and gatekeepers is essential for bridging gaps in the network.

This research work involves the advanced microstructural characterization and corrosion resistance of hybrid nanocomposites produced by friction stir-induced reaction in an Al–Mg alloy/TiO2 system tested by potentiodynamic and spectroscopy analyses in the form of polarization and impedance. The impact of TiO2 content and submerged cooling medium were assessed on the subsequent electrochemical behavior of the composites. The electrochemical polarization measurements reveal a substantial variation in the corrosion performance correlated to the chemistry of nanocomposites and aluminum matrix grain structure, depending on friction stirring parameters. The heterogeneity of reinforcing nanoparticles at high fractions can increase the corrosion rate in the stirred region by more than 140 times compared to the primary alloy. This is attributed to secondary phase interfaces and nanoparticle clustering at the grain boundaries, promoting galvanic and pitting corrosion phenomena. In contrast, submerged reactive methods employing a cooling medium led to the formation of ultra-fine/nano-sized cellular structured in-situ hybrid nanocomposites with superior corrosion resistance and an excellent combination of mechanical and chemical properties.

Abstract Background Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran. Methods We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated. Results A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively. Conclusion GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.

Abstract Excessive use of pesticides against pests has contaminated agricultural crops and raised global concerns about food safety. This research investigates the alleviation effects of 24-epibrassinolide (EBL) seed priming on diazinon (DZ) pesticide toxicity. The experiment was conducted with eight groups including control, DZ, EBL (10 µM), EBL (0.1 µM), EBL (0.01 µM), EBL (10 µM) + DZ, EBL (0.1 µM) + DZ, and EBL (0.01 µM) + DZ. Plants grown with the lowest concentration of EBL (0.01 µM) exhibited an upward increase in the activity of SOD, CAT, POD, APX, GR, and GST enzymes under DZ toxicity stress. In contrast, higher concentrations of EBL showed some inhibitory effects on the activity of antioxidant enzymes. In addition, low concentrations of EBL elevated the free radical scavenging capacity (DPPH), iron-reducing antioxidant power (FRAP), photosynthesis rate (Pn), stomatal conductance (Gs) and proline, and protein contents. EBL also reduced lipid peroxidation (MDA levels) in the DZ-exposed plants, leading to membrane integrity. The favorable effects of EBL were more evident when plants were exposed to pesticides than normal growth conditions. The results indicated that EBL seed priming intensifies the antioxidant enzymes system activity, and helps maize plants against toxic effects of DZ under proper concentration.

Introduction: Soil resources play an important role in providing the necessary material goods for humans and other organisms and also deliver multiple ecosystem services that are essential for life on earth. They have also served for a long time as an important green infrastructure in protecting agricultural and forest landscapes by providing plants a foothold for their roots and holding the necessary nutrients for their growth. In addition, soils can provide various ecosystem services such as contaminant immobilization, rainwater control, carbon sequestration, and habitat provision that are directly beneficial for humans. Services provided by ecosystems for humans are called ecosystem services. Soil retention, which refers to the potential of ecosystems for controlling soil erosion and conserving soil, is classified in the class of regulating services. Materials and Methods: The InVEST Sediment Delivery Ratio (SDR) model was used in InVEST Software to quantify soil retention and erosion. The required inputs for implementing this model include land use maps, K-factor (soil erodibility), R-factor (rain erosivity), C-factor (land use and land cover or LU/LC), P-factor (support practices), DEM (digital elevation model), and the biophysical table. Results: Based on the results, the potential of soil loss and sediment transport in the study area ranged from zero to 248.18 t/pixel and from zero to 57.25 tons per pixel, respectively. Soil retention is also estimated in a range from zero to 124.85 tons per pixel in the studied area. The largest amount of soil loss happened in sub-basin number 14 with 13716400 t/year and the smallest in sub-basin number 4 with 416594 t/year. Most of the ecosystem service of soil retention belonged to sub-basin number 13 with 4304414 t/ha/ year and the least to sub-basin number 4 with 5645 tons/ha/year. Discussion: The dense forests in the northernmost part of Semnan Province provide the most part of the ecosystem service of soil retention with more than 36 t/ha and the desert areas, the salt lake, and the salt marsh the least. Based on this, the province's forests, including dense, semi-dense, sparse and thin forests, contribute to the maintenance of soil in the province by a total of 4269166 tons per year. Also, good pastures maintain more than 18 tons per hectare of the province's soil every year, and the total function of soil maintenance by all types of pastures in the province, including good, medium and poor pastures, is 9395160 tons per year. Since the area covered by the pastures is 18 times more than that by the forests, we can say that most of the ecosystem service of soil retention is provided by the pastures due to the geographical distribution of this service in the province, despite the fact that forests are more capable in soil conservation than pastures. The orchards and rainfed agricultural land rank third and fourth, respectively, in soil retention with 7.86 and 2.15 tons of soil/ha, respectively. However, man-made land uses such as urban areas decrease this ecosystem service because they are usually accompanied by removing or reducing the vegetation. The urban areas are located in the northern part of the study area, and they have negative impacts on this ecosystem service. Therefore, protection of the forest and rangeland covers in the province is vitally important for the continued conservation of the ecosystem service of soil retention.

Abstract Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease. These findings provide a beginning to new avenues and pan-ethnic therapeutic approaches, as well as to potential genetic screening protocols. The causative virus, SARS-CoV-2, is still in the spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance and further research is warranted. We also note emphatically that to prevent future pandemics and other world-wide health crises, it is imperative to capitalize on what we have learnt from COVID-19: specifically, regarding its origins, the world’s response, and insufficient preparedness. This requires unprecedented international collaboration and timely data sharing for the coordination of effective response and the rapid implementation of containment measures.

Introduction: The development of the necessary infrastructure to enhance the walkability in urban areas has an important role in sustainable urban development and from various aspects of the environment, public health and social justice can improve the quality of life. This study aimed to investigate the pedestrian capability approach for the development of a sustainable city in District 16 of Tehran Municipality as one of the greenest urban areas in Tehran.Material and methods: In this research, the criteria, qualities, characteristics and physical, functional and spatial variables of the man-made environment that affect the amount of walking in the D16 of Tehran Municipality have been studied and collected. Then, using GIS spatial analysis and prioritization of indicators using Analytical Hierarchical Process, the pedestrianization of different parts of the region has been investigated.Results and discussion: Criteria affecting the location of sidewalks and greenways in the D16 in 9 main categories and 30 sub-criteria were collected in a hierarchical structure and their spatial information was collected. The diversity and wide range of indicators evaluated results in a comprehensive analysis of the current situation can be considered as one of the strengths of this study. Each of these indicators was analyzed for the study area and the situation of walking potential in the D16 was studied based on each of the indicators. Using the preference of criteria based on the opinion of experts and the overlap of different layers, finally, the map of the degree of walkability and the map of the degree of the walkability of the road network in the 16th district of Tehran Municipality was obtained. According to the results, the spatial value shows the highest values ​​in Khazaneh, Naziabad and Bagh Azari neighborhoods, respectively. In addition, Bukharai Street, Madaen Street, Rajaei Street and Street next to Besat Park are the axes with the highest amount of pedestrian traffic in the region, respectively.Conclusion: Based on detailed traffic studies, the best places to define sidewalks or urban greenways were identified, and since these axes have a high volume of pedestrian traffic, it is very important to pay attention to the needs of pedestrians in them. The three neighborhoods of Naziabad, Aliabad North and Khazaneh were identified as three suitable areas for the development of pedestrian axes in the region and were introduced to further concentrate the municipality of the region.

Abstract Background Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. Method We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. Results Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57–4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07–2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00–1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30–1.53), high physical activity (PR: 0.66; 95% CI 0.45–0.95), use of opiate ever (PR: 0.46; 95% CI 0.26–0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12–0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. Conclusion Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Abstract COVID-19, which is caused by the SARS-CoV-2, has ravaged the world for the past 2 years. Here, we review the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase. We are particularly concerned by the lack of solid information from the initial phases of the pandemic that highlighted the necessity for better preparation to face similar future threats. On the other hand, we are gratified by the progress into human genetic susceptibility investigations and we believe now is the time to explore the transition from the pandemic to the endemic phase. The latter will require worldwide vigilance and cooperation, especially in emerging countries. In the transition to the endemic phase, vaccination rates have lagged and developed countries should assist, as warranted, in bolstering vaccination rates worldwide. We also discuss the current status of vaccines and the outlook for COVID-19.

Polypharmacy, defined here as the concomitant use of five or more medications, is a significant health issue, particularly affecting individuals with chronic diseases like hypertension (HTN). To compare individuals with and without HTN in term of polypharmacy, and to investigate correlates of polypharmacy and medication use patterns in individuals with HTN in southwest Iran. This cross-sectional study used the baseline data of 9270 participants of the Pars Cohort Study (PCS) with a mean age of 52.6 ± 9.7 years. Poisson multivariable modeling was applied to identify correlates of polypharmacy, and Lexicomp® was used to assess drug-drug interactions. Anatomical Therapeutic Chemical classification was used to describe the pattern of medication use. The prevalence of polypharmacy in individuals without hypertension was 4.7 % (4.2%–5.2 %) vs. 23.7 % (22.1%–25.3 %) in individuals with hypertension (P < 0.001). Individuals with hypertension from middle-high socioeconomic status (SES) had a 1.51-fold higher prevalence of polypharmacy than vs. low SES. Those with more than three comorbidities had a 5.18 times higher prevalence of polypharmacy than those with isolated hypertension. Calcium channel blockers were the most common antihypertensives (20.9 %). In terms of drug-drug interactions, type C interactions were most prevalent among participants with hypertension and polypharmacy (76.0 %). Our findings imply a fairly high prevalence of polypharmacy and drug-drug interactions among individuals with hypertension; to tackle this issue, we recommend a national pharmacovigilance system, training programs for primary care physicians, public education and awareness campaigns, drug-checking campaigns, targeted screenings to alter modifiable risk factors, and the use of safe combination pills. [ABSTRACT FROM AUTHOR]

Abstract COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.

Background and Aim: Pulmonary tuberculosis (TB) infection is common in patients infected with the Human immunodeficiency virus (HIV). In this study, we evaluated thoracic CT scan findings of HIV/TB co-infection, before and after anti-TB treatment. Materials and Methods: In this retrospective cross-sectional study, pre-and post-treatment thoracic CT scans of patients diagnosed with HIV and definite pulmonary TB infection were evaluated. Results: A total of 101 patients (64 male, 37 female, mean age of 43±3.4) were included. The most common findings before treatment of TB were mediastinal or hilar lymphadenopathy with hypodense center (41.58%) and free pleural effusion (32.67%). The prevalence of these findings decreased to half after anti-TB treatment (P= 0.009 and P= 0.003 respectively). Loculated pleural effusion showed increased prevalence after treatment (P= 0.031) with no significant change in the prevalence of bronchiectasis, solitary pulmonary nodule, and lymphadenopathy without a hypodense center. Conclusion: The most prevalent thoracic CT scan findings in patients with HIV/TB co-infection before anti-TB treatment were lymphadenopathy with the hypodense center, pleural effusion, and ground-glass opacities. After treatment, numerous changes in imaging manifestations might be seen. The remaining residual CT scan findings (including bronchiectasis, lymphadenopathy with a hypodense center, and solitary pulmonary nodule) require more attention for accurate interpretation of thoracic CT scans in HIV patients.

Abstract The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.

Abstract It is crucial to use the wealth of information emerging from the ongoing SARS-CoV-2 pandemic and confront COVID-19 with a rational approach. There are proactive steps to prevent and fight COVID-19. Management of the disease should be according to clinical features and laboratory test markers and personalized therapeutic targets.

Hypersensitivity pneumonitis (HP) is an immune-mediated diffuse parenchymal lung disease induced by inhaled antigens. High-resolution computed tomography (HRCT) is widely used in the diagnosis and follow-up of patients and determining the progression and prognosis of the disease. In this retrospective study, 45 consecutive patients with the final diagnosis of HP, seen at a large tertiary care center during a period of 4 years, were included and their HRCT findings were evaluated. The most common HRCT findings were ground glass opacity and reticulation. Some HRCT patterns were detected more severely in bird fanciers in comparison with other etiologies. There is no “gold standard” for the diagnosis of HP. HRCT findings play an important role in hypersensitivity pneumonitis diagnosis and CT scan also help to define the severity of hypersensitivity pneumonitis injuries. In our study, reticulation and ground glass opacity were the most common findings in HRCT of patients with HP. We also find that patients with avian contacts had a significantly higher rate of fibrosis.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today we are facing a global epidemic. Fever, cough, fatigue, breathlessness, and smell or taste loss are the most frequent clinical symptoms. In most cases, the symptoms are mild. However, it may occasionally progress to widespread thrombosis, septic shock, or acute respiratory disease syndrome (ARDS). The incubation period is usually about 5 days, but can vary from 2 to 14 days. Early quarantine is vital for preventing the complications and rapid spread of the disease. Real-time reverse transcription-polymerase chain reaction (RT-PCR) of a nasopharyngeal sample is the standard diagnostic test. However, this method is expensive and unavailable in many parts of the country, and has delayed results. On the other hand, computerized tomography scan (CT-scan) is widely available and low-cost throughout the country, and provides immediate results with high sensitivity. Indeed, in some cases, CT-scan is capable of providing evidence for the disease before detection of viral RNA from upper respiratory samples. CT-scan exhibits higher sensitivity, but lower specificity for diagnosis of COVID-19, compared to RT-PCR (sensitivity of 59-78% and 95-98% as well as specificity of approximately 100% and 96% for RT-PCR and chest CT-scan, respectively). Low sensitivity for diagnosis of COVID-19 and ionizing radiation exposure are two major disadvantages of CT-scan, which can be resolved to a large extent by clinical and laboratory correlations and utilizing low-dose CT protocols. It seems that CT-scan can be ordered for diagnosis of COVID-19 when PCR test is not feasible, or in case of high clinical suspicion in spite of negative PCR. In addition, CT-scan plays a major role in assessing the severity, extent and prognosis of the disease in monitoring the response to treatment, and in diagnosis of complications.

Background: In the era of coronavirus disease 2019 (COVID-19) pandemic, many cases may be misdiagnosed based on their semiology, laboratory tests or chest computed tomography (CT) images and further evaluation might be helpful in appropriately selected cases. Methods:We are discussing usefulness of fluorodeoxyglucose (FDG) positron emission tomography PET/CT scan in appropriately selected suspicious cases of COVID-19 infection. We are discussing two interesting cases on how18F-FDG PET/CT scan might be helpful to avoid COVID-19 infection diagnostic error. Both cases had clinical symptoms suggestive for COVID-19 infection with nonspecific chest CT scan findings including lung nodules, ground glass opacities (GGOs), consolidations, and mosaic perfusion patterns. This case series was approved by our institutional review board and informed consent obtained from both patients. Results: In one case,18F-FDG PET/CT images demonstrated hypermetabolic mostly peripheral GGOs and nodules in both lungs with subsequent evaluation confirming COVID-19 infection. The second case demonstrated right perihilar consolidation, not well appreciated on noncontrast chest CT images in addition to GGOs and further evaluation confirmed diagnosis of poorly differentiated squamous cell carcinoma of the lung. Conclusion: During COVID-19 pandemic, many cases might be misdiagnosed by either clinicians or radiologists. In appropriately selected cases, FDG PET/CT scan may be helpful during COVID-19 outbreak to avoid diagnostic errors.

Urban green spaces are essential for improving the livability of cities. Urban parks as green and public open spaces and signs of nature in cities have special economic and social value. The existence of neighborhood parks and their proper distribution is a key element for improving the quality of life in the cities. Spatial equity and accessibility to parks are factors influencing the performance of parks. This study was conducted to determine the current situation of Urmia city in this regard by using the travel cost approach and network analysis, and also examining the impact of rapid urban growth on spatial inequalities. According to the results, 18% of the residential land in Urmia city is located outside of the park service area, and 68% of residential lands outside the park’s service area are areas that have developed as a result of urban growth in the last two decades. Based on the analysis, in 23 neighborhoods of Urmia city, the entire neighborhood is located in the service area of parks and has pedestrian access to this service. Other neighborhoods—to address the issue of spatial justice related to urban parks—fall into three categories: high, medium, and low priority.

Stem cell expansion on 3D porous scaffolds cultured in bioreactor systems has been shown to be beneficial for maintenance of the original cell functionality in tissue engineering strategies (TE). However, the production of extracellular matrix (ECM) makes harvesting the progenitor cell population from 3D scaffolds a challenge. Medium composition plays a role in stimulating cell proliferation over extracellular matrix (ECM) production. In this regard, a computational model describing tissue growth inside 3D scaffolds can be a great tool in designing optimal experimental conditions. In this study, a computational model describing cell and ECM growth in a perfusion bioreactor is developed, including a description of the effect of a (generic) growth factor on the biological processes taking place inside the 3D scaffold. In the model, the speed of cell and ECM growth depends on the flow-induced shear stress, curvature and the concentrations of oxygen, glucose, lactate, and growth factor. The effect of the simulated growth factor is to differentially enhance cell proliferation over ECM production. After model calibration with historic in-house data, a multi-objective optimization procedure is executed aiming to minimize the total experimental cost whilst maximizing cell growth during culture. The obtained results indicate there are multiple optimum points for the medium refreshment regime and the initial growth factor concentration where a trade-off is made between the final amount of cells and the culture cost. Finally, the model is applied to experiments reported in the literature studying the effects of perfusion-based cell culture and/or growth factor supplementation on cell expansion. The qualitative similarities between the simulation and experimental results, even in the absence of proper model calibration, reinforces the generic character of the proposed modeling framework. The model proposed in this study can contribute to the cost efficient production of cell-based TE products, ultimately contributing to their affordability and accessibility.

Abstract Background Genetic mutations that reduce intracellular superoxide production by granulocytes causes chronic granulomatous disease (CGD). These patients suffer from frequent and severe bacterial and fungal infections throughout their early life. Diagnosis is usually made in the first 2 years of life but is sometimes only diagnosed when the patient is an adult although they may have suffered from symptoms since childhood. Case presentation A 26-year-old man was referred with weight loss, fever, hepatosplenomegaly and coughing. He had previously been diagnosed with lymphadenopathy in the neck at age 8 and prescribed anti-tuberculosis treatment. A chest radiograph revealed extensive right-sided consolidation along with smaller foci of consolidation in the left lung. On admission to hospital he had respiratory problems with fever. Laboratory investigations including dihydrorhodamine-123 (DHR) tests and mutational analysis indicated CGD. Stimulation of his isolated peripheral blood neutrophils (PMN) with phorbol 12-myristate 13-acetate (PMA) produced low, subnormal levels of reactive oxygen species (ROS). Aspergillus terreus was isolated from bronchoalveolar lavage (BAL) fluid and sequenced. Conclusions We describe, for the first time, the presence of pulmonary A. terreus infection in an adult autosomal CGD patient on long-term corticosteroid treatment. The combination of the molecular characterization of the inherited CGD and the sequencing of fungal DNA has allowed the identification of the disease-causing agent and the optimal treatment to be given as a consequence.

One of the most important factors that affects the efficiency of the firefighting services in the metropolis, is reducing the response time of an urgent operation. This factor should be considered in site selection of the location of the stations. Spatial distribution of stations should be in a way that the services be provided justly and quickly. By modeling and analyzing the access network and by considering the speed and direction of movements in the network, service area can be determined in a defined time. The purpose of this research is assessing the spatial distribution of firefighting stations in Tehran metropolis by using modeling based on network analysis. Also, this research method is analytical- descriptive and on the basis of graph theory concepts. Areas out of service have been determined and a comparison between the various regions of the city for future developments, was done. Based on the results, region 10 and region 21 had the highest and lowest service area respectively.

Background: A few studies have evaluated the predictive value of fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) in patients with head-and-neck squamous cell carcinoma (HNSCC). Methods: We performed a retrospective study on 32 HNSCC patients, undergoing PET/CT after completion of planned treatment. The PET/CT volumetric parameters measured separately for primary tumor site and nodal or distant metastases. The primary outcome measure of the study was overall survival. Results: There was significant difference between alive and dead patients regarding some of volumetric parameters. Univariate and multivariate Cox regression analyses demonstrated association between metabolic tumor burdens with survival outcome. There was also significant difference in time to survival between patients with metastatic metabolic tumor burden and metastatic total lesion glycolysis (TLG) above and below 50th percentile. Conclusion: PET/CT volumetric parameters including metabolic tumor burden and TLG are significant prognostic markers for overall survival of patients with primary HNSCC after treatment.

Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important role in cancer pathogenesis and in the response to immunotherapy treatments. T lymphocytes are key elements for the response of the immune system to cancer cells and have been associated with prognosis of different cancers. Neutrophils on the other hand, which secrete pro-angiogenic and anti-apoptotic factors, enhance the ability of tumor cells to grow and develop into metastases. We conducted a retrospective study of 120 pediatric brain cancer patients and 171 elective pediatric patients hospitalized in Dana Children's Hospital and Sheba Medical Center. Data on age, sex, treatment, lymphocyte, neutrophil, and monocyte count were collected from routinely performed preoperative blood tests. Neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR) were calculated and significance was determined by paired T test. p < 0.05 was considered as statistically significant. NLR was significantly higher in the pediatric brain cancer patients. The high NLR in pediatric brain cancer patients is the result of a combination of low lymphocytes and high neutrophils. Both of these factors can have a role in cancer development and propagation and also in response to therapy.

Introduction & aim: With respect to the outbreak probability of dangerous infections among the patients, the water sources of dentistry units were taken into consideration, in view of microbial contamination. The objective of this study was to assess of pathogenic organisms of the water used in the dentistry units of Yasuj city. Methods: In this research 120 samples of water from poir and turbine of units (before and after flushing) and two samples of urban water were collected. Sampling was performed on the first weekday (48 hours after the units were switched off) and mid week(16 hours after the units were switched off) before starting work. The samples were cultured on EMB Agar and Blood Agar and incubated at 37oC for purification for Gram positive or Gram negative bacteria and it was identifying with biochemical diagnostic test .Also the samples were counted by standard plate count . Results: The average count of bacteria before flushing in Poir on the first weekday was 5360CFU/L and turbine was 2800 CFU/L and count of bacteria after flushing in Poir on the first weekday was 1040 CFU/L and turbine was 1020 CFU/L .While this result for midweek day : The average count of bacteria before flushing in Poir was 3220 CFU/L and turbine was 2720CFU/L and count of bacteria after flushing in Poir was 1772 CFU/L and turbine was 980 CFU/L . Several samples of before and after flushing were contaminated with E.coli, Pseudomonas ,Proteus, Kelebsiella ,gram positive bacilli ,Streptococci, Staphylococci , Diplo cocci and Yeast. Conclusion: According to the result of this study the contamination rate of the unit’s water was high and it’s rate reduced after flushing. The patients saliva causes water unit contamination and it constitutes biofilm in pipe of unit . Existence of E.coli shows the contamination of water to sewage and staphylococcus explains contamination due to return of the patient’s saliva into suctions. dental units waterlines showed bacterial contamination which was eliminated after flushing.

The importance of physical exercise as an essential factor for urban healthy life and welfare is currently well documented. As a result, the walkability of urban settings gains increasing importance in current planning practices. Nevertheless, there is no standard reliable methodology for assessing walkability of urban environments. This paper attempts to identify and apply such a methodology using District 6 of Tehran metropolitan area as a sample study case. To this end, first the physical properties of this district were fed into a geographic information system (GIS).Then, a set of walkability criteria were selected through a literature survey on this subject. The main set of criteria includes residential density, continuity of access network, mixed use and access to public transportation network, for each of which a GIS layer was formed. Using the analytic hierarchy process (AHP) method, these layers were weighted and combined at neighborhood level. The resulting map shows the overall walkability in diverse areas of district 6. The advantages of this methodology lie in the fact that it employs: all relevant walkability criteria and their subsets; a sound weighted rating methodology for combination of these criteria; and geo-referenced polygons based on urban physical properties rather than simple circles based on recommended radii.

Background: The use of imaging techniques is important for prompt diagnosis and treatment of atypical mycobacterial infections; it also reduces the burden of these infections. The purpose of the present study was to determine the association between computed tomography (CT) scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples. Methods: This cross-sectional, observational, comparative study included 50 consecutive patients with pulmonary infection caused by atypical mycobacteria, who were hospitalized in Masih-Daneshvari Hospital of Tehran, Iran during 2012–2017. The association between CT scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples was determined in these patients. Results: The results demonstrated that the presence of nodules smaller than 5 mm in diameter, consolidation, bronchiectasis, and pleural thickening were related to bacillus count in sputum samples (P < 0.05). Conclusion: Some CT scan findings, such as nodule diameter smaller than 5 mm, consolidation, bronchiectasis, and pleural thickening, may be indicators of atypical mycobacterial infection. Increased number of involved lobes with bronchiectasis can promote early diagnosis in patients with higher smear and culture grading.