Multi-variate multi-objective optimization of production conditions for electro-spun skin scaffold using RSM and investigation of gamma irradiation effects on the properties of the optimized sample.

Developing electro-spun scaffolds with ideal mechanical properties for skin purposes can profit from using the Response Surface Methodology technique to define and optimize the outcome quality and required sterilization for use in vivo. This study investigated the effects of four main independent electrospinning variables for polycaprolactone nanofibers scaffold using multi-variable and multi-objective optimization. It was done to determine significant parameters on responses and find optimal conditions to reach the preferred properties. Young's modulus, elongation-at-break, and tensile strength were the responses. After obtaining appropriate models, the impact share of variables on the responses was determined using Sobol sensitivity analysis. The results showed that flow rate is the most significant parameter of elastic modulus and tensile strength responses, with 76.45 % and 41.27 % impact shares, respectively. The polymer concentration is the following significant parameter on elongation at break, tensile strength and, Young's modulus responses with 64.35 %, 39.485 and, 14.28 % impact share, respectively. Based on the optimized results, a skin scaffold with desired mechanical properties was achieved (under solution concentration of 10 % w/v, flow rate of 2 mL/h, nuzzle-collector distance of 15 cm, and applied voltage of 20 kV). Then it was sterilized with gamma radiation of various doses (25, 40, and 55 kGy) to use in vivo. The SEM analysis indicated no significant change in fibrous morphology due to gamma irradiation at any dosage. FTIR analysis demonstrated the breakup of ester bonds due to gamma irradiation. For samples irradiated by 25 kGy, the crystallinity percentage decreased and chains crosslinking without losing the mechanical stability was dominant. The studies demonstrated that 25 kGy of gamma irradiation could improve the mechanical properties of the optimized PCL skin scaffold, which is very promising for wound healing.

Brownian motion of soft particles near a fluctuating lipid bilayer.

The dynamics of a soft particle suspended in a viscous fluid can be changed by the presence of an elastic boundary. Understanding the mechanisms and dynamics of soft-soft surface interactions can provide valuable insights into many important research fields, including biomedical engineering, soft robotics development, and materials science. This work investigates the anomalous transport properties of a soft nanoparticle near a visco-elastic interface, where the particle consists of a polymer assembly in the form of a micelle and the interface is represented by a lipid bilayer membrane. Mesoscopic simulations using a dissipative particle dynamics model are performed to examine the impact of micelle's proximity to the membrane on its Brownian motion. Two different sizes are considered, which correspond to ≈10-20nm in physical units. The wavelengths typically seen by the largest micelle fall within the range of wavenumbers where the Helfrich model captures fairly well the bilayer mechanical properties. Several independent simulations allowed us to compute the micelle trajectories during an observation time smaller than the diffusive time scale (whose order of magnitude is similar to the membrane relaxation time of the largest wavelengths), this time scale being hardly accessible by experiments. From the probability density function of the micelle normal position with respect to the membrane, it is observed that the position remains close to the starting position during ≈0.05τd (where τd corresponds to the diffusion time), which allowed us to compare the negative excess of mean-square displacement (MSD) to existing theories. In that time range, the MSD exhibits different behaviors along parallel and perpendicular directions. When the micelle is sufficiently close to the bilayer (its initial distance from the bilayer equals approximately twice its gyration radius), the micelle motion becomes quickly subdiffusive in the normal direction. Moreover, the temporal evolution of the micelle MSD excess in the perpendicular direction follows that of a nanoparticle near an elastic membrane. However, in the parallel direction, the MSD excess is rather similar to that of a nanoparticle near a liquid interface.

Effect of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of plasmon-exciton hybrid nanoshells for sensing application.

A proposed nanosensor based on hybrid nanoshells consisting of a core of metal nanoparticles and a coating of molecules is simulated by plasmon-exciton coupling in semi classical approach. We study the interaction of electromagnetic radiation with multilevel atoms in a way that takes into account both the spatial and the temporal dependence of the local fields. Our approach has a wide range of applications, from the description of pulse propagation in two-level media to the elaborate simulation of optoelectronic devices, including sensors. We have numerically solved the corresponding system of coupled Maxwell-Liouville equations using finite difference time domain (FDTD) method for different geometries. Plasmon-exciton hybrid nanoshells with different geometries are designed and simulated, which shows more sensitive to environment refractive index (RI) than nanosensor based on localized surface plasmon. The effects of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of nanosensors to changes in the RI of the environment were investigated. It was found that the cone-like nanoshell with a silver core and quantum emitter shell had the highest sensitivity. The tapered shape of the cone like nanoshell leads to a higher density of plasmonic excitations at the tapered end of the nanoshell. Under specific conditions, two sharp, deep LSPR peaks were evident in the scattering data. These distinguishing features are valuable as signatures in nanosensors requiring fast, noninvasive response.

Effect of Coenzyme Q10 Supplementation on Sarcopenia, Frailty, and Falls: A Scoping Review.

Coenzyme Q10 (CoQ10) is well-known for its antioxidant effects and has been highlighted in research related to aging and many age-related conditions. However, there is limited research on the benefit of CoQ10 supplementation in conditions impacting the physical robustness of older adults, such as sarcopenia, frailty, falls and osteoporosis. This scoping review identified and summarized 4 studies that assessed the effects of exogenous CoQ10 on outcomes relating to sarcopenia, frailty, and falls. Results of the studies showed statistically significant improvements in a variety of physical robustness related outcomes, however several limitations of these studies prevent conclusive recommendations from being drawn regarding the benefit of CoQ10 supplementation in these conditions. A well-designed randomized control trial assessing the benefit of CoQ10 supplementation on clinically relevant outcomes related to sarcopenia, frailty, and falls may be warranted.

Comparison of IgA Antibody Titer Induced by Human-Bovine Rotavirus Candidate Vaccine with Bovine Rotavirus and Rotarix.

Rotavirus (RV) is the most common cause of acute gastroenteritis in early childhood worldwide. Gastroenteritis is a preventable disease by the vaccine, and vigorous efforts were made to produce attenuated oral rotavirus vaccines. In recent years, despite the existence of three types of live attenuated rotavirus vaccines, several countries, such as China and Vietnam, have intended to produce indigenous vaccines based on rotavirus serotypes circulating among their population. In this study, the immunogenicity of homemade human-bovine reassortant RV candidate vaccine was tested in an animal model. Rabbits were randomly distributed into eight experimental groups with three animals per group. Afterward, three rabbits in each test group designated as P1, P2, and P3 were experimentally inoculated with the 106, 107, and 108 tissue culture infectious dose 50 (TCID50) of the reassortant virus, respectively. The N1 group received the reassortant rotavirus vaccine containing 107 TCID50+zinc. The N2, N3, and N4 groups received rotavirus vaccine strain, RV4 human rotavirus, and bovine rotavirus strain, respectively, and the control group received phosphate-buffered saline. It is noteworthy that three rabbits have been included in each group. The IgA total antibody titer was measured and evaluated by non-parametric Mann-Whitney and Kruskal-Wallis tests. The antibody titer produced in the studied groups did not significantly differ. The candidate vaccine showed immunogenicity, protectivity, stability, and safety. The findings of this study indicated a critical role of IgA production, which can induce immunity against a gastroenteritis viral pathogen. Regardless of purification, candidate reassortant vaccine and cell adapted animal strains could be used as a vaccine candidate for production.

A comprehensive sustainable development framework; community capitals and village-cooperative initiative.

Considering the cooperative sector capabilities in organizing rural people, primarily focusing on empowering manpower and adopting a sustainable approach to basic resources (water and soil), village-cooperative initiative has emerged as a new concept by registering and forming 4565 new cooperatives in Iran's rural regions. The present research which was conducted in two qualitative and quantitative phases designed a new model by integrating the new village-cooperative approach along with the sustainable livelihood's framework theory. The study sample of the qualitative phase included 32 theorists of the village-cooperative initiative. To analyze the data, the grounded theory and three-step process of open coding, axial coding and selective coding were used using MAXqda18 software. Finally, a paradigm model was designed whose most important components included causal conditions (shocks and seasonal conditions), contextual conditions (trends and governmental support), intervening conditions (control and market development), central categories (sustainable livelihoods with a village- cooperative approach), strategies (coping and adaptation) and consequences (creating jobs, establishing cooperatives, supporting smart agriculture and strengthening social capital). The statistical quantitative phase population consisted of cooperatives members in the village-cooperative initiative (N=405), being selected through Cochran's formula with proportional sampling method summing up to198 people from 5 provinces. The data collection tool was a researcher-made questionnaire whose validity and reliability were confirmed. The Bayesian structural equation modeling was used to analyze the data. The results of the research quantitative phase showed that the variables of financial capital, physical capital, social capital, coping and adaptation strategies, human capital and natural capital were the most effective variables on village-cooperative initiative members' sustainable livelihoods, respectively. Finally, a hybrid model based on the qualitative and quantitative studies was designed and suggestions were made; for instance, the creation of suitable grounds for off-farm activities such as rural industries and ecotourism.

A Comparative Morphometric Study on Odontobuthus bidentatus and Odontobuthus doriae (Scorpionida: Buthidae) in Iran.

Scorpions are one of the most venomous animals which cause serious public health problems. The sting of scorpions can sometimes be fatal depending on the scorpion species involved. So far, sixty-six (66) scorpion species have been identified in Iran. Annually, about 40-50000 cases of scorpionism are reported in Iran. Odontobuthus doriae and O. bidentatus are among the most medically important scorpion species in Iran, and they are very similar to each other in coloration, carination, and trichobotrial patterns. This morphometric study aimed to compare some of the important morphological characteristics in order to identify the key differences between these two species. A total of 45 morphological characters were measured using calipers and stereomicroscope, and 55 morphological characters and ratios (relative of length to width ratio of morphological characters of scorpions) were analyzed. The independent sample t-test in SPSS software (version 24) was used for the statistical analyses in this study. The mean total length, carapace width, length of fixed and moveable fingers, and chelicerae length of O. doriae were greater than those of O. bidentatus in our study area. The morphological measurements displayed a clear distinction between O. doriae and O. bidentatus in our study area; therefore, they can be used as morphological identification keys for distinguishing between these two species.

The TRIM proteins in cancer: from expression to emerging regulatory mechanisms

New clinical evidence suggests that dysregulation of the ubiquitin-mediated destruction of tumor suppressors or oncogene products is probably engaged in the etiology of leukemia and carcinoma. The superfamily of tripartite motif (TRIM)-containing protein family is among the biggest recognized single protein RING finger E3 ubiquitin ligases that are considered vital carcinogenesis regulators, which is not shocking since TRIM proteins are engaged in various biological processes, including cell growth, development, and differentiation; hence, TRIM proteins’ alterations may influence apoptosis, cell proliferation, and transcriptional regulation. In this review article, the various mechanisms through which TRIM proteins exert their role in the most prevalent malignancies including lung, prostate, colorectal, liver, breast, brain cancer, and leukemia are summarized.

Comparison of multiphase data from CT perfusion vs clinical 4-phase CT scans with respect to image quality, lesion detection, and LI-RADS classification in HCC patients.

PURPOSE: The aim of this study was to assess the image quality and diagnostic performance of reconstructed arterial (A) and portal venous (PV) phases in computed tomography perfusion (CTP) scans compared to the corresponding phases in standard 4-phase CT and to assess the utility for LI-RADS classification using CTP and 4-phase 4CT. METHODS: A total of 26 scans with each method (CTP and 4-phase CT) from 19 hepatocellular carcinoma patients were analyzed and compared. Arterial and PV phases reconstructed by advanced modeled iterative reconstruction at strength 4 (ADMIRE 4) from raw CTP data were compared with image sets from arterial and PV phases of 4-phase CT (ADMIRE 3) in the same patient with respect to image quality. RESULTS: Quantitative image analysis showed that reconstructed CTP datasets were equivalent to 4-phase CT image sets. Qualitative image analysis revealed similar lesion detection rates with the 2 methods for patients with an abdominal diameter ≤36 cm and body weight <90 kg, but lower detection rates with CTP for patients with an abdominal diameter >37 cm. There was no difference in Liver Imaging Reporting and Data System (LI-RADS) classifications between the 2 methods. CONCLUSION: Reconstructed CTP images can potentially replace 4-phase CT images in patients weighing <90 kg and with a body diameter <37 cm, as the 2 methods are comparable in terms of quantitative image quality and ability to detect and classify lesions based on LI-RADS criteria.

The TRIM proteins in cancer: from expression to emerging regulatory mechanisms.

New clinical evidence suggests that dysregulation of the ubiquitin-mediated destruction of tumor suppressors or oncogene products is probably engaged in the etiology of leukemia and carcinoma. The superfamily of tripartite motif (TRIM)-containing protein family is among the biggest recognized single protein RING finger E3 ubiquitin ligases that are considered vital carcinogenesis regulators, which is not shocking since TRIM proteins are engaged in various biological processes, including cell growth, development, and differentiation; hence, TRIM proteins' alterations may influence apoptosis, cell proliferation, and transcriptional regulation. In this review article, the various mechanisms through which TRIM proteins exert their role in the most prevalent malignancies including lung, prostate, colorectal, liver, breast, brain cancer, and leukemia are summarized.

Cytotoxic Effect of Biebersteinia multifida Alcoholic Extracts on MCF-7, HeLa, and A2780 Cell Lines.

Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of their minimal side effects, although there is little scientific knowledge about them. One of these remedies utilizes the root of Biebersteinia multifidi that has been used for years in Iran to treat different chronic genital diseases. The current study examined the effects of methanolic and ethanolic extracts of B. multifida (induction of necrosis and apoptosis) on breast cancer (MCF-7), ovarian cancer (A2780), and human cervix cancer (HeLa) cell lines in comparison with normal breast cells. These effects were determined to be morphological alterations in cell light microscopy, by flow cytometry (staining with annexin V and propidium iodide), and by measuring live cells and inhibition concentrations by MTT assay. IC50 of B. multifida on the MCF-7 cell line (methanolic extract) was 400 µg/ml and for A2780 was 250 µg/ml. The IC50 amount of B. multifida on the MCF-7 cell line (ethanolic extract) was 750 µg/ml and 1500 for A2780. Results demonstrated that apoptosis and necrosis occurred in MCF-7 and A2780 following the addition of ethanolic and methanolic extracts of B. multifida to the medium. These findings confirmed the anti-cancer effects of mehthanolic extracts of Biebersteinia multifida root and its safety for normal cells; thus, it can be applied in cancer therapy as a novel medication.

A Review on Rubella Vaccine: Iran (1975-2010).

The first Attenuated rubella vaccine was developed by Parkman and Meyer in 1966. Ten years later in the 1975s, the rubella vaccine was developed in Razi Vaccine and serum research institute) RVSRI). In 1977, the rubella TAKAHASHI vaccine successfully passed the clinical trial and was initially used voluntarily only in the private sector. Since 1987, the administration of rubella as MMR (Measles/AIK-C; Rubella/TAKAHASHI; Mumps/HOSHINO) strain vaccine has been included in the immunization program in Iran. This review article focused on the development and production of the rubella TAKAHASHI/HDC vaccine in RVSRI. The herd immunity and rubella cases were investigated in the pre- and post-vaccine era. The effectiveness and proper coverage of the rubella vaccine led to the elimination of rubella from Iran in 2019. The current study aimed to assess local rubella vaccine manufacturing and its consequences on rubella elimination from Iran, using various search engines. A complete search was carried out in medical databases, including PubMed, Scopus, Web of Science, Scientific Information Database, IranMedex, Magiran, and Google Scholar. Within 1972-1975, Rubella TAKAHASHI/HDC vaccine was developed by RVSRI and successfully passed clinical trial in 1977. Over the four last decades (1980-2020), more than 40 million infants, young, and adults were vaccinated by million doses of local Rubella, measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine in Iran. In 1972, the pre-vaccine era, the overall sensitivity to rubella infection was 69% in one-year-old Iranian children and 23% in childbearing women. The use of a safe, inexpensive, and effective vaccine increased herd immunity to 95% (85%-99%) in our country. During the last two decades, we have witnessed a 91% decline in the confirmed rubella cases, from 1124 in 2000 to 33 cases in 2018. The current article presented the process of vaccine development, tracked it through more than four decades, and discussed disease status before and after the rubella vaccine era, as well as the history of its elimination from Iran. The effectiveness of the local Razi Rubella vaccine resulted in a significant increase in seroprevalence in Iran. Expanded vaccination against rubella, usually with measles, has led to the elimination of Rubella from Iran as confirmed by World Health Organization in 2019.

The synergistic effect of turmeric aqueous extract and chitosan against multidrug-resistant bacteria.

We aimed to investigate the antibacterial and antibiofilm effects of turmeric and chitosan against the planktonic and biofilm forms of multidrug-resistant (MDR) bacteria. A group of MDR bacteria, including clinical isolates of methicillin-resistant Staphylococcus aureus, carbapenem-resistant Pseudomonas, carbapenem-resistant Enterobacteriaceae and AmpC-producing Enterobacteriaceae, were collected by phenotypic and genotypic assays. The broth microdilution method was used to investigate the MIC of turmeric aqueous extract and chitosan. To investigate the synergistic effect of the combination of these natural compounds, we used the checkerboard assay. According to the results of this study, turmeric and chitosan showed inhibitory effects on MDR bacteria, especially on the planktonic form of methicillin-resistant S. aureus as a Gram-positive compared to tested Gram-negative bacteria (carbapenem-resistant Pseudomonas, carbapenem-resistant Enterobacteriaceae and AmpC-producing Enterobacteriaceae). The antibiofilm effect of turmeric and chitosan was found more often in carbapenem-resistant Pseudomonas isolates. There was no significant difference between the tested Gram-negative bacteria because most of the tested strains were inhibited in 512 and 1024 µg/mL concentrations of chitosan and turmeric aqueous extract. In this study, turmeric aqueous extract and chitosan exhibited significant antibacterial and antibiofilm properties. However, the effect of these compounds should be investigated using in vivo models for use in pharmaceutical and disinfectant formulations.

Preparation of immunomagnetic beads coupled with a rhodamine hydrazine immunosensor for the detection of Mycobacterium avium subspecies paratuberculosis in bovine feces, milk, and colostrum.

The aim of this study was to develop and evaluate a method for detecting Mycobacterium avium ssp. paratuberculosis (MAP) bacteria in bovine fecal, milk, and colostrum samples using immunomagnetic beads (IMB) and a rhodamine hydrazone immunosensor. Immunomagnetic beads were prepared by using purified antibodies from hyperimmunized sera that were coupled to Fe nanoparticles with diethylene triamine pentaacetic acid (DTPA) or ethyl (dimethyl aminopropyl) carbodiimide (EDC)-N-hydroxy succinimide (NHS) as linkers. Rhodamine hydrazone particles were synthesized and coupled to IgY anti-MAP antibodies using DTPA or EDC-NHS linkers. Separation efficiency of the IMB was tested on bovine fecal, milk, and colostrum samples experimentally contaminated with MAP. The studied methods were evaluated on their ability to detect MAP and separate bacteria in complex mediums. The ELISA results indicated 95% efficacy in antibody coupling to IMB, with the DTPA-IMB method being more efficient than the EDC-NHS-IMB method. By using the DTPA-IMB method, MAP bacteria were successfully recovered from fecal, milk, and colostrum samples. The DTPA-IMB method used in combination with the rhodamine hydrazone immunosensor had a limit of detection equal to 30 and 30,000 MAP cells/mL using chromogenic and fluorescent properties, respectively. Combining the DTPA-IMB separation method with the rhodamine hydrazone immunosensor provides a fast, sensitive, and cost-beneficial method for detecting MAP in bovine feces, milk, and colostrum.

Identifying priority core habitats and corridors for effective conservation of brown bears in Iran.

Iran lies at the southernmost range limit of brown bears globally. Therefore, understanding the habitat associations and patterns of population connectivity for brown bears in Iran is relevant for the species' conservation. We applied species distribution modeling to predict habitat suitability and connectivity modeling to identify population core areas and corridors. Our results showed that forest density, topographical roughness, NDVI and human footprint were the most influential variables in predicting brown bear distribution. The most crucial core areas and corridor networks for brown bear are concentrated in the Alborz and Zagros Mountains. These two core areas were predicted to be fragmented into a total of fifteen isolated patches if dispersal of brown bear across the landscape is limited to 50,000 cost units, and aggregates into two isolated habitat patches if the species is capable of dispersing 400,000 cost units. We found low overlap between corridors, and core habitats with protected areas, suggesting that the existing protected area network may not be adequate for the conservation of brown bear in Iran. Our results suggest that effective conservation of brown bears in Iran requires protection of both core habitats and the corridors between them, especially outside Iran's network of protected areas.

Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.

The impact of cervical cytobrush sampling on cervico-vaginal immune parameters and microbiota relevant to HIV susceptibility.

The immunology and microbiota of the female genital tract (FGT) are key determinants of HIV susceptibility. Cervical cytobrush sampling is a relatively non-invasive method permitting the longitudinal assessment of endocervical immune cells, but effects on FGT immunology are unknown. Blood, cervico-vaginal secretions and cervical cytobrushes were collected from sexually transmitted infection (STI)-free women at baseline and after either 6 hours or 48 hours. Endocervical immune cell subsets were assessed by flow cytometry, and pro-inflammatory cytokines by multiplex ELISA. The density of Lactobacillus species and key bacterial vaginosis-associated bacterial taxa were determined by qPCR. Paired changes were assessed before and after cytobrush sampling. After 6 hours there were significant increases in CD4 + T cell, antigen presenting cell (APC) and neutrophil numbers; APC elevations persisted at 48 hours, while neutrophil and CD4 + T cell numbers returned to baseline. In addition, pro-inflammatory cytokine levels were increased at 6 hours and returned to baseline by 48 hours. No significant changes were observed in the absolute abundance of Lactobacillus species or BV-associated bacteria at either time point. Overall, cytobrush sampling altered genital immune parameters at 6 hours, but only APC number increases persisted at 48 hours. This should be considered in longitudinal analyses of FGT immunology.

Brown bear attacks on humans: a worldwide perspective.

The increasing trend of large carnivore attacks on humans not only raises human safety concerns but may also undermine large carnivore conservation efforts. Although rare, attacks by brown bears Ursus arctos are also on the rise and, although several studies have addressed this issue at local scales, information is lacking on a worldwide scale. Here, we investigated brown bear attacks (n = 664) on humans between 2000 and 2015 across most of the range inhabited by the species: North America (n = 183), Europe (n = 291), and East (n = 190). When the attacks occurred, half of the people were engaged in leisure activities and the main scenario was an encounter with a female with cubs. Attacks have increased significantly over time and were more frequent at high bear and low human population densities. There was no significant difference in the number of attacks between continents or between countries with different hunting practices. Understanding global patterns of bear attacks can help reduce dangerous encounters and, consequently, is crucial for informing wildlife managers and the public about appropriate measures to reduce this kind of conflicts in bear country.