Search results for: tissue engineered aortic heart valve

Authors: Jason Ting Jing Cheng, Lee Foo Wei, Yew Ming Kun, Mo Kim Hung, Yip Chun Chieh

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This research delves into the structural characteristics of distinct construction material, rubberized lightweight foam concrete (RLFC) wall panels, which have been developed as a sustainable alternative for the construction industry. These panels are engineered with a RLFC core, possessing a density of 1150 kg/m3, which is specifically formulated to bear structural loads. The core is enveloped with high-strength fiber cement boards, selected for their superior load-bearing capabilities, and enhanced flexural strength when compared to conventional concrete. A thin bed adhesive, known as TPS, is employed to create a robust bond between the RLFC core and the fiber cement cladding. This study underscores the potential of RLFC wall panels as a viable and eco-friendly option for modern building construction, offering a combination of structural efficiency and environmental benefits.

Keywords: structural performance, rubberized concrete wall panel, fiber cement board, insulation performance

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Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

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Authors: Nasrin Takzaree, Gholamreza Hassanzadeh, Abbas Hadjiakhoondi, Mohammadreza Rouini

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Introduction: Today herbal medicine are extensively used for various therapeutic reasons. Whereas Achillea millefolium L. comprises different chemical compounds it is used in classic and modern medicine for different purposes. Concerning the family planning as a principle matter, the idea of using specific herbal medicine is of great importance. Purpose: To investigate the effects of Achillea millefolium L. extract on fertility power and spermatogenesis process in male mature Wistar rats and the anti-fertility effects of this extract in male genital system. Material and methods: In this study 32 male mature Wistar rats were randomly divided in to 4 experimental groups. 1st experimental group included 8 rats receiving Achillea millefolium extract at the dose of 200 mg/kg intraperitoneally. Second and third groups received the extract the same at the doses of 400 and 800 mg/kg respectively. 4th group was considered as control group in which the parenteral distilled water was administered. after 20 days, rats were sacrificed and the spermatogenesis process was histologically examined. Results: In experimental groups receiving high doses of extract comparing with control group, thickness in seminiferous tubules basal membrane, decrease in germinal epithelium cells, congestion in testicular tissue, disarrangement in germinal epithelium cells as well as decrease in cellular condense were observed (p<0.001). Conclusion: Findings suggest that alcoholic extract of Achillea millefolium at high concentrations lead to the structural alterations and changes in spermatogenesis in testicular tissue.

Keywords: spermatogenesis, alcoholic extract of Achillea millefolium L., testis, Wistar rat

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Authors: Tushar K. Routh

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If inputs are engineered in certain manners, they can influence deep neural networks’ (DNN) performances by facilitating misclassifications, a phenomenon well-known as adversarial attacks that question networks’ vulnerability. Recent studies have unfolded the relationship between vulnerability of such networks with their complexity. In this paper, the distinctive influence of additional convolutional layers at the decision boundaries of several DNN architectures was investigated. Here, to engineer inputs from widely known image datasets like MNIST, Fashion MNIST, and Cifar 10, we have exercised One Step Spectral Attack (OSSA) and Fast Gradient Method (FGM) techniques. The aftermaths of adding layers to the robustness of the architectures have been analyzed. For reasoning, separation width from linear class partitions and local geometry (curvature) near the decision boundary have been examined. The result reveals that model complexity has significant roles in adjusting relative distances from margins, as well as the local features of decision boundaries, which impact robustness.

Keywords: DNN robustness, decision boundary, local curvature, network complexity

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Authors: Carlos Gonzalez, Ernesto Linan

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We propose a methodology to conciliate two apparently contradictory processes in the development of secure obfuscated software and good software engineered software. Our methodology consists first in the system designers defining the type of security level required for the software. There are four types of attackers: casual attackers, hackers, institution attack, and government attack. Depending on the level of threat, the methodology we propose uses five or six teams to accomplish this task. One Software Engineer Team and one or two software Obfuscation Teams, and Compiler Team, these four teams will develop and compile the secure obfuscated software, a Code Breakers Team will test the results of the previous teams to see if the software is not broken at the required security level, and an Intrusion Analysis Team will analyze the results of the Code Breakers Team and propose solutions to the development teams to prevent the detected intrusions. We also present an analytical model to prove that our methodology is no only easier to use, but generates an economical way of producing secure obfuscated software.

Keywords: development methodology, obfuscated software, secure software development, software engineering

Procedia PDF Downloads 250

Authors: Po-Ching Chou, Wen-Chen Liang, I. Chen Chen, Jong-Hau Hsu, Yuh-Jyh Jong

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Background：Cardiopulmonary complications seem to cause high morbidity and mortality in patients with neuromuscular diseases (NMD) but so far there is no domestic data reported in Taiwan. We, therefore attempted to analyze the factors to cause the death in NMD patients from our cohort. Methods：From 1998 to 2013, we retrospectively collected the information of the NMD patients treated and followed up in Kaohsiung Medical University Hospital. Forty-two patients with NMD who expired during these fifteen years were enrolled. The medical records of these patients were reviewed and the causes of death and the associated affecting factors were analyzed. Results：Eighteen patients with NMD (mean age=13.3, SD=12.4) with complete medical record and detailed information were finally included in this study, including spinal muscular atrophy (SMA) (n=9, 7/9: type 1), Duchenne muscular dystrophy (n=6), congenital muscular dystrophy (n=1), carnitine acyl-carnitine translocase (CACT) deficiency (n=1) and spinal muscular atrophy with respiratory distress (SMARD)(n=1). The place of death was in ICU (n=11, 61%), emergency room (n=3, 16.6%) or home (n=4, 22.2%). For SMA type 1 patients, most of them (71.4%, 5/7) died in emergency room or home and the other two expired during an ICU admission. The causes of death included acute respiratory failure due to pneumonia (n=13, 72.2 %), ventilator failure or dislocation (n=2, 11.1%), suffocation/choking (n=2, 11.1%), and heart failure with hypertrophic cardiomyopathy (n=1, 5.55%). Among the 15 patients died of respiratory failure or choking, 73.3% of the patients (n=11) received no ventilator care at home. 80% of the patients (n=12) received no cough assist at home. The patient died of cardiomyopathy received no medications for heart failure until the last admission. Conclusion: Respiratory failure and choking are the leading causes of death in NMD patients. Appropriate respiratory support and airway clearance play the critical role to reduce the mortality.

Keywords: neuromuscular disease, cause of death, tertiary care hospital, medical sciences

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Authors: M. Turmanauli, T. Todua, O. Gvaberidze, R. Javakhadze, N. Chkhaidze, N. Khatiashvili

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Background: Mining process has the significant influence on human health and quality of life. In recent years the events in Georgia were reflected on the industry working process, especially minimal requirements of labor safety, hygiene standards of workplace and the regime of work and rest are not observed. This situation is often caused by the lack of responsibility, awareness, and knowledge both of workers and employers. The control of working conditions and its protection has been worsened in many of industries. Materials and Methods: For evaluation of the current situation the prospective epidemiological study by face to face interview method was conducted at Georgian “Manganese Zestafoni Ferroalloy Plant” in 2011-2013. 65.7% of employees (1428 bulletin) were surveyed and the incidence rates of temporary disability days were studied. Results: The average length of a temporary disability single accident was studied taking into consideration as sex groups as well as the whole cohort. According to the classes of harmfulness the following results were received: Class 2.0-10.3%; 3.1-12.4%; 3.2-35.1%; 3.3-12.1%; 3.4-17.6%; 4.0-12.5%. Among the employees 47.5% and 83.1% were tobacco and alcohol consumers respectively. According to the age groups and years of work on the base of previous experience ≥50 ages and ≥21 years of work data prevalence respectively. The obtained data revealed increased morbidity rate according to age and years of work. It was found that the bone and articulate system and connective tissue diseases, aggravation of chronic respiratory diseases, ischemic heart diseases, hypertension and cerebral blood discirculation were the leading among the other diseases. High prevalence of morbidity observed in the workplace with not satisfactory labor conditions from the hygienic point of view. Conclusion: According to received data the causes of morbidity are the followings: unsafety labor conditions; incomplete of preventive medical examinations (preliminary and periodic); lack of access to appropriate health care services; derangement of gathering, recording, and analysis of morbidity data. This epidemiological study was conducted at the JSC “Manganese Ferro Alloy Plant” according to State program “ Prevention of Occupational Diseases” (Program code is 35 03 02 05).

Keywords: occupational health, mining process, morbidity level, cerebral blood discirculation

Procedia PDF Downloads 428

Authors: John Joseph S. Martis, Rohanchandra R. Gatty, Aaron Jose Fernandes, Rahul P. Nambiar

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Introduction: Surgery for breast cancer is either mastectomy or breast conservation surgery. The most commonly used incision for modified radical mastectomy is the transverse Stewart incision. But this incision may have the disadvantage of causing disparity between the closure lines of superior and inferior skin flaps in mastectomy and can cause overhanging of soft tissue below and behind the axilla. The curvizigzag incision, on principle, may help in this regard and can prevent scar migration beyond the anterior axillary line. This study aims to compare the two incisions in this regard. Methods: 100 patients with cancer of breast were included in the study after satisfying inclusion and exclusion criteria. They underwent surgery at Father Muller Medical College, Mangalore, India, between November 2019 to September 2021. The patients were divided into two groups. Group A patients were subjected to modified radical mastectomy with curvizigzag incision and group B patients with transverse Stewart incision. Results: Seroma on postoperative day1, day 2 was 0% in both the groups. Seroma on postoperative day 30 was present in 14% of patients in group B. 60% of patients in group B had sag of soft tissue below and behind the axilla, and none of the patients in group A had this problem. In 64% of the patients in group B, the incision crossed the anterior axillary fold, 64% of the patients in group B had tension in the incision site while approximation of the skin flaps. Conclusion: Curvizigzag incision is statistically better with lesser complications when compared to the transverse Stewart incision for modified radical mastectomy for carcinoma breast.

Keywords: breast cancer, curvizigzag incision, transverse Stewart incision, seroma, modified radical mastectomy

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Authors: Elhamalsadat Ghaffari, Moghan Amirhosseinian, Amir Khaleghipour

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Multifunctional bioactive glasses (BGs) are designed with a focus on the provision of bactericidal and biological properties desired for angiogenesis, osteogenesis, and ultimately potential applications in bone tissue engineering. To achieve these, six sol-gel copper/magnesium substituted derivatives of 58S-BG, i.e. a mol% series of 60SiO₂-4P₂O₅-5CuO-(31-x) CaO/xMgO (where x=0, 1, 3, 5, 8, and 10), were synthesized. Afterwards, the effect of MgO/CaO substitution on the in vitro formation of nano-hydroxyapatite (HA), osteoblast-like cell responses and BGs antibacterial performance were studied. During the BGs synthesis, the elimination of nitrates was achieved at 700 °C that prevented the BGs crystallization and stabilized the obtained dried gels. The structural and morphological evaluations were performed with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These characterizations revealed that Cu-substituted 58S-BG consisting of 5 mol% MgO (BG-5/5) slightly had retarded the formation of HA. In addition, Cu-substituted 58S-BGs consisting 8 mol% and 10 mol% MgO (BG-5/8 and BG-5/10) displayed lower bioactivity probably due to the lower ion release rate of Ca–Si into the simulated body fluid (SBF). The determination of 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and alkaline phosphate (ALP) activities proved that the highest values of both differentiation and proliferation of MC3T3-E1 cells can be obtained from a 5 mol% MgO substituted BG, while the over addition of MgO (8 mol% and 10 mol%) decreased the bioactivity. Furthermore, these novel Cu/Mg-substituted 58S-BGs displayed antibacterial effect against methicillin-resistant Staphylococcus aureus bacteria. Taken together, the results suggest the equally-substituted BG-5/5 (i.e. the one consists of 5 mol% of both CuO and MgO) as a promising candidate for bone tissue engineering, among all newly designed BGs in this work, owing to its desirable cell proliferation, ALP activity and antibacterial properties.

Keywords: apatite, bioactivity, biomedical applications, sol-gel processes

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Authors: Kumaran Narayanan, Andrew N. Osahor

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E. coli has been engineered by our group and by others as a vector to deliver DNA into cultured human and animal cells. However, so far conditions to improve gene delivery using this vector have not been investigated, resulting in a major gap in our understanding of the requirements for this vector to function optimally. Our group recently published novel data showing that simple addition of the DNA transfection reagent Lipofectamine increased the efficiency of the E. coli vector by almost 3-fold, providing the first strong evidence that further optimization of bactofection is possible. This presentation will discuss advances that demonstrate the effects of several intracellular strategies that improve the efficiency of this vector. Conditions that promote endosomal escape of internalized bacteria to evade lysosomal destruction after entry in the cell, a known obstacle limiting this vector, are elucidated. Further, treatments that increase bacterial lysis so that the vector can release its transgene into the mammalian environment for expression will be discussed. These experiments will provide valuable new insight to advance this E. coli system as an important class of vector technology for genetic correction of human disease models in cells and whole animals.

Keywords: DNA, E. coli, gene expression, vector

Procedia PDF Downloads 358

Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: I. A. Farhat

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The dynamic economic dispatch (DED) problem is one of the complex, constrained optimization problems that have nonlinear, con-convex and non-smooth objective functions. The purpose of the DED is to determine the optimal economic operation of the committed units while meeting the load demand. Associated to this constrained problem there exist highly nonlinear and non-convex practical constraints to be satisfied. Therefore, classical and derivative-based methods are likely not to converge to an optimal or near optimal solution to such a dynamic and large-scale problem. In this paper, an Artificial Immune System technique (AIS) is implemented and applied to solve the DED problem considering the transmission power losses and the valve-point effects in addition to the other operational constraints. To demonstrate the effectiveness of the proposed technique, two case studies are considered. The results obtained using the AIS are compared to those obtained by other methods reported in the literature and found better.

Keywords: artificial immune system, dynamic economic dispatch, optimal economic operation, large-scale problem

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Authors: R. Ziaie Moayed, H. Keshavarz Hedayati

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Over recent years, due to increased population and increased waste production, groundwater protection has become more important, therefore, designing engineered barrier systems such as landfill liners to prevent the entry of leachate into groundwater should be done with greater accuracy. These measures generally involve the application of low permeability soils such as clays. Bentonite is a natural clay with low permeability which makes it a suitable soil for using in liners. Also zeolite with high cation exchange capacity can help to reduce of hazardous materials risk. Bentonite expands when wet, absorbing as much as several times its dry mass in water. This property may effect on some structural properties of soil such as shear strength. In present study, shear strength parameters are determined by both leachates polluted and not polluted bentonite-amended zeolite soil with mixing rates (B/Z) of 5%-10% and 20% with unconfined compression test to obtain the differences. It is shown that leachate presence causes reduction in resistance in general.

Keywords: bentonite, leachate, shear strength parameters, unconfined compression test

Procedia PDF Downloads 107

Authors: Chiung-Yun Chang, Po-Chou Chen, Jiun-Shiang Tzeng, Ka-Wai Mac, Chia-Chi Hsiao, Jo-Chi Jao

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This study aimed to measure R2* relaxation rates in the liver of New Zealand White (NZW) rabbits. R2* relaxation rate has been widely used in various hepatic diseases for iron overload by quantifying iron contents in liver. R2* relaxation rate is defined as the reciprocal of T2* relaxation time and mainly depends on the composition of tissue. Different tissues would have different R2* relaxation rates. The signal intensity decay in Magnetic resonance imaging (MRI) may be characterized by R2* relaxation rates. In this study, a 1.5T GE Signa HDxt whole body MR scanner equipped with an 8-channel high resolution knee coil was used to observe R2* values in NZW rabbit’s liver and muscle. Eight healthy NZW rabbits weighted 2 ~ 2.5 kg were recruited. After anesthesia using Zoletil 50 and Rompun 2% mixture, the abdomen of rabbit was landmarked at the center of knee coil to perform 3-plane localizer scan using fast spoiled gradient echo (FSPGR) pulse sequence. Afterward, multi-planar fast gradient echo (MFGR) scans were performed with 8 various echo times (TEs) (2/4/6/8/10/12/14/16 ms) to acquire images for R2* calculations. Regions of interest (ROIs) at liver and muscle were measured using Advantage workstation. Finally, the R2* was obtained by a linear regression of ln(SI) on TE. The results showed that the longer the echo time, the smaller the signal intensity. The R2* values of liver and muscle were 44.8  10.9 s-1 and 37.4  9.5 s-1, respectively. It implies that the iron concentration of liver is higher than that of muscle. In conclusion, R2* is correlated with iron contents in tissue. The correlations between R2* and iron content in NZW rabbit might be valuable for further exploration.

Keywords: liver, magnetic resonance imaging, muscle, R2* relaxation rate

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Authors: Elham Ahmadi

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This study is conducted with the aim of investigating the effect of moderate physical activity (60% of maximal heart rate-MHR) on blood pressure in an elderly female with hypertension. Hypertension is considered a modifiable risk factor for cardiovascular disease through physical activity. The purpose and significance of this study were to investigate the role of exercise as an alternative therapy since some patients exhibit sensitivity/intolerance to some drugs. Initially, 65 hypertensive females (average age = 49.7 years) (systolic blood pressure, SBP >140 mmHg and/or diastolic blood pressure, DBP>85 mmHg) and 25 hypertensive females as a control group (average age = 50.3 years and systolic blood pressure, SBP >140 mmHg and/or diastolic blood pressure, DBP>85 mmHg) were selected. The subjects were divided based on their age, duration of disease, physical activity, and drug consumption. Then, blood pressure and heart rate (HR) were measured in all of the patients using a sphygmomanometer (pre-test). The exercise sessions consisted of warm-up, aerobic activity, and cooling down (total duration of 20 minutes for the first session up to 55 minutes in the last session). At the end of the 12th session (mid-test) and final session (24th session), blood pressure was measured for the last time (post-test). The control group was without any exercise during the study. The results were analyzed using a t-test. Our results indicated that moderate physical activity was effective in lowering blood pressure by 6.4/5.6–mm Hg for SBP and 2.4/4.3mm Hg for DBP in hypertensive patients, irrespective of age, duration of disease, and drug consumption ( P<.005). The control group indicates no changes in BP. Physical activity programs with moderate intensity (approximately at 60% MHR), three days per week, can be used not only as a preventive measure for diastolic hypertension (DBP>90 mmHg high blood pressure) but also as an alternative to drug therapy in the treatment of hypertension, as well.

Keywords: endurance exercise, elderly female, hypertension, physical activity

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Fruzsina Luca Kézér, Viktor Jurkovich, Ottó Szenci, János Tőzsér, Levente Kovács

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Positive interaction between people and animals could have a favorable effect on the welfare and production by reducing stress levels. However, to the repeated contact with humans (e.g. farm staff, veterinarians or herdsmen), animals may respond with escape behavior or avoidance, which both have negative effects on the ease of handling, welfare and may lead to the expression of aggressive behaviors. Rough or aversive handling can impair health and the function of the cardiac autonomic activity due to fear and stress, which also can be determined by certain parameters of heart rate variability (HRV). Although the essential relationships between fear from humans and basal tone of the autonomic nervous system were described by the authors previously, several questions remained unclear in terms of the associations between different coping strategies (behavioral syndromes) of the animals and physiological responsiveness to humans. The main goal of this study was to find out whether human behavior and emotions to the animals have an impact on cardiac function and behavior of animals with different coping styles in response situations. Therefore, in the present study, special (fear, approaching, restraint, novel arena, novel object) tests were performed on healthy, 2-year old heifers (n = 104) differing in coping styles [reactive (passive) vs. proactive (active) coping]. Animals were categorized as reactive or proactive based on the following tests: 1) aggressive behavior at the feeding bunk, 2) avoidance from an approaching person, 3) immobility, and 4) daily activity (number of posture changes). Heart rate, the high frequency (HF) component of HRV as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated for all individual during lying posture (baseline) and for response situations in novel object, novel arena, and unfamiliar person tests (both for 5 min), respectively. The differences between baseline and response were compared between groups. Higher sympathetic (higher heart rates and LF/HF ratios) and lower parasympathetic activity (lower HF) was found for proactive animals in response situations than for reactive (passive) animals either during the novel object, the novel arena and the unfamiliar person test. It suggests that animals with different behavioral traits differ in their immediate autonomic adaptation to novelty and people. Based on our preliminary results, it seems, that the analysis of HRV can help to understand the physiological manifestation of responsiveness to novelty and human presence in dairy cattle with different behavioral syndromes.

Keywords: behavioral syndromes, human-cattle interaction, novel arena test, physiological responsiveness, proactive coping, reactive coping

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Authors: M. Bagheri Varzaneh, H. R. Rahmani, R. Jahanian

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The present study aimed to investigate the effects of copper-methionine on ascites incidence and hematological, morphological and enzymatic responses in broiler chickens. A total of 480 one-day-old Ross 308 broiler chicks were used in a completely randomized design in a 2×3 factorial arrangement of treatments including two ambient temperatures (thermoneutral and cold stress) and three copper levels (0, 100, and 200 mg/kg as copper-methionine) with 4 replicates (20 birds in each replicate). Broilers were kept in an environmentally-controlled room from 1 to 28 days; then, half of them exposed to cold temperature from 28 to 45 days of age. The birds were sacrificed at days 38 and 45 of age. Heparinized blood samples were collected to measure hematocrit, hemoglobin concentration, red blood cell (RBC) count, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Heart, lungs, liver, and spleen were collected and weighed separately on a sensitive digital scale. At d 38 of age, none of hematological variables, enzymatic parameters, and relative weights of organs were affected by treatments. Ascitic broilers were observed in group subjected to cold temperature and control diet (without supplemental copper) at d 45 of age. Relative weight of lungs and relative weight of heart in broilers fed on copper-methionine supplemented diets in cold temperature were lower compared with other groups. Relative liver weight, ALT, AST activities, and hematological parameters such as hematocrit, hemoglobin concentration, red blood cell count in ascitic broilers were significantly increased. In contrast, a significant decrease of the relative weight of spleen was shown in these chickens. The results showed that dietary supplementation with copper–methionine can decrease probability of ascites incidence in broilers chicks, especially under cold condition.

Keywords: ascites, cold temperature, copper-methionine, cold-stressed broiler

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Authors: Odd Ivar Haugen

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This paper presents a framework for assessing the objectivity of the assurance effort for safety-critical complex systems. Assurance is the process of building justified confidence that a system will behave as expected. Objectivity, as a property of the inquiry process, is key to generating this confidence. The framework identifies three main dimensions of objectivity: the methods and processes used to generate system and assurance artefacts, the reasoning and values underlying those artefacts, and the social processes that enable agreement on their validity. Each dimension contributes to overall objectivity, however, not as a set of independent dimensions. Objectivity is not a binary but a matter of degree, and different levels are required depending on the criticality of the system. The framework provides guidance on how to apply the concept of objectivity to different aspects of the assurance effort, from identifying stakeholders and their concerns to communicating risk. Requirement identification and refinement, verification, and risk communication are illustrations of its use in various assurance activities. Overall, this work offers a systematic approach to building justified confidence in the safety of complex engineered systems.

Keywords: assurance, objectivity, risk, uncertainty, knowledge, system safety

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Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

Abstract:

Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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Authors: Samar Omar A. Rabah, Sahar Ragab El Hadad, Fatmah Albani

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Since the discovery of Agarwood (Incense tree), many studies reported its characteristic effects and variable benefits, as either to produce Arabian Incense or as a traditional medicine against many diseases. Laboratory experiments were carried out on the effect of different concentrations of Incense smoke inhalation on the lung weight and tissue in female mice. This research derives its importance from the fact that Incense is heavily used in Saudi Arabia in the absence of thorough studies of its effects on health. Eighty animals are used in this study, and they are divided into four groups, each is 20 animals. Three groups are exposed to different concentrations (2, 4 and 6 gm) of Incense smoke daily for three months, and the fourth group is the control. At the end of each month, five animals from each group were dissected. Obtained data showed an increase but not significant in animal body and lung weight, this results return to natural increase as a result of normal growth of animals. Light microscope reveals some changes in the lung tissue, such as focal emphysema, rupture in the alveolar walls, hemorrhage, congestion, edema and few peri-bronchial lymphoid cells. After continuous exposure to Incense smoke focal necrosis and degradation are observed in some cells of epithelial bronchioles. Also, fibrosis of peri-bronchial, thickening in alveolar walls and aggregation of lymphoid cells are demonstrated in some lungs sections. according to the above manifestations it could be concluded that exposure to Incense smoke causes pulmonary harmful effects. Therefore, we can recommend that Incense smoke will be used only in open places to reduce its harms.

Keywords: incense smoke, lungs, histological changes of lungs, agarwood

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Authors: C. Busuioc, G. Voicu, S. I. Jinga

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The field of tissue engineering brings new challenges in terms of proposing original solutions for ongoing medical issues, improving the biological performances of existing clinical systems and speeding the healing process for a faster recovery and a more comfortable life as patient. In this context, we propose the obtaining of 3D porous scaffolds of mineral nature, dedicated to bone repairing and regeneration purposes or employed as bioactive filler for bone cements. Thus, bacterial cellulose - calcium phosphates composite materials have been synthesized by successive immersing of the polymeric membranes in the precursor solution containing Ca2+ and [PO4]3- ions. The mineral phase deposited on the surface of biocellulose fibers was varied as amount through the number of immersing cycles. The intermediary composites were subjected to thermal treatments at different temperatures in order to remove the organic part and provide the formation of a self-sustained 3D architecture. The resulting phase composition consists of common phosphates, while the morphology largely depends on the preparation parameters. Thus, the aspect of the 3D mineral scaffolds can be tuned from a loose microstructure composed of large grains connected via monocrystalline nanorods to a trabecular pattern crossed by parallel internal channels, just like the natural bone. The bioactivity and biocompatibility of the obtained materials have been also assessed, with encouraging results in the clinical use direction. In conclusion, the compositional, structural, morphological and biological characterizations sustain the suitability of the reported biostructures for integration in hard tissue engineering applications.

Keywords: bacterial cellulose, bone reconstruction, calcium phosphates, mineral scaffolds

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Authors: Nikhil Yadav, Shubham Verma

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Gas lift is a common technique used to optimize oil production in wells. Prosper software is a powerful tool for modeling and optimizing gas lift systems in oil wells. This review paper examines the effectiveness of Prosper software in optimizing gas lift systems in oil-producing wells. The literature review identified several studies that demonstrated the use of Prosper software to adjust injection rate, depth, and valve characteristics to optimize gas lift system performance. The results showed that Prosper software can significantly improve production rates and reduce operating costs in oil-producing wells. However, the accuracy of the model depends on the accuracy of the input data, and the cost of Prosper software can be high. Therefore, further research is needed to improve the accuracy of the model and evaluate the cost-effectiveness of using Prosper software in gas lift system optimization

Keywords: gas lift, prosper software, injection rate, operating costs, oil-producing wells

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: S. Dalvi, N. Sane, V. Patil, D. Bansode, A. Tharakan, V. Mathur

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Measurement of routine clinical electrolyte tests is common in labs worldwide for screening of illness or diseases. All the analyzers for the measurement of electrolyte parameters have sensors, reagents, sampler, pump tubing, valve, other tubing’s separate that are either expensive, require heavy maintenance and have a short shelf-life. Moreover, the costs required to maintain such Lab instrumentation is high and this limits the use of the device to only highly specialized personnel and sophisticated labs. In order to provide Healthcare Diagnostics to ALL at affordable costs, there is a need for an All-in-one Universal Modular Cartridge that contains sensors, reagents, sampler, valve, pump tubing, and other tubing’s in one single integrated module-in-module cartridge that is affordable, reliable, easy-to-use, requires very low sample volume and is truly modular and maintenance-free. DiaSys India has developed a World’s first, Patent Pending, Versatile All-in-one Universal Module-in-Module Cartridge based Electrolyte Analyzer (QDx InstaLyte) that can perform sodium, potassium, chloride, calcium, pH, lithium tests. QDx InstaLyte incorporates High Performance, Inexpensive All-in-one Universal Cartridge for rapid quantitative measurement of electrolytes in body fluids. Our proposed methodology utilizes Advanced & Improved long life ISE sensors to provide a sensitive and accurate result in 120 sec with just 100 µl of sample volume. The All-in-One Universal Cartridge has a very low reagent consumption capable of maximum of 1000 tests with a Use-life of 3-4 months and a long Shelf life of 12-18 months at 4-25°C making it very cost-effective. Methods: QDx InstaLyte analyzers with All-in-one Universal Modular Cartridges were independently evaluated with three R&D lots for Method Performance (Linearity, Precision, Method Comparison, Cartridge Stability) to measure Sodium, Potassium, Chloride. Method Comparison was done against Medica EasyLyte Plus Na/K/Cl Electrolyte Analyzer, a mid-size lab based clinical chemistry analyzer with N = 100 samples run over 10 days. Within-run precision study was done using modified CLSI guidelines with N = 20 samples and day-to-day precision study was done for 7 consecutive days using Trulab N & P Quality Control Samples. Accelerated stability testing was done at 45oC for 4 weeks with Production Lots. Results: Data analysis indicates that the CV for within-run precision for Na is ≤ 1%, for K is ≤2%, and for Cl is ≤2% and with R2 ≥ 0.95 for Method Comparison. Further, the All-in-One Universal Cartridge is stable up to 12-18 months at 4-25oC storage temperature based on preliminary extrapolated data. Conclusion: The Developed Technology Platform of All-in-One Universal Module-in-Module Cartridge based QDx InstaLyte is Reliable and meets all the performance specifications of the lab and is Truly Modular and Maintenance-Free. Hence, it can be easily adapted for low cost, sensitive and rapid measurement of electrolyte tests in low resource settings such as in urban, semi-urban and rural areas in the developing countries and can be used as a Point-of-care testing system for worldwide applications.

Keywords: all-in-one modular catridge, electrolytes, maintenance free, QDx instalyte

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Authors: Cinthya Olivares Garita

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Untangling language processing in second language development has been either a taken-for-granted and overlooked task for some English language teaching (ELT) instructors or a considerable feat for others. From the most traditional language instruction to the most communicative methodologies, how to assist L2 learners in processing language in the classroom has become a challenging matter in second language teaching. Amidst an ample array of methods, strategies, and techniques to teach a target language, finding a suitable model to lead learners to process, interpret, and negotiate meaning to communicate in a second language has imposed a great responsibility on language teachers; committed teachers are those who are aware of their role in equipping learners with the appropriate tools to communicate in the target language in a 21stcentury society. Unfortunately, one might find some English language teachers convinced that their job is only to lecture students; others are advocates of textbook-based instruction that might hinder second language processing, and just a few might courageously struggle to facilitate second language learning effectively. Grounded on the most representative empirical studies on comprehensible input, processing instruction, and focus on form, this analysis aims to facilitate the understanding of how second language learners process and automatize input and propose a pedagogical framework for the successful development of a second language. In light of this, this paper is structured to tackle noticing and attention and structured input as the heart of processing instruction, comprehensible input as the missing link in second language learning, and form-meaning connections as opposed to traditional grammar approaches to language teaching. The author finishes by suggesting a pedagogical framework involving noticing-attention-comprehensible-input-form (NACIF based on their acronym) to support ELT instructors, teachers, and scholars on the challenging task of facilitating the understanding of effective second language development.

Keywords: second language development, pedagogical framework, noticing, attention, comprehensible input, form

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Authors: K. Hinde, R. Bookun, P. Tran

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Percutaneous CT guided biopsies provide a fast, minimally invasive, cost effective and safe method for obtaining tissue for histopathology and culture. Standards for diagnostic yield vary depending on whether the tissue is being obtained for histopathology or culture. We present a retrospective audit from Western Health in Melbourne Australia over a 12-month period which aimed to determine the diagnostic yield, technical success and complication rate for CT guided bone biopsies and identify factors affecting these results. The digital imaging storage program (Synapse Picture Archiving and Communication System – Fujifilm Australia) was analysed with key word searches from October 2015 to October 2016. Nineteen CT guided bone biopsies were performed during this time. The most common referring unit was oncology, work up imaging included CT, MRI, bone scan and PET scan. The complication rate was 0%, overall diagnostic yield was 74% with a technical success of 95%. When performing biopsies for histologic analysis diagnostic yield was 85% and when performing biopsies for bacterial culture diagnostic yield was 60%. There was no significant relationship identified between size of lesion, distance of lesion to skin, lesion appearance on CT, the number of samples taken or gauge of needle to diagnostic yield or technical success. CT guided bone biopsy at Western Health meets the standard reported at other major clinical centres for technical success and safety. It is a useful investigation in identification of primary malignancy in distal bone metastases.

Keywords: bone biopsy, computed tomography, core biopsy, histopathology

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Authors: Fatema-Tuz-Zohra Khanam, Ali Al-Naji, Asanka G. Perera, Kim Gibson, Javaan Chahl

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Conventional contact-based vital signs monitoring sensors such as pulse oximeters or electrocardiogram (ECG) may cause discomfort, skin damage, and infections, particularly in neonates with fragile, sensitive skin. Therefore, remote monitoring of the vital sign is desired in both clinical and non-clinical settings to overcome these issues. Camera-based vital signs monitoring is a recent technology for these applications with many positive attributes. However, there are still limited camera-based studies on neonates in a clinical setting. In this study, the heart rate (HR) and respiratory rate (RR) of eight infants at the Neonatal Intensive Care Unit (NICU) in Flinders Medical Centre were remotely monitored using a digital camera applying color and motion-based computational methods. The region-of-interest (ROI) was efficiently selected by incorporating an image decomposition method. Furthermore, spatial averaging, spectral analysis, band-pass filtering, and peak detection were also used to extract both HR and RR. The experimental results were validated with the ground truth data obtained from an ECG monitor and showed a strong correlation using the Pearson correlation coefficient (PCC) 0.9794 and 0.9412 for HR and RR, respectively. The RMSE between camera-based data and ECG data for HR and RR were 2.84 beats/min and 2.91 breaths/min, respectively. A Bland Altman analysis of the data also showed a close correlation between both data sets with a mean bias of 0.60 beats/min and 1 breath/min, and the lower and upper limit of agreement -4.9 to + 6.1 beats/min and -4.4 to +6.4 breaths/min for both HR and RR, respectively. Therefore, video camera imaging may replace conventional contact-based monitoring in NICU and has potential applications in other contexts such as home health monitoring.

Keywords: neonates, NICU, digital camera, heart rate, respiratory rate, image decomposition

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Authors: Ramandeep Kaur, Makula Ajitha

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Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

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Authors: Tim Bolle, Franziska Kreimendahl, Thomas Gries, Stefan Jockenhoevel

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The therapeutic treatment of extensive, deep wounds is limited. Autologous split-skin grafts are used as a so-called ‘gold standard’. Most common deficits are the defects at the donor site, the risk of scarring as well as the limited availability and quality of the autologous grafts. The aim of this project is a tissue engineered dermal-epidermal skin replacement to overcome the limitations of the gold standard. A key requirement for the development of such a three-dimensional implant is the formation of a functional capillary-like network inside the implant to ensure a sufficient nutrient and gas supply. Tailored three-dimensional warp knitted spacer fabrics are used to reinforce the mechanically week fibrin gel-based scaffold and further to create a directed in vitro pre-vascularization along the parallel-oriented pile yarns within a co-culture. In this study various three-dimensional warp knitted spacer fabrics were developed in a factorial design to analyze the influence of the machine parameters such as the stitch density and the pattern of the fabric on the scaffold performance and further to determine suitable parameters for a successful fibrin gel-incorporation and a physiological performance of the scaffold. The fabrics were manufactured on a Karl Mayer double-bar raschel machine DR 16 EEC/EAC. A fine machine gauge of E30 was used to ensure a high pile yarn density for sufficient nutrient, gas and waste exchange. In order to ensure a high mechanical stability of the graft, the fabrics were made of biocompatible PVDF yarns. Key parameters such as the pore size, porosity and stress/strain behavior were investigated under standardized, controlled climate conditions. The influence of the input parameters on the mechanical and morphological properties as well as the ability of fibrin gel incorporation into the spacer fabric was analyzed. Subsequently, the pile yarns of the spacer fabrics were colonized with Human Umbilical Vein Endothelial Cells (HUVEC) to analyze the ability of the fabric to further function as a guiding structure for a directed vascularization. The cells were stained with DAPI and investigated using fluorescence microscopy. The analysis revealed that the stitch density and the binding pattern have a strong influence on both the mechanical and morphological properties of the fabric. As expected, the incorporation of the fibrin gel was significantly improved with higher pore sizes and porosities, whereas the mechanical strength decreases. Furthermore, the colonization trials revealed a high cell distribution and density on the pile yarns of the spacer fabrics. For a tailored reinforcing structure, the minimum porosity and pore size needs to be evaluated which still ensures a complete incorporation of the reinforcing structure into the fibrin gel matrix. That will enable a mechanically stable dermal graft with a dense vascular network for a sufficient nutrient and oxygen supply of the cells. The results are promising for subsequent research in the field of reinforcing mechanically weak biological scaffolds and develop functional three-dimensional scaffolds with an oriented pre-vascularization.

Keywords: fibrin-gel, skin replacement, spacer fabric, pre-vascularization

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