Search results for: ineffective tissue cerebral perfusion

Authors: Afaf Alharbi, Qianni Zhang

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The identification of malignant tissue in histopathological slides holds significant importance in both clinical settings and pathology research. This paper introduces a methodology aimed at automatically categorizing cancerous tissue through the utilization of a multiple-instance learning framework. This framework is specifically developed to acquire knowledge of the Bernoulli distribution of the bag label probability by employing neural networks. Furthermore, we put forward a neural network based permutation-invariant aggregation operator, equivalent to attention mechanisms, which is applied to the multi-instance learning network. Through empirical evaluation of an openly available colon cancer histopathology dataset, we provide evidence that our approach surpasses various conventional deep learning methods.

Keywords: attention multiple instance learning, MIL and transfer learning, histopathological slides, cancer tissue classification

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Authors: Sunil Dehipawala, Aregama Sirisumana, stephan Smith, P. Schneider, G. Tremberger Jr, D. Lieberman, Todd Holden, T. Cheung

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The arsenic and iron environments in different growth stages have been studied with EXAFS and XANES using Brookhaven Synchrotron Light Source. Collard Greens plants were grown and tissue samples were harvested. The project studied the EXAFS and XANES of tissue samples using As and Fe K-edges. The Fe absorption and the Fourier transform bond length information were used as a control comparison. The Fourier transform of the XAFS data revealed the coexistence of As (III) and As (V) in the As bonding environment inside the studied plant tissue samples, although the soil only had As (III). The data suggests that Collard Greens has a novel pathway to handle arsenic absorption in soil.

Keywords: EXAFS, fourier transform, metalloproteins, XANES

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Authors: Dong Nyoung Heo, Il Keun Kwon

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Three-dimensional (3D) technology is a promising method for bone tissue engineering. In order to enhance bone tissue regeneration, it is important to have ideal 3D constructs with biomimetic mechanical strength, structure interconnectivity, roughened surface, and the presence of chemical functionality. In this respect, a 3D printing system combined with cold atmospheric plasma (CAP) was developed to fabricate a 3D construct that has a rough surface with polar functional chemical groups. The CAP-etching process leads to oxidation of chemical groups existing on the polycaprolactone (PCL) surface without conformational change. The surface morphology, chemical composition, mean roughness of the CAP-treated PCL surfaces were evaluated. 3D printed constructs composed of CAP-treated PCL showed an effective increment in the hydrophilicity and roughness of the PCL surface. Also, an in vitro study revealed that CAP-treated 3D PCL constructs had higher cellular behaviors such as cell adhesion, cell proliferation, and osteogenic differentiation. Therefore, a 3D printing system with CAP can be a highly useful fabrication method for bone tissue regeneration.

Keywords: bone tissue engineering, cold atmospheric plasma, PCL, 3D printing

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Authors: Michelangelo Liban, Debbie Liquete

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A 70-year-old right-handed Filipina was seen by the Neurology service due to a new onset headache, bi-occipital in location, dull squeezing in character with a pain score of 8/10 with associated nausea and one episode of non-projectile, which provided no relief. Due to the alarming features of the headache despite the absence of risk factors and an essentially normal neurologic examination, a cranial CTA+CTV was done, which revealed a small left frontal and small right pontine hyper density with minimal perilesional edema. Findings also revealed filling defects in the straight and right transverse sinus and a consideration of hypoplastic left transverse sinus with no definite evidence of aneurysm nor A-V malformation. She had normal levels of D-Dimer, Protein C, ANA and Anti-DS DNA but had a low Protein S of 56% (N.V is 70-120%). Antithrombin, homocysteine and Factor V Leiden were not done due to unavailability of the tests. She was then treated as a case of Cerebral Venous Thrombosis with multiple hemorrhage from venous infraction and was given anticoagulants which provided relief of the headache. She did not manifest with any further cortical, bulbar or sensorimotor deficits hence was discharged improved after 15 hospital days. To our knowledge, there are no case reports of patients with CVT from Protein S deficiency and venous anomaly that presented with multiple hemorrhage from venous infarction, more so affecting the brainstem. In this paper, a rare location of CVT in a newly diagnosed Protein S deficient patient is presented together with an uneventful course and favorable outcome.

Keywords: protein S deficiency, cerebral venous thrombosis, pontine hemorrhage from venous infarction, elderly

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Authors: Bummo Ahn

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Palpation is widely used to measure soft tissue firmness or stiffness in the living condition in order to apply detection, diagnosis, and treatment of tumors, scar tissue, abnormal muscle tone, or muscle spasticity. Since these methods are subjective and depend on the proficiency level, it is concluded that there are other diagnoses depending on the condition of the experts and the results are not objective. The mechanical property obtained by using the elasticity of the tissue is important to calculate a predictive variable for monitoring abnormal tissues. If the mechanical load such as reaction force on the foot increases in the same region under the same conditions, the mechanical property of the tissue is changed. Therefore, objective diagnosis is possible not only for experts but also for patients using this quantitative information. Furthermore, the portable system also allows non-experts to easily diagnose at home, not in hospitals or institutions. In this paper, we introduce a portable palpation system that can be used to measure the mechanical properties of human tissue, which can be applied to monitor diabetic foot ulceration patients with measuring the mechanical property change of foot tissue. The system was designed to be smaller and portable in comparison with the conventional palpation systems. It is consists of the probe, the force sensor, linear actuator, micro control unit, the display module, battery, and housing. Using this system, we performed validation experiments by applying different palpations (3 and 5 mm) to soft tissue (silicone rubber) and measured reaction forces. In addition, we estimated the elastic moduli of the soft tissue against different palpations and compare the estimated elastic moduli that show similar value even if the palpation depths are different.

Keywords: palpation probe, portable, diabetic foot ulceration, monitoring, mechanical property

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Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India

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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.

Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: A. Gharaei, R. Karami

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Rutilus frisii Kutum was exposed to various concentrations of mercuric chloride in water to determine its acute toxicity and bioaccumulation. We carried out ten treatments with three replicates and one control for each of the chemicals using the static O. E. C. D. method in 55-liter-tanks each containing 14 fingerlings. During the experiments, the average pH was recorded as 7.8, total hardness was measured to be 255 mg/l, the average water temperature was 27±1 degrees centigrade and dissolved oxygen was 7.2 mg/l. Mean LC50 values of Hgcl2 for juvenile R. frisii kutum with mean weight 1±0.2 gr were 0.102 and 0.86 mgHg/l at 24h and 96h, respectively. The bioaccumulation values during 24h in tissue, kidney, and gill were 1.55, 16.1, and 22.7 mgHg/l, respectively. So, these values during 96h were 2.8, 16.8, and 26.65 mgHg/l, respectively. The bioconcentration factors in tissue, kidney, and gill during 24h were 14.75, 153.39, and 216.11 and so during 96h were 33.8, 198.1, and 313.5 times. These results show that bioaccumulation was highest in the gill and then kidney and tissue, respectively. This study suggested that between mercury concentrations of water with bioaccumulation in tissue more than kidney and gill.

Keywords: HgCl2, LC5096h, bioaccumulation, Rutilus frisii Kutum, Caspian Sea

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Authors: Yifan Lu, Ying Cui, Ying Zhu, Edward S. Lu, Rebecca Zeng, Rohan Bajaj, Raviv Katz, Rongrong Le, Jay C. Wang, John B. Miller

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Purpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcome and is associated with an increased risk of cerebral stroke and cardiovascular events. Fluorescein angiography (FA) is the traditional diagnostic tool for RAO; however, wide-field swept-source optical coherence tomography angiography (WF SS-OCTA), as a nascent imaging technology, is able to provide quick and non-invasive angiographic information with a wide field of view. In this study, we looked for associations between OCT-A vascular metrics and visual acuity in patients with prior diagnosis of RAO. Methods: Patients with diagnoses of central retinal artery occlusion (CRAO) or branched retinal artery occlusion (BRAO) were included. A 6mm x 6mm Angio and a 15mm x 15mm AngioPlex Montage OCT-A image were obtained for both eyes in each patient using the Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm x 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. The average measurement of the central foveal subfield, inner ring, and outer ring was calculated for each parameter. Non-perfusion area (NPA) was manually measured using 15mm x 15mm Montage images. A linear regression model was utilized to identify a correlation between the imaging metrics and visual acuity. A P-value less than 0.05 was considered to be statistically significant. Results: Twenty-five subjects were included in the study. For RAO eyes, there was a statistically significant negative correlation between vision and retinal thickness as well as superficial capillary plexus vessel density (SCP VD). A negative correlation was found between vision and deep capillary plexus vessel density (DCP VD) without statistical significance. There was a positive correlation between vision and choroidal thickness as well as choroidal volume without statistical significance. No statistically significant correlation was found between vision and the above metrics in contralateral eyes. For NPA measurements, no significant correlation was found between vision and NPA. Conclusions: This is the first study to our best knowledge to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between various retinal vascular imaging metrics and visual outcomes. Further investigations should explore the associations between these imaging findings and cardiovascular risk as RAO patients are at elevated risk for symptomatic stroke. The results of this study provide a basis to understand the structural changes involved in visual outcomes in RAO. Furthermore, they may help guide management of RAO and prevention of cerebral stroke and cardiovascular accidents in patients with RAO.

Keywords: OCTA, swept-source OCT, retinal artery occlusion, Zeiss Plex Elite

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Authors: Alisan Kayabolen, Dilek Keskin, Ferit Avcu, Andac Aykan, Fatih Zor, Aysen Tezcaner

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Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, only very thin implants can be used in vivo since vascularization is still a problem for thick implants. Another problem is finding a biocompatible scaffold with good mechanical properties. In this study, the aim is to develop a thick vascularized adipose tissue that will integrate with the host, and perform its in vitro and in vivo characterizations. For this purpose, a hydrogel of decellularized adipose tissue (DAT) and fibroin was produced, and both endothelial cells and adipocytes that were differentiated from adipose derived stem cells were encapsulated in this hydrogel. Mixing DAT with fibroin allowed rapid gel formation by vortexing. It also provided to adjust mechanical strength by changing fibroin to DAT ratio. Based on compression tests, gels of DAT/fibroin ratio with similar mechanical properties to adipose tissue was selected for cell culture experiments. In vitro characterizations showed that DAT is not cytotoxic; on the contrary, it has many natural ECM components which provide biocompatibility and bioactivity. Subcutaneous implantation of hydrogels resulted with no immunogenic reaction or infection. Moreover, localized empty hydrogels gelled successfully around host vessel with required shape. Implantations of cell encapsulated hydrogels and histological analyses are under study. It is expected that endothelial cells inside the hydrogel will form a capillary network and they will bind to the host vessel passing through hydrogel.

Keywords: adipose tissue engineering, decellularization, encapsulation, hydrogel, vascularization

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Authors: Hassan Athari, Abdurrahim Bolukbasi, Dogan Ciloglu

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This study represented the respiratory alveoli system, and determined the trajectory of inhaled particles more accurately using the modified three-dimensional model with deformable walls of alveoli. The study also considered the tissue tension in the model to demonstrate the effect of lung. Tissue tensions are transferred by the lung parenchyma and produce the pressure gradient. This load expands the alveoli and establishes a sub-ambient (vacuum) pressure within the lungs. Thus, at the alveolar level, the flow field and movement of alveoli wall lead to an integrated effect. In this research, we assume that the three-dimensional alveolus has a visco-elastic tissue (walls). For accurate investigation of pulmonary tissue mechanical properties on particle transport and alveolar flow field, the actual relevance between tissue movement and airflow is solved by two-way FSI (Fluid Structure Interaction) simulation technique in the alveolus. Therefore, the essence of real simulation of pulmonary breathing mechanics can be achieved by developing a coupled FSI computational model. We, therefore conduct a series of FSI simulations over a range of tissue models and breathing rates. As a result, the fluid flows and streamlines have changed during present flexible model against the rigid models and also the two-way coupling particle trajectories have changed against the one-way particle coupling.

Keywords: FSI, two-way particle coupling, alveoli, CDF

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Authors: Ana Teixeira, Joao Orvalho

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This paper describes experiments using Scratch games, to check the feasibility of employing cerebral palsy users gestures as an alternative of interaction with a computer carried out by students of Master Human Computer Interaction (HCI) of IPC Coimbra. The main focus of this work is to study the usability of a Web Camera as a motion tracking device to achieve a virtual human-computer interaction used by individuals with CP. An approach for Human-computer Interaction (HCI) is present, where individuals with cerebral palsy react and interact with a scratch game through the use of a webcam as an external interaction device. Motion tracking interaction is an emerging technology that is becoming more useful, effective and affordable. However, it raises new questions from the HCI viewpoint, for example, which environments are most suitable for interaction by users with disabilities. In our case, we put emphasis on the accessibility and usability aspects of such interaction devices to meet the special needs of people with disabilities, and specifically people with CP. Despite the fact that our work has just started, preliminary results show that, in general, computer vision interaction systems are very useful; in some cases, these systems are the only way by which some people can interact with a computer. The purpose of the experiments was to verify two hypothesis: 1) people with cerebral palsy can interact with a computer using their natural gestures, 2) scratch games can be a research tool in experiments with disabled young people. A game in Scratch with three levels is created to be played through the use of a webcam. This device permits the detection of certain key points of the user’s body, which allows to assume the head, arms and specially the hands as the most important aspects of recognition. Tests with 5 individuals of different age and gender were made throughout 3 days through periods of 30 minutes with each participant. For a more extensive and reliable statistical analysis, the number of both participants and repetitions in further investigations should be increased. However, already at this stage of research, it is possible to draw some conclusions. First, and the most important, is that simple scratch games on the computer can be a research tool that allows investigating the interaction with computer performed by young persons with CP using intentional gestures. Measurements performed with the assistance of games are attractive for young disabled users. The second important conclusion is that they are able to play scratch games using their gestures. Therefore, the proposed interaction method is promising for them as a human-computer interface. In the future, we plan to include the development of multimodal interfaces that combine various computer vision devices with other input devices improvements in the existing systems to accommodate more the special needs of individuals, in addition, to perform experiments on a larger number of participants.

Keywords: motion tracking, cerebral palsy, rehabilitation, HCI

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Authors: K. M. Damodara Gowda

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Background: Maternal health and nutrition are considered as the predominant factors influencing brain functional development. If the mother is free of illness and genetic defects, maternal nutrition would be one of the most critical factors affecting the brain development. Calorie restrictions cause significant impairment in spatial learning ability and the levels of Brain Derived Neurotrophic Factor (BDNF) in rats. But, the mechanism by which the prenatal under-nutrition leads to impairment in brain learning and memory function is still unclear. In the present study, prenatal Astaxanthin supplementation on BDNF level, spatial learning and memory performance in the offspring’s of normal, calorie restricted and Astaxanthin supplemented rats was investigated. Methodology: The rats were administered with 6mg and 12 mg of astaxanthin /kg bw for 21 days following which acquisition and retention of spatial memory was tested in a partially-baited eight arm radial maze. The BDNF level in different regions of the brain (cerebral cortex, hippocampus and cerebellum) was estimated by ELISA method. Results: Calorie restricted animals treated with astaxanthin made significantly more correct choices (P < 0.05), and fewer reference memory errors (P < 0.05) on the tenth day of training compared to offsprings of calorie restricted animals. Calorie restricted animals treated with astaxanthin also made significantly higher correct choices (P < 0.001) than untreated calorie restricted animals in a retention test 10 days after the training period. The mean BDNF level in cerebral cortex, Hippocampus and cerebellum in Calorie restricted animals treated with astaxanthin didnot show significant variation from that of control animals. Conclusion: Findings of the study indicated that memory and learning was impaired in the offspring’s of calorie restricted rats which was effectively modulated by astaxanthin at the dosage of 12 mg/kg body weight. In the same way the BDNF level at cerebral cortex, Hippocampus and Cerebellum was also declined in the offspring’s of calorie restricted animals, which was also found to be effectively normalized by astaxanthin.

Keywords: calorie restiction, learning, Memory, Cerebral cortex, Hippocampus, Cerebellum, BDNF, Astaxanthin

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Authors: Basuki Supartono

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Introduction: Diabetic wound risks limb amputation, and the healing remains challenging. Chronic Hyperglycemia caused the insufficient inflammatory response and impaired ability of the cells to regenerate. Tissue Engineering Technique is mandatory. Methods: Tissue engineering (TE)-based therapy Utilizing mononuclear cells, plasma rich platelets, and collagen applied on the damaged tissue Results: TE technique resulting in acceptable outcomes. The wound healed completely in 2 months. No adverse effects. No allergic reaction. No morbidity and mortality Discussion: TE-based therapy utilizing mononuclear cells, plasma rich platelets, and collagen are safe and comfortable to fix damaged tissues. These components stop the chronic inflammatory process and increase cells' ability for regeneration and restoration of damaged tissues. Both of these allow the wound to regenerate and heal. Conclusion: TE-based therapy is safe and effectively treats unhealed diabetic lesion.

Keywords: diabetic foot lesion, tissue engineering technique, wound healing, stemcells

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Authors: Hang T. T. Tran, Ha T. Le, Hanh T. P. Tran, Hung V. Cao, Giang T. H. Nguyen, Dien M. Tran, Tobias Alfvén, Linus Olson

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Background: Hypoxic Ischemic Encephalopathy is one of the major causes of neonatal death and those who survive with severe encephalopathy are more likely to develop adverse long-term outcomes such as neurocognitive impairment and cerebral palsy, which is a huge burden, especially in low-middle income countries. It is important to have a long-term follow-up for early detection and promote early intervention for these groups of high-risk infants. Aim: To determine the neurological outcome of cooling infants at 18 months and identify an optimized neurological examination scale for Hypoxic Ischemic Encephalopathy infants in Vietnam. Method: Descriptive study of neurodevelopmental outcomes at 18 months of HIE infants who underwent therapeutic hypothermia treatment in Vietnam. All survived cooling infants were assessed at discharge and at 6, 12, and 18 months by a pediatric physical therapist and a neurologist using two assessment tools: Ages and Stages Questionnaires and the Hammersmith Infant Neurological Examination scale to detect impairments and promote early intervention for those who require it. Results: During a 3-year period, a total of 130 neonates with moderate to severe HIE underwent therapeutic hypothermia treatment using Phase change material mattress (65% moderate, 35% severe – Sarnat). 43 (33%) died during hospitalization and infancy; among survivors, 69 (79%) completed 3 follow-ups at 18 months. At 18 months, 25 had cerebral palsy, 11 had mild delayed neurodevelopment. At each time-point, infants with a normal/mildly delayed neurodevelopment had significantly higher Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination scores (p<0.05) than those with cerebral palsy. Conclusion: The study showed that the Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination is a helpful tool in the process of early diagnosis of infants at low and high neurological risk and identifying those infants needing specific rehabilitation programme.

Keywords: encephalopathy, phase-change-material, neurodevelopment, cerebral palsy

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Authors: A. Beatti, L. Chipchase, A. Rayner, T. Souvlis

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The aims of this study were to investigate the depth of interferential current (IFC) penetration through soft tissue and to investigate the area over which IFC spreads during clinical application. Premodulated IFC and ‘true’ IFC at beat frequencies of 4, 40 and 90Hz were applied via four electrodes to the distal medial thigh of 15 healthy subjects. The current was measured via three Teflon coated fine needle electrodes that were inserted into the superficial layer of skin, then into the subcutaneous tissue (≈1 cm deep) and then into muscle tissue (≈2 cm deep). The needle electrodes were placed in the middle of the four IFC electrodes, between two channels and outside the four electrodes. Readings were taken at each tissue depth from each electrode during each treatment frequency then digitized and stored for analysis. All voltages were greater at all depths and locations than baseline (p < 0.01) and voltages decreased with depth (P=0.039). Lower voltages of all currents were recorded in the middle of the four electrodes with the highest voltage being recorded outside the four electrodes in all depths (P=0.000).For each frequency of ‘true’ IFC, the voltage was higher in the superficial layer outside the electrodes (P ≤ 0.01).Premodulated had higher voltages along the line of one circuit (P ≤ 0.01). Clinically, IFC appears to pass through skin layers to depth and is more efficient than premodulated IFC when targeting muscle tissue.

Keywords: electrotherapy, interferential current, interferential therapy, medium frequency current

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Authors: Ashraf Ali, Kriti Upadhyay, Puja Sohal, Anant Mohan, Randeep Guleria

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Background: Gene silencing by aberrant promoter hypermethylation is common in lung cancer and is an initiating event in its development. Aim: To evaluate the gene promoter hypermethylation frequency in serum and tissue of lung cancer patients. Method: 95 newly diagnosed untreated advance stage lung cancer patients and 50 cancer free matched controls were studied. Bisulfite modification of tissue and serum DNA was done; modified DNA was used as a template for methylation-specific PCR analysis. Survival was assessed for one year. Results: Of 95 patients, 82% were non-small cell lung cancer (34% squamous cell carcinoma, 34% non-small cell lung cancer and 14% adenocarcinoma) and 18% were small cell lung cancer. Biopsy revealed that tissue of 89% and 75% of lung cancer patients and 85% and 52% of controls had promoter hypermethylated for MGMT (p=0.35) and p16(p<0.001) gene, respectively. In serum, 33% and 49% of lung cancer patients and 28% and 43% controls were positive for MGMT and p16 gene. No significant correlation was found between survival and clinico-pathological parameters. Conclusion: High gene promoter methylation frequency of p16 gene in tissue biopsy may be linked with early stages of carcinogenesis. Appropriate follow-up is required for confirmation of this finding.

Keywords: lung cancer, MS- PCR, methylation, molecular biology

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Authors: M. Alam, P. Seshaiyer

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The rupture predictability of intracranial aneurysm is one of the most important parameters for physicians in surgical treatment. As most of the intracranial aneurysms are asymptomatic, still the rupture potential of both symptomatic and asymptomatic lesions is relatively unknown. Moreover, an intracranial aneurysm constrained by a nerve tissue might be a common scenario for a physician to deal with during the treatment process. Here, we perform a computational modeling of nerve tissue constrained intracranial saccular aneurysm to show a protective role of constrained tissue on the aneurysm. A comparative parametric study of the model also performs taking long constraint, medium constraint, short constraint, point contact, narrow neck aneurysm, wide neck aneurysm as parameters for the analysis. Results show that contact constraint aneurysm generates less stress near the fundus compared to no constraint aneurysm, hence works as a protective wall for the aneurysm not to be ruptured.

Keywords: rupture potential, intracranial saccular aneurysm, anisotropic hyper-elastic material, finite element analysis

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Authors: Eman G. Alayad, Mazen G. Aleyad, Mohammed Alshahrani, Ibrahim Alnaami

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Introduction: Cerebral venous thrombosis (CVT) is a rare type of cerebrovascular disease that can occur at any age. Patients with CVT commonly present with headache, focal neurological deficit, decreased level of consciousness and seizures. Many etiologic risk factors have been reported for CVT, high altitude and oral contraceptive pill some of them. Case Presentation: A 37-year-old woman living in Abha city in the southeastern area of Saudi Arabia. (about 10,000 feet-3000 m) over the sea. complaining acute onset of severe diffuse headache and generalized tonic clonic convulsions. Followed by loss of consciousness. She was on contraceptive pills for the last 3 years. No significant Medical or surgical history. Brain CT revealed subarachnoid hemorrhage, with MRI findings showing thrombosis in transvers sinus. There was no vascular malformations such as aneurysm, arteriovenous malformation (AVM), or dural arteriovenous fistula. A CVT with subarachnoid hemorrhage was our final diagnosis based on clinical presentation and radiographic findings. Discussion: Patients with CVT had evidence of cortical SAH by 10 of 233, others found 3% of SAH was caused by CVT, indicating that the presence of cortical SAH without involvement of the basal cisterns may provide an early sign of underlying CVT. However, what is more interesting in this case, is the relationship of high altitude with CVT and SAH, which previously undescribed. Conclusion: High-altitude climbing per se was described as a risk factor for the development of CVT, though its occurrence was probably rare. Whether it is primary in etiology due to high altitude induced hypercoagulable state of unknown origin or due to cerebrovascular disturbances there is a need for further investigation especially at this unusual presentation of subarachnoid hemorrhage.

Keywords: cerebral venous thrombosis, high-altitude, subarachnoid hemorrhage, stroke

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Authors: Karen Cilliers, Benedict J. Page

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Limited research focuses on the anatomy of the posterior cerebral artery (PCA) and its cortical branches, even though there can be variation in the presence, size, and origin. The PCA branching pattern has not been adequately reported, and the true division point remains unclear. Anomalies of the PCA have been described in the previous literature; however, few examples have been reported. Furthermore, possible differences between right and left, sex, population and age groups may exist. Therefore, the aim of this study was to report on these aspects from a South African population. One hundred and twenty-six hemispheres were obtained consisting of 86 males and 38 females, between the ages of 22 and 84 (average 45 years of age). This comprised of three population groups, namely coloured (n=74), black (n=38), white (n=10) and two unknown cases. The PCA was injected with an isotonic saline and a colored silicone. The external diameter was measured with a digital micrometer, and length was measured with a string and a ruler. Presence and origins of the cortical branches were similar to the literature; however, duplications, triplications, and unusual origins were observed. The diameter and lengths indicated significant differences between the right and left sides, sex, population and age groups. Branching patterns were identified and compared to the prevalence from previous studies. Two fenestrations were observed in the P2A segment. The presence, size, origin, branching pattern and anomalies of the PCA were investigated in this study. The diameter and length can be significantly different, especially between the right and left-hand side. Changes in the diameter and length can be indicative of certain neuropathological conditions and can play a role in aneurysms formation. Adequate knowledge of the normal and abnormal PCA anatomy is crucial for surgery in the vicinity of the PCA. Therefore, future studies should focus on these aspects.

Keywords: branching, cortical branches, fenestration, posterior cerebral artery

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Authors: Lin Feng, E. Lingling, Hongchen Liu

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In order to evaluate the effects of autologous blood vessels and nerves on vascularization. A dog model of tissue-engineered bone vascularization was established by constructing inferior alveolar neurovascular bundles through the mandibular canal. Sixteen 12-month-old healthy beagles were randomly divided into two groups (n=8). Group A retained inferior alveolar neurovascular bundles, and Group B retained inferior alveolar nerves. Bone marrow mesenchymal stem cells were injected into β-tricalcium phosphate to prepare internal tissue-engineered bone scaffold. A personalized titanium mesh was then prepared by rapid prototyping and fixed by external titanium scaffold. Two dogs in each group were sacrificed on the 30th, 45th, 60th, and 90th postoperative days respectively. The bone was visually examined, scanned by CT, and subjected to HE staining, immunohistochemical staining, vascular casting and PCR to detect the changes in osteogenesis and vascularization.The two groups had similar outcomes in regard to osteogenesis and vascularization (P>0.05) both showed remarkable regenerative capacities. The model of tissue-engineered bone vascularization is potentially applicable in clinical practice to allow satisfactory osteogenesis and vascularization.

Keywords: inferior alveolar neurovascular bundle, osteogenesis, tissue-engineered bone, vascularization

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Authors: Souradip Paul, Arijit Paramanick, M. Suheshkumar Singh

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Traumatic injury is the leading worldwide health problem. Annually, millions of surgical wounds are created for the sake of routine medical care. The healing of these unintended injuries is always monitored based on visual inspection. The maximal restoration of tissue functionality remains a significant concern of clinical care. Although minor injuries heal well with proper care and medical treatment, large injuries negatively influence various factors (vasculature insufficiency, tissue coagulation) and cause poor healing. Demographically, the number of people suffering from severe wounds and impaired healing conditions is burdensome for both human health and the economy. An incomplete understanding of the functional and molecular mechanism of tissue healing often leads to a lack of proper therapies and treatment. Hence, strong and promising medical guidance is necessary for monitoring the tissue regeneration processes. Photoacoustic imaging (PAI), is a non-invasive, hybrid imaging modality that can provide a suitable solution in this regard. Light combined with sound offers structural, functional and molecular information from the higher penetration depth. Therefore, molecular and structural mechanisms of tissue repair will be readily observable in PAI from the superficial layer and in the deep tissue region. Blood vessel formation and its growth is an essential tissue-repairing components. These vessels supply nutrition and oxygen to the cell in the wound region. Angiogenesis (formation of new capillaries from existing blood vessels) contributes to new blood vessel formation during tissue repair. The betterment of tissue healing directly depends on angiogenesis. Other optical microscopy techniques can visualize angiogenesis in micron-scale penetration depth but are unable to provide deep tissue information. PAI overcomes this barrier due to its unique capability. It is ideally suited for deep tissue imaging and provides the rich optical contrast generated by hemoglobin in blood vessels. Hence, an early angiogenesis detection method provided by PAI leads to monitoring the medical treatment of the wound. Along with functional property, mechanical property also plays a key role in tissue regeneration. The wound heals through a dynamic series of physiological events like coagulation, granulation tissue formation, and extracellular matrix (ECM) remodeling. Therefore tissue elasticity changes, can be identified using non-contact photoacoustic elastography (PAE). In a nutshell, angiogenesis and biomechanical properties are both critical parameters for tissue healing and these can be characterized in a single imaging modality (PAI).

Keywords: PAT, wound healing, tissue coagulation, angiogenesis

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Authors: Ashok K. Gupta

Abstract:

Over the past few decades, since the bio-engineering revolution, autologous cell therapy (ACT) has become a rapidly evolving field. Currently, this form of therapy has broad applications in modern medicine and plastic surgery, ranging from the treatment/improvement of wound healing to life-saving operations. A study was conducted on 50 patients having to disfigure, and deform post burn scars and was treated by injection of extracted, refined adipose tissue grafts with their unique stem cell properties. To compare the outcome, a control of 20 such patients was treated with conventional skin or soft-tissue flaps or skin grafting, and a control of 10 was treated with more advanced microsurgical techniques such as Pre-fabricated flaps/pre laminated flaps / free flaps. Assessment of fat volume and survival post- follow up period was done by radiological aid, using MRI and clinically (Survival of the autograft and objective parameters for scar elasticity were evaluated skin elasticity parameters 3 to 9 months postoperatively). Recently, an enzyme that is involved in collagen crosslinking in fibrotic tissue, lysyl hydroxylase (LH2), was identified. This enzyme is normally active in bone and cartilage but hardly in the skin. It has been found that this enzyme is highly expressed in scar tissue and subcutaneous fat; this is in contrast to the dermis, where the enzyme is hardly expressed. Adipose tissue-derived stem cell injections are an effective method in the treatment of various extensive post-burn scar deformities that makes it possible to re-create the lost sub-dermal tissue for improvement in the function of involved joint movements.

Keywords: adipose tissue-derived stem cell injections, treatment of various extensive post-burn scar deformities, re-create the lost sub-dermal tissue, improvement in function of involved joint movements

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Authors: Azadeh Rouhandeh, Chris Joslin, Zhen Qu, Yuu Ono

Abstract:

The centre of rotation of the hip joint is needed for an accurate simulation of the joint performance in many applications such as pre-operative planning simulation, human gait analysis, and hip joint disorders. In human movement analysis, the hip joint center can be estimated using a functional method based on the relative motion of the femur to pelvis measured using reflective markers attached to the skin surface. The principal source of errors in estimation of hip joint centre location using functional methods is soft tissue artefacts due to the relative motion between the markers and bone. One of the main objectives in human movement analysis is the assessment of soft tissue artefact as the accuracy of functional methods depends upon it. Various studies have described the movement of soft tissue artefact invasively, such as intra-cortical pins, external fixators, percutaneous skeletal trackers, and Roentgen photogrammetry. The goal of this study is to present a non-invasive method to assess the displacements of the markers relative to the underlying bone using optical motion capture data and tissue thickness from ultrasound measurements during flexion, extension, and abduction (all with knee extended) of the hip joint. Results show that the artefact skin marker displacements are non-linear and larger in areas closer to the hip joint. Also marker displacements are dependent on the movement type and relatively larger in abduction movement. The quantification of soft tissue artefacts can be used as a basis for a correction procedure for hip joint kinematics.

Keywords: hip joint center, motion capture, soft tissue artefact, ultrasound depth measurement

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Authors: G. K. Guseynova, V. V. Krylov, L. T. Khamidova, N. A. Polunina, V. A. Lukyanchikov

Abstract:

The report presents complex ultrasound diagnostics in patients with symptomatic steno-occlusive lesions of extra- and intracranial branches of brachiocephalic arteries (BCA). The tasks and possibilities of ultrasound diagnostics at different stages of treatment of patients with symptomatic occlusion of internal carotid artery (ICA) are covered in detail; qualitative and quantitative characteristics of blood flow; parameters of the wall and lumen of the main arteries of the head; methods of ultrasound examination of indirect assessment of the functional status are presented. Special attention is paid to the description of indicators that are predictors of the consistency of formed extra-intracranial low-flow shunts, examples of functioning and failed anastomoses are analyzed.

Keywords: CBF, cerebral blood flow; CTA, external carotid artery; ICA, internal carotid artery; MCA, middle cerebral artery; MRA, magnetic resonance angiography; OEF, oxygen extraction fraction; TIA, transient ischaemic attack, ultrasound, low-flow bypass, anastomoses

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Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

Abstract:

Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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Authors: Singh Deepeshwar, Suhas Vinchurkar

Abstract:

Similar to neuroimaging findings through functional magnetic resonance imaging (fMRI) assessing regional cerebral blood oxygenation, the functional near infrared spectroscopy (fNIRS) has also been used to assess hemodynamic responses in the imaged region of the brain. The present study assessed hemodynamic responses in terms of changes in oxygenation (HbO), deoxygenation (HbR) and total hemoglobin (THb) on the prefrontal cortex (PFC), bilaterally, using fNIRS in 10 participants who performed three voluntary regulated breathing (pranayama) practices viz. (i) Left nostril breathing (LNB), (ii) Right nostril breathing (RNB); and (iii) Alternating nostril breathing (ANB) and compared with normal breathing as baseline (BS). For this, we used 64 channel NIRS system covering left and the right prefrontal cortex. The normal breathing kept as baseline (BS) measures as regressors in the investigation of hemodynamic responses when compared with LNB, RNB and ANB. In the results, we found greater oxygenation in contralateral side i.e., higher activation on the left prefrontal cortex (lPFC) during RNB, and right prefrontal cortex (rPFC) during LNB, whereas ANB showed greater deoxygenation responses on both sides of PFC. Interestingly, LNB showed increased oxygenation on ipsilateral side i.e., lPFC but not during RNB. This suggests that voluntary regulated breathing produced an immediate effect not only on contralateral but ipsilateral sides of the brain as well. In conclusion, breathing practices are tightly coupled to cerebral rhythms of alternating cerebral hemispheric activity during particular nostril breathing. These results of the specific nostril breathing do not support previous findings of contralateral hemispheric improvement while left or right nostril breathing only.

Keywords: hemodynamic responses, brain, pranayama, voluntary regulated breathing practices, prefrontal cortex

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

Abstract:

Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Mitchell Stanton

Abstract:

Background: Endovascular management is well established as a mainstay treatment option for cerebral aneurysms. It is also well established that immediate post procedural imaging can be difficult to interpret due to the presence of contrast material. However, through the use of Dual-Energy computed tomography, it has become possible to differentiate contrast extravasation and intracranial haemorrhage. This case illustrates the importance of this technology following endovascular treatment of an unruptured cerebral aneurysm. Case Presentation: A 79-year-old female was found to have an unruptured large intracavernous ICA fusiform aneurysm on CT Brain Angiogram after presenting with acute ophthalmoplegia. This ophthalmoplegia was caused by mass effect from the aneurysm and subsequently the aneurysm was treated with an endovascular flow diverting stent. CT brain was performed post operatively due to a reduced level of consciousness and this showed diffuse subarachnoid hyperdensity of the left hemisphere. The use of Dual-Energy CT allowed accurate differentiation and illustrated diffuse contrast material extravasation, allowing patient to continue on dual-antiplatelets and therapeutic anticoagulation to reduce the risk of ischaemic injury post endovascular stent. Conclusion: Endovascular treatment options for management of intracranial aneurysms are constantly evolving. The use of Dual-Energy CT therefore has an integral role in accurately diagnosing any post-operative complications. Specifically, differentiating between subarachnoid haemorrhage and contrast extravasation is vital in these patients due to the significant consequences to their ongoing management in regards to continuation or cessation of antiplatelets or anticoagulation. With increasing access to this technology, its use should become standard practice in the post-operative investigation of these patients undergoing endovascular treatment.

Keywords: aneurysm, computed tomography, contrast extravasation, dual-energy CT, endovascular, subarachnoid haemorrhage

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Authors: P. I. Bobyleva, E. R. Andreeva, I. V. Andrianova, E. V. Maslova, L. B. Buravkova

Abstract:

This work studied the ability of adipose tissue-derived mesenchymal stromal cells (MSCs) to form stroma for expansion of cord blood hematopoietic cells. We showed that 72-hour interaction of MSCs with cord blood mononuclear cells (MNCs) in vitro at atmospheric (20%) and low (5%) O2 conditions increased the expression of ICAM-1, HCAM (at the beginning of interaction) on MSCs. Viability of MSCs and MNCs were maintained at high level. Adhesion of MNCs to MSCs was faster at 20% O2. MSCs promoted the proliferation of adhered MNCs to form the suspension containing great number of hematopoietic colony-forming units, and this effect was more pronounced at 5% O2. Thus, adipose-derived MSCs supplied sufficient stromal support to cord blood MNCs both at 20% and 5% О2, providing their adhesion with further expansion of new generation of different hematopoietic lineages.

Keywords: hematopoietic stem and progenitor cells, mesenchymal stromal cells, tissue-related oxygen, adipose tissue

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