Search results for: drug target
Commenced in January 2007
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Edition: International
Paper Count: 4420

Search results for: drug target

670 Update on Epithelial Ovarian Cancer (EOC), Types, Origin, Molecular Pathogenesis, and Biomarkers

Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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669 Prevalence of Emotional Problems among Adolescent Students of Corporation Schools in Chennai

Authors: Vithya Veeramani, Karunanidhi Subbaiah

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Emotional problems were found to be the predominant cause of suicide and second leading cause of death among adolescents in India. Emotional problems seem to be the underlying cause for various other severe psycho-social problems experienced in adolescence and also in later years of life. The Corporation schools in Chennai city are named as Chennai High School or Chennai Higher Secondary School run by the Corporation of Chennai. These schools fulfill the educational needs of students who hail from lower socio-economic status living in slums of the Chennai city. Adolescent students of Chennai schools tend to lack basic needs like food, clothes, shelter, etc. Some of the other significant problems faced by them are broken family, lack of parental support, frequent quarrel between parents, alcoholic parents, drug abuse and substance abuse among parents and neighbors, extended family, illiterate parents, deprivation of love and care, and lack of sense of belongingness. This prevailing condition may affect them emotionally and could lead to maladaptive behaviour, aggressiveness, poor interpersonal relationship with others, school refusal behaviour, school drop-out, suicide, etc. Therefore, it is very important to investigate the emotional problems faced by the adolescent students studying in Chennai schools, Chennai. A cross-sectional survey design was used to find the prevalence of emotional problems among adolescent students. Cluster sampling technique was used to select the schools for the present study considering the school as a cluster. In total, there are 15 zones, under the control of Chennai Corporation, of which only 7 zones have Corporation Schools in Chennai city, comprising of 32 Chennai Higher Secondary Schools and 38 Chennai High Schools. Out of these 70 schools, 29 schools comprising of 17 high schools and 12 higher secondary schools were selected randomly using lottery method. A sample of 2594 adolescent students from 9th standard and 11th standard was chosen for the study. Percentage analysis was done to find out the prevalence rate of emotional problems among adolescents students studying in Chennai Schools. Results of the study revealed that, out of 2594 students surveyed, 21.04% adolescent students were found to have academic problems (n = 546), 15.99% adolescent students had social problems (n = 415), behaviour problems was found to be prevalent among 12.87% adolescent students (n = 334), depression was prevalent among 15.88% adolescent students (n = 412) and anxiety was prevalent among 14.42% adolescent students (n = 374). Prevalence of emotional problems among male and female revealed that academic problems were more prevalent compared to other problems. Behaviour problems were least prevalent among boys and anxiety was least prevalent among girls than other problems. The overall prevalence rate of emotional problems was found to be on an increasing trend among adolescent students of low socio-economic status in Chennai city. The findings indicated the need for intervention to prevent and rehabilitate these adolescent students.

Keywords: adolescents, corporation schools, emotional problems, prevalence

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668 Parenting Practices, Challenges and Prospectus of Working Mothers in Arsi University: Oromia Regional State, Ethiopia

Authors: Endalew Fufa Kufi

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Every married person aspires to be a parent regardless of the situation in which s/he lives. Such aspiration meets with reality when the destined parent is able to give adequate supports and services to his/her children, whether the latter are got by birth or through adoption. The adequacy of services parents provide their children is both enriched and tempted by the work on which they involve. On the one hand, parents need to work and earn a living in order to support their family. On the other hand, they must spend most of their time outside home to do the work, which shortens the time and might they spare to care for their children. Where the sufficiency of services parents owe their children could be ascertained by in terms of life skills, physical care and related provisions, the role of working fathers and mothers in providing such supports could be diverse across cultures and work traditions. Hence, this research deals with the investigation of working mothers’ parental practices, challenges they face in providing parental services and the implication for the future progress of the parents and their children. Target of the study will be Arsi University in Oromia Regional State of Ethiopia. Descriptive survey design in holding the research, and data for the research will be collected in the form of experiential self-report from 150 working mothers selected from the entire working women population of Colleges of Agriculture and Environmental Studies and College of Health Sciences through stratified random-sampling. Instruments of data collection will be closed and open-ended questionnaire. Complementary data will also be collected from purposively selected samples through semi-structured interview. Data for the research will be collected through questionnaire first and then through interview. Data analysis will also follow the same procedure. The collected data will systematically be organized and statistically and thematically analyzed in order to come up with indicative findings. The overarching thesis is that, working mothers in the study area bear a lot of responsibilities both at home and at work place which leave them very little time for parenting services. Unless due attention is given to the way they can spare time for their children, they are more likely to be tense between work-life and family care services, which tempt them in different directions.

Keywords: challenges, mothers, practices, university, working

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667 25 Years of the Neurolinguistic Approach: Origin, Outcomes, Expansion and Current Experiments

Authors: Steeve Mercier, Joan Netten, Olivier Massé

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The traditional lack of success of most Canadian students in the regular French program in attaining the ability to communicate spontaneously led to the conceptualization of a modified program. This program, called Intensive French, introduced and evaluated as an experiment in several school districts, formed the basis for the creation of a more effective approach for the development of skills in a second/foreign language and literacy: the Neurolinguistic Approach (NLA).The NLA expresses the major change in the understanding of how communication skills are developed: learning to communicate spontaneously in a second language depends on the reuse of structures in a variety of cognitive situations to express authentic messages rather than on knowledge of the way a language functions. Put differently, it prioritises the acquisition of implicit competence over the learning of grammatical knowledge. This is achieved by the adoption of a literacy-based approach and an increase in intensity of instruction.Besides having strong support empirically from numerous experiments, the NLA has sound theoretical foundation, as it conforms to research in neurolinguistics. The five pedagogical principles that define the approach will be explained, as well as the differences between the NLA and the paradigm on which most current resources and teaching strategies are based. It is now 25 years since the original research occurred. The use of the NLA, as it will be shown, has expanded widely. With some adaptations, it is used for other languages and in other milieus. In Canada, classes are offered in mandarin, Ukrainian, Spanish and Arabic, amongst others. It has also been used in several indigenous communities, such as to restore the use of Mohawk, Cri and Dene. Its use has expanded throughout the world, as in China, Japan, France, Germany, Belgium, Poland, Russia, as well as Mexico. The Intensive French program originally focussed on students in grades 5 or 6 (ages 10 -12); nowadays, the programs based on the approach include adults, particularly immigrants entering new countries. With the increasing interest in inclusion and cultural diversity, there is a demand for language learning amongst pre-school and primary children that can be successfully addressed by the NLA. Other current experiments target trilingual schools and work with Inuit communities of Nunavik in the province of Quebec.

Keywords: neuroeducation, neurolinguistic approach, literacy, second language acquisition, plurilingualism, foreign language teaching and learning

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666 Ways to Effectively Use Tourism Potential Through International Marketing and PR Communication Strategy in the Post-pandemic Period (On the Example of Georgia)

Authors: Marine Kobalava

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The article analyzes the level of Georgia's tourism potential usage during the pandemic. The conclusion is drawnthat Georgia, as a tourism brand, is in a significant crisis at this stage, revenues from this sector have been substantially reduced, communication with potential customers is interrupted, no international marketing and PR communication strategies have been developed for the post-pandemic period. In order to rehabilitate the tourism industry of Georgia, it is considered vital to take measures using international marketing and PR communication strategies adjusted to the needs of the sectorthat will improve the use of tourism potential and stimulate the development of the sector. The goal of the research is to identify the factors hindering the use of tourism potential in the direction of international marketing and PR communication strategies in the post-pandemic period and to develop recommendations on ways to solve them. Research methods. The paper uses various theoretical and methodological tools of research, including Bibliographic research has been conducted on the main research issues; Analysis, synthesis, induction, and other methods are used to select and group data, identify similarities and differences, and identify trends; Endogenous and exogenous factors affecting the field of tourism have been studied by means of SWOT and PESTEL analyzes. A comparison model is used to analyze the strategy documents. Primary accounting materials are obtained from the National Statistics Office and the relevant ministries. Based on the results of the research, the directions of correct positioning of tourism products and marketing communication in the post-pandemic period have been developed. It is substantiated that a short-term international marketing strategy should include: probable goals of communication, maintaining a position on a potential traveler's “radar,” focusing communication on key motivating factors (gastronomy, winemaking, folklore, protected areas, mountainous regions). From a marketing point of view, it is important: holding international marketing events, compiling a list of target countries, formation of stimulus mechanisms, development of incentive programs for international tour operators, etc. The paper draws conclusions about the problems of using the tourism potential, recommendations on ways to solve this problems through international marketing and PR communication strategies are offered

Keywords: PR communication, international marketing strategy, tourism potential, post-pandemic period

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665 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation

Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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664 Rural Livelihood under a Changing Climate Pattern in the Zio District of Togo, West Africa

Authors: Martial Amou

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This study was carried out to assess the situation of households’ livelihood under a changing climate pattern in the Zio district of Togo, West Africa. The study examined three important aspects: (i) assessment of households’ livelihood situation under a changing climate pattern, (ii) farmers’ perception and understanding of local climate change, (iii) determinants of adaptation strategies undertaken in cropping pattern to climate change. To this end, secondary sources of data, and survey data collected from 235 farmers in four villages in the study area were used. Adapted conceptual framework from Sustainable Livelihood Framework of DFID, two steps Binary Logistic Regression Model and descriptive statistics were used in this study as methodological approaches. Based on Sustainable Livelihood Approach (SLA), various factors revolving around the livelihoods of the rural community were grouped into social, natural, physical, human, and financial capital. Thus, the study came up that households’ livelihood situation represented by the overall livelihood index in the study area (34%) is below the standard average households’ livelihood security index (50%). The natural capital was found as the poorest asset (13%) and this will severely affect the sustainability of livelihood in the long run. The result from descriptive statistics and the first step regression (selection model) indicated that most of the farmers in the study area have clear understanding of climate change even though they do not have any idea about greenhouse gases as the main cause behind the issue. From the second step regression (output model) result, education, farming experience, access to credit, access to extension services, cropland size, membership of a social group, distance to the nearest input market, were found to be the significant determinants of adaptation measures undertaken in cropping pattern by farmers in the study area. Based on the result of this study, recommendations are made to farmers, policy makers, institutions, and development service providers in order to better target interventions which build, promote or facilitate the adoption of adaptation measures with potential to build resilience to climate change and then improve rural livelihood.

Keywords: climate change, rural livelihood, cropping pattern, adaptation, Zio District

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663 Refusal Speech Acts in French Learners of Mandarin Chinese

Authors: Jui-Hsueh Hu

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This study investigated various models of refusal speech acts among three target groups: French learners of Mandarin Chinese (FM), Taiwanese native Mandarin speakers (TM), and native French speakers (NF). The refusal responses were analyzed in terms of their options, frequencies, and sequences and the contents of their semantic formulas. This study also examined differences in refusal strategies, as determined by social status and social distance, among the three groups. The difficulties of refusal speech acts encountered by FM were then generalized. The results indicated that Mandarin instructors of NF should focus on the different reasons for the pragmatic failure of French learners and should assist these learners in mastering refusal speech acts that rely on abundant cultural information. In this study, refusal policies were mainly classified according to the research of Beebe et al. (1990). Discourse completion questionnaires were collected from TM, FM, and NF, and their responses were compared to determine how refusal policies differed among the groups. This study not only emphasized the dissimilarities of refusal strategies between native Mandarin speakers and second-language Mandarin learners but also used NF as a control group. The results of this study demonstrated that regarding overall strategies, FM were biased toward NF in terms of strategy choice, order, and content, resulting in pragmatic transfer under the influence of social factors such as 'social status' and 'social distance,' strategy choices of FM were still closer to those of NF, and the phenomenon of pragmatic transfer of FM was revealed. Regarding the refusal difficulties among the three groups, the F-test in the analysis of variance revealed statistical significance was achieved for Role Playing Items 13 and 14 (P < 0.05). A difference was observed in the average number of refusal difficulties between the participants. However, after multiple comparisons, it was found that item 13 (unrecognized heterosexual junior colleague requesting contacts) was significantly more difficult for NF than for TM and FM; item 14 (contacts requested by an unrecognized classmate of the opposite sex) was significantly more difficult to refuse for NF than for TM. This study summarized the pragmatic language errors that most FM often perform, including the misuse or absence of modal words, hedging expressions, and empty words at the end of sentences, as the reasons for pragmatic failures. The common social pragmatic failures of FM include inaccurately applying the level of directness and formality.

Keywords: French Mandarin, interlanguage refusal, pragmatic transfer, speech acts

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662 Value of FOXP3 Expression in Prediction of Neoadjuvant Chemotherapy Effect in Triple Negative Breast Cancer

Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

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Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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661 Levels of Heavy Metals and Arsenic in Sediment and in Clarias Gariepinus, of Lake Ngami

Authors: Nashaat Mazrui, Oarabile Mogobe, Barbara Ngwenya, Ketlhatlogile Mosepele, Mangaliso Gondwe

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Over the last several decades, the world has seen a rapid increase in activities such as deforestation, agriculture, and energy use. Subsequently, trace elements are being deposited into our water bodies, where they can accumulate to toxic levels in aquatic organisms and can be transferred to humans through fish consumption. Thus, though fish is a good source of essential minerals and omega-3 fatty acids, it can also be a source of toxic elements. Monitoring trace elements in fish is important for the proper management of aquatic systems and the protection of human health. The aim of this study was to determine concentrations of trace elements in sediment and muscle tissues of Clarias gariepinus at Lake Ngami, in the Okavango Delta in northern Botswana, during low floods. The fish were bought from local fishermen, and samples of muscle tissue were acid-digested and analyzed for iron, zinc, copper, manganese, molybdenum, nickel, chromium, cadmium, lead, and arsenic using inductively coupled plasma optical emission spectroscopy (ICP-OES). Sediment samples were also collected and analyzed for the elements and for organic matter content. Results show that in all samples, iron was found in the greatest amount while cadmium was below the detection limit. Generally, the concentrations of elements in sediment were higher than in fish except for zinc and arsenic. While the concentration of zinc was similar in the two media, arsenic was almost 3 times higher in fish than sediment. To evaluate the risk to human health from fish consumption, the target hazard quotient (THQ) and cancer risk for an average adult in Botswana, sub-Saharan Africa, and riparian communities in the Okavango Delta was calculated for each element. All elements were found to be well below regulatory limits and do not pose a threat to human health except arsenic. The results suggest that other benthic feeding fish species could potentially have high arsenic levels too. This has serious implications for human health, especially riparian households to whom fish is a key component of food and nutrition security.

Keywords: Arsenic, African sharp tooth cat fish, Okavango delta, trace elements

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660 Thermoregulatory Responses of Holstein Cows Exposed to Intense Heat Stress

Authors: Rodrigo De A. Ferrazza, Henry D. M. Garcia, Viviana H. V. Aristizabal, Camilla De S. Nogueira, Cecilia J. Verissimo, Jose Roberto Sartori, Roberto Sartori, Joao Carlos P. Ferreira

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Environmental factors adversely influence sustainability in livestock production system. Dairy herds are the most affected by heat stress among livestock industries. This clearly implies in development of new strategies for mitigating heat, which should be based on physiological and metabolic adaptations of the animal. In this study, we incorporated the effect of climate variables and heat exposure time on the thermoregulatory responses in order to clarify the adaptive mechanisms for bovine heat dissipation under intense thermal stress induced experimentally in climate chamber. Non-lactating Holstein cows were contemporaneously and randomly assigned to thermoneutral (TN; n=12) or heat stress (HS; n=12) treatments during 16 days. Vaginal temperature (VT) was measured every 15 min with a microprocessor-controlled data logger (HOBO®, Onset Computer Corporation, Bourne, MA, USA) attached to a modified vaginal controlled internal drug release insert (Sincrogest®, Ourofino, Brazil). Rectal temperature (RT), respiratory rate (RR) and heart rate (HR) were measured twice a day (0700 and 1500h) and dry matter intake (DMI) was estimated daily. The ambient temperature and air relative humidity were 25.9±0.2°C and 73.0±0.8%, respectively for TN, and 36.3± 0.3°C and 60.9±0.9%, respectively for HS. Respiratory rate of HS cows increased immediately after exposure to heat and was higher (76.02±1.70bpm; P<0.001) than TN (39.70±0.71bpm), followed by rising of RT (39.87°C±0.07 for HS versus 38.56±0.03°C for TN; P<0.001) and VT (39.82±0.10°C for HS versus 38.26±0.03°C for TN; P<0.001). A diurnal pattern was detected, with higher (P<0.01) afternoon temperatures than morning and this effect was aggravated for HS cows. There was decrease (P<0.05) of HR for HS cows (62.13±0.99bpm) compared to TN (66.23±0.79bpm), but the magnitude of the differences was not the same over time. From the third day, there was a decrease of DMI for HS in attempt to maintain homeothermy, while TN cows increased DMI (8.27kg±0.33kg d-1 for HS versus 14.03±0.29kg d-1 for TN; P<0.001). By regression analysis, RT and RR better reflected the response of cows to changes in the Temperature Humidity Index and the effect of climate variables from the previous day to influence the physiological parameters and DMI was more important than the current day, with ambient temperature the most important factor. Comparison between acute (0 to 3 days) and chronic (13 to 16 days) exposure to heat stress showed decreasing of the slope of the regression equations for RR and DMI, suggesting an adaptive adjustment, however with no change for RT. In conclusion, intense heat stress exerted strong influence on the thermoregulatory mechanisms, but the acclimation process was only partial.

Keywords: acclimation, bovine, climate chamber, hyperthermia, thermoregulation

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659 Theta-Phase Gamma-Amplitude Coupling as a Neurophysiological Marker in Neuroleptic-Naive Schizophrenia

Authors: Jun Won Kim

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Objective: Theta-phase gamma-amplitude coupling (TGC) was used as a novel evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. However, to our best knowledge, no studies have reported the diagnostic utility of the TGC in the resting-state electroencephalographic (EEG) of neuroleptic-naive patients with schizophrenia compared to healthy controls. Thus, the purpose of this EEG study was to understand the underlying mechanisms in patients with schizophrenia by comparing the TGC at rest between two groups and to evaluate the diagnostic utility of TGC. Method: The subjects included 90 patients with schizophrenia and 90 healthy controls. All patients were diagnosed with schizophrenia according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) by two independent psychiatrists using semi-structured clinical interviews. Because patients were either drug-naïve (first episode) or had not been taking psychoactive drugs for one month before the study, we could exclude the influence of medications. Five frequency bands were defined for spectral analyses: delta (1–4 Hz), theta (4–8 Hz), slow alpha (8–10 Hz), fast alpha (10–13.5 Hz), beta (13.5–30 Hz), and gamma (30-80 Hz). The spectral power of the EEG data was calculated with fast Fourier Transformation using the 'spectrogram.m' function of the signal processing toolbox in Matlab. An analysis of covariance (ANCOVA) was performed to compare the TGC results between the groups, which were adjusted using a Bonferroni correction (P < 0.05/19 = 0.0026). Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of the TGC data for schizophrenia diagnosis. Results: The patients with schizophrenia showed a significant increase in the resting-state TGC at all electrodes. The delta, theta, slow alpha, fast alpha, and beta powers showed low accuracies of 62.2%, 58.4%, 56.9%, 60.9%, and 59.0%, respectively, in discriminating the patients with schizophrenia from the healthy controls. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, displaying an overall classification accuracy of 92.5%. Conclusion: As TGC includes phase, which contains information about neuronal interactions from the EEG recording, TGC is expected to be useful for understanding the mechanisms the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The resting-state TGC value was increased in the patients with schizophrenia compared to that in the healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Further research exploring the association between TGC and medical or psychiatric conditions that may confound EEG signals will help clarify the potential utility of TGC.

Keywords: quantitative electroencephalography (QEEG), theta-phase gamma-amplitude coupling (TGC), schizophrenia, diagnostic utility

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658 Digital Immunity System for Healthcare Data Security

Authors: Nihar Bheda

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Protecting digital assets such as networks, systems, and data from advanced cyber threats is the aim of Digital Immunity Systems (DIS), which are a subset of cybersecurity. With features like continuous monitoring, coordinated reactions, and long-term adaptation, DIS seeks to mimic biological immunity. This minimizes downtime by automatically identifying and eliminating threats. Traditional security measures, such as firewalls and antivirus software, are insufficient for enterprises, such as healthcare providers, given the rapid evolution of cyber threats. The number of medical record breaches that have occurred in recent years is proof that attackers are finding healthcare data to be an increasingly valuable target. However, obstacles to enhancing security include outdated systems, financial limitations, and a lack of knowledge. DIS is an advancement in cyber defenses designed specifically for healthcare settings. Protection akin to an "immune system" is produced by core capabilities such as anomaly detection, access controls, and policy enforcement. Coordination of responses across IT infrastructure to contain attacks is made possible by automation and orchestration. Massive amounts of data are analyzed by AI and machine learning to find new threats. After an incident, self-healing enables services to resume quickly. The implementation of DIS is consistent with the healthcare industry's urgent requirement for resilient data security in light of evolving risks and strict guidelines. With resilient systems, it can help organizations lower business risk, minimize the effects of breaches, and preserve patient care continuity. DIS will be essential for protecting a variety of environments, including cloud computing and the Internet of medical devices, as healthcare providers quickly adopt new technologies. DIS lowers traditional security overhead for IT departments and offers automated protection, even though it requires an initial investment. In the near future, DIS may prove to be essential for small clinics, blood banks, imaging centers, large hospitals, and other healthcare organizations. Cyber resilience can become attainable for the whole healthcare ecosystem with customized DIS implementations.

Keywords: digital immunity system, cybersecurity, healthcare data, emerging technology

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657 Tapping Traditional Environmental Knowledge: Lessons for Disaster Policy Formulation in India

Authors: Aparna Sengupta

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The paper seeks to find answers to the question as to why India’s disaster management policies have been unable to deliver the desired results. Are the shortcomings in policy formulation, effective policy implementation or timely prevention mechanisms? Or is there a fundamental issue of policy formulation which sparsely takes into account the cultural specificities and uniqueness, technological know-how, educational, religious and attitudinal capacities of the target population into consideration? India was slow in legislating disaster policies but more than that the reason for lesser success of disaster polices seems to be the gap between policy and the people. We not only keep hearing about the failure of governmental efforts but also how the local communities deal far more efficaciously with disasters utilizing their traditional knowledge. The 2004 Indian Ocean tsunami which killed 250,000 people (approx.) could not kill the tribal communities who saved themselves due to their age-old traditional knowledge. This large scale disaster, considered as a landmark event in history of disasters in the twenty-first century, can be attributed in bringing and confirming the importance of Traditional Environmental Knowledge in managing disasters. This brings forth the importance of cultural and traditional know-how in dealing with natural disasters and one is forced to question as to why shouldn’t traditional environmental knowledge (TEK) be taken into consideration while formulating India’s disaster resilience policies? Though at the international level, many scholars have explored the connectedness of disaster to cultural dimensions and several research examined how culture acts as a stimuli in perceiving disasters and their management (Clifford, 1956; Mcluckie, 1970; Koentjaraningrat, 1985; Peacock, 1997; Elliot et.al, 2006; Aruntoi, 2008; Kulatunga, 2010). But in the Indian context, this field of inquiry i.e. linking disaster policies with tradition and generational understanding has seldom received attention of the government, decision- making authorities, disaster managers and even in the academia. The present study attempts to fill this gap in research and scholarship by presenting an historical analysis of disaster and its cognition by cultural communities in India. The paper seeks to interlink the cultural comprehension of Indian tribal communities with scientific-technology towards more constructive disaster policies in India.

Keywords: culture, disasters, local communities, traditional knowledge

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656 Language Errors Used in “The Space between Us” Movie and Their Effects on Translation Quality: Translation Study toward Discourse Analysis Approach

Authors: Mochamad Nuruz Zaman, Mangatur Rudolf Nababan, M. A. Djatmika

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Both society and education areas teach to have good communication for building the interpersonal skills up. Everyone has the capacity to understand something new, either well comprehension or worst understanding. Worst understanding makes the language errors when the interactions are done by someone in the first meeting, and they do not know before it because of distance area. “The Space between Us” movie delivers the love-adventure story between Mars Boy and Earth Girl. They are so many missing conversations because of the different climate and environment. As the moviegoer also must be focused on the subtitle in order to enjoy well the movie. Furthermore, Indonesia subtitle and English conversation on the movie still have overlapping understanding in the translation. Translation hereby consists of source language -SL- (English conversation) and target language -TL- (Indonesia subtitle). These research gap above is formulated in research question by how the language errors happened in that movie and their effects on translation quality which is deepest analyzed by translation study toward discourse analysis approach. The research goal is to expand the language errors and their translation qualities in order to create a good atmosphere in movie media. The research is studied by embedded research in qualitative design. The research locations consist of setting, participant, and event as focused determined boundary. Sources of datum are “The Space between Us” movie and informant (translation quality rater). The sampling is criterion-based sampling (purposive sampling). Data collection techniques use content analysis and questioner. Data validation applies data source and method triangulation. Data analysis delivers domain, taxonomy, componential, and cultural theme analysis. Data findings on the language errors happened in the movie are referential, register, society, textual, receptive, expressive, individual, group, analogical, transfer, local, and global errors. Data discussions on their effects to translation quality are concentrated by translation techniques on their data findings; they are amplification, borrowing, description, discursive creation, established equivalent, generalization, literal, modulation, particularization, reduction, substitution, and transposition.

Keywords: discourse analysis, language errors, The Space between Us movie, translation techniques, translation quality instruments

Procedia PDF Downloads 194
655 An Optimal Hybrid EMS System for a Hyperloop Prototype Vehicle

Authors: J. F. Gonzalez-Rojo, Federico Lluesma-Rodriguez, Temoatzin Gonzalez

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Hyperloop, a new mode of transport, is gaining significance. It consists of the use of a ground-based transport system which includes a levitation system, that avoids rolling friction forces, and which has been covered with a tube, controlling the inner atmosphere lowering the aerodynamic drag forces. Thus, hyperloop is proposed as a solution to the current limitation on ground transportation. Rolling and aerodynamic problems, that limit large speeds for traditional high-speed rail or even maglev systems, are overcome using a hyperloop solution. Zeleros is one of the companies developing technology for hyperloop application worldwide. It is working on a concept that reduces the infrastructure cost and minimizes the power consumption as well as the losses associated with magnetic drag forces. For this purpose, Zeleros proposes a Hybrid ElectroMagnetic Suspension (EMS) for its prototype. In the present manuscript an active and optimal electromagnetic suspension levitation method based on nearly zero power consumption individual modules is presented. This system consists of several hybrid permanent magnet-coil levitation units that can be arranged along the vehicle. The proposed unit manages to redirect the magnetic field along a defined direction forming a magnetic circuit and minimizing the loses due to field dispersion. This is achieved using an electrical steel core. Each module can stabilize the gap distance using the coil current and either linear or non-linear control methods. The ratio between weight and levitation force for each unit is 1/10. In addition, the quotient between the lifted weight and power consumption at the target gap distance is 1/3 [kg/W]. One degree of freedom (DoF) (along the gap direction) is controlled by a single unit. However, when several units are present, a 5 DoF control (2 translational and 3 rotational) can be achieved, leading to the full attitude control of the vehicle. The proposed system has been successfully tested reaching TRL-4 in a laboratory test bench and is currently in TRL-5 state development if the module association in order to control 5 DoF is considered.

Keywords: active optimal control, electromagnetic levitation, HEMS, high-speed transport, hyperloop

Procedia PDF Downloads 124
654 Development of Two Phage Therapy-Based Strategies for the Treatment of American Foulbrood Disease Affecting Apis Mellifera capensis

Authors: Ridwaan N. Milase, Leonardo J. Van Zyl, Marla Trindade

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American foulbrood (AFB) is the world’s most devastating honeybee disease that has drastically reduced the population of Apis mellifera capensis since 2009. The outbreak has jeopardized the South African bee keeping industry as well as the agricultural sector dependent on honeybees for honey production and pollination, leading to significant economic losses. AFB is caused by Paenibacillus larvae, a spore-forming, Gram positive facultative anaerobic and flagellated bacterium. The use of antibiotics within beehives has selected for resistant strains of P. larvae, while the current practice of burning spore contaminated beehives and equipment contributes to the economic losses in the honeybee-keeping industry. Therefore, phage therapy is proposed as a promising alternative to combat P. larvae strains affecting A. mellifera capensis. The genomes of two P. larvae strains isolated from infected combs in the Western Cape have been sequenced and annotated using bioinformatics tools. Genome analyses has revealed that these P. larvae strains are lysogens to more than 6 different prophages and possess different type of clustered regularly interspaced short palindromic repeat (CRISPRs) regions per strain. Active prophages from one of the two P. larvae strains were detected and identified using PCR. Electron microscopy was used to determine the family of the identified active prophages. Lytic bacteriophages that specifically target the two P. larvae strains were purified from sewage wastewater, beehive materials, and soil samples to investigate their potential development as anti-P. larvae agents. Another alternative treatment being investigated is the development of a prophage endolysin cocktail. Endolysin genes of the prophages have been targeted, cloned and expressed in Escherichia coli. The heterologously expressed endolysins have been purified and are currently being assessed for their lytic activity against P. larvae strains and other commensal microorganisms that compose the honeybee larvae microbiota. The study has shown that phage therapy and endolysins have a great potential as alternative control methods for AFB disease affecting A. mellifera capensis.

Keywords: American foulbrood, bacteriophage, honeybee, Paenibacillus larvae

Procedia PDF Downloads 157
653 Ceratocystis manginecans Causal Agent of a Destructive Mangoes in Pakistan

Authors: Asma Rashid, Shazia Iram, Iftikhar Ahmad

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Mango sudden death is an emerging problem in Pakistan. As its prevalence is observed in almost all mango growing areas and severity varied from 2-5% in Punjab and 5-10% in Sindh. Symptoms on affected trees include bark splitting, discoloration of the vascular tissue, wilting, gummosis and at the end rapid death. Total of n= 45 isolates were isolated from different mango growing areas of Punjab and Sindh. Pathogenicity of these fungal isolates was tested through artificial inoculation method on different hosts (potato tubers, detached mango leaves, detached mango twigs and mango plants) under controlled conditions and all were proved pathogenic with varying degree of aggressiveness in reference to control. The findings of the present study proved that out of these four methods, potato tubers inoculation method was the most ideal as this fix the inoculums on the target site. Increased fungal growth and spore numbers may be due to soft tissues of potato tubers from which Ceratocystis isolates can easily pass. Lesion area on potato tubers was in the range of 7.09-0.14 cm2 followed by detached mango twigs which were ranged from 0.48-0.09 cm2). All pathological results were proved highly significant at P<0.05 through ANOVA but isolate to isolate showed non-significant behaviour but they have the positive effect on lesion area. Re-isolation of respective fungi was achieved with 100 percent success which results in the verification of Koch’s postulates. DNA of fungal pathogens was successfully extracted through phenol chloroform method. Amplification was done through ITS, b-tubulin gene, and Transcription Elongation Factor (EF1-a) gene primers and the amplified amplicons were sequenced and compared from NCBI which showed 99-100 % similarity with Ceratocystis manginecans. Fungus Ceratocystis manginecans formed one of strongly supported sub-clades through phylogenetic tree. Results obtained through this work would be supportive in establishment of relation of isolates with their region and will give information about pathogenicity level of isolates that would be useful to develop the management policies to reduce the afflictions in orchards caused by mango sudden death.

Keywords: artificial inoculation, mango, Ceratocystis manginecans, phylogenetic, screening

Procedia PDF Downloads 228
652 Portable and Parallel Accelerated Development Method for Field-Programmable Gate Array (FPGA)-Central Processing Unit (CPU)- Graphics Processing Unit (GPU) Heterogeneous Computing

Authors: Nan Hu, Chao Wang, Xi Li, Xuehai Zhou

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The field-programmable gate array (FPGA) has been widely adopted in the high-performance computing domain. In recent years, the embedded system-on-a-chip (SoC) contains coarse granularity multi-core CPU (central processing unit) and mobile GPU (graphics processing unit) that can be used as general-purpose accelerators. The motivation is that algorithms of various parallel characteristics can be efficiently mapped to the heterogeneous architecture coupled with these three processors. The CPU and GPU offload partial computationally intensive tasks from the FPGA to reduce the resource consumption and lower the overall cost of the system. However, in present common scenarios, the applications always utilize only one type of accelerator because the development approach supporting the collaboration of the heterogeneous processors faces challenges. Therefore, a systematic approach takes advantage of write-once-run-anywhere portability, high execution performance of the modules mapped to various architectures and facilitates the exploration of design space. In this paper, A servant-execution-flow model is proposed for the abstraction of the cooperation of the heterogeneous processors, which supports task partition, communication and synchronization. At its first run, the intermediate language represented by the data flow diagram can generate the executable code of the target processor or can be converted into high-level programming languages. The instantiation parameters efficiently control the relationship between the modules and computational units, including two hierarchical processing units mapping and adjustment of data-level parallelism. An embedded system of a three-dimensional waveform oscilloscope is selected as a case study. The performance of algorithms such as contrast stretching, etc., are analyzed with implementations on various combinations of these processors. The experimental results show that the heterogeneous computing system with less than 35% resources achieves similar performance to the pure FPGA and approximate energy efficiency.

Keywords: FPGA-CPU-GPU collaboration, design space exploration, heterogeneous computing, intermediate language, parameterized instantiation

Procedia PDF Downloads 87
651 The Relations between Coping Strategies, Caregiver Bonding, and Dating Violence of Emerging Adults: Cross-Cultural Comparison between China and Turkiye

Authors: Zubaidan Yushan, Hudayar Cıhan

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Turkiye and China are countries that have collective cultures, but they have different cultural backgrounds. They have different cultures, different religions, and different levels of economic development. The aim of this study is to test the moderation effect of caregiver bonding on the relationship between dating violence and coping strategies among unmarried emerging adults in China and Turkiye. Participants ages were 19 and 26 years (X=23.66, SD=3.66), unmarried emerging adults Turkish 171 participants (72.5% women, 24% men, 3.5% prefer not to say), Chinese 170 participants (71.8% women, 21.8% men, 6.5% prefer not to say). All participants had been in a relationship for more than six months. Participants completed The Conflict Tactics Scales—(CTS2), The Cope Inventory, and The Parental Bonding Instrument (PBI). Examining the dating violence and coping strategies of the participant's relationship through caregiver bonding moderation analysis was performed using the Jamovi. Significance was tested using the bootstrapping method with bias-corrected confidence estimates. The outcome variable for analysis was dating violence, and the predictor variable for the analysis was coping strategies. The moderator variable evaluated for the analysis was parent attachment. Before the analysis, the mean-centered scores of each variable and moderator were calculated. Furthermore, the moderation analysis was conducted separately for each outcome. The Moderation analysis results show that the sub-dimension of over-protection moderates psychological aggression perpetration and avoidance coping in China. The sub-dimension of care moderates injury victimization and avoidance management in Turkiye; also, over-protection moderates injury victimization and social support coping. Moreover, the sub-dimension of care moderates sexual coercion perpetration and avoidance coping. In the results, caregiver bonding moderates the relationship between coping strategies and dating violence, which may be explained by the fact that our ways of coping with problems are learned, and people are influenced by their parents when they face problems. Therefore, problem-solving is permanently fixed, and each person has his or her fixed solution, which leads to a habit of using solutions to problems. However, sometimes, these solutions become the justification for the injured or abusive person. The quality of the attachment between parents can regulate this state. The results are somewhat similar to and slightly different from those in the previous literature. These mixed results indicate the need for further exploration. Many other factors, such as alcohol, drug violence, and pathological problems, maybe the reasons for these differences. In addition, diverse factors such as the study environment and the applied measurement scales may also affect the results.

Keywords: caregiver bonding, coping strategies, dating violence, emerging adulthood, cross-cultural, comparison

Procedia PDF Downloads 36
650 Liposomal Antihelmintics in Parasitology

Authors: Nina Ivanova

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More than one third of the population and animals are infected with parasitic helminths. It is especially difficult to cure the larval forms of parasites. The larvae of Hymenolepis nana invade the villi of the intestinal mucosa. Toxocara larvae can live in the liver, heart, lungs, brain, eyes, and pancreas. Commercial antiparasitic drugs cannot guarantee a 100% cure after a single course of treatment, because parasite larvae invade the villi of the intestinal mucosa and the anthelmintics do not reach and kill cestode larvae. The aim of this work was to conduct a study of liposomal antihelminthics on the laboratory animals under the certification received from the Committee on Bioethics and Deontology. It has been checked: 1) anthelmintic activity of the liposomal form of fenasal in experimental hymenolepidosis of white mice (larval stage - Hymenolepis nana). 2) anthelmintic activity of the liposomal form of albendazole in experimental toxocariasis of white mice (in the lungs at the stage of larval migration). Since some helminths cause hemolysis of erythrocytes as we used a mixture of polar lipids developed by us with antihemolytic activity to obtain liposomes Fenasal and albendazole were included in the liposome membrane in the ratio of anthelmintic: lipids 1:10. . The average size of liposomes was 180 nm, and the concentration of lipids in liposomes was 1%. The researches were carried out on white male mice who were infected with Hymenolepis Nana invasional eggs in a peroral way with a doze of 100 eggs per animal. On the 5th day after infection, a liposomal fenasal and commercial fenasal were administered orally for comparison. The animals were observed for 15 days. Before the introduction of liposomes and on the 3rd, 5th, 15th day after the administration of the drug, studies were carried out on the presence of helminths in the organs of animals. The liposomal fenasal, when administered orally, had an anthelmintic effect on Hymenolepis Nana cysticercoids at a dose of 25 mg/kg. The percentage of efficiency was 90.06, 91.36 96.85% on days 3, 5, 15, respectively. For comparison, the commercial activity was at a dose of 200 mg/ml, which is 8 times higher than the dose of liposomal fenasal. To evaluate the anthelmintic effect of the liposomal form of albendazole in experimental toxocariasis of white mice (toxascaris in the lungs at the stage of larval migration), studies were also carried out on white mice. The animals were infected with invasive eggs of Toxocara canis, orally, at a dose of 100 eggs per animal. On the 5th day after infection, the liposomal albendazole was administered orally. The efficacy of the study dosage form was determined by counting Larva mirgans larvae in the lungs. The results obtained showed that the liposomal albendazole had the greatest anthelmintic effect on Toxocara larvae at a dose of 2.0 mg/kg, which was 3.75 times less than the therapeutic one. At the same time, the percentage of efficiency was 93.75% on the 3rd day, and 98.66% on the 5th day.

Keywords: hymenolepis, Toxocara, larvae, liposomes

Procedia PDF Downloads 88
649 Phage Therapy as a Potential Solution in the Fight against Antimicrobial Resistance

Authors: Sanjay Shukla

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Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

Procedia PDF Downloads 103
648 The Need to Teach the Health Effects of Climate Change in Medical Schools

Authors: Ábrám Zoltán

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Introduction: Climate change is now a major health risk, and its environmental and health effects have become frequently discussed topics. The consequences of climate change are clearly visible in natural disasters and excess deaths caused by extreme weather conditions. Global warming and the increasingly frequent extreme weather events have direct, immediate effects or long-term, indirect effects on health. For this reason, it is a need to teach the health effects of climate change in medical schools. Material and methods: We looked for various surveys, studies, and reports on the main pathways through which global warming affects health. Medical schools face the challenge of teaching the health implications of climate change and integrating knowledge about the health effects of climate change into medical training. For this purpose, there were organised World Café workshops for three target groups: medical students, academic staff, and practising medical doctors. Results: Among the goals of the research is the development of a detailed curriculum for medical students, which serves to expand their knowledge in basic education. At the same time, the project promotes the increase of teacher motivation and the development of methodological guidelines for university teachers; it also provides further training for practicing doctors. The planned teaching materials will be developed in a format suitable for traditional face-to-face teaching, as well as e-learning teaching materials. CLIMATEMED is a project based on the cooperation of six universities and institutions from four countries, the aim of which is to improve the curriculum and expand knowledge about the health effects of climate change at medical universities. Conclusions: In order to assess the needs, summarize the proposals, to develop the necessary strategy, World Café type, one-and-a-half to two-hour round table discussions will take place separately for medical students, academic staff, and practicing doctors. The CLIMATEMED project can facilitate the integration of knowledge about the health effects of climate change into curricula and can promote practical use. The avoidance of the unwanted effects of global warming and climate change is not only a public matter, but it is also a challenge to change our own lifestyle. It is the responsibility of all of us to protect the Earth's ecosystem and the physical and mental health of ourselves and future generations.

Keywords: climate change, health effects, medical schools, World Café, medical students

Procedia PDF Downloads 58
647 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens

Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott

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In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.

Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF

Procedia PDF Downloads 151
646 Nursing Students’ Opinions about Theoretical Lessons and Clinical Area: A Survey in a Nursing Department

Authors: Ergin Toros, Manar Aslan

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This study was planned as a descriptive study in order to learn the opinions of the students who are studying in nursing undergraduate program about their theoretical/practical lessons and departments. The education in the undergraduate nursing programs has great importance because it contains the knowledge and skills to prepare student nurses to the clinic in the future. In order to provide quality-nursing services in the future, the quality of nursing education should be measured, and opinions of student nurses about education should be taken. The research population was composed of students educated in a university with 1-4 years of theoretical and clinical education (N=550), and the sample was composed of 460 students that accepted to take part in the study. It was reached to 83.6% of target population. Data collected through a survey developed by the researchers. Survey consists of 48 questions about sociodemographic characteristics (9 questions), theoretical courses (9 questions), laboratory applications (7 questions), clinical education (14 questions) and services provided by the faculty (9 questions). It was determined that 83.3% of the nursing students found the nursing profession to be suitable for them, 53% of them selected nursing because of easy job opportunity, and 48.9% of them stayed in state dormitory. Regarding the theoretical courses, 84.6% of the students were determined to agree that the question ‘Course schedule is prepared before the course and published on the university web page.’ 28.7% of them were determined to do not agree that the question ‘Feedback is given to students about the assignments they prepare.’. It has been determined that 41,5% of the students agreed that ‘The time allocated to laboratory applications is sufficient.’ Students said that physical conditions in laboratory (41,5%), and the materials used are insufficient (44.6%), and ‘The number of students in the group is not appropriate for laboratory applications.’ (45.2%). 71.3% of the students think that the nurses view in the clinics the students as a tool to remove the workload, 40.7% of them reported that nurses in the clinic area did not help through the purposes of the course, 39.6% of them said that nurses' communication with students is not good. 37.8% of students stated that nurses did not provide orientation to students, 37.2% of them think that nurses are not role models for students. 53.7% of the students stated that the incentive and support for the student exchange program were insufficient., %48 of the students think that career planning services, %47.2 security services,%45.4 the advisor spent time with students are not enough. It has been determined that nursing students are most disturbed by the approach of the nurses in the clinical area within the undergraduate education program. The clinical area education which is considered as an integral part of nursing education is important and affect to student satisfaction.

Keywords: nursing education, student, clinical area, opinion

Procedia PDF Downloads 160
645 Building Student Empowerment through Live Commercial Projects: A Reflective Account of Participants

Authors: Nilanthi Ratnayake, Wen-Ling Liu

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Prior research indicates an increasing gap between the skills and capabilities of graduates in the contemporary workplace across the globe. The challenge of addressing this issue primarily lies on the hands of higher education institutes/universities. In particular, surveys of UK employers and retailers found that soft skills including communication, numeracy, teamwork, confidence, analytical ability, digital/IT skills, business sense, language, and social skills are highly valued by graduate employers, and in achieving this, there are various assessed and non-assessed learning exercises have already been embedded into the university curriculum. To this end, this research study aims to explore the reflections of postgraduate student participation in a live commercial project (i.e. designing an advertising campaign for open days, summer school etc.) implemented with the intention of offering a transformative experience by deploying this project. Qualitative research methodology has been followed in this study, collecting data from three types of target audiences; students, academics and employers via a series of personal interviews and focus group discussions. Recorded data were transcribed, entered into NVIVO, and analysed using meaning condensation and content analysis. Students reported that they had a very positive impact towards improving self-efficacy, especially in relation to soft skills and confidence in seeking employment opportunities. In addition, this project has reduced cultural barriers for international students in general communications. Academic staff and potential employers who attended on the presentation day expressed their gratitude for offering a lifelong experience for students, and indeed believed that these type of projects contribute significantly to enhance skills and capabilities of students to cater the demands of employers. In essence, key findings demonstrate that an integration of knowledge-based skills into a live commercial project facilitate individuals to make the transition from education to employment in terms of skills, abilities and work behaviours more effectively in comparison to some other activities/assuagements that are currently in place in higher education institutions/universities.

Keywords: soft skills, commercially live project, higher education, student participation

Procedia PDF Downloads 335
644 Selenuranes as Cysteine Protease Inhibitors: Theorical Investigation on Model Systems

Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

Procedia PDF Downloads 282
643 Targeting APP IRE mRNA to Combat Amyloid -β Protein Expression in Alzheimer’s Disease

Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

Procedia PDF Downloads 20
642 Microbiological Profile of UTI along with Their Antibiotic Sensitivity Pattern with Special Reference to Nitrofurantoin

Authors: Rupinder Bakshi, Geeta Walia, Anita Gupta

Abstract:

Introduction: Urinary tract infections (UTI) are considered to be one of the most common bacterial infections with an estimated annual global incidence of 150 million. Antimicrobial drug resistance is one of the major threats due to widespread usage of uncontrolled antibiotics. Materials and Methods: A total number of 9149 urine samples were collected from R.H Patiala and processed in the Department of Microbiology G.M.C Patiala. Urine samples were inoculated on MacConkey’s and blood agar plates by using calibrated loop delivering 0.001 ml of sample and incubated at 37 °C for 24 hrs. The organisms were identified by colony characters, gram’s staining and biochemical reactions. Antimicrobial susceptibility of the isolates was determined against various antimicrobial agents (Hi – Media Mumbai India) by Kirby-Bauer disk diffusion method on Muller Hinton agar plates. Results: Maximum patients were in the age group of 21-30 yrs followed by 31-40 yrs. Males (34%) are less prone to urinary tract infections than females (66%). Out of 9149 urine sample, the culture was positive in 25% (2290) samples. Esch. coli was the most common isolate 60.3% (n = 1378) followed by Klebsiella pneumoniae 13.5% (n = 310), Proteus spp. 9% (n = 209), Staphylococcus aureus 7.6 % (n = 173), Pseudomonas aeruginosa 3.7% (n = 84), Citrobacter spp. 3.1 % (70), Staphylococcus saprophyticus 1.8 % (n = 142), Enterococcus faecalis 0.8%(n=19) and Acinetobacter spp. 0.2%(n=5). Gram negative isolates showed higher sensitivity towards, Piperacillin +Tazobactum (67%), Amikacin (80%), Nitrofurantoin (82%), Aztreonam (100%), Imipenem (100%) and Meropenam (100%) while gram positive showed good response towards Netilmicin (69%), Nitrofurantoin (79%), Linezolid (98%), Vancomycin (100%) and Teicoplanin (100%). 465 (23%) isolates were resistant to Penicillins, 1st generation and 2nd generation Cehalosporins which were further tested by double disk approximation test and combined disk method for ESBL production. Out of 465 isolates, 375 were ESBLs consisting of n 264 (70.6%) Esch.coli and 111 (29.4%) Klebsiella pneumoniae. Susceptibility of ESBL producers to Imipenem, Nitrofurantoin and Amikacin were found to be 100%, 76%, and 75% respectively. Conclusion: Uropathogens are increasingly showing resistance to many antibiotics making empiric management of outpatients UTIs challenging. Ampicillin, Cotrimoxazole, and Ciprofloxacin should not be used in empiric treatment. Nitrofurantoin could be used in lower urinary tract infection. Knowledge of uropathogens and their antimicrobial susceptibility pattern in a geographical region will help inappropriate and judicious antibiotic usage in a health care setup.

Keywords: Urinary Tract Infection, UTI, antibiotic susceptibility pattern, ESBL

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641 Exploring Penicillin Resistance in Gonococcal Penicillin Binding Protein-2: Molecular Docking and Ligand Interaction Analysis

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

Abstract:

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

Procedia PDF Downloads 47