In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury

Objective(s): Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment. Material and Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route. Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups. Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications

Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity

Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient's demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5-5.2) years; a total of 66 (40.7%) of these patients initially presented with these manifestations. Patients with cutaneous involvement were generally older at the time of diagnosis [5.0 (1.6-8.0) vs. 3.0 (1.0-7.0) years; p = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, p < 0.001). The overall skin infection rate and the type of dominant pathogens were significantly different among the IEI patients in different phenotypical classifications (p < 0.001). Atopic presentation, including urticaria, was highly prevalent among patients with congenital defects of phagocytes (p = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency (p = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation (p = 0.001) and defects in intrinsic or innate immunity (p = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients (p = 0.21). In conclusion, cutaneous manifestations were observed in nearly 44% of Iranian patients with monogenic IEI. A considerable number of patients with cutaneous involvements developed these disorders as their first manifestation of the disease, which was particularly noticeable in patients with non-syndromic combined immunodeficiency and phagocytic defects. The neglected skin disorders in IEI patients might delay diagnosis, which is generally established within a 3-year interval from the development of skin-related problems. Cutaneous disorders, especially autoimmune features, might indicate a mild prognosis in IEI patients

Gender Differences in Obesogenic Behaviour, Socioeconomic and Metabolic Factors in a Population-based Sample of Iranians: The IHHP Study

This study investigated the gender differences in association of some behavioural and socioeconomic factors with obesity indices in a population-based sample of 12,514 Iranian adults. The mean body mass index (BMI), waist circumference (WC), and the waist-to-hip ratio (WHR) were significantly higher in women than in men. Current and passive smoking had an inverse association with BMI among males whereas current smoking, transportation by a private car, and longer duration of watching television (TV) had a positive association with BMI among females. Current and passive smoking, cycling, and Global Dietary Index (GDI) had an inverse association with WC among males. Higher consumption of fruits and vegetables, current and passive smoking, duration of daily sleep, and GDI had an inverse association with WC among females. Using a private car for transportation had a significant positive association with WHR among both males and females. Living in an urban area, being married, and having a higher education level increased the odds ratio of obesity among both the genders. Non-manual work also increased this risk among males whereas watching TV and current smoking increased this risk among females. Such gender differences should be considered for culturally-appropriate interventional strategies to be implemented at the population level for tackling obesity and associated cardiometabolic risk factors

Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography

18 pags, 11 figs, 5 tabsHere, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXFEL). The high repetition rate of the EuXFEL combined with our mix-and-inject technology enables the initial phase of ceftriaxone binding to the Mycobacterium tuberculosis β-lactamase to be followed using time-resolved crystallography in real time. It is shown how a diffusion coefficient in enzyme crystals can be derived directly from the X-ray data, enabling the determination of ligand and enzyme-ligand concentrations at any position in the crystal volume as a function of time. In addition, the structure of the irreversible inhibitor sulbactam bound to the enzyme at a 66 ms time delay after mixing is described. This demonstrates that the EuXFEL can be used as an important tool for biomedically relevant research.This work was supported by the National Science Foundation Science and Technology Center 'BioXFEL' through award STC-1231306, and in part by the US Department of Energy, Office of Science, Basic Energy Sciences under contract DESC0002164 (AO, algorithm design and development) and by the National Science Foundation under contract Nos. 1551489 (AO, underlying analytical models) and DBI-2029533 (AO, functional conformations). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1450681 to JLO. The work was also supported by funds from the National Institutes of Health grant R01 GM117342-0404. Funding and support are also acknowledged from the National Institutes of Health grant R01 GM095583, from the Biodesign Center for Applied Structural Discovery at ASU, from National Science Foundation award No. 1565180 and the US Department of Energy through Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. KAZ was supported by the Cornell Molecular Biophysics Training Program (NIH T32-GM008267). This work was also supported by the Cluster of Excellence 'CUI: Advanced Imaging of Matter' of the Deutsche Forschungsgemeinschaft (DFG), EXC 2056, project ID 390715994. CFEL is supported by the Gottfried Wilhelm Leibniz Program of the DFG, the 'X-probe' project funded by the European Union 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 637295, the European Research Council, 'Frontiers in Attosecond X-ray Science: Imaging and Spectroscopy (AXSIS)', ERC-2013-SyG 609920, and the Human Frontiers Science Program grant RGP0010 2017. This work is also supported by the AXSIS project funded by the European Research Council under the European Union Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement No. 609920.Peer reviewe

Portal image contrast enhancement

SummaryAimThe delivery of radiation doses to the target volume, while minimizing the dose delivered to normal tissues, is the main objective in radiotherapy. The intention in our study was to enhance the contrast of portal images, in order to increase the accuracy of delineation of the organs in the irradiated field.Materials/MethodsSoftware was written, based on local enhancements to the pixel values in the image matrix. Portal images were digitized by CCD and stored in a format compatible with this program.We applied this program, as an m-file in a MATLAB imaging tool box, to the matrices of the portal images. The imaging parameters, before and after application of the program, were compared.ResultsQuantitative information was obtained from images. Analysis of the means, and standard deviations, of these data showed that the differences between criteria in the two groups of images were significant (p<0.01). In the case of the qualitative analysis, final images scores were based on “special weight”. The result of this test confirmed the superior quality of the post-processed images, from the professional point of view.ConclusionThe superior final images, as judged by experts using three studied parameters (superiority of lung images, superior images of the thorax and its soft tissue), can be used to increase the accuracy of the treatment set up and therefore decrease the likelihood of complications in the normal tissues

Evaluating optimal sites for combined-cycle power plants using GIS: comparison of two aggregation methods in Iran

This study aims to use an integration of GIS and multi-criteria evaluation for combined-cycle power plant site selection and compares two aggregation methods for Iran. The information layers of the criteria are prepared in the GIS environment and then the layers standardised using fuzzy functions in IDRISI. All layers are combined using two conventional methods of fuzzy logic and weighted linear combination; from this information, the suitability maps were created. Results show that only 2.0% of the region under study is scored high-suitable using the fuzzy logic, while 21% of the area is considered as highly suitable when the weighted linear combination is used. Despite this significant difference, both approaches recommend the ideal place in the north and northwest of the study area. In conclusion, integrating GIS and multi-criteria evaluation is a comprehensive approach that improves and strengthens the suitability of site selection studies