Search results for: soft tissue sarcomas

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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Authors: Carolina Schencke, Cristian Sandoval, Belgica Vasquez, Mariano Del Sol

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Introduction: In a burn injury, the successful repair requires not only the participation of various cells, such as granulocytes and fibroblasts, but also of collagen, which plays a crucial role as a structural and regulatory molecule of scar tissue. Since honey and ascorbic acid have presented a great therapeutic potential to cellular and structural level, experimental studies have proposed its combination in the treatment of wounds. Aim: To evaluate stereological and morphometric parameters of healing wounds, caused by burns, treated with honey Ulmo (Eucryphia cordifolia) unsupplemented, comparing its effect with Ulmo honey supplemented with ascorbic acid. Materials and Methods: Fifteen healthy adult guinea pigs (Cavia porcellus) were used, of both sexes, average weight 450 g from the Centro de Excelencia en Estudios Morfológicos y Quirúrgicos (CEMyQ) at the Universidad de La Frontera, Chile. The animals were divided at random into three groups: positive control (C+), honey only (H) and supplemented honey (SH) and were fed on pellets supplemented with ascorbic acid and water ad libitum, under ambient conditions controlled for temperature, ambient noise and a cycle of 12h light–darkness. The protocol for the experiment was approved by the Scientific Ethics Committee of the Universidad de La Frontera, Chile. The parameters measured were number density per area (NA), volume density (VV), and surface density (SV) of fibroblast; NA and VV of polymorphonuclear cells (PMN) and, evaluation of the content of collagen fibers in the scar dermis. One-way ANOVA was used for statistics analysis and its respective Post hoc tests. Results: The ANOVA analysis for NA, VV and SV of fibroblasts, NA and VV of PMN, and evaluation of collagen content, type I and III, showed that at least one group differs from other (P≤ 0.001). There were differences (P= 0.000) in NA of fibroblast between the groups [C+= 3599.560 mm-2 (SD= 764.461), H= 3355.336 mm-2 (SD= 699.443) and SH= 4253.025 mm-2 (SD= 1041.751)]. The VV and SV of fibroblast increased (P= 0.000) in the SH group [20.400% (SD= 5.897) and 100.876 mm2/mm3 (SD= 29.431), respectively], compared to the C+ [16.324% (SD= 7.719) and 81.676 mm2/mm3 (SD= 28.884), respectively). The mean values of NA and VV of PMN were higher (P= 0.000) in the H [756.875 mm-2 (SD= 516.489) and 2.686% (SD= 2.380), respectively) group. Regarding to the evaluation of the content of collagen fibers, type I and III, the one-way analysis of ANOVA showed a statistically significant difference (P< 0.05). The content of collagen fibers type I was higher in C+ (1988.292 μm2; SD= 1312.379), while the content of collagen fibers type III was higher in SH (1967.163 μm2; SD= 1047.944 μm2) group. Conclusions: The stereological results were correlated with the stage of healing observed for each group. These results suggest that the combination of honey with ascorbic acid potentiate the healing effect, where both participated synergistically.

Keywords: ascorbic acid, morphometry, stereology, Ulmo honey

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Authors: M. Ghasemi, S.Fazelifar

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Abstract Aim: Over-weight is not desirable and has implications for health and in the case of athletes affects performance. Exercise is a strategy used to counteract overweight owing to create a negative energy balance by increasing energy expenditure and influencing appetite regulating hormones. Interestingly, recent studies have revealed inhibitory effects of exercise on the hunger associated with these hormones in healthy subjects Neuropeptide Y(NPY) is a 36 amino acid protein that is a powerful stimulant appetite. NPY is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue. This neurotransmitter is secreted in the brain and autonomic nervous system. On the other hand, research has shown that thyme in addition to various properties, also affects the appetite. The purpose of this study was to determine Effects of eight weeks endurance training and thyme consumption on neuropeptide Y in untrained men. Methodology: 36 Healthy untrained men (mean body weight 78.25±3.2 kg, height 176±6.8 cm, age 34.32±4.54 years and BMI 29.1±4.3 kg/m2) voluntarily participated in this study . Subjects were randomly divided into four groups: 1. control, 2. Endurance training, 3. Thyme 4. Endurance training + Thyme. Amount of 10cc Blood sampling were obtained pre-test and post-test (after 8 weeks). The taken blood samples were centrifuged at 1500 × g for 15 min then plasma was stored at -20 °C until analysis. Endurance training consisted three session per week with 60% -75% of reserve heart rate for eight weeks. Exclusion criteria were history of gastrointestinal, endocrine, cardiovascular or psychological disease, and consuming any supplementation, alcohol and tobacco products. Descriptive statistics including means, standard deviations, and ranges were calculated for all measures. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p<0/05 accepted. Results: Results showed that aerobic training significantly reduced body weight, body mass index, percent body fat, but significant increase observed in maximal oxygen consumption level (p ≤ 0/05). The neuropeptide Y levels were significantly increased after exercise. Analysis of data determined that there was no significant difference between the four groups. Conclusion: Appetite control plays a critical role in the competition between energy consumption and energy expenditure. The results of this study showed that endurance training and thyme consumption can be cause improvement in physiological parameters such as increasing aerobic capacity, reduction of fat mass and improve body composition in untrained men.

Keywords: Endurance training, neuropeptide Y, thyme, untrained men

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Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

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Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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Authors: John T. Leman, James Gibson, Peter J. Bonitatibus

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There have been no potential clinically translatable developments of intravenous CT contrast materials over decades, and iodinated contrast agents (ICA) remain the only FDA-approved media for CT. Small molecule ICA used to highlight vascular anatomy have weak CT signals in large-to-obese patients due to their rapid redistribution from plasma into interstitial fluid, thereby diluting their intravascular concentration, and because of a mismatch of iodine’s K-edge and the high kVp settings needed to image this patient population. The use of ICA is also contraindicated in a growing population of renally impaired patients who are hypersensitive to these contrast agents; a transformative intravenous contrast agent with improved capabilities is urgently needed. Tantalum oxide nanoparticles (TaO NPs) with zwitterionic siloxane polymer coatings have high potential as clinically translatable general-purpose CT contrast agents because of (1) substantially improved imaging efficacy compared to ICA in swine/phantoms emulating medium-sized and larger adult abdomens and superior thoracic vascular contrast enhancement of thoracic arteries and veins in rabbit, (2) promising biological safety profiles showing near-complete renal clearance and low tissue retention at 3x anticipated clinical dose (ACD), and (3) clinically acceptable physiochemical parameters as concentrated bulk solutions(250-300 mgTa/mL). Here, we review requirements for general-purpose intravenous CT contrast agents in terms of patient safety, X-ray attenuating properties and contrast-producing capabilities, and physicochemical and pharmacokinetic properties. We report the current status of a TaO NP-based contrast agent, including chemical process technology developments and results of newly defined scaled-up processes for NP synthesis and purification, yielding reproducible formulations with appropriate size and concentration specifications. We discuss recent results of recent pre-clinical in vitro immunology, non-GLP high dose tolerability in rats (10x ACD), non-GLP long-term biodistribution in rats at 3x ACD, and non-GLP repeat dose in rats at ACD. We also include a discussion of NP characterization, in particular size-stability testing results under accelerated conditions (37C), and insights into TaO NP purity, surface structure, and bonding of the zwitterionic siloxane polymer coating by multinuclear (1H, 13C, 29Si) and multidimensional (2D) solution NMR spectroscopy.

Keywords: nanoparticle, imaging, diagnostic, process technology, nanoparticle characterization

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Authors: Alessandra Panico, Francesco Bagordo, Tiziana Grassi, Adele Idolo, Marcello Guido, Francesca Serio, Mattia De Giorgi, Antonella De Donno

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In the Province of Lecce (Southeastern Italy) an area with unusual high incidence of chronic respiratory diseases, including lung cancer, was recently identified. The causes of this health emergency are still not entirely clear. In order to determine the risk profile of children living in five municipalities included in this area an epidemiological-molecular study was performed in the years 2014-2016: the IMP.AIR. (Impact of air quality on health of residents in the Municipalities of Sternatia, Galatina, Cutrofiano, Sogliano Cavour and Soleto) study. 122 children aged 6-8 years attending primary school in the study area were enrolled to evaluate the frequency of micronuclei (MNs) in their buccal exfoliated cells. The samples were collected in May 2015 by rubbing the oral mucosa with a soft bristle disposable toothbrush. At the same time, a validated questionnaire was administered to parents to obtain information about health, lifestyle and eating habits of the children. In addition, information on airborne pollutants, routinely detected by the Regional Environmental Agency (ARPA Puglia) in the study area, was acquired. A multivariate analysis was performed to detect any significant association between frequency of MNs (dependent variable) and behavioral factors (independent variables). The presence of MNs was highlighted in the buccal exfoliated cells of about 42% of recruited children with a mean frequency of 0.49 MN/1000 cells, greater than in other areas of Salento. The survey on individual characteristics and lifestyles showed that one in three children was overweight and that most of them had unhealthy eating habits with frequent consumption of foods considered ‘risky’. Moreover many parents (40% of fathers and 12% of mothers) were smokers and about 20% of them admitted to smoking in the house where the children lived. Information regarding atmospheric contaminants was poor. Of the few substances routinely detected by the only one monitoring station located in the study area (PM2.5, SO2, NO2, CO, O3) only ozone showed high concentrations exceeding the limits set by the legislation for 67 times in the year 2015. The study showed that the level of early biological effect markers in children was not negligible. This critical condition could be related to some individual factors and lifestyles such as overweight, unhealthy eating habits and exposure to passive smoking. At present, no relationship with airborne pollutants can be established due to the lack of information on many substances. Therefore, it would be advisable to modify incorrect behaviors and to intensify the monitoring of airborne pollutants (e.g. including detection of PM10, heavy metals, aromatic polycyclic hydrocarbons, benzene) given the epidemiology of chronic respiratory diseases registered in this area.

Keywords: chronic respiratory diseases, environmental pollution, lifestyle, micronuclei

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Authors: Milos Beran, Josef Drahorad, Ondrej Vltavsky, Martin Fronek, Jiri Sova

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While most nanofibers are produced using electrospinning, this technique suffers from several drawbacks, such as the requirement for specialized equipment, high electrical potential, and electrically conductive targets. Consequently, recent years have seen the increasing emergence of novel strategies in generating nanofibers in a larger scale and higher throughput manner. The centrifugal spinning is simple, cheap and highly productive technology for nanofiber production. In principle, the drawing of solution filament into nanofibers using centrifugal spinning is achieved through the controlled manipulation of centrifugal force, viscoelasticity, and mass transfer characteristics of the spinning solutions. Engineering efforts of researches of the Food research institute Prague and the Czech Technical University in the field the centrifugal nozzleless spinning led to introduction of a pilot plant demonstrator NANOCENT. The main advantages of the demonstrator are lower investment cost - thanks to simpler construction compared to widely used electrospinning equipments, higher production speed, new application possibilities and easy maintenance. The centrifugal nozzleless spinning is especially suitable to produce submicron fibers from polymeric solutions in highly volatile solvents, such as chloroform, DCM, THF, or acetone. To date, submicron fibers have been prepared from PS, PUR and biodegradable polyesters, such as PHB, PLA, PCL, or PBS. The products are in form of 3D structures or nanofiber membranes. Unique self-supporting nanofiber membranes were prepared from the biodegradable polyesters in different mixtures. The nanofiber membranes have been tested for different applications. Filtration efficiencies for water solutions and aerosols in air were evaluated. Different active inserts were added to the solutions before the spinning process, such as inorganic nanoparticles, organic precursors of metal oxides, antimicrobial and wound healing compounds or photocatalytic phthalocyanines. Sintering can be subsequently carried out to remove the polymeric material and transfer the organic precursors to metal oxides, such as Si02, or photocatalytic Zn02 and Ti02, to obtain inorganic nanofibers. Electrospinning is more suitable technology to produce membranes for the filtration applications than the centrifugal nozzleless spinning, because of the formation of more homogenous nanofiber layers and fibers with smaller diameters. The self-supporting nanofiber membranes prepared from the biodegradable polyesters are especially suitable for medical applications, such as wound or burn healing dressings or tissue engineering scaffolds. This work was supported by the research grants TH03020466 of the Technology Agency of the Czech Republic.

Keywords: polymeric nanofibers, self-supporting nanofiber membranes, biodegradable polyesters, active inserts

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Authors: Cristina Chaminade, Mandar Kulkarni, Balaji Parthasarathy, Monica Plechero

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The characteristics of a regional innovation system (RIS) and the specificity of the knowledge base of an industry may contribute to create peculiar paths for innovation and development of firms’ geographic extended innovation networks. However, the relative empirical evidence in emerging economies remains underexplored. The paper aims to fill the research gap by means of some recent qualitative research conducted in 2016 in Beijing (China) and Bangalore (India). It analyzes cases studies of firms in the new media industry, a sector that merges different IT competences with competences from other knowledge domains and that is emerging in those RIS. The results show that while in Beijing the new media sector results to be more in line with the existing institutional setting and governmental goals aimed at targeting specific social aspects and social problems of the population, in Bangalore it remains a more spontaneous firms-led process. In Beijing what matters for the development of innovation networks is the governmental setting and the national and regional strategies to promote science and technology in this sector, internet and mass innovation. The peculiarities of recent governmental policies aligned to the domestic goals may provide good possibilities for start-ups to develop innovation networks. However, due to the specificities of those policies targeting the Chinese market, networking outside the domestic market are not so promoted. Moreover, while some institutional peculiarities, such as a culture of collaboration in the region, may be favorable for local networking, regulations related to Internet censorship may limit the use of global networks particularly when based on virtual spaces. Mainly firms with already some foreign experiences and contact take advantage of global networks. In Bangalore, the role of government in pushing networking for the new media industry at the present stage is quite absent at all geographical levels. Indeed there is no particular strategic planning or prioritizing in the region toward the new media industry, albeit one industrial organization has emerged to represent the animation industry interests. This results in a lack of initiatives for sustaining the integration of complementary knowledge into the local portfolio of IT specialization. Firms actually involved in the new media industry face institutional constrains related to a poor level of local trust and cooperation, something that does not allow for full exploitation of local linkages. Moreover, knowledge-provider organizations in Bangalore remain still a solid base for the IT domain, but not for other domains. Initiatives to link to international networks seem therefore more the result of individual entrepreneurial actions aimed at acquiring complementary knowledge and competencies from different domains and exploiting potentiality in different markets. From those cases, it emerges that role of government, soft institutions and organizations in the two RIS differ substantially in the creation of barriers and opportunities for the development of innovation networks and their specific aim.

Keywords: regional innovation system, emerging economies, innovation network, institutions, organizations, Bangalore, Beijing

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Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan

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This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

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Authors: Alena Kulikova, Leonid Parmaksiz, Ekaterina Orel

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Social and emotional skills are considered by modern researchers as predictors of a person's success both in specific areas of activity and in the life of a person as a whole. The popularity of this scientific direction ensures the emergence of a large number of practices aimed at developing and evaluating socio-emotional skills. Assessment of social and emotional development is carried out at the national level, as well as at the level of individual regions and institutions. Despite the fact that many of the already existing social and emotional skills assessment tools are quite convenient and reliable, there are now more and more new technologies and task formats which improve the basic characteristics of the tools. Thus, the goal of the current study is to develop a tool for assessing social and emotional skills such as emotion recognition, emotion regulation, empathy and a culture of self-care. To develop a tool assessing social and emotional skills, Rasch-Gutman scenario-based approach was used. This approach has shown its reliability and merit for measuring various complex constructs: parental involvement; teacher practices that support cultural diversity and equity; willingness to participate in the life of the community after psychiatric rehabilitation; educational motivation and others. To assess emotion recognition, we used a situational judgment task based on OCC (Ortony, Clore, and Collins) emotions theory. The main advantage of these two approaches compare to classical Likert scales is that it reduces social desirability in answers. A field test to check the psychometric properties of the developed instrument was conducted. The instrument was developed for the presidential autonomous non-profit organization “Russia - Land of Opportunity” for nationwide soft skills assessment among higher education students. The sample for the field test consisted of 500 people, students aged from 18 to 25 (mean = 20; standard deviation 1.8), 71% female. 67% of students are only studying and are not currently working and 500 employed adults aged from 26 to 65 (mean = 42.5; SD 9), 57% female. Analysis of the psychometric characteristics of the scales was carried out using the methods of IRT (Item Response Theory). A one-parameter rating scale model RSM (Rating scale model) and Graded Response model (GRM) of the modern testing theory were applied. GRM is a polyatomic extension of the dichotomous two-parameter model of modern testing theory (2PL) based on the cumulative logit function for modeling the probability of a correct answer. The validity of the developed scales was assessed using correlation analysis and MTMM (multitrait-multimethod matrix). The developed instrument showed good psychometric quality and can be used by HR specialists or educational management. The detailed results of a psychometric study of the quality of the instrument, including the functioning of the tasks of each scale, will be presented. Also, the results of the validity study by MTMM analysis will be discussed.

Keywords: social and emotional skills, psychometrics, MTMM, IRT

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Authors: Kusno Kamil, Andi Asni, Sungkono

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According to a report of the World Food and Agriculture Agency (FAO): the post-harvest fish losses in Indonesia reaches 30 percent from 170 trillion rupiahs of marine fisheries reserves, then the potential loss reaches 51 trillion rupiahs (end of 2016 data). This condition is caused by traditionally vulnerable fish catches damaged due to disruption of the cold chain of preservation. The physical and chemical changes in fish flesh increase rapidly, especially if exposed to the scorching heat in the middle of the sea, exacerbated by the low awareness of catch hygiene; many unclean catches which contain blood are often treated without special attention and mixed with freshly caught fish, thereby increasing the potential for faster fish spoilage. This background encourages research on traditional fisherman catch preservation methods that aim to find the best and most affordable methods and/or combinations of fish preservation methods so that they can help fishermen increase their fishing duration without worrying that their catch will be damaged, thereby reducing their economic value when returning to the beach to sell their catches. This goal is expected to be achieved through experimental methods of treatment of fresh fish catches in containers with the addition of anti-bacterial copper, liquid smoke solution, and the use of vacuum containers. The other three treatments combined the three previous treatment variables with an electrically powered cooler (temperature 0~4 ᵒC). As a control specimen, the untreated fresh fish (placed in the open air and in the refrigerator) were also prepared for comparison for 1, 3, and 6 days. To test the level of freshness of fish for each treatment, physical observations were used, which were complemented by tests for bacterial content in a trusted laboratory. The content of copper (Cu) in fish meat (which is suspected of having a negative impact on consumers) was also part of the examination on the 6th day of experimentation. The results of physical observations on the test specimens (organoleptic method) showed that preservation assisted by the use of coolers was still better for all treatment variables. The specimens, without cooling, sequentially showed that the best preservation effectiveness was the addition of copper plates, the use of vacuum containers, and then liquid smoke immersion. Especially for liquid smoke, soaking for 6 days of preservation makes the fish meat soft and easy to crumble, even though it doesn't have a bad odor. The visual observation was then complemented by the results of testing the amount of growth (or retardation) of putrefactive bacteria in each treatment of test specimens within similar observation periods. Laboratory measurements report that the minimum amount of putrefactive bacteria achieved by preservation treatment combining cooler with liquid smoke (sample A+), then cooler only (D+), copper layer inside cooler (B+), vacuum container inside cooler (C+), respectively. Other treatments in open air produced a hundred times more putrefactive bacteria. In addition, treatment of the copper layer contaminated the preserved fresh fish more than a thousand times bigger compared to the initial amount, from 0.69 to 1241.68 µg/g.

Keywords: fish, preservation, traditional, fishermen, boat

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Authors: Marta Paszkiewicz, Justyna Łuczak, Martyna Marchelek, Adriana Zaleska-Medynska

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In recent years, photocatalytical processes have been intensively investigated for destruction of pollutants, hydrogen evolution, disinfection of water, air and surfaces, for the construction of self-cleaning materials (tiles, glass, fibres, etc.). Titanium dioxide (TiO2) is the most popular material used in heterogeneous photocatalysis due to its excellent properties, such as high stability, chemical inertness, non-toxicity and low cost. It is well known that morphology and microstructure of TiO2 significantly influence the photocatalytic activity. This characteristics as well as other physical and structural properties of photocatalysts, i.e., specific surface area or density of crystalline defects, could be controlled by preparation route. In this regard, TiO2 particles can be obtained by sol-gel, hydrothermal, sonochemical methods, chemical vapour deposition and alternatively, by ionothermal synthesis using ionic liquids (ILs). In the TiO2 particles synthesis ILs may play a role of a solvent, soft template, reagent, agent promoting reduction of the precursor or particles stabilizer during synthesis of inorganic materials. In this work, the effect of the ILs anion type on morphology and photoactivity of TiO2 is presented. The preparation of TiO2 microparticles with spherical structure was successfully achieved by solvothermal method, using tetra-tert-butyl orthotitatane (TBOT) as the precursor. The reaction process was assisted by an ionic liquids 1-butyl-3-methylimidazolium bromide [BMIM][Br], 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4] and 1-butyl-3-methylimidazolium haxafluorophosphate [BMIM][PF6]. Various molar ratios of all ILs to TBOT (IL:TBOT) were chosen. For comparison, reference TiO2 was prepared using the same method without IL addition. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brenauer-Emmett-Teller surface area (BET), NCHS analysis, and FTIR spectroscopy were used to characterize the surface properties of the samples. The photocatalytic activity was investigated by means of phenol photodegradation in the aqueous phase as a model pollutant, as well as formation of hydroxyl radicals based on detection of fluorescent product of coumarine hydroxylation. The analysis results showed that the TiO2 microspheres had spherical structure with the diameters ranging from 1 to 6 µm. The TEM micrographs gave a bright observation of the samples in which the particles were comprised of inter-aggregated crystals. It could be also observed that the IL-assisted TiO2 microspheres are not hollow, which provides additional information about possible formation mechanism. Application of the ILs results in rise of the photocatalytic activity as well as BET surface area of TiO2 as compared to pure TiO2. The results of the formation of 7-hydroxycoumarin indicated that the increased amount of ·OH produced at the surface of excited TiO2 for samples TiO2_ILs well correlated with more efficient degradation of phenol. NCHS analysis showed that ionic liquids remained on the TiO2 surface confirming structure directing role of that compounds.

Keywords: heterogeneous photocatalysis, IL-assisted synthesis, ionic liquids, TiO2

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Authors: M. Karzhauov, А. Mukhambetova, M. Sarsenova, E. Raimagambetov, V. Ogay

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Regeneration of injured articular cartilage remains one of the most difficult and unsolved problems in traumatology and orthopedics. Currently, for the treatment of cartilage defects surgical techniques for stimulation of the regeneration of cartilage in damaged joints such as multiple microperforation, mosaic chondroplasty, abrasion and microfractures is used. However, as shown by clinical practice, they can not provide a full and sustainable recovery of articular hyaline cartilage. In this regard, the current high hopes in the regeneration of cartilage defects reasonably are associated with the use of tissue engineering approaches to restore the structural and functional characteristics of damaged joints using stem cells, growth factors and biopolymers or scaffolds. The purpose of the present study was to investigate the effects of chondroinductive growth factors and synovium-derived mesenchymal stem cells (SD-MSCs) on the regeneration of cartilage defects in rabbits. SD-MSCs were isolated from the synovium membrane of Flemish giant rabbits, and expanded in complete culture medium α-MEM. Rabbit SD-MSCs were characterized by CFU-assay and by their ability to differentiate into osteoblasts, chondrocytes and adipocytes. The effects of growth factors (TGF-β1, BMP-2, BMP-4 and IGF-I) on MSC chondrogenesis were examined in micromass pellet cultures using histological and biochemical analysis. Articular cartilage defect (4mm in diameter) in the intercondylar groove of the patellofemoral joint was performed with a kit for the mosaic chondroplasty. The defect was made until subchondral bone plate. Delivery of SD-MSCs and growth factors was conducted in combination with hyaloronic acid (HA). SD-MSCs, growth factors and control groups were compared macroscopically and histologically at 10, 30, 60 and 90 days aftrer intra-articular injection. Our in vitro comparative study revealed that TGF-β1 and BMP-4 are key chondroinductive factors for both the growth and chondrogenesis of SD-MSCs. The highest effect on MSC chondrogenesis was observed with the synergistic interaction of TGF-β1 and BMP-4. In addition, biochemical analysis of the chondrogenic micromass pellets also revealed that the levels of glycosaminoglycans and DNA after combined treatment with TGF-β1 and BMP-4 was significantly higher in comparison to individual application of these factors. In vivo study showed that for complete regeneration of cartilage defects with intra-articular injection of SD-MSCs with HA takes time 90 days. However, single injection of SD-MSCs in combiantion with TGF-β1, BMP-4 and HA significantly promoted regeneration rate of the cartilage defects in rabbits. In this case, complete regeneration of cartilage defects was observed in 30 days after intra-articular injection. Thus, our in vitro and in vivo study demonstrated that combined application of rabbit SD-MSC with chondroinductive growth factors and HA results in strong synergistic effect on the chondrogenesis significantly enhancing regeneration of the damaged cartilage.

Keywords: Mesenchymal stem cells, synovium, chondroinductive factors, TGF-β1, BMP-2, BMP-4, IGF-I

Procedia PDF Downloads 306

Authors: Mustafa M. Donma, Orkide Donma

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Obesity is associated with cardiovascular disease risk factors and metabolic syndrome (MetS). In this study, associations between adipokines and adipokine as well as obesity indices were evaluated. Plasma adipokine levels may exhibit variations according to body adipose tissue mass. Besides, upon consideration of obesity as an inflammatory disease, adipokines may play some roles in this process. The ratios of proinflammatory adipokines to adiponectin may act as highly sensitive indicators of body adipokine status. The aim of the study is to present some adipokine indices, which are thought to be helpful for the evaluation of childhood obesity and also to determine the best discriminators in the diagnosis of MetS. 80 prepubertal children (aged between 6-9.5 years) included in the study were divided into three groups; 30 children with normal weight (NW), 25 morbid obese (MO) children and 25 MO children with MetS. Physical examinations were performed. Written informed consent forms were obtained from the parents. The study protocol was approved by Ethics Committee of Namik Kemal University Medical Faculty. Anthropometric measurements, such as weight, height, waist circumference (C), hip C, head C, neck C were recorded. Values for body mass index (BMI), diagnostic obesity notation model assessment Index-II (D2 index) as well as waist-to-hip, head-to-neck ratios were calculated. Adiponectin, resistin, leptin, chemerin, vaspin, progranulin assays were performed by ELISA. Adipokine-to-adiponectin ratios were obtained. SPSS Version 20 was used for the evaluation of data. p values ≤ 0.05 were accepted as statistically significant. Values of BMI and D2 index, waist-to-hip, head-to-neck ratios did not differ between MO and MetS groups (p ≥ 0.05). Except progranulin (p ≤ 0.01), similar patterns were observed for plasma levels of each adipokine. There was not any difference in vaspin as well as resistin levels between NW and MO groups. Significantly increased leptin-to-adiponectin, chemerin-to-adiponectin and vaspin-to-adiponectin values were noted in MO in comparison with those of NW. The most valuable adipokine index was progranulin-to-adiponectin (p ≤ 0.01). This index was strongly correlated with vaspin-to-adiponectin ratio in all groups (p ≤ 0.05). There was no correlation between vaspin-to-adiponectin and chemerin-to--adiponectin in NW group. However, a correlation existed in MO group (r = 0.486; p ≤ 0.05). Much stronger correlation (r = 0.609; p ≤ 0.01) was observed in MetS group between these two adipokine indices. No correlations were detected between vaspin and progranulin as well as vaspin and chemerin levels. Correlation analyses showed a unique profile confined to MetS children. Adiponectin was found to be correlated with waist-to-hip (r = -0.435; p ≤ 0.05) as well as head-to-neck (r = 0.541; p ≤ 0.05) ratios only in MetS children. In this study, it has been investigated if adipokine indices have priority over adipokine levels. In conclusion, vaspin-to-adiponectin, progranulin-to-adiponectin, chemerin-to-adiponectin along with waist-to-hip and head-to-neck ratios were the optimal combinations. Adiponectin, waist-to-hip, head-to-neck, vaspin-to-adiponectin, chemerin-to-adiponectin ratios had appropriate discriminatory capability for MetS children.

Keywords: adipokine indices, metabolic syndrome, obesity indices, pediatric obesity

Procedia PDF Downloads 205

Authors: Patrícia Severino, Luciana Nalone, Daniele Martins, Marco Chaud, Classius Ferreira, Cristiane Bani, Ricardo Albuquerque

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Hydrogels produced with polymers have been used in the development of dressings for wound treatment and tissue revitalization. Our study on polymer nanocomposites containing silver nanoparticles shows antimicrobial activity and applications in wound healing. The effects are linked with the slow oxidation and Ag⁺ liberation to the biological environment. Furthermore, bacterial cell membrane penetration and metabolic disruption through cell cycle disarrangement also contribute to microbial cell death. The silver antimicrobial activity has been known for many years, and previous reports show that low silver concentrations are safe for human use. This work aims to develop a hydrogel using natural polymers (sodium alginate and gelatin) combined with silver nanoparticles for wound healing and with antimicrobial properties in cutaneous lesions. The hydrogel development utilized different sodium alginate and gelatin proportions (20:80, 50:50 and 80:20). The silver nanoparticles incorporation was evaluated at the concentrations of 1.0, 2.0 and 4.0 mM. The physico-chemical properties of the formulation were evaluated using ultraviolet-visible (UV-Vis) absorption spectroscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric (TG) analysis. The morphological characterization was made using transmission electron microscopy (TEM). Human fibroblast (L2929) viability assay was performed with a minimum inhibitory concentration (MIC) assessment as well as an in vivo cicatrizant test. The results suggested that sodium alginate and gelatin in the (80:20) proportion with 4 mM of AgNO₃ in the (UV-Vis) exhibited a better hydrogel formulation. The nanoparticle absorption spectra of this analysis showed a maximum band around 430 - 450 nm, which suggests a spheroidal form. The TG curve exhibited two weight loss events. DSC indicated one endothermic peak at 230-250 °C, due to sample fusion. The polymers acted as stabilizers of a nanoparticle, defining their size and shape. Human fibroblast viability assay L929 gave 105 % cell viability with a negative control, while gelatin presented 96% viability, alginate: gelatin (80:20) 96.66 %, and alginate 100.33 % viability. The sodium alginate:gelatin (80:20) exhibited significant antimicrobial activity, with minimal bacterial growth at a ratio of 1.06 mg.mL⁻¹ in Pseudomonas aeruginosa and 0.53 mg.mL⁻¹ in Staphylococcus aureus. The in vivo results showed a significant reduction in wound surface area. On the seventh day, the hydrogel-nanoparticle formulation reduced the total area of injury by 81.14 %, while control reached a 45.66 % reduction. The results suggest that silver-hydrogel nanoformulation exhibits potential for wound dressing therapeutics.

Keywords: nanocomposite, wound healing, hydrogel, silver nanoparticle

Procedia PDF Downloads 101

Authors: Rania Raouf Sedky

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Adaptive architecture relates to buildings specifically designed to adapt to their residents and their environments. To design a biologically adaptive system, we can observe how living creatures in nature constantly adapt to different external and internal stimuli to be a great inspiration. The issue is not just how to create a system that is capable of change but also how to find the quality of change and determine the incentive to adapt. The research examines the possibilities of transforming spaces using the human body as an active tool. The research also aims to design and build an effective dynamic structural system that can be applied on an architectural scale and integrate them all into the creation of a new adaptive system that allows us to conceive a new way to design, build and experience architecture in a dynamic manner. The main objective was to address the possibility of a reciprocal transformation between the user and the architectural element so that the architecture can adapt to the user, as the user adapts to architecture. The motivation is the desire to deal with the psychological benefits of an environment that can respond and thus empathize with human emotions through its ability to adapt to the user. Adaptive affiliations of kinematic structures have been discussed in architectural research for more than a decade, and these issues have proven their effectiveness in developing kinematic structures, responsive and adaptive, and their contribution to 'smart architecture'. A wide range of strategies have been used in building complex kinetic and robotic systems mechanisms to achieve convertibility and adaptability in engineering and architecture. One of the main contributions of this research is to explore how the physical environment can change its shape to accommodate different spatial displays based on the movement of the user’s body. The main focus is on the relationship between materials, shape, and interactive control systems. The intention is to develop a scenario where the user can move, and the structure interacts without any physical contact. The soft form of shifting language and interaction control technology will provide new possibilities for enriching human-environmental interactions. How can we imagine a space in which to construct and understand its users through physical gestures, visual expressions, and response accordingly? How can we imagine a space whose interaction depends not only on preprogrammed operations but on real-time feedback from its users? The research also raises some important questions for the future. What would be the appropriate structure to show physical interaction with the dynamic world? This study concludes with a strong belief in the future of responsive motor structures. We imagine that they are developing the current structure and that they will radically change the way spaces are tested. These structures have obvious advantages in terms of energy performance and the ability to adapt to the needs of users. The research highlights the interface between remote sensing and a responsive environment to explore the possibility of an interactive architecture that adapts to and responds to user movements. This study ends with a strong belief in the future of responsive motor structures. We envision that it will improve the current structure and that it will bring a fundamental change to the way in which spaces are tested.

Keywords: adaptive architecture, interactive architecture, responsive architecture, tensegrity

Procedia PDF Downloads 156

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

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Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 114

Authors: Evgeny A. Ermakov, Lyudmila P. Smirnova, Valentina N. Buneva

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Schizophrenia associated with dysregulation of neurotransmitter processes in the central nervous system and disturbances in the humoral immune system resulting in the formation of antibodies (Abs) to the various components of the nervous tissue. Abs to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes. It is believed that DNA-hydrolyzing abzymes are cytotoxic, cause nuclear DNA fragmentation and induce cell death by apoptosis. Abzymes with DNAase activity are interesting because of the mechanism of formation and the possibility of use as diagnostic markers. Therefore, in our work we have set following goals: to determine the level anti-DNA Abs in the serum of patients with schizophrenia and to study DNA-hydrolyzing activity of IgG of patients with schizophrenia. Materials and methods: In our study there were included 41 patients with a verified diagnosis of paranoid or simple schizophrenia and 24 healthy donors. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the serum proteins on protein G-Sepharose and gel filtration. The levels of anti-DNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level of supercoiled pBluescript DNA transition in circular and linear forms, the hydrolysis products were analyzed by agarose electrophoresis followed by ethidium bromide stain. To correspond the registered catalytic activity directly to the antibodies we carried out a number of strict criteria: electrophoretic homogeneity of the antibodies, gel filtration (acid shock analysis) and in situ activity. Statistical analysis was performed in ‘Statistica 9.0’ using the non-parametric Mann-Whitney test. Results: The sera of approximately 30% of schizophrenia patients displayed a higher level of Abs interacting with single-stranded (ssDNA) and double-stranded DNA (dsDNA) compared with healthy donors. The average level of Abs interacting with ssDNA was only 1.1-fold lower than that for interacting with dsDNA. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. Using affinity chromatography, electrophoretic analysis of isolated IgG homogeneity, gel filtration in acid shock conditions and in situ DNAse activity analysis we proved that the observed activity is intrinsic property of studied antibodies. We have shown that the relative DNAase activity of IgG in patients with schizophrenia averaged 55.4±32.5%, IgG of healthy donors showed much lower activity (average of 9.1±6.5%). It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher (73.3±23.8%), than in patients with positive symptoms (43.3±33.1%). Conclusion: Anti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. The data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.

Keywords: anti-DNA antibodies, abzymes, DNA hydrolysis, schizophrenia

Procedia PDF Downloads 328

Authors: Beste Ozcan, Valerio Sperati, Laura Romano, Tania Moretta, Simone Scaffaro, Noemi Faedda, Federica Giovannone, Carla Sogos, Vincenzo Guidetti, Gianluca Baldassarre

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+me is an experimental interactive toy with the appearance of a soft, pillow-like, panda. Shape and consistency are designed to arise emotional attachment in young children: a child can wear it around his/her neck and treat it as a companion (i.e. a transitional object). When caressed on paws or head, the panda emits appealing, interesting outputs like colored lights or amusing sounds, thanks to embedded electronics. Such sensory patterns can be modified through a wirelessly connected tablet: by this, an adult caregiver can adapt +me responses to a child's reactions or requests, for example, changing the light hue or the type of sound. The toy control is therefore shared, as it depends on both the child (who handles the panda) and the adult (who manages the tablet and mediates the sensory input-output contingencies). These features make +me a potential tool for therapy with children with Neurodevelopmental Disorders (ND), characterized by impairments in the social area, like Autism Spectrum Disorders (ASD) and Language Disorders (LD): as a proposal, the toy could be used together with a therapist, in rehabilitative play activities aimed at encouraging simple social interactions and reinforcing basic relational and communication skills. +me was tested in two pilot experiments, the first one involving 15 Typically Developed (TD) children aged in 8-34 months, the second one involving 7 children with ASD, and 7 with LD, aged in 30-48 months. In both studies a researcher/caregiver, during a one-to-one, ten-minute activity plays with the panda and encourages the child to do the same. The purpose of both studies was to ascertain the general acceptability of the device as an interesting toy that is an object able to capture the child's attention and to maintain a high motivation to interact with it and with the adult. Behavioral indexes for estimating the interplay between the child, +me and caregiver were rated from the video recording of the experimental sessions. Preliminary results show how -on average- participants from 3 groups exhibit a good engagement: they touch, caress, explore the panda and show enjoyment when they manage to trigger luminous and sound responses. During the experiments, children tend to imitate the caregiver's actions on +me, often looking (and smiling) at him/her. Interesting behavioral differences between TD, ASD, and LD groups are scored: for example, ASD participants produce a fewer number of smiles both to panda and to a caregiver with respect to TD group, while LD scores stand between ASD and TD subjects. These preliminary observations suggest that the interactive toy +me is able to raise and maintain the interest of toddlers and therefore it can be reasonably used as a supporting tool during therapy, to stimulate pivotal social skills as imitation, turn-taking, eye contact, and social smiles. Interestingly, the young age of participants, along with the behavioral differences between groups, seem to suggest a further potential use of the device: a tool for early differential diagnosis (the average age of a child

Keywords: autism spectrum disorders, interactive toy, social interaction, therapy, transitional wearable companion

Procedia PDF Downloads 123

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

Procedia PDF Downloads 281

Authors: Irina Veselova, Maria Makedonskaya, Olga Eremina, Alexandr Sidorov, Eugene Goodilin, Tatyana Shekhovtsova

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Such catecholamines as dopamine, norepinephrine, and epinephrine are the principal neurotransmitters in the sympathetic nervous system. Catecholamines and their metabolites are considered to be important markers of socially significant diseases such as atherosclerosis, diabetes, coronary heart disease, carcinogenesis, Alzheimer's and Parkinson's diseases. Currently, neurotransmitters can be studied via electrochemical and chromatographic techniques that allow their characterizing and quantification, although these techniques can only provide crude spatial information. Besides, the difficulty of catecholamine determination in biological materials is associated with their low normal concentrations (~ 1 nM) in biomaterials, which may become even one more order lower because of some disorders. In addition, in blood they are rapidly oxidized by monoaminooxidases from thrombocytes and, for this reason, the determination of neurotransmitter metabolism indicators in an organism should be very rapid (15—30 min), especially in critical states. Unfortunately, modern instrumental analysis does not offer a complex solution of this problem: despite its high sensitivity and selectivity, HPLC-MS cannot provide sufficiently rapid analysis, while enzymatic biosensors and immunoassays for the determination of the considered analytes lack sufficient sensitivity and reproducibility. Fluorescent and SERS-sensors remain a compelling technology for approaching the general problem of selective neurotransmitter detection. In recent years, a number of catecholamine sensors have been reported including RNA aptamers, fluorescent ribonucleopeptide (RNP) complexes, and boronic acid based synthetic receptors and the sensor operated in a turn-off mode. In this work we present the fluorescent and SERS turn-on sensor systems based on the bio- or chemorecognizing nanostructured films {chitosan/collagen-Tb/Eu/Cu-nanoparticles-indicator reagents} that provide the selective recognition, visualization, and sensing of the above mentioned catecholamines on the level of nanomolar concentrations in biomaterials (cell cultures, tissue etc.). We have (1) developed optically transparent porous films and gels of chitosan/collagen; (2) ensured functionalization of the surface by molecules-'recognizers' (by impregnation and immobilization of components of the indicator systems: biorecognizing and auxiliary reagents); (3) performed computer simulation for theoretical prediction and interpretation of some properties of the developed materials and obtained analytical signals in biomaterials. We are grateful for the financial support of this research from Russian Foundation for Basic Research (grants no. 15-03-05064 a, and 15-29-01330 ofi_m).

Keywords: biomaterials, fluorescent and SERS-recognition, neurotransmitters, solid-phase turn-on sensor system

Procedia PDF Downloads 406

Authors: Chris Miskelly, Eoin Cunningham, Beatrice Smyth, John. D. Holbrey, Gosia Swadzba-Kwasny, Emily L. Byrne, Yoan Delavoux, Mantian Li.

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Recently, the use of ionic liquids (ILs) for the preparation of lignocellulose derived cellulosic materials as alternatives to petrochemical feedstocks has been the focus of considerable research interest. While the technical viability of IL-based lignocellulose treatment methodologies has been well established, the high cost of reagents inhibits commercial feasibility. This work aimed to assess the technoeconomic viability of the preparation of cellulose rich materials (CRMs) using protic ionic liquids (PILs) synthesized from low cost alkylamines and sulphuric acid. For this purpose, the tertiary alkylamines, triethylamine, and dimethylbutylamine were selected. Bulk scale production cost of the synthesized PILs, triethylammonium hydrogen sulphate and dimetheylbutylammonium hydrogen sulphate, was reported as $0.78 kg-1 to $1.24 kg-1. CRMs were prepared through the treatment of common wheat (Triticum aestivum) straw with these PILs. By controlling treatment parameters, CRMs with a cellulose content of ≥ 80 wt% were prepared. This was achieved using a T. aestivum straw to PIL loading ratio of 1:15 w/w, a treatment duration of 180 minutes, and ethanol as a cellulose antisolvent. Infrared spectra data and decreased onset degradation temperature of CRMs (ΔTONSET ~ 70 °C) suggested the formation of cellulose sulphate esters during treatment. Chemical derivatisation can aid the dispersion of prepared CRMs in non-polar polymer/ composite matrices, but act as a barrier to thermal processing at temperatures above 150 °C. It was also shown that treatment increased the crystallinity of CRMs (ΔCrI ~ 40 %) without altering the native crystalline structure or crystallite size (~ 2.6 nm) of cellulose; peaks associated with the cellulose I crystalline planes (110), (200), and (004) were observed at Bragg angles 16.0 °, 22.5 ° and 35.0 ° respectively. This highlighted the inability of assessed PILs to dissolve crystalline cellulose and was attributed to the high acidity (pKa ~ - 1.92 to - 6.42) of sulphuric acid derived anions. Electron micrographs revealed that the stratified multilayer tissue structure of untreated T. aestivum straw was significantly modified during treatment. T. aestivum straw particles were disassembled during treatment, with prepared CRMs adopting a golden-brown film-like appearance. This work demonstrated the degradation of non-cellulosic fractions of lignocellulose without dissolution of cellulose. It is the first to report on the derivatisation of cellulose during treatment with protic hydrogen sulphate ionic liquids, and the potential implications of this with reference to biopolymer feedstock preparation.

Keywords: cellulose, extraction, protic ionic liquids, esterification, thermal stability, waste valorisation, biopolymer feedstock

Procedia PDF Downloads 36

Authors: Kiran Sharma, Viktor Kunder, Zerha Rizvi, Ricardo Soubelet

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Platelet rich plasma (PRP) has been recognized as a method of treatment in medicine since the 1980s. It primarily functions by releasing cytokines and growth factors that promote wound healing; these growth promoting factors released by PRP enact new processes such as angiogenesis, collagen deposition, and tissue formation that can change wound healing outcomes. Many studies recognize that PRP aids in chronic wound healing, which is advantageous for patients who suffer from chronic diabetic foot ulcers (DFUs). This scoping review aims to examine literature to identify the efficacy of PRP use in the healing of DFUs. Following PRISMA guidelines, we searched randomized-controlled trials involving PRP use in diabetic patients with foot ulcers using PubMed, Medline, CINAHL Complete, and Cochrane Database of Systematic Reviews. We restricted the search to articles published during 2005-2022, full texts in the English language, articles involving patients aged 19 years or older, articles that used PRP on specifically DFUs, articles that included a control group, articles on human subjects. The initial search yielded 119 articles after removing duplicates. Final analysis for relevance yielded 8 articles. In all cases except one, the PRP group showed either faster healing, more complete healing, or a larger percentage of healed participants. There were no situations in the included studies where the control group had a higher rate of healing or decreased wound size as compared to a group with isolated PRP-only use. Only one study did not show conclusive evidence that PRP caused accelerated healing in DFUs, and this study did not have an isolated PRP variable group. Application styles of PRP for treatment were shown to influence the level of healing in patients, with injected PRP appearing to achieve the best results as compared to topical PRP application. However, this was not conclusive due to the involvement of several other variables. Two studies additionally found PRP to be useful in healing refractory DFUs, and one study found that PRP use in patients with additional comorbidities was still more effective in healing DFUs than the standard control groups. The findings of this review suggest that PRP is a useful tool in reducing healing times and improving rates of complete wound healing in DFUs. There is room for further research in the application styles of PRP before conclusive statements can be made on the efficacy of injected versus topical PRP healing based on the findings in this study. The results of this review provide a baseline for further research in PRP use in diabetic patients and can be used by both physicians and public health experts to guide future treatment options for DFUs.

Keywords: diabetic foot ulcer, DFU, platelet rich plasma, PRP

Procedia PDF Downloads 75

Authors: Justin Byrne, Jose Ramon Cobo

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The growing importance of cross- or intercultural competencies (used here interchangeably) for the business and management professionals is now a commonplace in both academic and professional literature. This reflects two parallel developments. On the one hand, it is a consequence of the increased attention paid to a whole range of 'soft skills', now seen as fundamental in both individuals' and corporate success. On the other hand, and more specifically, the increasing demand for interculturally competent professionals is a corollary of ongoing processes of globalization, which multiply and intensify encounters between individuals and companies from different cultural backgrounds. Business schools have, for some decades, responded to the needs of the job market and their own students by providing students with training in intercultural skills, as they are encouraged to do so by the major accreditation agencies on both sides of the Atlantic. Adapting Early and Ang's (2003) formulation of Cultural Intelligence (CQ), this paper aims to help fill the lagunae in the current literature on intercultural training in three main ways. First, it offers an in-depth analysis of the CQ of a little studied group: contemporary Millenial and 'Generation Z' Business School students. The level of analysis distinguishes between the four different dimensions of CQ, cognition, metacognition, motivation and behaviour, and thereby provides a detailed picture of the strengths and weaknesses in CQ of the group as a whole, as well as of different sub-groups and profiles of students. Secondly, by crossing these individual-level findings with respondents' socio-cultural and educational data, this paper also proposes and tests hypotheses regarding the relative impact and importance of four possible antecedents of intercultural skills identified in the literature: prior international experience; intercultural training, foreign language proficiency, and experience of cultural diversity in habitual country of residence. Third, we use this analysis to suggest data-based intercultural training priorities for today's management students. These conclusions are based on the statistical analysis of individual responses of some 300 Bachelor or Masters students in a major European Business School provided to two on-line surveys: Ang, Van Dyne, et al's (2007) standard 20-question self-reporting CQ Scale, and an original questionnaire designed by the authors to collate information on respondent's socio-demographic and educational profile relevant to our four hypotheses and explanatory variables. The data from both instruments was crossed in both descriptive statistical analysis and regression analysis. This research shows that there is no statistically significant and positive relationship between the four antecedents analyzed and overall CQ level. The exception in this respect is the statistically significant correlation between international experience, and the cognitive dimension of CQ. In contrast, the results show that the combination of international experience and foreign language skills acting together, does have a strong overall impact on CQ levels. These results suggest that selecting and/or training students with strong foreign language skills and providing them with international experience (through multinational programmes, academic exchanges or international internships) constitutes one effective way of training culturally intelligent managers of tomorrow.

Keywords: business school, cultural intelligence, millennial, training

Procedia PDF Downloads 158

Authors: Rizvi Hasan

Abstract:

Male factor infertility due to abnormalities in prolactin levels is encountered in a significant proportion. This was a case-control study carried out to determine the effects of prolactin abnormalities in normal males with infertility, recruiting 297 male infertile patients with informed written consent. All underwent a Basic Seminal Fluid Analysis (BSA) and endocrine profiles of FSH, LH, testosterone and prolactin (PRL) hormones using the random access chemiluminescent immunoassay method (normal range 2.5-17ng/ml). Age, weight, and height matched voluntary controls were recruited for comparison. None of the cases had anatomical, medical or surgical disorders related to infertility. Among the controls; mean age 33.2yrs ± 5.2, BMI 21.04 ± 1.39kgm-2, BSA 34×106, a number of children fathered 2±1, PRL 6.78 ± 2.92ng/ml. Of the 297 patients, 28 were hyperprolactinaemic while one was hypoprolactinaemic. All the hyperprolactinaemic patients had oligoasthenospermia, abnormal morphology and decreased viability. The serum testosterone levels were markedly lowered in 26 (92.86%) of the hyperprolactinaemic subjects. In the other 2 hyperprolactinaemic subjects and the single hypoprolactinaemic subject, the serum testosterone levels were normal. FSH and LH were normal in all patients. The 29 male patients with abnormalities in their serum PRL profiles were followed up for 12 months. The 28 patients suffering from hyperprolactinaemia were treated with oral bromocriptine in a dose of 2.5 mg twice daily. The hypoprolactinaemic patient defaulted treatment. From the follow-up, it was evident that 19 (67.86%) of the treated patients responded after 3 months of therapy while 4 (14.29%) showed improvement after approximately 6 months of bromocriptine therapy. One patient responded after 1 year of therapy while 2 patients showed improvements although not up to normal levels within the same period. Response to treatment was assessed by improvement in their BSA parameters. Prolactin abnormalities affect the male reproductive system and semen parameters necessitating further studies to ascertain the exact role of prolactin on the male reproductive tract. A parallel study was carried out incorporating 200 male white rats that were grouped and subjected to variations in their serum PRL levels. At the end of 100 days of treatment, these rats were subjected to morphological studies of their male reproductive tracts.Varying morphological changes depending on the levels of PRL changes induced were evident. Notable changes were arrest of spermatogenesis at the spermatid stage, a reduced testicular cellularity, a reduction in microvilli of the pseudostratified epithelial lining of the epididymis, while measurement of the tubular diameter showed a 30% reduction compared to normal tissue. There were no changes in the vas deferens, seminal vesicles, and the prostate. It is evident that both hyperprolactinaemia and hypoprolactinaemia have a direct effect on the morphology and function of the male reproductive tract. The morphological studies carried out on the groups of rats who were subjected to variations in their PRL levels could be the basis for infertility in male human beings.

Keywords: male factor infertility, morphological studies, prolactin, seminal fluid analysis

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Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Constantinos S. Mammas, Andreas Lazaris, Adamantia S. Mamma-Graham, Georgia Kostopanagiotou, Chryssa Lemonidou, John Mantas, Eustratios Patsouris

Abstract:

The process to build a better safety culture, methods of error analysis, and preventive measures, starts with an understanding of the effects when human factors engineering refer to remote microscopic diagnosis in surgery and specially in organ transplantation for the evaluation of the grafts. Α high percentage of solid organs arrive at the recipient hospitals and are considered as injured or improper for transplantation in the UK. Digital microscopy adds information on a microscopic level about the grafts (G) in Organ Transplant (OT), and may lead to a change in their management. Such a method will reduce the possibility that a diseased G will arrive at the recipient hospital for implantation. Aim: The aim of this study is to analyze the ergonomics of digital microscopy (DM) based on virtual slides, on telemedicine systems (TS) for tele-pathological evaluation (TPE) of the grafts (G) in organ transplantation (OT). Material and Methods: By experimental simulation, the ergonomics of DM for microscopic TPE of renal graft (RG), liver graft (LG) and pancreatic graft (PG) tissues is analyzed. In fact, this corresponded to the ergonomics of digital microscopy for TPE in OT by applying virtual slide (VS) system for graft tissue image capture, for remote diagnoses of possible microscopic inflammatory and/or neoplastic lesions. Experimentation included the development of an OTE-TS similar experimental telemedicine system (Exp.-TS) for simulating the integrated VS based microscopic TPE of RG, LG and PG Simulation of DM on TS based TPE performed by 2 specialists on a total of 238 human renal graft (RG), 172 liver graft (LG) and 108 pancreatic graft (PG) tissues digital microscopic images for inflammatory and neoplastic lesions on four electronic spaces of the four used TS. Results: Statistical analysis of specialist‘s answers about the ability to accurately diagnose the diseased RG, LG and PG tissues on the electronic space among four TS (A,B,C,D) showed that DM on TS for TPE in OT is elaborated perfectly on the ES of a desktop, followed by the ES of the applied Exp.-TS. Tablet and mobile-phone ES seem significantly risky for the application of DM in OT (p<.001). Conclusion: To make the largest reduction in errors and adverse events referring to the quality of the grafts, it will take application of human factors engineering to procurement, design, audit, and awareness-raising activities. Consequently, it will take an investment in new training, people, and other changes to management activities for DM in OT. The simulating VS based TPE with DM of RG, LG and PG tissues after retrieval, seem feasible and reliable and dependable on the size of the electronic space of the applied TS, for remote prevention of diseased grafts from being retrieved and/or sent to the recipient hospital and for post-grafting and pre-transplant planning.

Keywords: digital microscopy, organ transplantation, tele-pathology, virtual slides

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim

Abstract:

Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.

Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic

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Authors: Rana Mohamed, Ahmed E. Gomaa, Gehan Safwat, Ayman Diab

Abstract:

Background: Bio-fabrication is a multidisciplinary research field that combines several principles, fabrication techniques, and protocols from different fields. The open-source-software movement is a movement that supports the use of open-source licenses for some or all software as part of the broader notion of open collaboration. Additive manufacturing is the concept of 3D printing, where it is a manufacturing method through adding layer-by-layer using computer-aided designs (CAD). There are several types of AM system used, and they can be categorized by the type of process used. One of these AM technologies is Digital light processing (DLP) which is a 3D printing technology used to rapidly cure a photopolymer resin to create hard scaffolds. DLP uses a projected light source to cure (Harden or crosslinking) the entire layer at once. Current applications of DLP are focused on dental and medical applications. Other developments have been made in this field, leading to the revolutionary field 3D bioprinting. The open-source movement was started to spread the concept of open-source software to provide software or hardware that is cheaper, reliable, and has better quality. Objective: Modification of desktop 3D printer into 3D bio-printer and the integration of DLP technology and bio-fabrication to produce an antibacterial dental model. Method: Modification of a desktop 3D printer into a 3D bioprinter. Gelatin hydrogel and sodium alginate hydrogel were prepared with different concentrations. Rhizome of Zingiber officinale, Flower buds of Syzygium aromaticum, and Bulbs of Allium sativum were extracted, and extractions were selected on different levels (Powder, aqueous extracts, total oils, and Essential oils) prepared for antibacterial bioactivity. Agar well diffusion method along with the E. coli have been used to perform the sensitivity test for the antibacterial activity of the extracts acquired by Zingiber officinale, Syzygium aromaticum, and Allium sativum. Lastly, DLP printing was performed to produce several dental models with the natural extracted combined with hydrogel to represent and simulate the Hard and Soft tissues. Result: The desktop 3D printer was modified into 3D bioprinter using open-source software Marline and modified custom-made 3D printed parts. Sodium alginate hydrogel and gelatin hydrogel were prepared at 5% (w/v), 10% (w/v), and 15%(w/v). Resin integration with the natural extracts of Rhizome of Zingiber officinale, Flower buds of Syzygium aromaticum, and Bulbs of Allium sativum was done following the percentage 1- 3% for each extract. Finally, the Antimicrobial dental model was printed; exhibits the antimicrobial activity, followed by merging with sodium alginate hydrogel. Conclusion: The open-source movement was successful in modifying and producing a low-cost Desktop 3D Bioprinter showing the potential of further enhancement in such scope. Additionally, the potential of integrating the DLP technology with bioprinting is a promising step toward the usage of the antimicrobial activity using natural products.

Keywords: 3D printing, 3D bio-printing, DLP, hydrogel, antibacterial activity, zingiber officinale, syzygium aromaticum, allium sativum, panax ginseng, dental applications

Procedia PDF Downloads 93