Search results for: preimplantation genetic screening
Commenced in January 2007
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Edition: International
Paper Count: 2689

Search results for: preimplantation genetic screening

229 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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228 Curcumin and Its Analogues: Potent Natural Antibacterial Compounds against Staphylococcus aureus

Authors: Prince Kumar, Shamseer Kulangara Kandi, Diwan S. Rawat, Kasturi Mukhopadhyay

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Staphylococcus aureus is the most pathogenic of all staphylococci, a major cause of nosocomial infections, and known for acquiring resistance towards various commonly used antibiotics. Due to the widespread use of synthetic drugs, clinicians are now facing a serious threat in healthcare. The increasing resistance in staphylococci has created a need for alternatives to these synthetic drugs. One of the alternatives is a natural plant-based medicine for both disease prevention as well as the treatment of chronic diseases. Among such natural compounds, curcumin is one of the most studied molecules and has been an integral part of traditional medicines and Ayurveda from ancient times. It is a natural polyphenolic compound with diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancerous and antibacterial activities. In spite of its efficacy and potential, curcumin has not been approved as a therapeutic agent yet, because of its low solubility, low bioavailability, and rapid metabolism in vivo. The presence of central β-diketone moiety in curcumin is responsible for its rapid metabolism. To overcome this, in the present study, curcuminoids were designed by modifying the central β-diketone moiety of curcumin into mono carbonyl moiety and their antibacterial potency against S. aureus ATCC 29213 was determined. Further, the mode of action and hemolytic activity of the most potent curcuminoids were studied. Minimum inhibitory concentration (MIC) and in vitro killing kinetics were used to study the antibacterial activity of the designed curcuminoids. For hemolytic assay, mouse Red blood cells were incubated with curcuminoids and hemoglobin release was measured spectrophotometrically. The mode of action of curcuminoids was analysed by membrane depolarization assay using membrane potential sensitive dye 3,3’-dipropylthiacarbocyanine iodide (DiSC3(5)) through spectrofluorimetry and membrane permeabilization assay using calcein-AM through flow cytometry. Antibacterial screening of the designed library (61 curcuminoids) revealed excellent in vitro potency of six compounds against S. aureus (MIC 8 to 32 µg/ml). Moreover, these six compounds were found to be non-hemolytic up to 225 µg/ml that is much higher than their corresponding MIC values. The in vitro killing kinetics data showed five of these lead compounds to be bactericidal causing >3 log reduction in the viable cell count within 4 hrs at 5 × MIC while the sixth compound was found to be bacteriostatic. Depolarization assay revealed that all the six curcuminoids caused depolarization in their corresponding MIC range. Further, the membrane permeabilization assay showed that all the six curcuminoids caused permeabilization at 5 × MIC in 2 hrs. This membrane depolarization and permeabilization caused by curcuminoids found to be in correlation with their corresponding killing efficacy. Both these assays point out that membrane perturbations might be a primary mode of action for these curcuminoids. Overall, the present study leads us six water soluble, non-hemolytic, membrane-active curcuminoids and provided an impetus for further research on therapeutic use of these lead curcuminoids against S. aureus.

Keywords: antibacterial, curcumin, minimum inhibitory concentration , Staphylococcus aureus

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227 Cluster-Based Exploration of System Readiness Levels: Mathematical Properties of Interfaces

Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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A key factor in technological immaturity in defense weapons acquisition is lack of understanding critical integrations at the subsystem and component level. To address this shortfall, recent research in integration readiness level (IRL) combines with technology readiness level (TRL) to form a system readiness level (SRL). SRL can be enriched with more robust quantitative methods to provide the program manager a useful tool prior to committing to major weapons acquisition programs. This research harnesses previous mathematical models based on graph theory, Petri nets, and tropical algebra and proposes a modification of the desirable SRL mathematical properties such that a tightly integrated (multitude of interfaces) subsystem can display a lower SRL than an inherently less coupled subsystem. The synthesis of these methods informs an improved decision tool for the program manager to commit to expensive technology development. This research ties the separately developed manufacturing readiness level (MRL) into the network representation of the system and addresses shortfalls in previous frameworks, including the lack of integration weighting and the over-importance of a single extremely immature component. Tropical algebra (based on the minimum of a set of TRLs or IRLs) allows one low IRL or TRL value to diminish the SRL of the entire system, which may not be reflective of actuality if that component is not critical or tightly coupled. Integration connections can be weighted according to importance and readiness levels are modified to be a cardinal scale (based on an analytic hierarchy process). Integration arcs’ importance are dependent on the connected nodes and the additional integrations arcs connected to those nodes. Lack of integration is not represented by zero, but by a perfect integration maturity value. Naturally, the importance (or weight) of such an arc would be zero. To further explore the impact of grouping subsystems, a multi-objective genetic algorithm is then used to find various clusters or communities that can be optimized for the most representative subsystem SRL. This novel calculation is then benchmarked through simulation and using past defense acquisition program data, focusing on the newly introduced Middle Tier of Acquisition (rapidly field prototypes). The model remains a relatively simple, accessible tool, but at higher fidelity and validated with past data for the program manager to decide major defense acquisition program milestones.

Keywords: readiness, maturity, system, integration

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226 A Description Analysis of Mortality Rate of Human Infection with Avian Influenza A(H7N9) Virus in China

Authors: Lei Zhou, Chao Li, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: Since the first human infection with avian influenza A(H7N9) case was reported in China on 31 March 2013, five epidemics have been observed in China through February 2013 and September 2017. Though the overall mortality rate of H7N9 has remained as high as around 40% throughout the five epidemics, the specific mortality rate in Mainland China varied by provinces. We conducted a descriptive analysis of mortality rates of H7N9 cases to explore the various severity features of the disease and then to provide clues of further analyses of potential factors associated with the severity of the disease. Methods: The data for analysis originated from the National Notifiable Infectious Disease Report and Surveillance System (NNIDRSS). The surveillance system and identification procedure for H7N9 infection have not changed in China since 2013. The definition of a confirmed H7N9 case is as same as previous reports. Mortality rates of H7N9 cases are described and compared by time and location of reporting, age and sex, and genetic features of H7N9 virus strains. Results: The overall mortality rate, the male and female specific overall rates of H7N9 is 39.6% (608/1533), 40.3% (432/1072) and 38.2% (176/461), respectively. There was no significant difference between the mortality rates of male and female. The age-specific mortality rates are significantly varied by age groups (χ²=38.16, p < 0.001). The mortality of H7N9 cases in the age group between 20 and 60 (33.17%) and age group of over 60 (51.16%) is much higher than that in the age group of under 20 (5.00%). Considering the time of reporting, the mortality rates of cases which were reported in the first (40.57%) and fourth (42.51%) quarters of each year are significantly higher than the mortality of cases which were reported in the second (36.02%) and third (27.27%) quarters (χ²=75.18, p < 0.001). The geographic specific mortality rates vary too. The mortality rates of H7N9 cases reported from the Northeast China (66.67%) and Westeast China (56.52%) are significantly higher than that of H7N9 cases reported from the remained area of mainland China. The mortality rate of H7N9 cases reported from the Central China is the lowest (34.38%). The mortality rates of H7N9 cases reported from rural (37.76%) and urban (38.96%) areas are similar. The mortality rate of H7N9 cases infected with the highly pathogenic avian influenza A(H7N9) virus (48.15%) is higher than the rate of H7N9 cases infected with the low pathogenic avian influenza A(H7N9) virus (37.57%), but the difference is not statistically significant. Preliminary analyses showed that age and some clinical complications such as respiratory failure, heart failure, and septic shock could be potential risk factors associated with the death of H7N9 cases. Conclusions: The mortality rates of H7N9 cases varied by age, sex, time of reporting and geographical location in mainland China. Further in-depth analyses and field investigations of the factors associated with the severity of H7N9 cases need to be considered.

Keywords: H7N9 virus, Avian Influenza, mortality, China

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225 Cultural Adaptation of an Appropriate Intervention Tool for Mental Health among the Mohawk in Quebec

Authors: Liliana Gomez Cardona, Mary McComber, Kristyn Brown, Arlene Laliberté, Outi Linnaranta

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The history of colonialism and more contemporary political issues have resulted in the exposure of Kanien'kehá:ka: non (Kanien'kehá:ka of Kahnawake) to challenging and even traumatic experiences. Colonization, religious missions, residential schools as well as economic and political marginalization are the factors that have challenged the wellbeing and mental health of these populations. In psychiatry, screening for mental illness is often done using questionnaires with which the patient is expected to respond to how often he/she has certain symptoms. However, the Indigenous view of mental wellbeing may not fit well with this approach. Moreover, biomedical treatments do not always meet the needs of Indigenous people because they do not understand the culture and traditional healing methods that persist in many communities. Assess whether the questionnaires used to measure symptoms, commonly used in psychiatry are appropriate and culturally safe for the Mohawk in Quebec. Identify the most appropriate tool to assess and promote wellbeing and follow the process necessary to improve its cultural sensitivity and safety for the Mohawk population. Qualitative, collaborative, and participatory action research project which respects First Nations protocols and the principles of ownership, control, access, and possession (OCAP). Data collection based on five focus groups with stakeholders working with these populations and members of Indigenous communities. Thematic analysis of the data collected and emerging through an advisory group that led a revision of the content, use, and cultural and conceptual relevance of the instruments. The questionnaires measuring psychiatric symptoms face significant limitations in the local indigenous context. We present the factors that make these tools not relevant among Mohawks. Although the scale called Growth and Empowerment Measure (GEM) was originally developed among Indigenous in Australia, the Mohawk in Quebec found that this tool comprehends critical aspects of their mental health and wellbeing more respectfully and accurately than questionnaires focused on measuring symptoms. We document the process of cultural adaptation of this tool which was supported by community members to create a culturally safe tool that helps in growth and empowerment. The cultural adaptation of the GEM provides valuable information about the factors affecting wellbeing and contributes to mental health promotion. This process improves mental health services by giving health care providers useful information about the Mohawk population and their clients. We believe that integrating this tool in interventions can help create a bridge to improve communication between the Indigenous cultural perspective of the patient and the biomedical view of health care providers. Further work is needed to confirm the clinical utility of this tool in psychological and psychiatric intervention along with social and community services.

Keywords: cultural adaptation, cultural safety, empowerment, Mohawks, mental health, Quebec

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224 Survey of Prevalence of Noise Induced Hearing Loss in Hawkers and Shopkeepers in Noisy Areas of Mumbai City

Authors: Hitesh Kshayap, Shantanu Arya, Ajay Basod, Sachin Sakhuja

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This study was undertaken to measure the overall noise levels in different locations/zones and to estimate the prevalence of Noise induced hearing loss in Hawkers & Shopkeepers in Mumbai, India. The Hearing Test developed by American Academy Of Otolaryngology, translated from English to Hindi, and validated is used as a screening tool for hearing sensitivity was employed. The tool is having 14 items. Each item is scored on a scale 0, 1, 2 and 3. The score 6 and above indicated some difficulty or definite difficulty in hearing in daily activities and low score indicated lesser difficulty or normal hearing. The subjects who scored 6 or above or having tinnitus were made to undergo hearing evaluation by Pure tone audiometer. Further, the environmental noise levels were measured from Morning to Evening at road side at different Location/Hawking zones in Mumbai city using SLM9 Agronic 8928B & K type Digital Sound Level Meter) in dB (A). The maximum noise level of 100.0 dB (A) was recorded during evening hours from Chattrapati Shivaji Terminal to Colaba with overall noise level of 79.0 dB (A). However, the minimum noise level in this area was 72.6 dB (A) at any given point of time. Further, 54.6 dB (A) was recorded as minimum noise level during 8-9 am at Sion Circle. Further, commencement of flyovers with 2-tier traffic, sky walks, increasing number of vehicular traffic at road, high rise buildings and other commercial & urbanization activities in the Mumbai city most probably have resulted in increasing the overall environmental noise levels. Trees which acted as noise absorbers have been cut owing to rapid construction. The study involved 100 participants in the age range of 18 to 40 years of age, with the mean age of 29 years (S.D. =6.49). 46 participants having tinnitus or have obtained the score of 6 were made to undergo Pure Tone Audiometry and it was found that the prevalence rate of hearing loss in hawkers & shopkeepers is 19% (10% Hawkers and 9 % Shopkeepers). The results found indicates that 29 (42.6%) out of 64 Hawkers and 17 (47.2%) out of 36 Shopkeepers who underwent PTA had no significant difference in percentage of Noise Induced Hearing loss. The study results also reveal that participants who exhibited tinnitus 19 (41.30%) out of 46 were having mild to moderate sensorineural hearing loss between 3000Hz to 6000Hz. The Pure tone Audiogram pattern revealed Hearing loss at 4000 Hz and 6000 Hz while hearing at adjacent frequencies were nearly normal. 7 hawkers and 8 shopkeepers had mild notch while 3 hawkers and 1 shopkeeper had a moderate degree of notch. It is thus inferred that tinnitus is a strong indicator for presence of hearing loss and 4/6 KHz notch is a strong marker for road/traffic/ environmental noise as an occupational hazard for hawkers and shopkeepers. Mass awareness about these occupational hazards, regular hearing check up, early intervention along with sustainable development juxtaposed with social and urban forestry can help in this regard.

Keywords: NIHL, noise, sound level meter, tinnitus

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223 A Valid Professional Development Framework For Supporting Science Teachers In Relation To Inquiry-Based Curriculum Units

Authors: Fru Vitalis Akuma, Jenna Koenen

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The science education community is increasingly calling for learning experiences that mirror the work of scientists. Although inquiry-based science education is aligned with these calls, the implementation of this strategy is a complex and daunting task for many teachers. Thus, policymakers and researchers have noted the need for continued teacher Professional Development (PD) in the enactment of inquiry-based science education, coupled with effective ways of reaching the goals of teacher PD. This is a complex problem for which educational design research is suitable. The purpose at this stage of our design research is to develop a generic PD framework that is valid as the blueprint of a PD program for supporting science teachers in relation to inquiry-based curriculum units. The seven components of the framework are the goal, learning theory, strategy, phases, support, motivation, and an instructional model. Based on a systematic review of the literature on effective (science) teacher PD, coupled with developer screening, we have generated a design principle per component of the PD framework. For example, as per the associated design principle, the goal of the framework is to provide science teachers with experiences in authentic inquiry, coupled with enhancing their competencies linked to the adoption, customization and design; then the classroom implementation and the revision of inquiry-based curriculum units. The seven design principles have allowed us to synthesize the PD framework, which, coupled with the design principles, are the preliminary outcomes of the current research. We are in the process of evaluating the content and construct validity of the framework, based on nine one-on-one interviews with experts in inquiry-based classroom and teacher learning. To this end, we have developed an interview protocol with the input of eight such experts in South Africa and Germany. Using the protocol, the expert appraisal of the PD framework will involve three experts from Germany, South Africa, and Cameroon, respectively. These countries, where we originate and/or work, provide a variety of inquiry-based science education contexts, making the countries suitable in the evaluation of the generic PD framework. Based on the evaluation, we will revise the framework and its seven design principles to arrive at the final outcomes of the current research. While the final content and construct a valid version of the framework will serve as an example of the needed ways through which effective inquiry-based science teacher PD may be achieved, the final design principles will be useful to researchers when transforming the framework for use in any specific educational context. For example, in our further research, we will transform the framework to one that is practical and effective in supporting inquiry-based practical work in resource-constrained physical sciences classrooms in South Africa. Researchers in other educational contexts may similarly consider the final framework and design principles in their work. Thus, our final outcomes will inform practice and research around the support of teachers to increase the incorporation of learning experiences that mirror the work of scientists in a worldwide manner.

Keywords: design principles, educational design research, evaluation, inquiry-based science education, professional development framework

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222 Evaluation of Anti-inflammatory Activities of Extracts Obtained from Capparis Erythrocarpos In-Vivo

Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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221 Genetic Analysis of CYP11A1 Gene with Polycystic Ovary Syndrome from North India

Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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220 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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219 Composing Method of Decision-Making Function for Construction Management Using Active 4D/5D/6D Objects

Authors: Hyeon-Seung Kim, Sang-Mi Park, Sun-Ju Han, Leen-Seok Kang

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As BIM (Building Information Modeling) application continually expands, the visual simulation techniques used for facility design and construction process information are becoming increasingly advanced and diverse. For building structures, BIM application is design - oriented to utilize 3D objects for conflict management, whereas for civil engineering structures, the usability of nD object - oriented construction stage simulation is important in construction management. Simulations of 5D and 6D objects, for which cost and resources are linked along with process simulation in 4D objects, are commonly used, but they do not provide a decision - making function for process management problems that occur on site because they mostly focus on the visual representation of current status for process information. In this study, an nD CAD system is constructed that facilitates an optimized schedule simulation that minimizes process conflict, a construction duration reduction simulation according to execution progress status, optimized process plan simulation according to project cost change by year, and optimized resource simulation for field resource mobilization capability. Through this system, the usability of conventional simple simulation objects is expanded to the usability of active simulation objects with which decision - making is possible. Furthermore, to close the gap between field process situations and planned 4D process objects, a technique is developed to facilitate a comparative simulation through the coordinated synchronization of an actual video object acquired by an on - site web camera and VR concept 4D object. This synchronization and simulation technique can also be applied to smartphone video objects captured in the field in order to increase the usability of the 4D object. Because yearly project costs change frequently for civil engineering construction, an annual process plan should be recomposed appropriately according to project cost decreases/increases compared with the plan. In the 5D CAD system provided in this study, an active 5D object utilization concept is introduced to perform a simulation in an optimized process planning state by finding a process optimized for the changed project cost without changing the construction duration through a technique such as genetic algorithm. Furthermore, in resource management, an active 6D object utilization function is introduced that can analyze and simulate an optimized process plan within a possible scope of moving resources by considering those resources that can be moved under a given field condition, instead of using a simple resource change simulation by schedule. The introduction of an active BIM function is expected to increase the field utilization of conventional nD objects.

Keywords: 4D, 5D, 6D, active BIM

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218 Maternal Risk Factors Associated with Low Birth Weight Neonates in Pokhara, Nepal: A Hospital Based Case Control Study

Authors: Dipendra Kumar Yadav, Nabaraj Paudel, Anjana Yadav

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Background: Low Birth weight (LBW) is defined as the weight at birth less than 2500 grams, irrespective of the period of their gestation. LBW is an important indicator of general health status of population and is considered as the single most important predictors of infant mortality especially of deaths within the first month of life that is birth weight determines the chances of newborn survival. Objective of this study was to identify the maternal risk factors associated with low birth weight neonates. Materials and Methods: A hospital based case-control study was conducted in maternity ward of Manipal Teaching Hospital, Pokhara, Nepal from 23 September 2014 to 12 November 2014. During study period 59 cases were obtained and twice number of control group were selected with frequency matching of the mother`s age with ± 3 years and total controls were 118. Interview schedule was used for data collection along with record review. Data were entered in Epi-data program and analysis was done with help of SPSS software program. Results: From bivariate logistic regression analysis, eighteen variables were found significantly associated with LBW and these were place of residence, family monthly income, education, previous still birth, previous LBW, history of STD, history of vaginal bleeding, anemia, ANC visits, less than four ANC visits, de-worming status, counseling during pregnancy, CVD, physical workload, stress, extra meal during pregnancy, smoking and alcohol consumption status. However after adjusting confounding variables, only six variables were found significantly associated with LBW. Mothers who had family monthly income up to ten thousand rupees were 4.83 times more likely to deliver LBW with CI (1.5-40.645) and p value 0.014 compared to mothers whose family income NRs.20,001-60,000. Mothers who had previous still birth were 2.01 times more likely to deliver LBW with CI (0.69-5.87) and p value 0.02 compared to mothers who did not has previous still birth. Mothers who had previous LBW were 5.472 times more likely to deliver LBW with CI (1.2-24.93) and p value 0.028 compared to mothers who did not has previous LBW. Mothers who had anemia during pregnancy were 3.36 times more likely to deliver LBW with CI (0.77-14.57) and p value 0.014 compared to mothers who did not has anemia. Mothers who delivered female newborn were 2.96 times more likely to have LBW with 95% CI (1.27-7.28) and p value 0.01 compared to mothers who deliver male newborn. Mothers who did not get extra meal during pregnancy were 6.04 times more likely to deliver LBW with CI (1.11-32.7) and p value 0.037 compared to mothers who getting the extra meal during pregnancy. Mothers who consumed alcohol during pregnancy were 4.83 times more likely to deliver LBW with CI (1.57-14.83) and p value 0.006 compared to mothers who did not consumed alcohol during pregnancy. Conclusions: To reduce low birth weight baby through economic empowerment of family and individual women. Prevention and control of anemia during pregnancy is one of the another strategy to control the LBW baby and mothers should take full dose of iron supplements with screening of haemoglobin level. Extra nutritional food should be provided to women during pregnancy. Health promotion program will be focused on avoidance of alcohol and strengthen of health services that leads increasing use of maternity services.

Keywords: low birth weight, case-control, risk factors, hospital based study

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217 Cellular Technologies in Urology

Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

Procedia PDF Downloads 106
216 Patterns and Predictors of Intended Service Use among Frail Older Adults in Urban China

Authors: Yuanyuan Fu

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Background and Purpose: Along with the change of society and economy, the traditional home function of old people has gradually weakened in the contemporary China. Acknowledging these situations, to better meet old people’s needs on formal services and improve the quality of later life, this study seeks to identify patterns of intended service use among frail old people living in the communities and examined determinants that explain heterogeneous variations in old people’s intended service use patterns. Additionally, this study also tested the relationship between culture value and intended service use patterns and the mediating role of enabling factors in terms of culture value and intended service use patterns. Methods:Participants were recruited from Haidian District, Beijing, China in 2015. The multi-stage sampling method was adopted to select sub-districts, communities and old people aged 70 years old or older. After screening, 577 old people with limitations in daily life, were successfully interviewed. After data cleaning, 550 samples were included for data analysis. This study establishes a conceptual framework based on the Anderson Model (including predisposing factors, enabling factors and need factors), and further developed it by adding culture value factors (including attitudes towards filial piety and attitudes towards social face). Using a latent class analysis (LCA), this study classifies overall patterns of old people’s formal service utilization. Fourteen types of formal services were taken into account, including housework, voluntary support, transportation, home-delivered meals, and home-delivery medical care, elderly’s canteen and day-care center/respite care and so on. Structural equation modeling (SEM) was used to examine the direct effect of culture value on service use pattern, and the mediating effect of the enabling factors. Results: The LCA classified a hierarchical structure of service use patterns: multiple intended service use (N=69, 23%), selective intended service use (N=129, 23%), and light intended service use (N=352, 64%). Through SEM, after controlling predisposing factors and need factors, the results showed the significant direct effect of culture value on older people’s intended service use patterns. Enabling factors had a partial mediation effect on the relationship between culture value and the patterns. Conclusions and Implications: Differentiation of formal services may be important for meeting frail old people’s service needs and distributing program resources by identifying target populations for intervention, which may make reference to specific interventions to better support frail old people. Additionally, culture value had a unique direct effect on the intended service use patterns of frail old people in China, enriching our theoretical understanding of sources of culture value and their impacts. The findings also highlighted the mediation effects of enabling factors on the relationship between culture value factors and intended service use patterns. This study suggests that researchers and service providers should pay more attention to the important role of culture value factors in contributing to intended service use patterns and also be more sensitive to the mediating effect of enabling factors when discussing the relationship between culture value and the patterns.

Keywords: frail old people, intended service use pattern, culture value, enabling factors, contemporary China, latent class analysis

Procedia PDF Downloads 214
215 Safety Profile of Human Papillomavirus Vaccines: A Post-Licensure Analysis of the Vaccine Adverse Events Reporting System, 2007-2017

Authors: Giulia Bonaldo, Alberto Vaccheri, Ottavio D'Annibali, Domenico Motola

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The Human Papilloma Virus (HPV) was shown to be the cause of different types of carcinomas, first of all of the cervical intraepithelial neoplasia. Since the early 80s to today, thanks first to the preventive screening campaigns (pap-test) and following to the introduction of HPV vaccines on the market; the number of new cases of cervical cancer has decreased significantly. The HPV vaccines currently approved are three: Cervarix® (HPV2 - virus type: 16 and 18), Gardasil® (HPV4 - 6, 11, 16, 18) and Gardasil 9® (HPV9 - 6, 11, 16, 18, 31, 33, 45, 52, 58), which all protect against the two high-risk HPVs (6, 11) that are mainly involved in cervical cancers. Despite the remarkable effectiveness of these vaccines has been demonstrated, in the recent years, there have been many complaints about their risk-benefit profile due to Adverse Events Following Immunization (AEFI). The purpose of this study is to provide a support about the ongoing discussion on the safety profile of HPV vaccines based on real life data deriving from spontaneous reports of suspected AEFIs collected in the Vaccine Adverse Events Reporting System (VAERS). VAERS is a freely-available national vaccine safety surveillance database of AEFI, co-administered by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). We collected all the reports between January 2007 to December 2017 related to the HPV vaccines with a brand name (HPV2, HPV4, HPV9) or without (HPVX). A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Over the 10-year period, 54889 reports of AEFI related to HPV vaccines reported in VAERS, corresponding to 224863 vaccine-event pairs, were retrieved. The highest number of reports was related to Gardasil (n = 42244), followed by Gardasil 9 (7212) and Cervarix (3904). The brand name of the HPV vaccine was not reported in 1529 cases. The two events more frequently reported and statistically significant for each vaccine were: dizziness (n = 5053) ROR = 1.28 (CI95% 1.24 – 1.31) and syncope (4808) ROR = 1.21 (1.17 – 1.25) for Gardasil. For Gardasil 9, injection site pain (305) ROR = 1.40 (1.25 – 1.57) and injection site erythema (297) ROR = 1.88 (1.67 – 2.10) and for Cervarix, headache (672) ROR = 1.14 (1.06 – 1.23) and loss of consciousness (528) ROR = 1.71 (1.57 – 1.87). In total, we collected 406 reports of death and 2461 cases of permanent disability in the ten-year period. The events consisting of incorrect vaccine storage or incorrect administration were not considered. The AEFI analysis showed that the most frequently reported events are non-serious and listed in the corresponding SmPCs. In addition to these, potential safety signals arose regarding less frequent and severe AEFIs that would deserve further investigation. This already happened with the referral of the European Medicines Agency (EMA) for the adverse events POTS (Postural Orthostatic Tachycardia Syndrome) and CRPS (Complex Regional Pain Syndrome) associated with anti-papillomavirus vaccines.

Keywords: adverse drug reactions, pharmacovigilance, safety, vaccines

Procedia PDF Downloads 152
214 Liquid Waste Management in Cluster Development

Authors: Abheyjit Singh, Kulwant Singh

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There is a gradual depletion of the water table in the earth's crust, and it is required to converse and reduce the scarcity of water. This is only done by rainwater harvesting, recycling of water and by judicially consumption/utilization of water and adopting unique treatment measures. Domestic waste is generated in residential areas, commercial settings, and institutions. Waste, in general, is unwanted, undesirable, and nevertheless an inevitable and inherent product of social, economic, and cultural life. In a cluster, a need-based system is formed where the project is designed for systematic analysis, collection of sewage from the cluster, treating it and then recycling it for multifarious work. The liquid waste may consist of Sanitary sewage/ Domestic waste, Industrial waste, Storm waste, or Mixed Waste. The sewage contains both suspended and dissolved particles, and the total amount of organic material is related to the strength of the sewage. The untreated domestic sanitary sewage has a BOD (Biochemical Oxygen Demand) of 200 mg/l. TSS (Total Suspended Solids) about 240 mg/l. Industrial Waste may have BOD and TSS values much higher than those of sanitary sewage. Another type of impurities of wastewater is plant nutrients, especially when there are compounds of nitrogen N phosphorus P in the sewage; raw sanitary contains approx. 35 mg/l Nitrogen and 10 mg/l of Phosphorus. Finally, the pathogen in the waste is expected to be proportional to the concentration of facial coliform bacteria. The coliform concentration in raw sanitary sewage is roughly 1 billion per liter. The system of sewage disposal technique has been universally applied to all conditions, which are the nature of soil formation, Availability of land, Quantity of Sewage to be disposed of, The degree of treatment and the relative cost of disposal technique. The adopted Thappar Model (India) has the following designed parameters consisting of a Screen Chamber, a Digestion Tank, a Skimming Tank, a Stabilization Tank, an Oxidation Pond and a Water Storage Pond. The screening Chamber is used to remove plastic and other solids, The Digestion Tank is designed as an anaerobic tank having a retention period of 8 hours, The Skimming Tank has an outlet that is kept 1 meter below the surface anaerobic condition at the bottom and also help in organic solid remover, Stabilization Tank is designed as primary settling tank, Oxidation Pond is a facultative pond having a depth of 1.5 meter, Storage Pond is designed as per the requirement. The cost of the Thappar model is Rs. 185 Lakh per 3,000 to 4,000 population, and the Area required is 1.5 Acre. The complete structure will linning as per the requirement. The annual maintenance will be Rs. 5 lakh per year. The project is useful for water conservation, silage water for irrigation, decrease of BOD and there will be no longer damage to community assets and economic loss to the farmer community by inundation. There will be a healthy and clean environment in the community.

Keywords: collection, treatment, utilization, economic

Procedia PDF Downloads 67
213 Cockpit Integration and Piloted Assessment of an Upset Detection and Recovery System

Authors: Hafid Smaili, Wilfred Rouwhorst, Paul Frost

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The trend of recent accident and incident cases worldwide show that the state-of-the-art automation and operations, for current and future demanding operational environments, does not provide the desired level of operational safety under crew peak workload conditions, specifically in complex situations such as loss-of-control in-flight (LOC-I). Today, the short term focus is on preparing crews to recognise and handle LOC-I situations through upset recovery training. This paper describes the cockpit integration aspects and piloted assessment of both a manually assisted and automatic upset detection and recovery system that has been developed and demonstrated within the European Advanced Cockpit for Reduction Of StreSs and workload (ACROSS) programme. The proposed system is a function that continuously monitors and intervenes when the aircraft enters an upset and provides either manually pilot-assisted guidance or takes over full control of the aircraft to recover from an upset. In order to mitigate the highly physical and psychological impact during aircraft upset events, the system provides new cockpit functionalities to support the pilot in recovering from any upset both manually assisted and automatically. A piloted simulator assessment was made in Oct-Nov 2015 using ten pilots in a representative civil large transport fly-by-wire aircraft in terms of the preference of the tested upset detection and recovery system configurations to reduce pilot workload, increase situational awareness and safe interaction with the manually assisted or automated modes. The piloted simulator evaluation of the upset detection and recovery system showed that the functionalities of the system are able to support pilots during an upset. The experiment showed that pilots are willing to rely on the guidance provided by the system during an upset. Thereby, it is important for pilots to see and understand what the aircraft is doing and trying to do especially in automatic modes. Comparing the manually assisted and the automatic recovery modes, the pilot’s opinion was that an automatic recovery reduces the workload so that they could perform a proper screening of the primary flight display. The results further show that the manually assisted recoveries, with recovery guidance cues on the cockpit primary flight display, reduced workload for severe upsets compared to today’s situation. The level of situation awareness was improved for automatic upset recoveries where the pilot could monitor what the system was trying to accomplish compared to automatic recovery modes without any guidance. An improvement in situation awareness was also noticeable with the manually assisted upset recovery functionalities as compared to the current non-assisted recovery procedures. This study shows that automatic upset detection and recovery functionalities are likely to positively impact the operational safety by means of reduced workload, improved situation awareness and crew stress reduction. It is thus believed that future developments for upset recovery guidance and loss-of-control prevention should focus on automatic recovery solutions.

Keywords: aircraft accidents, automatic flight control, loss-of-control, upset recovery

Procedia PDF Downloads 201
212 Characteristics of the Mortars Obtained by Radioactive Recycled Sand

Authors: Claudiu Mazilu, Ion Robu, Radu Deju

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At the end of 2011 worldwide there were 124 power reactors shut down, from which: 16 fully decommissioned, 50 power reactors in a decommissioning process, 49 reactors in “safe enclosure mode”, 3 reactors “entombed”, for other 6 reactors it was not yet have specified the decommissioning strategy. The concrete radioactive waste that will be generated from dismantled structures of VVR-S nuclear research reactor from Magurele (e.g.: biological shield of the reactor core and hot cells) represents an estimated amount of about 70 tons. Until now the solid low activity radioactive waste (LLW) was pre-placed in containers and cementation with mortar made from cement and natural fine aggregates, providing a fill ratio of the container of approximately 50 vol. % for concrete. In this paper is presented an innovative technology in which radioactive concrete is crushed and the mortar made from recycled radioactive sand, cement, water and superplasticizer agent is poured in container with radioactive rubble (that is pre-placed in container) for cimentation. Is achieved a radioactive waste package in which the degree of filling of radioactive waste increases substantially. The tests were carried out on non-radioactive material because the radioactive concrete was not available in a good time. Waste concrete with maximum size of 350 mm were crushed in the first stage with a Liebhher type jaw crusher, adjusted to nominal size of 50 mm. Crushed concrete less than 50 mm was sieved in order to obtain useful sort for preplacement, 10 to 50 mm. The rest of the screening > 50 mm obtained from primary crushing of concrete was crushed in the second stage, with different working principles crushers at size < 2.5 mm, in order to produce recycled fine aggregate (sand) for the filler mortar and which fulfills the technical specifications proposed: –jaw crusher, Retsch type, model BB 100; –hammer crusher, Buffalo Shuttle model WA-12-H; presented a series of characteristics of recycled concrete aggregates by predefined class (the granulosity, the granule shape, the absorption of water, behavior to the Los Angeles test, the content of attached mortar etc.), most in comparison with characteristics of natural aggregates. Various mortar recipes were used in order to identify those that meet the proposed specification (flow-rate: 16-50s, no bleeding, min. 30N/mm2 compressive strength of the mortar after 28 days, the proportion of recycled sand used in mortar: min. 900kg/m3) and allow obtaining of the highest fill ratio for mortar. In order to optimize the mortars following compositional factors were varied: aggregate nature, water/cement (W/C) ratio, sand/cement (S/C) ratio, nature and proportion of additive. To confirm the results obtained on a small scale, it made an attempt to fill the mortar in a container that simulates the final storage drums. Was measured the mortar fill ratio (98.9%) compared with the results of laboratory tests and targets set out in the proposed specification. Although fill ratio obtained on the mock-up is lower by 0.8 vol. % compared to that obtained in the laboratory tests (99.7%), the result meets the specification criteria.

Keywords: characteristics, radioactive recycled concrete aggregate, mortars, fill ratio

Procedia PDF Downloads 186
211 Relative Expression and Detection of MUB Adhesion Domains and Plantaricin-Like Bacteriocin among Probiotic Lactobacillus plantarum-Group Strains Isolated from Fermented Foods

Authors: Sundru Manjulata Devi, Prakash M. Halami

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The immemorial use of fermented foods from vegetables, dairy and other biological sources are of great demand in India because of their health benefits. However, the diversity of Lactobacillus plantarum group (LPG) of vegetable origin has not been revealed yet, particularly with reference to their probiotic functionalities. In the present study, the different species of probiotic Lactobacillus plantarum group (LPG) i.e., L. plantarum subsp. plantarum MTCC 5422 (from fermented cereals), L. plantarum subsp. argentoratensis FG16 (from fermented bamboo shoot) and L. paraplantarum MTCC 9483 (from fermented gundruk) (as characterized by multiplex recA PCR assay) were considered to investigate their relative expression of MUB domains of mub gene (mucin binding protein) by Real time PCR. Initially, the allelic variation in the mub gene was assessed and found to encode three different variants (Type I, II and III). All the three types had 8, 9 and 10 MUB domains respectively (as analysed by Pfam database) and were found to be responsible for adhesion of bacteria to the host intestinal epithelial cells. These domains either get inserted or deleted during speciation or evolutionary events and lead to divergence. The reverse transcriptase qPCR analysis with mubLPF1+R1 primer pair supported variation in amplicon sizes with 300, 500 and 700 bp among different LPG strains. The relative expression of these MUB domains significantly unregulated in the presence of 1% mucin in overnight grown cultures. Simultaneously, the mub gene expressed efficiently by 7 fold in the culture L. paraplantarum MTCC 9483 with 10 MUB domains. An increase in the expression levels for L. plantarum subsp. plantarum MTCC 5422 and L. plantarum subsp. argentoratensis FG16 (MCC 2974) with 9 and 8 repetitive domains was around 4 and 2 fold, respectively. The detection and expression of an integrase (int) gene in the upstream region of mub gene reveals the excision and integration of these repetitive domains. Concurrently, an in vitro adhesion assay to mucin and exclusion of pathogens (such as Listeria monocytogenes and Micrococcus leuteus) was investigated and observed that the L. paraplantarum MTCC 9483 with more adhesion domains has more ability to adhere to mucin and inhibited the growth of pathogens. The production and expression of plantaricin-like bacteriocin (plnNC8 type) in MTCC 9483 suggests the pathogen inhibition. Hence, the expression of MUB domains can act as potential biomarkers in the screening of a novel probiotic LPG strain with adherence property. The present study provides a platform for an easy, rapid, less time consuming, low-cost methodology for the detection of potential probiotic bacteria. It was known that the traditional practices followed in the preparation of fermented bamboo shoots/gundruk/cereals of Indian foods contain different kinds of neutraceuticals for functional food and novel compounds with health promoting factors. In future, a detailed study of these food products can add more nutritive value, consumption and suitable for commercialization.

Keywords: adhesion gene, fermented foods, MUB domains, probiotics

Procedia PDF Downloads 259
210 Prognostic Factors for Mortality and Duration of Admission in Malnourished Hospitalized, Elderly Patients: A Cross-Sectional Study

Authors: Christos E. Lampropoulos, Maria Konsta, Vicky Dradaki, Irini Dri, Tamta Sirbilatze, Ifigenia Apostolou, Christina Kordali, Konstantina Panouria, Kostas Argyros, Georgios Mavras

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Malnutrition in hospitalized patients is related to increased morbidity and mortality. Purpose of our study was to assess nutritional status of hospitalized, elderly patients with various nutritional scores and to detect unfavorable prognostic factors, related to increased mortality and extended duration of admission. Methods: 150 patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. Nutritional status was assessed by Mini Nutritional Assessment (MNA full, short-form), Malnutrition Universal Screening Tool (MUST) and short Nutritional Appetite Questionnaire (sNAQ). The following data were incorporated in analysis: Anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits and mediterranean diet (assessed by MedDiet score), cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were the mortality (from admission until 6 months afterwards) and duration of admission, compared to national guidelines for closed consolidated medical expenses. Mann-Whitney two-sample statistics or t-test was used for group comparisons and Spearman or Pearson coefficients for testing correlation between variables. Results: Normal nutrition was assessed in 54/150 (36%), 92/150 (61.3%) and in 106/150 (70.7%) of patients, according to full MNA, MUST and sNAQ questionnaires respectively. Mortality rate was 20.7% (31/150 patients). The patients who died until 6 months after admission had lower BMI (24±4.4 vs 26±4.8, p=0.04) and albumin levels (2.9±0.7 vs 3.4±0.7, p=0.002), significantly lower full MNA (14.5±7.3 vs 20.7±6, p<0.0001) and short-form MNA scores (7.3±4.2 vs 10.5±3.4, p=0.0002) compared to non-dead one. In contrast, the aforementioned patients had higher MUST (2.5±1.8 vs 0.5±1.02, p=<0.0001) and sNAQ scores (2.9±2.4 vs 1.1±1.3, p<0.0001). Additionally, they showed significantly lower MedDiet (23.5±4.3 vs 31.1±5.6, p<0.0001) and IPAQ scores (37.2±156.2 vs 516.5±1241.7, p<0.0001) compared to remaining one. These patients had extended hospitalization [5 (0-13) days vs 0 (-1-3) days, p=0.001]. Patients who admitted due to cancer depicted higher mortality rate (10/13, 77%), compared to those who admitted due to infections (12/73, 18%), stroke (4/15, 27%) or other causes (4/49, 8%) (p<0.0001). Extension of hospitalization was negatively correlated to both full (Spearman r=-0.35, p<0.0001) and short-form MNA (Spearman r=-0.33, p<0.0001) and positively correlated to MUST (Spearman r=0.34, p<0.0001) and sNAQ (Spearman r=0.3, p=0.0002). Additionally, the extension was inversely related to MedDiet score (Spearman r=-0.35, p<0.0001), IPAQ score (Spearman r=-0.34, p<0.0001), albumin levels (Pearson r=-0.36, p<0.0001), Ht (Pearson r=-0.2, p=0.02) and Hb (Pearson r=-0.18, p=0.02). Conclusion: A great proportion of elderly, hospitalized patients are malnourished or at risk of malnutrition. All nutritional scores, physical activity and albumin are significantly related to mortality and increased hospitalization.

Keywords: dietary habits, duration of admission, malnutrition, prognostic factors for mortality

Procedia PDF Downloads 275
209 Epigenetic and Archeology: A Quest to Re-Read Humanity

Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

Procedia PDF Downloads 97
208 Climate Change and Health: Scoping Review of Scientific Literature 1990-2015

Authors: Niamh Herlihy, Helen Fischer, Rainer Sauerborn, Anneliese Depoux, Avner Bar-Hen, Antoine Flauhault, Stefanie Schütte

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In the recent decades, there has been an increase in the number of publications both in the scientific and grey literature on the potential health risks associated with climate change. Though interest in climate change and health is growing, there are still many gaps to adequately assess our future health needs in a warmer world. Generating a greater understanding of the health impacts of climate change could be a key step in inciting the changes necessary to decelerate global warming and to target new strategies to mitigate the consequences on health systems. A long term and broad overview of existing scientific literature in the field of climate change and health is currently missing in order to ensure that all priority areas are being adequately addressed. We conducted a scoping review of published peer-reviewed literature on climate change and health from two large databases, PubMed and Web of Science, between 1990 and 2015. A scoping review allowed for a broad analysis of this complex topic on a meta-level as opposed to a thematically refined literature review. A detailed search strategy including specific climate and health terminology was used to search the two databases. Inclusion and exclusion criteria were applied in order to capture the most relevant literature on the human health impact of climate change within the chosen timeframe. Two reviewers screened the papers independently and any differences arising were resolved by a third party. Data was extracted, categorized and coded both manually and using R software. Analytics and infographics were developed from results. There were 7269 articles identified between the two databases following the removal of duplicates. After screening of the articles by both reviewers 3751 were included. As expected, preliminary results indicate that the number of publications on the topic has increased over time. Geographically, the majority of publications address the impact of climate change and health in Europe and North America, This is particularly alarming given that countries in the Global South will bear the greatest health burden. Concerning health outcomes, infectious diseases, particularly dengue fever and other mosquito transmitted infections are the most frequently cited. We highlight research gaps in certain areas e.g climate migration and mental health issues. We are developing a database of the identified climate change and health publications and are compiling a report for publication and dissemination of the findings. As health is a major co-beneficiary to climate change mitigation strategies, our results may serve as a useful source of information for research funders and investors when considering future research needs as well as the cost-effectiveness of climate change strategies. This study is part of an interdisciplinary project called 4CHealth that confronts results of the research done on scientific, political and press literature to better understand how the knowledge on climate change and health circulates within those different fields and whether and how it is translated to real world change.

Keywords: climate change, health, review, mapping

Procedia PDF Downloads 304
207 A Digital Health Approach: Using Electronic Health Records to Evaluate the Cost Benefit of Early Diagnosis of Alpha-1 Antitrypsin Deficiency in the UK

Authors: Sneha Shankar, Orlando Buendia, Will Evans

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Alpha-1 antitrypsin deficiency (AATD) is a rare, genetic, and multisystemic condition. Underdiagnosis is common, leading to chronic pulmonary and hepatic complications, increased resource utilization, and additional costs to the healthcare system. Currently, there is limited evidence of the direct medical costs of AATD diagnosis in the UK. This study explores the economic impact of AATD patients during the 3 years before diagnosis and to identify the major cost drivers using primary and secondary care electronic health record (EHR) data. The 3 years before diagnosis time period was chosen based on the ability of our tool to identify patients earlier. The AATD algorithm was created using published disease criteria and applied to 148 known AATD patients’ EHR found in a primary care database of 936,148 patients (413,674 Biobank and 501,188 in a single primary care locality). Among 148 patients, 9 patients were flagged earlier by the tool and, on average, could save 3 (1-6) years per patient. We analysed 101 of the 148 AATD patients’ primary care journey and 20 patients’ Hospital Episode Statistics (HES) data, all of whom had at least 3 years of clinical history in their records before diagnosis. The codes related to laboratory tests, clinical visits, referrals, hospitalization days, day case, and inpatient admissions attributable to AATD were examined in this 3-year period before diagnosis. The average cost per patient was calculated, and the direct medical costs were modelled based on the mean prevalence of 100 AATD patients in a 500,000 population. A deterministic sensitivity analysis (DSA) of 20% was performed to determine the major cost drivers. Cost data was obtained from the NHS National tariff 2020/21, National Schedule of NHS Costs 2018/19, PSSRU 2018/19, and private care tariff. The total direct medical cost of one hundred AATD patients three years before diagnosis in primary and secondary care in the UK was £3,556,489, with an average direct cost per patient of £35,565. A vast majority of this total direct cost (95%) was associated with inpatient admissions (£3,378,229). The DSA determined that the costs associated with tier-2 laboratory tests and inpatient admissions were the greatest contributors to direct costs in primary and secondary care, respectively. This retrospective study shows the role of EHRs in calculating direct medical costs and the potential benefit of new technologies for the early identification of patients with AATD to reduce the economic burden in primary and secondary care in the UK.

Keywords: alpha-1 antitrypsin deficiency, costs, digital health, early diagnosis

Procedia PDF Downloads 155
206 Single Cell Rna Sequencing Operating from Benchside to Bedside: An Interesting Entry into Translational Genomics

Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

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205 Differentially Expressed Genes in Atopic Dermatitis: Bioinformatics Analysis Of Pooled Microarray Gene Expression Datasets In Gene Expression Omnibus

Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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204 Performance of the Abbott RealTime High Risk HPV Assay with SurePath Liquid Based Cytology Specimens from Women with Low Grade Cytological Abnormalities

Authors: Alexandra Sargent, Sarah Ferris, Ioannis Theofanous

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The Abbott RealTime High Risk HPV test (RealTime HPV) is one of five assays clinically validated and approved by the English NHS Cervical Screening Programme (CSP) for HPV triage of low grade dyskaryosis and test-of-cure of treated Cervical Intraepithelial Neoplasia. The assay is a highly automated multiplex real-time PCR test for detecting 14 high risk (hr) HPV types, with simultaneous differentiation of HPV 16 and HPV 18 versus non-HPV 16/18 hrHPV. An endogenous internal control ensures sample cellularity, controls extraction efficiency and PCR inhibition. The original cervical specimen collected in SurePath (SP) liquid-based cytology (LBC) medium (BD Diagnostics) and the SP post-gradient cell pellets (SPG) after cytological processing are both CE marked for testing with the RealTime HPV test. During the 2011 NHSCSP validation of new tests only the original aliquot of SP LBC medium was investigated. Residual sample volume left after cytology slide preparation is low and may not always have sufficient volume for repeat HPV testing or for testing of other biomarkers that may be implemented in testing algorithms in the future. The SPG samples, however, have sufficient volumes to carry out additional testing and necessary laboratory validation procedures. This study investigates the correlation of RealTime HPV results of cervical specimens collected in SP LBC medium from women with low grade cytological abnormalities observed with matched pairs of original SP LBC medium and SP post-gradient cell pellets (SPG) after cytology processing. Matched pairs of SP and SPG samples from 750 women with borderline (N = 392) and mild (N = 351) cytology were available for this study. Both specimen types were processed and parallel tested for the presence of hrHPV with RealTime HPV according to the manufacturer´s instructions. HrHPV detection rates and concordance between test results from matched SP and SPGCP pairs were calculated. A total of 743 matched pairs with valid test results on both sample types were available for analysis. An overall-agreement of hrHPV test results of 97.5% (k: 0.95) was found with matched SP/SPG pairs and slightly lower concordance (96.9%; k: 0.94) was observed on 392 pairs from women with borderline cytology compared to 351 pairs from women with mild cytology (98.0%; k: 0.95). Partial typing results were highly concordant in matched SP/SPG pairs for HPV 16 (99.1%), HPV 18 (99.7%) and non-HPV16/18 hrHPV (97.0%), respectively. 19 matched pairs were found with discrepant results: 9 from women with borderline cytology and 4 from women with mild cytology were negative on SPG and positive on SP; 3 from women with borderline cytology and 3 from women with mild cytology were negative on SP and positive on SPG. Excellent correlation of hrHPV DNA test results was found between matched pairs of SP original fluid and post-gradient cell pellets from women with low grade cytological abnormalities tested with the Abbott RealTime High-Risk HPV assay, demonstrating robust performance of the test with both specimen types and reassuring the utility of the assay for cytology triage with both specimen types.

Keywords: Abbott realtime test, HPV, SurePath liquid based cytology, surepath post-gradient cell pellet

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203 Influenza Virus Circulation among the Population of Kazakhstan in 2012-2014

Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

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The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

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202 Microfluidic Plasmonic Bio-Sensing of Exosomes by Using a Gold Nano-Island Platform

Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: exosomes, gold nano-islands, microfluidics, plasmonic biosensing

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201 Relationship between Glycated Hemoglobin in Adolescents with Type 1 Diabetes Mellitus and Parental Anxiety and Depression

Authors: Evija Silina, Maris Taube, Maksims Zolovs

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Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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200 Safety of Implementation the Gluten - Free Diet in Children with Autism Spectrum Disorder

Authors: J. Jessa

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Background: Autism is a pervasive developmental disorder, the incidence of which has significantly increased in recent years. Children with autism have impairments in social skills, communication, and imagination. Children with autism has more common than healthy children feeding problems: food selectivity, problems with gastrointestinal tract: diarrhea, constipations, abdominal pain, reflux and others. Many parents of autistic children report that after implementation of gluten-, casein- and sugar free diet those symptoms disappear and even cognitive functions become better. Some children begin to understand speech and to communicate with parents, regain eye contact, become more calm, sleep better and has better concentration. Probably at the root of this phenomenon lies elimination from the diet peptides construction of which is similar to opiates. Enhanced permeability of gut causes absorption of not fully digested opioid-like peptides from food, like gluten and casein and probably others (proteins from soy and corn) which impact on brain of autistic children. Aim of the study: The aim of the study is to assess the safety of gluten-free diet in children with autism, aged 2,5-7. Methods: Participants of the study (n=70) – children aged 2,5-7 with autism are divided into 3 groups. The first group (research group) are patients whose parents want to implement a gluten-free diet. The second group are patients who have been recommended to eliminate from the diet artificial substances, such as preservatives, artificial colors and flavors, and others (control group 1). The third group (control group 2) are children whose parents did not agree for implementation of the diet. Caregivers of children on the diet are educated about the specifics of the diet and how to avoid malnutrition. At the start of the study we exclude celiac disease. Before the implementation of the diet we performe a blood test for patients (morphology, ferritin, total cholesterol, dry peripheral blood drops to detect some genetic metabolic diseases), plasma aminogram) and urine tests (excretion of ions: Mg, Na, Ca, the profile of organic acids in urine), which assess nutritional status as well as the psychological test assessing the degree of the child's psychological functioning (PEP-R). All of these tests will be repeated after one year from the implementation of the diet. Results: To the present moment we examined 42 children with autism. 12 of children are on gluten- free diet. Our preliminary results are promising. Parents of 9 of them report that, there is a big improvement in child behavior, concentration, less aggression incidents, better eye contact and better verbal skills. Conclusion: Our preliminary results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD.

Keywords: gluten free diet, autism spectrum disorder, autism, blood test

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