Search results for: breast tissue

Authors: Tayyaba Bari, Muhammad Hamza Anjum, Samra Kanwal, Fakhera Ikram

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Osteoarthritis, a degenerative condition, affects more than 213 million individuals globally. Since articular cartilage has no or limited vessels, therefore, after deteriorating, it is unable to rejuvenate. Traditional approaches for cartilage repair, like autologous chondrocyte implantation, microfracture and cartilage transplantation are often associated with postoperative complications and lead to further degradation. Decellularized human umbilical cord has gained interest as a viable treatment for cartilage repair. Decellularization removes all cellular contents as well as debris, leaving a biologically active 3D network known as extracellular matrix (ECM). This matrix is biodegradable, non-immunogenic and provides a microenvironment for homeostasis, growth and repair. UC derived bioink function as 3D scaffolding material, not only mediates cell-matrix interactions but also adherence, proliferation and propagation of cells for 3D organoids. This study comprises different physical, chemical and biological approaches to optimize the decellularization of human umbilical cord (UC) tissues followed by the solubilization of these tissues to bioink formation. The decellularization process consisted of two cycles of freeze thaw where the umbilical cord at -20˚C was thawed at room temperature followed by dissection in small sections from 0.5 to 1cm. Similarly decellularization with ionic and non-ionic detergents Sodium dodecyl sulfate (SDS) and Triton-X 100 revealed that both concentrations of SDS i.e 0.1% and 1% were effective in complete removal of cells from the small UC tissues. The results of decellularization was further confirmed by running them on 1% agarose gel. Histological analysis revealed the efficacy of decellularization, which involves paraffin embedded samples of 4μm processed for Hematoxylin-eosin-safran and 4,6-diamidino-2-phenylindole (DAPI). ECM preservation was confirmed by Alcian Blue, and Masson’s trichrome staining on consecutive sections and images were obtained. Sulfated GAG’s content were determined by 1,9-dimethyl-methylene blue (DMMB) assay, similarly collagen quantification was done by hydroxy proline assay. This 3D bioengineered scaffold will provide a typical atmosphere as in the extracellular matrix of the tissue, which would be seeded with the mesenchymal cells to generate the desired 3D ink for in vitro and in vivo cartilage regeneration applications.

Keywords: umbilical cord, 3d printing, bioink, tissue engineering, cartilage regeneration

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Authors: May Fadheel Estephan, Richard Perks

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Context: Cancer is a serious health concern that affects millions of people worldwide. Early detection and treatment are essential for improving patient outcomes. However, current methods for cancer detection have limitations, such as low sensitivity and specificity. Research Aim: The aim of this study was to develop an optical sensor for cancer detection using elastic light scattering spectroscopy (ELSS). ELSS is a noninvasive optical technique that can be used to characterize the size and concentration of particles in a solution. Methodology: An optical probe was fabricated with a 100-μm-diameter core and a 132-μm centre-to-centre separation. The probe was used to measure the ELSS spectra of polystyrene spheres with diameters of 2, 0.8, and 0.413 μm. The spectra were then analysed to determine the size and concentration of the spheres. Findings: The results showed that the optical probe was able to differentiate between the three different sizes of polystyrene spheres. The probe was also able to detect the presence of polystyrene spheres in suspension concentrations as low as 0.01%. Theoretical Importance: The results of this study demonstrate the potential of ELSS for cancer detection. ELSS is a noninvasive technique that can be used to characterize the size and concentration of cells in a tissue sample. This information can be used to identify cancer cells and assess the stage of the disease. Data Collection: The data for this study were collected by measuring the ELSS spectra of polystyrene spheres with different diameters. The spectra were collected using a spectrometer and a computer. Analysis Procedures: The ELSS spectra were analysed using a software program to determine the size and concentration of the spheres. The software program used a mathematical algorithm to fit the spectra to a theoretical model. Question Addressed: The question addressed by this study was whether ELSS could be used to detect cancer cells. The results of the study showed that ELSS could be used to differentiate between different sizes of cells, suggesting that it could be used to detect cancer cells. Conclusion: The findings of this research show the utility of ELSS in the early identification of cancer. ELSS is a noninvasive method for characterizing the number and size of cells in a tissue sample. To determine cancer cells and determine the disease's stage, this information can be employed. Further research is needed to evaluate the clinical performance of ELSS for cancer detection.

Keywords: elastic light scattering spectroscopy, polystyrene spheres in suspension, optical probe, fibre optics

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Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

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Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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Authors: Samuel Oluwafemi Oyamakin, Angela Unna Chukwu

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Richrads growth equation being a generalized logistic growth equation was improved upon by introducing an allometric parameter using the hyperbolic sine function. The integral solution to this was called hyperbolic Richards growth model having transformed the solution from deterministic to a stochastic growth model. Its ability in model prediction was compared with the classical Richards growth model an approach which mimicked the natural variability of heights/diameter increment with respect to age and therefore provides a more realistic height/diameter predictions using the coefficient of determination (R2), Mean Absolute Error (MAE) and Mean Square Error (MSE) results. The Kolmogorov-Smirnov test and Shapiro-Wilk test was also used to test the behavior of the error term for possible violations. The mean function of top height/Dbh over age using the two models under study predicted closely the observed values of top height/Dbh in the hyperbolic Richards nonlinear growth models better than the classical Richards growth model.

Keywords: height, diameter at breast height, DBH, hyperbolic sine function, Pinus caribaea, Richards' growth model

Procedia PDF Downloads 378

Authors: Youssef. K. A. Abdalhafid, Ezaldin A. M. Mohammed, Masoud M. M. Zatout

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This study described the changes in the liver of Uromastyx acanthinura (Bell, 1825) males and females during hibernation and activity seasons. The results revealed that, hibernation causes increase fatty liver and pigment cells with abundant damage, comparing with nearly normal structure and less fatty liver after the hibernation with almost normal pattern. Genomic DNA showed apparent separation during hibernation. Also, caspase 3 and caspase 7 activity reached a high level in the liver tissue during hibernation comparing with activity season.

Keywords: histological liver, DNA fragmentation, hibernation, caspase 3 and caspase 7

Procedia PDF Downloads 300

Authors: Xiquan Weng, Chaoge Wang, Guoqin Xu, Wentao Lin

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Objective: Cold exposure and exercise serve as two powerful physiological stimuli to launch the conversion of fat-accumulating white adipose tissue (WAT) into energy-dissipating brown adipose tissue (BAT). So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting WAT browning. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and successfully established an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; For intermittent cold exposure, the rats were exposed to cold for only 4h per day. The protocol for treadmill exercises were as follows: 25m/min (speed), 0°C (slope), 30mins each time, an interval for 10 mins between two exercises, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. The body length and weight of the rats were measured, and the Lee's index was calculated. The visceral fat rate (VFR), subcutaneous fat rate (SFR), brown fat rate (BrFR) and body fat rate (BoFR) were measured by Micro-CT LCT200, and the expression of UCP1 protein in inguinal fat was examined by Western-blot. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (P < 0.05 was significant). Results: (1) Compared with the NC group, the weight of obese rats was significantly declined in the NE, CE and IE groups (P < 0.05), the Lee's index of obese rats significantly declined in the CE group (P < 0.05). Compared with the NE group, the weight of obese rats was significantly declined in the CE and IE groups (P < 0.05). (2)Compared with the NC group, the VFR and BoFR of the rats significantly declined in the NE, CE and IE groups (P < 0.05), the SFR of the rats significantly declined in the CE and IE groups (P < 0.05), and the BFR of the rats was significantly higher in the CC and IC groups (P < 0.05), respectively. Compared with the NE group, the VFR and BoFR of the rats significantly declined in the CE group (P < 0.05), the SFR of the rats was significantly higher in the CC and IS groups (P < 0.05), and the BrFR of the rats was significantly higher in the IC group (P < 0.05). (3)Compared with the NC group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the NE, CC, CE, IC and IE groups (P < 0.05). Compared with the NE group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the CC, CE and IE groups (P < 0.05). Conclusions: Exercise in the continuous and intermittent cold, especially in the former, can effectively decline the weight and body fat rate of obese rats. This is related to the effect of cold and exercise on the browning of white fat in rats.

Keywords: cold, browning of white fat, exercise, obesity

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

Procedia PDF Downloads 126

Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

Procedia PDF Downloads 237

Authors: Zeena Dcosta, Junaid Ahmed, Ceena Denny, Nandita Shenoy

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In the field of dentistry, there are many conditions which warrant the requirement of three-dimensional imaging that can aid in diagnosis and therapeutic management. Cone beam computed tomography (CBCT) is considered highly accurate in producing a three-dimensional image of an object and provides a complete insight of various findings in the captured volume. But, most of the clinicians focus primarily on the teeth and jaws and numerous unanticipated clinically significant incidental findings may be missed out. Rapid integration of CBCT into the practice of dentistry has led to the detection of various incidental findings. However, the prevalence of these incidental findings is still unknown. Thus, the study aimed to discern the reason for referral and to identify incidental findings on the referred CBCT scans. Patient’s demographic data such as age and gender was noted. CBCT scans of multiple fields of views (FOV) were considered. The referral for CBCT scans was broadly classified into two major categories: diagnostic scan and treatment planning scan. Any finding on the CBCT volumes, other than the area of concern was recorded as incidental finding which was noted under airway, developmental, pathological, endodontics, TMJ, bone, soft tissue calcifications and others. Few of the incidental findings noted under airway were deviated nasal septum, nasal turbinate hypertrophy, mucosal thickening and pneumatization of sinus. Developmental incidental findings included dilaceration, impaction, pulp stone and gubernacular canal. Resorption of teeth and periapical pathologies were noted under pathological incidental findings. Root fracture along with over and under obturation was noted under endodontics. Incidental findings under TMJ were flattening, erosion and bifid condyle. Enostosis and exostosis were noted under bone lesions. Tonsillolth, sialolith and calcified styloid ligament were noted under soft tissue calcifications. Incidental findings under others included foreign body, fused C1- C2 vertebrae, nutrient canals, and pneumatocyst. Maxillofacial radiologists should be aware of possible incidental findings and should be vigilant about comprehensively evaluating the entire captured volume, which can help in early diagnosis of any potential pathologies that may go undetected. Interpretation of CBCT is truly an art and with the experience, we can unravel the secrets hidden in the grey shades of the radiographic image.

Keywords: cone beam computed tomography, incidental findings, maxillofacial region, radiologist

Procedia PDF Downloads 193

Authors: Yuri V. Bykov, V. A. Baturin

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Aim of the study: The aim of the study was to perform a comparative analysis of the levels of autoantibodies (AAB) to the S-100 protein as well as to the dopamine and NMDA receptors in children with type 1 diabetes mellitus (DM) in therapeutic remission. Materials and methods: Blood serum obtained from 42 children ages 4 to 17 years (20 boys and 22 girls) was analyzed. Twenty-one of these children had a diagnosis of type 1 DM and were in therapeutic remission (study group). The mean duration of disease in children with type 1 DM was 9.6±0.36 years. Children without DM were included in a group of "apparently healthy children" (21 children, comparison group). AAB to the S-100 protein, the dopamine, and NMDA receptors were measured by ELISA. The normal range of IgG AAB was specified as up to 10 µg/mL. In order to compare the central parameters of the groups, the following parametric and non-parametric methods were used: Student's t-test or Mann-Whitney U test. The level of significance for inter-group comparisons was set at p<0.05. Results: The mean levels of AAB to the S-100B protein were significantly higher (p=0.0045) in children with DM (16.84±1.54 µg/mL) when compared with "apparently healthy children" (2.09±0.05 µg/mL). The detected elevated levels of AAB to NMDA receptors may indicate that in children with type 1 DM, there is a change in the activity of the glutamatergic system, which in its turn suggests the presence of excitotoxicity. The mean levels of AAB to dopamine receptors were higher (p=0.0082) in patients comprising the study group than in the children of the comparison group (40.47±2.31 µg/mL and 3.91±0.09 µg/mL). The detected elevated levels of AAB to dopamine receptors suggest an altered activity of the dopaminergic system in children with DM. This can also be viewed as indirect evidence of altered activity of the brain's glutamatergic system. The mean levels of AAB to NMDA receptors were higher in patients with type 1 DM compared with the "apparently healthy children," at 13.16±2.07 µg/mL and 1.304±0.05 µg/mL, respectively (p=0.0021). The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in children with type 1 DM. A difference was also detected between the mean values of the measured AABs, and this difference depended on the duration of the disease: mean AAB values were significantly higher in patients whose disease had lasted more than five years. Conclusions: The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in the setting of excitotoxicity in children with type 1 DM. The discovered elevation of the levels of AAB to NMDA and dopamine receptors may indicate the activation of the glutamatergic and dopaminergic systems. The observed abnormalities indicate the presence of central nervous system damage in children with type 1 DM, with a tendency towards the elevation of the levels of the studied AABs with disease progression.

Keywords: autoantibodies, brain damage, children, diabetes mellitus

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Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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Authors: Sneha Noble, Rahul Krishnan, Uma G., D. K. Vijaykumar

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Breast-Cancer related Lymphedema is a major problem that affects many women. Lymphedema is the swelling that generally occurs in the arms or legs caused by the removal of or damage to lymph nodes as a part of cancer treatment. Treating it at the earliest possible stage is the best way to manage the condition and prevent it from leading to pain, recurrent infection, reduced mobility, and impaired function. So, this project aims to focus on the multi-modal approaches to identify the risks of Lymphedema in post-surgical oncology patients and prevent it at the earliest. The Kinect IR Sensor is utilized to capture the images of the body and after image processing techniques, the region of interest is obtained. Then, performing the voxelization method will provide volume measurements in pre-operative and post-operative periods in patients. The formation of a mathematical model will help in the comparison of values. Clinical pathological data of patients will be investigated to assess the factors responsible for the development of lymphedema and its risks.

Keywords: Kinect IR sensor, Lymphedema, voxelization, lymph nodes

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Authors: Oshma Chakoory, Sophie Comtet-Marre, Pierre Peyret

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Metagenomic classifiers are widely used for the taxonomic profiling of metagenomic data and estimation of taxa relative abundance. Small subunit rRNA genes are nowadays a gold standard for the phylogenetic resolution of complex microbial communities, although the power of this marker comes down to its use as full-length. We benchmarked the performance and accuracy of rRNA-specialized versus general-purpose read mappers, reference-targeted assemblers and taxonomic classifiers. We then built a pipeline called RiboTaxa to generate a highly sensitive and specific metataxonomic approach. Using metagenomics data, RiboTaxa gave the best results compared to other tools (Kraken2, Centrifuge (1), METAXA2 (2), PhyloFlash (3)) with precise taxonomic identification and relative abundance description, giving no false positive detection. Using real datasets from various environments (ocean, soil, human gut) and from different approaches (metagenomics and gene capture by hybridization), RiboTaxa revealed microbial novelties not seen by current bioinformatics analysis opening new biological perspectives in human and environmental health. In a study focused on corals’ health involving 20 metagenomic samples (4), an affiliation of prokaryotes was limited to the family level with Endozoicomonadaceae characterising healthy octocoral tissue. RiboTaxa highlighted 2 species of uncultured Endozoicomonas which were dominant in the healthy tissue. Both species belonged to a genus not yet described, opening new research perspectives on corals’ health. Applied to metagenomics data from a study on human gut and extreme longevity (5), RiboTaxa detected the presence of an uncultured archaeon in semi-supercentenarians (aged 105 to 109 years) highlighting an archaeal genus, not yet described, and 3 uncultured species belonging to the Enorma genus that could be species of interest participating in the longevity process. RiboTaxa is user-friendly, rapid, allowing microbiota structure description from any environment and the results can be easily interpreted. This software is freely available at https://github.com/oschakoory/RiboTaxa under the GNU Affero General Public License 3.0.

Keywords: metagenomics profiling, microbial diversity, SSU rRNA genes, full-length phylogenetic marker

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Authors: Payman A. A. Zibari, Mosleh M. S. Duhoky

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These experiments were conducted at Tissue Culture Laboratory/ Faculty of Agriculture / University of Duhok during the period from January 2011 to May 2013. The objectives of this study were to study the effects of interaction between colchcine concentrations and treatment time duration of Creps capilaris (with and without 2B chromosome) on chromosome polyploidy during fifteen passages until regeneration of plants from the callus. Data showed that high percentage of chromosome polyploidy approximately can be obtained from high concentration of colchicin and long time of duration.

Keywords: polyploidy, Crepis capilaris, colchicine, B chromosome

Procedia PDF Downloads 173

Authors: Arlan S. Freitas, Leila M. Carvalho, Adriana L. Soares, Arnoud Neto, Marta S. Madruga, Rafael H. Carvalho, Elza I. Ida, Massami Shimokomaki

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The objective of this work was to evaluate the influence of microclimatic profile of broiler transport trucks and holding time (340) min under commercial conditions over the breast meat quality and DOA (Dead On Arrival) in a tropical Brazilian regions as the NorthEast. In this particular region routinely the season is divided into dry and wet seasons. Three loads of 4,100 forty seven days old broiler were monitored from farm to slaughterhouse in a distance of 273 km (320 min), morning periods of August, September and October 2015 rainy days. Meat qualities were evaluated by determining the occurrence of PSE (pale, soft, exudative) meat and DFD (dark, firm, dry) meat. The percentage of DOA per loaded truck was determined by counting the dead broiler during the hanging step at the slaughtering plant. Results showed the occurrence of 26.30% of PSE and 2.49% of DFD and 0.45% of DOA. By having PSE- and DFD- meat means that the birds were under thermal and cold stress leading as consequence to a relative high DOA index.

Keywords: animal welfare, DFD, microclimatic profile, PSE

Procedia PDF Downloads 398

Authors: Sudip Mondal, Biswanath Mondal, Sudit S. Mukhopadhyay, Apurba Dey

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Bioactive materials improve devices for a long lifespan but have mechanical limitations. Mechanical characterization is one of the very important characteristics to evaluate the life span and functionality of the scaffold material. After implantation of scaffold material the primary stage rejection of scaffold occurs due to non biocompatible effect of host body system. The second major problems occur due to the effect of mechanical failure. The mechanical and biocompatibility failure of the scaffold materials can be overcome by the prior evaluation of the scaffold materials. In this study chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterial. Thermo-gravimetric and differential thermal analysis (TG-DTA) is carried out to ensure thermal stability. The chemical composition and bond structures of wet ball-milled calcined HAp powder is characterized by Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX) analysis. Fish scale derived apatite materials consists of nano-sized particles with Ca/P ratio of 1.71. The biocompatibility through cytotoxicity evaluation and MTT assay are carried out in MG63 osteoblast cell lines. In the cell attachment study, the cells are tightly attached with HAp scaffolds developed in the laboratory. The result clearly suggests that HAp material synthesized in this study do not have any cytotoxic effect, as well as it has a natural binding affinity for mammalian cell lines. The synthesized HAp powder further successfully used to develop porous scaffold material with suitable mechanical property of ~0.8GPa compressive stress, ~1.10 GPa a hardness and ~ 30-35% porosity which is acceptable for implantation in trauma region for animal model. The histological analysis also supports the bio-affinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface for biomedical function. This study suggests the natural sourced fish scale-derived HAp material could be used as a suitable alternative biomaterial for tissue engineering application in near future.

Keywords: biomaterials, hydroxyapatite, scaffold, mechanical property, tissue engineering

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Authors: Yousif Mohamed Y. Abdallah, Khalid H. Eltom

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This is an experimental study deals with measurement of the periodic physiological organ motion during lung external irradiation in order to reduce the exposure of healthy tissue during radiation treatments. The results showed for left lung displacement reading (4.52+1.99 mm) and right lung is (8.21+3.77 mm) which the radiotherapy physician should take suitable countermeasures in case of significant errors. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, the calculation of tumour mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a high resolution CT scan with a margin of 3-5 mm is appropriate.

Keywords: physiological motion, lung, external irradiation, radiation medicine

Procedia PDF Downloads 397

Authors: Messis A., Adjebli A., Ayeche R., Talbi M., Tighilet K., Louardiane M.

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Cancers are the second cause of death worldwide. Prevalence and incidence of cancers is getting increased by aging and population growth. This study aims to predict and modeling the evolution of breast, Colorectal, Lung, Bladder and Prostate cancers over the period of 2014-2019. In this study, data were analyzed using time series analysis with double exponential smoothing method to forecast the future pattern. To describe and fit the appropriate models, Minitab statistical software version 17 was used. Between 2014 and 2019, the overall trend in the raw number of new cancer cases registered has been increasing over time; the change in observations over time has been increasing. Our forecast model is validated since we have good prediction for the period 2020 and data not available for 2021 and 2022. Time series analysis showed that the double exponential smoothing is an efficient tool to model the future data on the raw number of new cancer cases.

Keywords: cancer, time series, prediction, double exponential smoothing

Procedia PDF Downloads 70

Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

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The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

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Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

Abstract:

Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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Authors: Tuji Mohammed Sani

Abstract:

Back ground: An open tibial fracture is an injury where the fractured bone directly communicates with the outside environment. Due to the specific anatomical features of the tibia (limited soft tissue coverage), more than quarter of its fractures are classified as open, representing the most common open long-bone injuries. Open tibial fractures frequently cause significant bone comminution, periosteal stripping, soft tissue loss, contamination and are prone to bacterial entry with biofilm formation, which increases the risk of deep bone infection. Objective: The main objective of the study was to determine Prevalence of infection and its associated factors in surgically treated open tibial fracture in Addis Ababa Burn Emergency and Trauma (AaBET) center. Method: A facility based retrospective cross-sectional study was conducted among patient treated for open tibial fracture at AaBET center from September 2018 to September 2021. The data was collected from patient’s chart using structured data collection form, and Data was entered and analyzed using SPSS version 26. Bivariable and multiple binary logistic regression were fitted. Multicollinearity was checked among candidate variables using variance inflation factor and tolerance, which were less than 5 and greater than 0.2, respectively. Model adequacy were tested using Hosmer-Lemeshow goodness of fitness test (P=0.711). AOR at 95% CI was reported, and P-value < 0.05 was considered statistically significant. Result: This study found that 33.9% of the study participants had an infection. Initial IV antibiotic time (AOR=2.924, 95% CI:1.160- 7.370) and time of wound closure from injury (AOR=3.524, 95% CI: 1.798-6.908), injury to admission time (AOR=2.895, 95% CI: 1.402 – 5.977). and definitive fixation method (AOR=0.244, 95% CI: 0.113 – 0.4508) were the factors found to have a statistically significant association with the occurrence of infection. Conclusion: The rate of infection in open tibial fractures indicates that there is a need to improve the management of open tibial fracture treated at AaBET center. Time from injury to admission, time from injury to first debridement, wound closure time, and initial Intra Venous antibiotic time from the injury are an important factor that can be readily amended to improve the infection rate. Whether wound closed before seven days or not were more important factor associated with occurrences of infection.

Keywords: infection, open tibia, fracture, magnitude

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Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

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Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

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Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

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Authors: Nicole Harley, Mahmoud Eid, Abdurahman Tarmal, Vishal Dey

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Histological sampling plays an integral role in the diagnostic process of renal diseases. Percutaneous native renal biopsy is typically performed under ultrasound guidance, with this service usually being provided by nephrologists. In some centers, there is a role for radiologists in performing renal biopsies. Previous comparative studies have demonstrated non-inferiority between outcomes of percutaneous native renal biopsies performed by nephrologists compared with radiologists. We sought to compare biopsy adequacy between nephrologists and radiologists in University Hospital Crosshouse. The online system SERPR (Scottish Electronic Renal Patient Record) contains information pertaining to patients who have undergone renal biopsies. An online search was performed to acquire a list of all patients who underwent renal biopsy between 2013 and 2020 in University Hospital Crosshouse. 355 native renal biopsies were performed in total across this 7-year period. A retrospective analysis was performed on these cases, with records and reports being assessed for: the total number of glomeruli obtained per biopsy, whether the number of glomeruli obtained was adequate for diagnosis, as per an internationally agreed standard, and whether a histological diagnosis was achieved. Nephrologists performed 43.9% of native renal biopsies (n=156) and radiologists performed 56.1% (n=199). The mean number of glomeruli obtained by nephrologists was 17.16+/-10.31. The mean number of glomeruli obtained by radiologists was 18.38+/-10.55. T-test demonstrated no statistically significant difference between specialties comparatively (p-value 0.277). Native renal biopsies are required to obtain at least 8 glomeruli to be diagnostic as per internationally agreed criteria. Nephrologists met these criteria in 88.5% of native renal biopsies (n=138) and radiologists met this criteria in 89.5% (n=178). T-test and Chi-squared analysis demonstrate there was no statistically significant difference between the specialties comparatively (p-value 0.663 and 0.922, respectively). Biopsies performed by nephrologists yielded tissue that was diagnostic in 91.0% (n=142) of sampling. Biopsies performed by radiologists yielded tissue that was diagnostic in 92.4% (n=184) of sampling. T-test and Chi-squared analysis demonstrate there was no statistically significant difference between the specialties comparatively (p-value 0.625 and 0.889, respectively). This project demonstrates that at University Hospital Crosshouse, there is no statistical difference between radiologists and nephrologists in terms of glomeruli acquisition or samples achieving a histological diagnosis. Given the non-inferiority between specialties demonstrated by previous studies and this project, this evidence could support the restructuring of services to allow more renal biopsies to be performed by renal services and allow reallocation of radiology department resources.

Keywords: biopsy, medical imaging, nephrology, radiology

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Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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Authors: Yu-Chen Hu

Abstract:

Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

Abstract:

Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: Samantha Meyerholz

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MSKCC offers patients cutting edge cancer care with the highest quality standards. However, many patients and industry members do not realize that the operations of the Immunology Histology Lab (IHC) are the backbone for carrying out this mission. The IHC lab manufactures blocks and slides containing critical tissue samples that will be read by a Pathologist to diagnose and dictate a patient’s treatment course. The lab processes 200 requests daily, leading to the generation of approximately 2,000 slides and 1,100 blocks each day. Lab material is transported through labeling, cutting, staining and sorting manufacturing stations, while being managed by multiple techs throughout the space. The quality of the stain as well as wait times associated with processing requests, is directly associated with patients receiving rapid treatments and having a wider range of care options. This project aims to improve slide request turnaround time for rush and non-rush cases, while increasing the quality of each request filled (no missing slides or poorly stained items). Rush cases are to be filled in less than 24 hours, while standard cases are allotted a 48 hour time period. Reducing turnaround times enable patients to communicate sooner with their clinical team regarding their diagnosis, ultimately leading faster treatments and potentially better outcomes. Additional project goals included streamlining tech and material workflow, while reducing waste and increasing efficiency. This project followed a DMAIC structure with emphasis on lean and ergonomic principles that could be integrated into an evolving lab culture. Load times and batching processes were analyzed using process mapping, FMEA analysis, waste analysis, engineering observation, 5S and spaghetti diagramming. Reduction of lab technician movement as well as their body position at each workstation was of top concern to pathology leadership. With new equipment being brought into the lab to carry out workflow improvements, screen and tool placement was discussed with the techs in focus groups, to reduce variation and increase comfort throughout the workspace. 5S analysis was completed in two phases in the IHC lab, helping to drive solutions that reduced rework and tech motion. The IHC lab plans to continue utilizing these techniques to further reduce the time gap between tissue analysis and cancer care.

Keywords: engineering, ergonomics, healthcare, lean

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

Abstract:

In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: Keivan Jamshidi, Fateme Behbahani, Sara Omidi, Nadia Shahi, Alireza Farkhonde

Abstract:

Amyloidosis represents a heterogenous group of diseases that have in common the deposition of fibrils composed of proteins of beta-pleated sheet structure, which can be specifically identified by histochemistry using the Congo red or similar stains. Between October 2013 to April 2014 (6 months) different patterns of renal amyloidosis was diagnosed on histopathological examination of kidneys belong to 196 out of 7065 slaughtered sheep subjected to postmortem examination. Microscopic examination of renal tissue sections stained with H&E and CR staining techniques revealed 3 patterns of renal amyloid deposition; including glomerular (22.72%), medullary (68.18%), and vascular (9.09%) were recognized. Renal medullary amyloidosis (RMA) was detected as the most prevalence pattern of renal amyloidosis in domestic sheep.

Keywords: sheep, amyloidosis, kidney, slaughterhouse

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