Search results for: drug target

Authors: Yasser R. Tawfic, Mohamed A. Eid

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Foundation differential settlement and supported structure tilting is an occasionally occurred engineering problem. This may be caused by overloading, changes in ground soil properties or unsupported nearby excavations. Engineering thinking points directly toward the logic solution for such problem by uplifting the settled side. This can be achieved with deep foundation elements such as micro-piles and macro-piles™, jacked piers and helical piers, jet grouted soil-crete columns, compaction grout columns, cement grouting or with chemical grouting, or traditional pit underpinning with concrete and mortar. Although, some of these techniques offer economic, fast and low noise solutions, many of them are quite the contrary. For tilted structures, with limited inclination, it may be much easier to cause a balancing settlement on the less-settlement side which shall be done carefully in a proper rate. This principal has been applied in Leaning Tower of Pisa stabilization with soil extraction from the ground surface. In this research, the authors attempt to introduce a new solution with a different point of view. So, micro-tunneling technique is presented in here as an intended ground deformation cause. In general, micro-tunneling is expected to induce limited ground deformations. Thus, the researchers propose to apply the technique to form small size ground unsupported holes to produce the target deformations. This shall be done in four phases: •Application of one or more micro-tunnels, regarding the existing differential settlement value, under the raised side of the tilted structure. •For each individual tunnel, the lining shall be pulled out from both sides (from jacking and receiving shafts) in slow rate. •If required, according to calculations and site records, an additional surface load can be applied on the raised foundation side. •Finally, a strengthening soil grouting shall be applied for stabilization after adjustment. A finite element based numerical model is presented to simulate the proposed construction phases for different tunneling positions and tunnels group. For each case, the surface settlements are calculated and induced plasticity points are checked. These results show the impact of the suggested procedure on the tilted structure and its feasibility. Comparing results also show the importance of the position selection and tunnels group gradual effect. Thus, a new engineering solution is presented to one of the structural and geotechnical engineering challenges.

Keywords: differential settlement, micro-tunneling, soil-structure interaction, tilted structures

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Authors: Mohsen Rabbani, Trista McLaughlin, Ehsan Vahidi

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the remediation of polluted sites with heavy metals, such as rare earth elements (REEs), has been a primary concern of researchers to decontaminate the soil. Among all developed methods to address this concern, phytoremediation has been established as efficient, cost-effective, easy-to-use, and environmentally friendly way, providing a long-term solution for addressing this global concern. Furthermore, this technology has another great potential application in the metals production sector through returning metals buried in soil via metals cropping. Considering the significant metal concentration in hyper-accumulators, the utilization of bioaccumulated metals to extract metals from plant matter has been proposed as a sub-economic area called phytomining. As a recent, more advanced technology to eliminate such pollutants from the soil and produce critical metals, bioharvesting (phytomining/agromining) has been considered another compromising way to produce metals and meet the global demand for critical/target metals. The bio-ore obtained from phytomining can be safely disposed of or introduced to metal production pathways to obtain the most demanded metals, such as REEs. It is well-known that some hyperaccumulators, e.g., fern Dicranopteris linearis, can be used to absorb REE metals from the polluted soils and accumulate them in plant organs, such as leaves and stems. After soil remediation, the plant species can be harvested and introduced to the downstream steps, namely crushing/grinding, leaching, and purification processes, to extract REEs from plant matter. This novel interdisciplinary field can fill the gap between agriculture, mining, metallurgy, and the environment. Despite the advantages of agromining for the REEs production industry, key issues related to the environmental sustainability of the entire life cycle of this new concept have not been assessed yet. Hence, a comparative life cycle assessment (LCA) study was conducted to quantify the environmental footprints of REEs phytomining. The current LCA study aims to estimate and calculate environmental effects associated with phytomining by considering critical factors, such as climate change, land use, and ozone depletion. The results revealed that phytomining is an easy-to-use and environmentally sustainable approach to either eliminate REEs from polluted sites or produce REEs, offering a new source of such metals production. This LCA research provides guidelines for researchers active in developing a reliable relationship between agriculture, mining, metallurgy, and the environment to encounter soil pollution and keep the earth green and clean.

Keywords: phytoremediation, phytomining, life cycle assessment, environmental impacts, rare earth elements, hyperaccumulator

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Authors: Eun-Jeong Jang

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Inequality has been considered as a core issue in public policy. Korea is categorized into one of the countries in the high level of inequality, which matters to not only current but also future generations. The relationship between individuals' origin and destination has an implication of intergenerational inequality. The previous work on this was mostly conducted at macro level using panel data to our knowledge. However, in this level, there is no room to track down what happened during the time between origin and destination. Individuals' origin is represented by their parents' socio-economic status, and in the same way, destination is translated into their own socio-economic status. The first research question is that how origin is related to the destination. Certainly, destination is highly affected by origin. In this view, people's destination is already set to be more or less than a reproduction of previous generations. However, educational achievement is widely believed as an independent factor from the origin. From this point of view, there is a possibility to change the path given by parents by educational attainment. Hence, the second research question would be that how education is related to destination and also, which factor is more influential to destination between origin and education. Also, the focus lies in the mediation of education between origin and destination, which would be the third research question. Socio-economic status in this study is referring to class as a sociological term, as well as wealth including labor and capital income, as an economic term. The combination of class and wealth would be expected to give more accurate picture about the hierarchy in a society. In some cases of non-manual and professional occupations, even though they are categorized into relatively high class, their income is much lower than those who in the same class. Moreover, it is one way to overcome the limitation of the retrospective view during survey. Education is measured as an absolute term, the years of schooling, and also as a relative term, the rank of school. Moreover, all respondents were asked the effort scaled by time intensity, self-motivation, before and during the course of their college based on a standard questionnaire academic achieved model provides. This research is based on a survey at an individual level. The target for sampling is an individual who has a job, regardless of gender, including income-earners and self-employed people and aged between thirties and forties because this age group is considered to reach the stage of job stability. In most cases, the researcher met respondents person to person visiting their work place or home and had a chance to interview some of them. One hundred forty individual data collected from May to August in 2017. It will be analyzed by multiple regression (Q1, Q2) and structural equation modeling (Q3).

Keywords: class, destination, educational achievement, effort, income, origin, socio-economic status, South Korea

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Samar Alarif

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Smart sustainable educational campuses are the latest paradigm of innovation in the education domain. Campuses become a hub for sustainable environmental innovations. University has a vital role in paving the road for digital transformations in the infrastructure domain by preparing skilled engineers and specialists. The open digital platform enables smart campuses to simulate real education experience by managing their infrastructure within the curriculums. Moreover, it allows the engagement between governments, businesses, and citizens to push for innovation and sustainable services. Urban and building information modeling platforms have recently attained widespread attention in smart campuses due to their applications and benefits for creating the campus's digital twin in the form of an open digital platform. Qualitative and quantitative strategies were used in directing this research to develop and validate the UIM/BIM platform benefits for smart campuses FM and its impact on the institution's sustainable vision. The research findings are based on literature reviews and case studies of the TU berlin El-Gouna campus. Textual data will be collected using semi-structured interviews with actors, secondary data like BIM course student projects, documents, and publications related to the campus actors. The study results indicated that UIM/BIM has several benefits for the smart campus. Universities can achieve better capacity-building by integrating all the actors in the UIM/BIM process. Universities would achieve their community outreach vision by launching an online outreach of UIM/BIM course for the academic and professional community. The UIM/BIM training courses would integrate students from different disciplines and alumni graduated as well as engineers and planners and technicians. Open platforms enable universities to build a partnership with the industry; companies should be involved in the development of BIM technology courses. The collaboration between academia and the industry would fix the gap, promote the academic courses to reply to the professional requirements, and transfer the industry's academic innovations. In addition to that, the collaboration between academia, industry, government vocational and training centers, and civil society should be promoted by co-creation workshops, a series of seminars, and conferences. These co-creation activities target the capacity buildings and build governmental strategies and policies to support expanding the sustainable innovations and to agree on the expected role of all the stakeholders to support the transformation.

Keywords: smart city, smart educational campus, UIM, urban platforms, sustainable campus

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Authors: Celine Shi Ying Lee, Jong Jian Lee

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Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: Juan-Pedro Rica-Peromingo

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Nowadays, corpus linguistics has become a key research methodology for Translation Studies, which broadens the scope of cross-linguistic studies. In the case of the study presented here, the approach used focuses on learners with little or no experience to study, at an early stage, general mistakes and errors, the correct or incorrect use of translation strategies, and to improve the translational competence of the students. Led by Sylviane Granger and Marie-Aude Lefer of the Centre for English Corpus Linguistics of the University of Louvain, the MUST corpus (MUltilingual Student Translation Corpus) is an international project which brings together partners from Europe and worldwide universities and connects Learner Corpus Research (LCR) and Translation Studies (TS). It aims to build a corpus of translations carried out by students including both direct (L2 > L1) an indirect (L1 > L2) translations, from a great variety of text types, genres, and registers in a wide variety of languages: audiovisual translations (including dubbing, subtitling for hearing population and for deaf population), scientific, humanistic, literary, economic and legal translation texts. This paper focuses on the work carried out by the Spanish team from the Complutense University (UCMA), which is part of the MUST project, and it describes the specific features of the corpus built by its members. All the texts used by UCMA are either direct or indirect translations between English and Spanish. Students’ profiles comprise translation trainees, foreign language students with a major in English, engineers studying EFL and MA students, all of them with different English levels (from B1 to C1); for some of the students, this would be their first experience with translation. The MUST corpus is searchable via Hypal4MUST, a web-based interface developed by Adam Obrusnik from Masaryk University (Czech Republic), which includes a translation-oriented annotation system (TAS). A distinctive feature of the interface is that it allows source texts and target texts to be aligned, so we can be able to observe and compare in detail both language structures and study translation strategies used by students. The initial data obtained point out the kind of difficulties encountered by the students and reveal the most frequent strategies implemented by the learners according to their level of English, their translation experience and the text genres. We have also found common errors in the graduate and postgraduate university students’ translations: transfer errors, lexical errors, grammatical errors, text-specific translation errors, and cultural-related errors have been identified. Analyzing all these parameters will provide more material to bring better solutions to improve the quality of teaching and the translations produced by the students.

Keywords: corpus studies, students’ corpus, the MUST corpus, translation studies

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Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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Authors: Jong H. Kim, Kathleen L. Chan, Luisa W. Cheng

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Control of fungal pathogens, such as foodborne mycotoxin producers, is problematic as effective antimycotic agents are often very limited. Mycotoxin contamination significantly interferes with the safe production of foods or crops worldwide. Moreover, expansion of fungal resistance to commercial drugs or fungicides is a global human health concern. Therefore, there is a persistent need to enhance the efficacy of commercial antimycotic agents or to develop new intervention strategies. Disruption of the cellular antioxidant system should be an effective method for pathogen control. Such disruption can be achieved with safe, redox-active compounds. Natural phenolic derivatives are potent redox cyclers that inhibit fungal growth through destabilization of the cellular antioxidant system. The goal of this study is to identify novel, redox-active compounds that disrupt the fungal antioxidant system. The identified compounds could also function as sensitizing agents to conventional antimycotics (i.e., chemosensitization) to improve antifungal efficacy. Various benzo derivatives were tested against fungal pathogens. Gene deletion mutants of the yeast Saccharomyces cerevisiae were used as model systems for identifying molecular targets of benzo analogs. The efficacy of identified compounds as potent antifungal agents or as chemosensitizing agents to commercial drugs or fungicides was examined with methods outlined by the Clinical Laboratory Standards Institute or the European Committee on Antimicrobial Susceptibility Testing. Selected benzo derivatives possessed potent antifungal or antimycotoxigenic activity. Molecular analyses by using S. cerevisiae mutants indicated antifungal activity of benzo derivatives was through disruption of cellular antioxidant or cell wall integrity system. Certain benzo analogs screened overcame tolerance of Aspergillus signaling mutants, namely mitogen-activated protein kinase mutants, to fludioxonil fungicide. Synergistic antifungal chemosensitization greatly lowered minimum inhibitory or fungicidal concentrations of test compounds, including inhibitors of mitochondrial respiration. Of note, salicylaldehyde is a potent antimycotic volatile that has some practical application as a fumigant. Altogether, benzo derivatives targeting cellular antioxidant system of fungi (along with cell wall integrity system) effectively suppress fungal growth. Candidate compounds possess the antifungal, antimycotoxigenic or chemosensitizing capacity to augment the efficacy of commercial antifungals. Therefore, chemogenetic approaches can lead to the development of novel antifungal intervention strategies, which enhance the efficacy of established microbe intervention practices and overcome drug/fungicide resistance. Chemosensitization further reduces costs and alleviates negative side effects associated with current antifungal treatments.

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Xincheng Jiang, Yanyan An, Yaoyao Huang, Wei Ding, Manli Sun, Hong Li, Huaili Zheng

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The residual antibiotics in the environment will pose a threat to the environment and human health. Thus, efficient removal and rapid detection of norfloxacin (NOR) in wastewater is very important. The main sources of NOR pollution are the agricultural, pharmaceutical industry and hospital wastewater. The total consumption of NOR in China can reach 5440 tons per year. It is found that neither animals nor humans can totally absorb and metabolize NOR, resulting in the excretion of NOR into the environment. Therefore, residual NOR has been detected in water bodies. The hazards of NOR in wastewater lie in three aspects: (1) the removal capacity of the wastewater treatment plant for NOR is limited (it is reported that the average removal efficiency of NOR in the wastewater treatment plant is only 68%); (2) NOR entering the environment will lead to the emergence of drug-resistant strains; (3) NOR is toxic to many aquatic species. At present, the removal and detection technologies of NOR are applied separately, which leads to a cumbersome operation process. The development of simultaneous adsorption-flocculation removal and FTIR detection of pollutants has three advantages: (1) Adsorption-flocculation technology promotes the detection technology (the enrichment effect on the material surface improves the detection ability); (2) The integration of adsorption-flocculation technology and detection technology reduces the material cost and makes the operation easier; (3) FTIR detection technology endows the water treatment agent with the ability of molecular recognition and semi-quantitative detection for pollutants. Thus, it is of great significance to develop a smart water treatment material with high removal capacity and detection ability for pollutants. This study explored the feasibility of combining NOR removal method with the semi-quantitative detection method. A magnetic Cu-Ni-S/Ni foam was synthesized by in-situ loading Cu-Ni-S nanostructures on the surface of Ni foam. The novelty of this material is the combination of adsorption-flocculation technology and semi-quantitative detection technology. Batch experiments showed that Cu-Ni-S/Ni foam has a high removal rate of NOR (96.92%), wide pH adaptability (pH=4.0-10.0) and strong ion interference resistance (0.1-100 mmol/L). According to the Langmuir fitting model, the removal capacity can reach 417.4 mg/g at 25 °C, which is much higher than that of other water treatment agents reported in most studies. Characterization analysis indicated that the main removal mechanisms are surface complexation, cation bridging, electrostatic attraction, precipitation and flocculation. Transmission FTIR detection experiments showed that NOR on Cu-Ni-S/Ni foam has easily recognizable FTIR fingerprints; the intensity of characteristic peaks roughly reflects the concentration information to some extent. This semi-quantitative detection method has a wide linear range (5-100 mg/L) and a low limit of detection (4.6 mg/L). These results show that Cu-Ni-S/Ni foam has excellent removal performance and semi-quantitative detection ability of NOR molecules. This paper provides a new idea for designing and preparing multi-functional water treatment materials to achieve simultaneous removal and semi-quantitative detection of organic pollutants in water.

Keywords: adsorption-flocculation, antibiotics detection, Cu-Ni-S/Ni foam, norfloxacin

Procedia PDF Downloads 49

Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

Procedia PDF Downloads 303

Authors: Saori Fujimoto, Hiromi Kawasaki, Mari Murakami, Yoko Ueno

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Background: Coronavirus disease (COVID-19) has been spreading throughout the world. In Japan, many nursing universities have conducted online clinical practices to secure students’ learning opportunities. In the field of women’s health nursing, even after the pandemic ended, it will be worthwhile to utilize online practice in declining birthrate and reducing the burden of mothers. This study examined the learning effects of conducting online visits for mothers with infants during the COVID-19 pandemic by nursing students to enhance the students’ ability to carry out the online practice even in ordinary times effectively. Methods: Students were divided into groups of three, and information on the mothers was assessed, and the visits were planned. After role-play was conducted by the students and teachers, an online visit was conducted. The analysis target was the self-evaluation score of nine students who conducted online visits in June 2020 and had consented to participate. The evaluation contents included three items for assessment, two items for planning, one item for ethical consideration, five items for nursing practice, and two items for evaluation. The self-evaluation score ranged from 4 (‘Can do with a little advice’) to 1 (‘Can’t do with a little advice’). A univariate statistical analysis was performed. This study was approved by the Ethical Committee for Epidemiology of Hiroshima University. Results: The items with the highest mean (standard deviation) scores were ‘advocates for the dignity and the rights of mothers’ (3.89 (0.31)) and ‘communication behavior needed to create a trusting relationship’ (3.89 (0.31)).’ Next were the ‘individual nursing practice tailored to mothers (3.78 (0.42))’ and ‘review own practice and work on own task (3.78 (0.42)).’ The mean (standard deviation) of the items by type were as follows: three assessment items, 3.26 (0.70), two planning items, 3.11 (0.49), one ethical consideration item, 3.89 (0.31), five nursing practice items, 3.56 (0.54), and two evaluation items, 3.67 (0.47). Conclusion: The highest self-evaluations were for ‘advocates for the dignity and the rights of mothers’ and ‘communication behavior needed to create a trusting relationship.’ These findings suggest that the students were able to form good relationships with the mothers by improving their ability to effectively communicate and by presenting a positive attitude, even when conducting health visits online. However, the self-evaluation scores for assessment and planning were lower than those of ethical consideration, nursing practice, and evaluation. This was most likely due to a lack of opportunities and time to gather information and the need to modify and add plans in a short amount of time during one online visit. It is necessary to further consider the methods used in conducting online visits from the following viewpoints: methods of gathering information and the ability to make changes through multiple visits.

Keywords: infants, learning effects, mothers, online visit practice

Procedia PDF Downloads 112

Authors: Samantha Jeffries, Chontit Chuenurah

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Thailand incarcerates the largest number of women and has the highest female incarceration rate in South East Asia. Since the 1990s, there has been a substantial increase in the number, rate and proportion of women imprisoned. Thailand places a high priority on the gender specific contexts out of which offending arises and the different needs of women in the criminal justice system. This is manifested in work undertaken to guide the development of the United Nations Rules for the Treatment of Women Prisoners and Non-Custodial Measures for Women Offenders (the Bangkok Rules); adopted by the United Nations General Assembly in 2010. The Bangkok Rules make a strong statement about Thailand’s recognition of and commitment to the fair and equitable treatment of women throughout their contact with the criminal justice system including at sentencing and in prison. This makes the comparatively high use of imprisonment for women in Thailand particularly concerning and raises questions about the relationship between gender, crime and criminal justice. While there is an extensive body of research in Western jurisdictions exploring women’s pathways to prison, there is a relative dearth of methodologically robust research examining the possible gendered circumstances leading to imprisonment in Thailand. In this presentation, we will report preliminary findings from a qualitative study of women’s pathways to prison in Thailand. Our research aims were to ascertain: 1) the type, frequency, and context of criminal behavior that led to women’s incarceration, 2) women’s experiences of the criminal justice system, 3) the broader life experiences and circumstances that led women to prison in Thailand. In-depth life history interviews (n=77) were utilized to gain a comprehensive understanding of women’s journeys into prison. The interview schedule was open-ended consisting of prisoner responses to broad discussion topics. This approach provided women with the opportunity to describe significant experiences in their lives, to bring together distinct chronologies of events, and to analyze links between their varied life experiences, offending, and incarceration. Analyses showed that women’s journey’s to prison take one of eight pathways which tentatively labelled as follows, the: 1) harmed and harming pathway, 2) domestic/family violence victimization pathway, 3) drug connected pathway, 4) street woman pathway, 5) economically motivated pathway, 6) jealousy anger and/or revenge pathway, 7) naivety pathway, 8) unjust and/or corrupted criminal justice pathway. Each will be fully discussed during the presentation. This research is significant because it is the first in-depth methodologically robust exploration of women’s journeys to prison in Thailand and one of a few studies to explore gendered pathways outside of western contexts. Understanding women’s pathways into Thailand’s prisons is crucial to the development of effective planning, policy and program responses not only while women are in prison but also post-release. To best meet women’s needs in prison and effectively support their reintegration, we must have a comprehensive understanding of who these women are, what offenses they commit, the reasons that trigger their confrontations with the criminal justice system and the impact of the criminal justice system on them.

Keywords: pathways, prison, women, Thailand

Procedia PDF Downloads 223

Authors: Robert H. Bradley, Robert F. Corwyn

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There is abundant research showing that socio-economic status is implicated in parenting. However, additional factors such as family context, parent personality, parenting history and child behavior also help determine how parents enact the role of caregiver. Each of these factors not only helps determine how a parent will act in a given situation, but each can serve to moderate the influence of the other factors. Personality has long been studied as a factor that influences parental behavior, but it has almost never been considered as a moderator of family contextual factors. For this study, relations between three maternal personality characteristics (agreeableness, extraversion, neuroticism) and four aspects of parenting (harshness, sensitivity, stimulation, learning materials) were examined when children were 6 months, 36 months, and 54 months old and again at 5th grade. Relations between these three aspects of personality and the overall home environment were also examined. A key concern was whether maternal personality characteristics moderated relations between household income and the four aspects of parenting and between household income and the overall home environment. The data for this study were taken from the NICHD Study of Early Child Care and Youth Development (NICHD SECCYD). The total sample consisted of 1364 families living in ten different sites in the United States. However, the samples analyzed included only those with complete data on all four parenting outcomes (i.e., sensitivity, harshness, stimulation, and provision of learning materials), income, maternal education and all three measures of personality (i.e., agreeableness, neuroticism, extraversion) at each age examined. Results from hierarchical regression analysis showed that mothers high in agreeableness were more likely to demonstrate sensitivity and stimulation as well as provide more learning materials to their children but were less likely to manifest harshness. Maternal agreeableness also consistently moderated the effects of low income on parental behavior. Mothers high in extraversion were more likely to provide stimulation and learning materials, with extraversion serving as a moderator of low income on both. By contrast, mothers high in neuroticism were less likely to demonstrate positive aspects of parenting and more likely to manifest negative aspects (e.g., harshness). Neuroticism also served to moderate the influence of low income on parenting, especially for stimulation and learning materials. The most consistent effects of parent personality were on the overall home environment, with significant main and interaction effects observed in 11 of the 12 models tested. These findings suggest that it may behoove professional who work with parents living in adverse circumstances to consider parental personality in helping to better target prevention or intervention efforts aimed at supporting parental efforts to act in ways that benefit children.

Keywords: home environment, household income, learning materials, personality, sensitivity, stimulation

Procedia PDF Downloads 188

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

Procedia PDF Downloads 41

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

Procedia PDF Downloads 177

Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

Procedia PDF Downloads 78

Authors: Chunhua Liao, Jinfei Wang, Bo Shan, Yang Song, Yongjun He, Taifeng Dong

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Winter wheat is one of the main crops in Canada. Forecasting of within-field variability of yield in winter wheat at the early stages is essential for precision farming. However, the crop yield modelling based on high spatial resolution satellite data is generally affected by the lack of continuous satellite observations, resulting in reducing the generalization ability of the models and increasing the difficulty of crop yield forecasting at the early stages. In this study, the correlations between Sentinel-2 data (vegetation indices and reflectance) and yield data collected by combine harvester were investigated and a generalized multivariate linear regression (MLR) model was built and tested with data acquired in different years. It was found that the four-band reflectance (blue, green, red, near-infrared) performed better than their vegetation indices (NDVI, EVI, WDRVI and OSAVI) in wheat yield prediction. The optimum phenological stage for wheat yield prediction with highest accuracy was at the growing stages from the end of the flowering to the beginning of the filling stage. The best MLR model was therefore built to predict wheat yield before harvest using Sentinel-2 data acquired at the end of the flowering stage. Further, to improve the ability of the yield prediction at the early stages, three simple unsupervised domain adaptation (DA) methods were adopted to transform the reflectance data at the early stages to the optimum phenological stage. The winter wheat yield prediction using multiple vegetation indices showed higher accuracy than using single vegetation index. The optimum stage for winter wheat yield forecasting varied with different fields when using vegetation indices, while it was consistent when using multispectral reflectance and the optimum stage for winter wheat yield prediction was at the end of flowering stage. The average testing RMSE of the MLR model at the end of the flowering stage was 604.48 kg/ha. Near the booting stage, the average testing RMSE of yield prediction using the best MLR was reduced to 799.18 kg/ha when applying the mean matching domain adaptation approach to transform the data to the target domain (at the end of the flowering) compared to that using the original data based on the models developed at the booting stage directly (“MLR at the early stage”) (RMSE =1140.64 kg/ha). This study demonstrated that the simple mean matching (MM) performed better than other DA methods and it was found that “DA then MLR at the optimum stage” performed better than “MLR directly at the early stages” for winter wheat yield forecasting at the early stages. The results indicated that the DA had a great potential in near real-time crop yield forecasting at the early stages. This study indicated that the simple domain adaptation methods had a great potential in crop yield prediction at the early stages using remote sensing data.

Keywords: wheat yield prediction, domain adaptation, Sentinel-2, within-field scale

Procedia PDF Downloads 40

Authors: Folajinmi Oluwasina, Towolawi Adetayo, Kate Ssamula, Penninah Iutung, Daniel Reijer

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Objective: Routine HIV screening has been promoted as an essential component of efforts to reduce incidence, morbidity, and mortality. The objectives of this study were to identify the optimal annual volume needed to realize the public health goals of HIV screening in the AIDS Healthcare Foundation supported hospitals and establish an implementation process to realize that optimal annual volume. Methods: Starting in 2011 a program was established to routinize HIV screening within communities and government hospitals. In 2016 Five-years of HIV screening data were reviewed to identify the optimal annual proportions of age-eligible patients screened to realize the public health goals of reducing new diagnoses and ending late-stage diagnosis (tracked as concurrent HIV/AIDS diagnosis). Analysis demonstrated that rates of new diagnoses level off when 42% of age-eligible patients were screened, providing a baseline for routine screening efforts; and concurrent HIV/AIDS diagnoses reached statistical zero at screening rates of 70%. Annual facility based targets were re-structured to meet these new target volumes. Restructuring efforts focused on right-sizing HIV screening programs to align and transition programs to integrated HIV screening within standard medical care and treatment. Results: Over one million patients were screened for HIV during the five years; 16, 033 new HIV diagnoses and access to care and treatment made successfully for 82 % (13,206), and concurrent diagnosis rates went from 32.26% to 25.27%. While screening rates increased by 104.7% over the 5-years, volume analysis demonstrated that rates need to further increase by 62.52% to reach desired 20% baseline and more than double to reach optimal annual screening volume. In 2011 facility targets for HIV screening were increased to reflect volume analysis, and in that third year, 12 of the 19 facilities reached or exceeded new baseline targets. Conclusions and Recommendation: Quantifying targets against routine HIV screening goals identified optimal annual screening volume and allowed facilities to scale their program size and allocate resources accordingly. The program transitioned from utilizing non-evidence based annual volume increases to establishing annual targets based on optimal volume analysis. This has allowed efforts to be evaluated on the ability to realize quantified goals related to the public health value of HIV screening. Optimal volume analysis helps to determine the size of an HIV screening program. It is a public health tool, not a tool to determine if an individual patient should receive screening.

Keywords: HIV screening, optimal volume, HIV diagnosis, routine

Procedia PDF Downloads 239

Authors: Mohammad Nazri Mustafa, Sh Norliza Sy Salim, Pedram Hatami Abdullah

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Civil and structural assets normally have an average of more than 30 years of design life. Adding to this advantage, the assets are normally subjected to slow degradation process. Due to the fact that repair and strengthening work for these assets are normally not dependent on plant shut down, the maintenance and integrity restoration of these assets are mostly done based on “as required” and “run to failure” basis. However unlike other industries, the exposure in oil and gas environment is harsher as the result of corrosive soil and groundwater, chemical spill, frequent wetting and drying, icing and de-icing, steam and heat, etc. Due to this type of exposure and the increasing level of structural defects and rectification in line with the increasing age of plants, assets integrity assessment requires a more defined scope and procedures that needs to be based on risk and assets criticality. This leads to the establishment of risk based inspection and proactive maintenance procedure for civil and structural assets. To date there is hardly any procedure and guideline as far as integrity assessment and systematic inspection and maintenance of civil and structural assets (onshore) are concerned. Group Technical Solutions has developed a procedure and guideline that takes into consideration credible failure scenario, assets risk and criticality from process safety and structural engineering perspective, structural importance, modeling and analysis among others. Detailed inspection that includes destructive and non-destructive tests (DT & NDT) and structural monitoring is also being performed to quantify defects, assess severity and impact on integrity as well as identify the timeline for integrity restoration. Each defect and its credible failure scenario is assessed against the risk on people, environment, reputation and production loss. This technical paper is intended to share on the established procedure and guideline and their execution in oil & gas plants. In line with the overall roadmap, the procedure and guideline will form part of specialized solutions to increase production and to meet the “Operational Excellence” target while extending service life of civil and structural assets. As the result of implementation, the management of civil and structural assets is now more systematically done and the “fire-fighting” mode of maintenance is being gradually phased out and replaced by a proactive and preventive approach. This technical paper will also set the criteria and pose the challenge to the industry for innovative repair and strengthening methods for civil & structural assets in oil & gas environment, in line with safety, constructability and continuous modification and revamp of plant facilities to meet production demand.

Keywords: assets criticality, credible failure scenario, proactive and preventive maintenance, risk based inspection

Procedia PDF Downloads 371

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

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The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

Procedia PDF Downloads 198

Authors: Dewan Ahsan

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Denmark is well ahead in generating electricity from renewable sources. The offshore wind sector is playing the pivotal role to achieve this target. Though there is a rapid growth of offshore wind sector in Denmark, still there is a dearth of synchronization in OHS (occupational health and safety) regulation and standards. Therefore, this paper attempts to ascertain: i) what are the major challenges of the company specific OHS standards? ii) why does the offshore wind industry need a standardized OHS management system? and iii) who can play the key role in this process? To achieve these objectives, this research applies the interview and survey techniques. This study has identified several key challenges in OHS management system which are; gaps in coordination and communication among the stakeholders, gaps in incident reporting systems, absence of a harmonized OHS standard and blame culture. Furthermore, this research has identified eleven key stakeholders who are actively involve with the offshore wind business in Denmark. As noticed, the relationships among these stakeholders are very complex specially between operators and sub-contractors. The respondent technicians are concerned with the compliance of various third-party OHS standards (e.g. ISO 31000, ISO 29400, Good practice guidelines by G+) which are applying by various offshore companies. On top of these standards, operators also impose their own OHS standards. From the technicians point of angle, many of these standards are not even specific for the offshore wind sector. So, it is a big challenge for the technicians and sub-contractors to comply with different company specific standards which also elevate the price of their services offer to the operators. For instance, when a sub-contractor is competing for a bidding, it must fulfill a number of OHS requirements (which demands many extra documantions) set by the individual operator and/the turbine supplier. According to sub-contractors’ point of view these extra works consume too much time to prepare the bidding documents and they also need to train their employees to pass the specific OHS certification courses to accomplish the demand for individual clients and individual project. The sub-contractors argued that in many cases these extra documentations and OHS certificates are inessential to ensure the quality service. So, a standardized OHS management procedure (which could be applicable for all the clients) can easily solve this problem. In conclusion, this study highlights that i) development of a harmonized OHS standard applicable for all the operators and turbine suppliers, ii) encouragement of technicians’ active participation in the OHS management, iii) development of a good safety leadership, and, iv) sharing of experiences among the stakeholders (specially operators-operators-sub contractors) are the most vital strategies to overcome the existing challenges and to achieve the goal of 'zero accident/harm' in the offshore wind industry.

Keywords: green energy, offshore, safety, Denmark

Procedia PDF Downloads 190

Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Camille Rich, Nadine Ferris France, Ann Nolan, Webster Mavhu, Vongai Munatsi

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Background and Aim: Zimbabwe has one of the highest HIV rates in the world, with a 12.7% adult prevalence rate. Young adults are a key group affected by HIV, and one-third of all new infections in Zimbabwe are amongst people ages 18-24 years. Stigma remains one of the main barriers to managing and reducing the HIV crisis, especially for young adults. There are several types of stigma, including enacted stigma, the outward discrimination towards someone and self-stigma, the negative self-judgments one has towards themselves. Self-stigma can have severe consequences, including feelings of worthlessness, shame, suicidal thoughts, and avoidance of medical help. This can have detrimental effects on those living with HIV. However, the unique beliefs and impacts of self-stigma amongst key groups living with HIV have not yet been explored. Therefore, the focus of this study is on the beliefs and experiences of HIV-related self-stigma, as experienced by young adults living in Harare, Zimbabwe. Research Methods: A qualitative approach was taken for this study, using sixteen semi-structured interviews with young adults (18-24 years) who are living with HIV in Harare. Participants were conveniently and purposefully sampled as members of Africa, an organization dedicated to young people living with HIV. Interviews were conducted over Zoom due to the COVID-19 pandemic, recorded and then coded using the software NVivo. The data was analyzed using both inductive and deductive Thematic Analysis to find common themes. Results: All of the participants experienced HIV-related self-stigma, and both beliefs and experiences were explored. These negative self-perceptions included beliefs of worthlessness, hopelessness, and negative body image. The young adults described believing they were not good enough to be around HIV negative people or that they could never be loved due to their HIV status. Developing self-stigmatizing thoughts came from internalizing negative cultural values, stereotypes about people living with HIV, and adverse experiences. Three main themes of self-stigmatizing experiences emerged: disclosure difficulties, relationship complications, and being isolated. Fear of telling someone their status, rejection in a relationship, and being excluded by others due to their HIV status contributed to their self-stigma. These experiences caused feelings of loneliness, sadness, shame, fear, and low self-worth. Conclusions: This study explored the beliefs and experiences of HIV-related self-stigma of these young adults. The emergence of negative self-perceptions demonstrated deep-rooted beliefs of HIV-related self-stigma that adversely impact the participants. The negative self-perceptions and self-stigmatizing experiences caused the participants to feel worthless, hopeless, shameful, and alone-negatively impacting their physical and mental health, personal relationships, and sense of self-identity. These results can now be used to pursue interventions to target the specific beliefs and experiences of young adults living with HIV and reduce the adverse consequences of self-stigma.

Keywords: beliefs, HIV, self-stigma, stigma, Zimbabwe

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Authors: Szymon Rutkowski, Tomasz Korbak

Abstract:

We present a reinforcement-learning-based method of training neural machine translation models without parallel corpora. The standard encoder-decoder approach to machine translation suffers from two problems we aim to address. First, it needs parallel corpora, which are scarce, especially for low-resource languages. Second, it lacks psychological plausibility of learning procedure: learning a foreign language is about learning to communicate useful information, not merely learning to transduce from one language’s 'encoding' to another. We instead pose the problem of learning to translate as learning a policy in a communication game between two agents: the translator and the classifier. The classifier is trained beforehand on a natural language inference task (determining the entailment relation between a premise and a hypothesis) in the target language. The translator produces a sequence of actions that correspond to generating translations of both the hypothesis and premise, which are then passed to the classifier. The translator is rewarded for classifier’s performance on determining entailment between sentences translated by the translator to disciple’s native language. Translator’s performance thus reflects its ability to communicate useful information to the classifier. In effect, we train a machine translation model without the need for parallel corpora altogether. While similar reinforcement learning formulations for zero-shot translation were proposed before, there is a number of improvements we introduce. While prior research aimed at grounding the translation task in the physical world by evaluating agents on an image captioning task, we found that using a linguistic task is more sample-efficient. Natural language inference (also known as recognizing textual entailment) captures semantic properties of sentence pairs that are poorly correlated with semantic similarity, thus enforcing basic understanding of the role played by compositionality. It has been shown that models trained recognizing textual entailment produce high-quality general-purpose sentence embeddings transferrable to other tasks. We use stanford natural language inference (SNLI) dataset as well as its analogous datasets for French (XNLI) and Polish (CDSCorpus). Textual entailment corpora can be obtained relatively easily for any language, which makes our approach more extensible to low-resource languages than traditional approaches based on parallel corpora. We evaluated a number of reinforcement learning algorithms (including policy gradients and actor-critic) to solve the problem of translator’s policy optimization and found that our attempts yield some promising improvements over previous approaches to reinforcement-learning based zero-shot machine translation.

Keywords: agent-based language learning, low-resource translation, natural language inference, neural machine translation, reinforcement learning

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

Abstract:

Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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