Search results for: antiresorptive drug related osteonecrosis

Authors: Abdulrahman Fahim M. Alsulami

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This paper is dedicated to a detailed investigation of the interaction between the agreement on trade-related aspects of intellectual property rights (TRIPS) and bilateral investment treaties (BITs) in the regulation of health-related intellectual property rights in Australia and the Kingdom of Saudi Arabia. The chosen research object is complex and requires a thorough examination of a set of factors influencing the problem under investigation. At the moment, to the author’s best knowledge’ there is no academic research that would conceptualize and critically compare the regulation of health-related intellectual property rights in these two countries. While there is a substantial amount of information in the literature on certain aspects of the problem, the existing knowledge about certain aspects of the health-related regulatory frameworks in Australia and Saudi Arabia barely explains in detail the specifics of the ways in which the TRIPS agreement interacts with (BITs) in the regulation of health-related intellectual property rights. Therefore, this paper will address an evident research gap by studying an intriguing yet under-researched problem. The paper comprises five subsections. The first subsection provides an overview of the investment climate in Saudi Arabia and Australia with an emphasis on the health care industry. It will cover political, economic, and social factors influencing the investment climate in these countries, the systems of intellectual property rights protection, recent patterns relevant to the investment climate’s development, and key characteristics of the investment climate in the health care industry. The second subsection analyses BITs in Saudi Arabia and Australia in light of the countries’ responsibilities under the TRIPS Agreement. The third subsection provides a critical examination of the interaction between the TRIPS Agreement and BITs in Saudi Arabia on the basis of data collected and analyzed in previous subsections. It will investigate key discrepancies concerning the regulation of health-related intellectual property rights in Saudi Arabia and Australia from the position of BITs’ interaction with the TRIPS Agreement and explore the existing procedures for clarifying priorities between them in regulating health-related intellectual property rights. The fourth subsection of the paper provides recommendations concerning the transformation of BITS into a TRIPS+ dimension in regulating health-related intellectual property rights in Saudi Arabia and Australia. The final subsection provides a summary of differences between the Australian and Saudi BITs from the perspective of the regulation of health-related intellectual property rights under the TRIPS agreement and bilateral investment treaties.

Keywords: Australia, bilateral investment treaties, IP law, public health sector, Saudi Arabia

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Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

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Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

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Authors: B. Kenny, M. Dixon, A. Boshell

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The use of alcoholic surgical prep was recently introduced into the Royal Newcastle Center for elective procedures. In the past 3 months there have been a significant number of burns believed to be related to ‘pooling’ of this surgical prep in patients undergoing procedures where they are placed in the lateral position with hip bolsters. The aim of the audit was to determine the reason for the burns, analyze what pre-existing factors may contribute to the development of the burns and what can be changed to prevent further burns occurring. All patients undergoing a procedure performed on the hip who were placed in the lateral position with sacral and anterior, superior iliac spine (ASIS) support with ‘bolsters’ were included in the audit. Patients who developed a ‘burn’ were recorded, details of the surgery, demographics, surgical prep used and length of surgery were obtained as well as photographs taken to document the burn. Measures were then taken to prevent further burns and the efficacy was documented. Overall 14 patients developed burns over the ipsilateral ASIS. Of these, 13 were Total Hip Arthroplasty (THA) and 1 was a removal of femoral nail. All patients had Chlorhexidine 0.5% in Alcohol 70% Tinted Red surgical preparation or Betadine Alcoholic Skin Prep (70% etoh). Patients were set up in the standard lateral decubitus position with sacral and bilateral ASIS bolsters with a valband covering. 86% of patients were found to have pre-existing hypersensitivities to various substances. There is very little literature besides a few case reports on surgical prep-related burns. The case reports that do exist are related to the use of tourniquet-related burns and there is no mention in the literature examining ‘bolster’ related burns. The burns are hypothesized to be caused by pooling of the alcoholic solution which is amplified by the use of Valband.

Keywords: arthroplasty, chemical burns, wounds, rehabilitation

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Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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Authors: Daniel Walker, Adam Qureshi, David Marchant, Alex Bahrami Balani

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The present study aimed to assess the impact of concussion and physical pain on depression and health-related quality of life. Depressive symptoms were assessed using the Center for Epidemiological Studies' Depression Scale, and scores of health-related quality of life were measured by health-related quality of life short form-12. Data analysis of 67 participants (concussed 32 vs. 35 non-concussed) revealed that (i) 52% were displaying depressive symptoms (concussed 30% vs. non-concussed 22%) (ii) concussion had a significant effect on depressive symptoms when controlling for pain but no effect on the quality of life scores when controlling the same variable (iii) pain had a significant effect on depressive symptoms and quality of life. With this, both concussion and physical pain seem to have a negative impact on mental health; however, individuals may only recognise a reduction in quality of life with increased physical pain, hence a deterioration in mental well-being could be disregarded as a factor of health-related quality of life.

Keywords: depression, quality of life, concussion, physical pain

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Authors: Badino Manuel, Farias Maria Alejandra

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Telemedicine (TM) has the potential to develop efficient and cost-effective means for delivering quality health care services and outcomes, showing equal or, in some cases, better results than in-person treatment. To analyze patient satisfaction with the use of TM becomes relevant because this can affect the results of treatment and the adherence to it. The aim is to assess patient satisfaction with telemedicine for treating substance-related disorders in a mental health service in Córdoba, Argentina. A descriptive cross-sectional study was conducted among patients with substance-related disorders (N=115). A patient satisfaction survey was conducted from December 2021 to March 2022. For a total of 115 participants, 59,1% were male, 38,3% were female and 2,6% non-binary. In relation to educational status, 40% finished university, 39,1% high school, and 20,9 % only primary school. Regarding age, 4,3 % were young, 92,2% were adults, and 3,5% were elderly. Regarding TM treatment, 95,7% reported being satisfied. Furthermore, 85,2% of users declared that they would continueTM treatment, and 14,8% said that they would not resume TM treatment. To conclude, high levels of patient satisfaction contributes to the continuity of TM modality.

Keywords: telemedicine, mental health, substance-related disorders, patient satisfaction

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Nasrine Olson

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With over 70,000 scholarly publications on the topic of biosensors, an overview of the field has become a challenge. To facilitate, there are currently over 700 expert-reviews of publications on biosensors and related topics. This study focuses on these review papers in order to provide a Meta-Review of the area. This paper provides a statistical analysis and overview of biosensor-related review papers. Comprehensive searches are conducted in the Web of Science, and PubMed databases and the resulting empirical material are analyzed using bibliometric methods and tools. The study finds that the biosensor-related review papers can be categorized in five related subgroups, broadly denoted by (i) properties of materials and particles, (ii) analysis and indicators, (iii) diagnostics, (iv) pollutant and analytical devices, and (v) treatment/ application. For an easy and clear access to the findings visualization of clusters and networks of connections are presented. The study includes a temporal dimension and identifies the trends over the years with an emphasis on the most recent developments. This paper provides useful insights for those who wish to form a better understanding of the research trends in the area of biosensors.

Keywords: bibliometrics, biosensors, meta-review, statistical analysis, trends visualization

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Authors: Prakash Singh

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In this exploratory qualitative case study, the voices of female teachers are captured that describe their fear of failure in coping with their daily anxieties, stresses, and tensions in their classrooms. When teachers are usually appointed, the curriculum forms the heart of all their professional obligations. The policy of quality and equality of education for all learners is a must as part of these deliberations, otherwise it would spell the inevitable failure for teachers. Yet, how often have teachers been asked whether they are happy during their professional tenure. Research affirms that this question is not a priority, seeing that the happiness of learners and the educational administrators enjoy precedence. Teachers are often subject to undue pressures and tensions because of environmental factors that extends beyond the curriculum. School violence, bullying, drug abuse, and gangsters are not uncommon to the school milieu, no matter where such schools can be located. In this case study, the voices of female teachers find space concerning their experiences of tobephobia (TBP). The questions that inevitably arise are: Are the educational authorities aware of the effects of TBP in education? What can be done to arrest and eliminate the debilitating effects of TBP? This exploratory study contributes to the growing concerns of TBP in education. It is therefore imperative that the effects of TBP on human resources in education must be accentuated so that meaningful solutions can be found to address challenging educational issues such as school violence, bullying, and drug abuse amongst learners.

Keywords: curriculum, female teachers, school violence, tobephobia

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Authors: Bishoy Abouelsoud Saad Amin

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This paper examines the use of computer and its related health hazard among computer users in South-Western zone of Nigeria. Two hundred and eighteen (218) computer users constituted the population used to evaluate association between posture, extensive computer use and related health hazard. The instruments for the study are a questionnaire on demographics, lifestyle, body features and work ability index while mean rating, standard deviation and t test were used for data analysis. Identified health related hazard include damages to the eyesight, bad posture, arthritis, musculoskeletal disorders, headache, stress and so on. The results showed that factors such as work demand, posture, closeness to computer screen and excessive working hours on computers constitute health hazards in both old and young computer users of various gender. It is therefore recommended that total number of hours spent with computer should be monitored and controlled.

Keywords: computer game, metaphor, middle school students, virtual environments computer auditing, risk, measures to prevent, information management computer-related health hazard, musculoskeletal disorders, computer usage, work ability index

Procedia PDF Downloads 41

Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

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The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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Authors: Anna Kesoyan

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The present paper deals with the syntax-related problems of translation from English into Armenian. Although Syntax is a part of grammar, syntax-related problems of translation are studied separately during the process of translation. Translation from one language to another is widely accepted as a challenging problem. This becomes even more challenging when the source and target languages are widely different in structure and style, as is the case with English and Armenian. Syntax-related problems of translation from English into Armenian are mainly connected with the syntactical structures of these languages, and particularly, with the word order of the sentence. The word order of the sentence of the Armenian language, which is a synthetic language, is usually characterized as “rather free”, and the word order of the English language, which is an analytical language, is characterized “fixed”. The following research examines the main translation means, particularly, syntactical transformations as the translator has to take real steps while trying to solve certain syntax-related problems. Most of the means of translation are based on the transformation of grammatical components of the sentence, without changing the main information of the text. There are several transformations that occur during translation such as word order of the sentence, transformations of certain grammatical constructions like Infinitive participial construction, Nominative with the Infinitive and Elliptical constructions which have been covered in the following research.

Keywords: elliptical constructions, nominative with the infinitive constructions, fixed and free word order, syntactic structures

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Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

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Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

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Authors: Sun Jin Park, Kyung-Ja Cho

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This study focused on characteristics related to hasty behaviour. To investigate the relation between personal characteristics and hasty behaviour, 601 data were collected, 335 males and 256 females answered their own 'social avoidance and distress’, ‘anxiety’, ‘sensation seeking', 'hope', and ' hasty behaviour. And then 591 data were used for the analysis. The factor analysis resulted hasty behaviour consisted of 5 factors, time pressure, isolation, uncomfortable situation, boring condition, and expectation of reward. The result showed anxiety, sensation seeking, and hope related to hasty behaviour. Specifically, anxiety was involved in every hasty behaviour. This result means that psychological tension and worry are related to hasty behaviour in common. 'Social avoidance and distress', 'sensation seeking' and 'hope' influenced on hasty behaviour under time pressure, in isolation, in expectation of rewards respectively. This means that each factor of hasty behaviour has anxiety as its basis, expressed through a varied nature.

Keywords: hasty behaviour, social avoidance and distress, anxiety, sensation seeking, hope

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Authors: Odd Jarl Borch, Marina Z. Solesvik

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The paper analyses partner selection approaches related to large scale R&D-based innovation projects at the different stages of development. We emphasize innovation projects in the maritime value chain and how partners are selected to improve quality according to high spec customer demands, and to reduce investment costs on new production technology such as advanced offshore service vessels. We elaborate on the differences in innovation approach and especially the role that purposive inflows and outflows of knowledge from external partners may be used to accelerate internal innovation. We present three cases related to different projects in terms of specificity and scope. We explore how the partner selection criteria change over time when the goals move from wide scope to a very specific R&D tasks.

Keywords: partner selection, innovation, offshore industry, concept design

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Veronika Sharok

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Research relevance on psychological determinants of risky behaviors is caused by high prevalence of such behaviors, particularly among youth. Risky sexual behavior, including unprotected and casual sex, frequent change of sexual partners, drug and alcohol use lead to negative social consequences and contribute to the spread of HIV infection and other sexually transmitted diseases. Data were obtained from 302 respondents aged 15-35 which were divided into 3 empirical groups: persons prone to risky sexual behavior, drug users and alcohol users; and 3 control groups: the individuals who are not prone to risky sexual behavior, persons who do not use drugs and the respondents who do not use alcohol. For processing, we used the following methods: Qualitative method for nominative data (Chi-squared test) and quantitative methods for metric data (student's t-test, Fisher's F-test, Pearson's r correlation test). Statistical processing was performed using Statistica 6.0 software. The study identifies two groups of factors that prevent risky behaviors. Internal factors, which include the moral and value attitudes; significance of existential values: love, life, self-actualization and search for the meaning of life; understanding independence as a responsibility for the freedom and ability to get attached to someone or something up to a point when this relationship starts restricting the freedom and becomes vital; awareness of risky behaviors as dangerous for the person and for others; self-acknowledgement. External factors (prevent risky behaviors in case of absence of the internal ones): absence of risky behaviors among friends and relatives; socio-demographic characteristics (middle class, marital status); awareness about the negative consequences of risky behaviors; inaccessibility to psychoactive substances. These factors are common for proneness to each type of risky behavior, because it usually caused by the same reasons. It should be noted that if prevention of risky behavior is based only on elimination of external factors, it is not as effective as it may be if we pay more attention to internal factors. The results obtained in the study can be used to develop training programs and activities for prevention of risky behaviors, for using values preventing such behaviors and promoting healthy lifestyle.

Keywords: existential values, prevention, psychological features, risky behavior

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Authors: Eunjoo Lee

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Background: As the number of surgeries increases, the incidence of adverse events is likely to become more prevalent. Patients who are somewhat knowledgeable about surgery-related adverse events are more likely to engage in safety initiatives to prevent them. Objectives: To evaluate the impact of a smartphone application developed during the study to enhance patients’ knowledge of surgery-related adverse events during hospitalization. Design: Non-randomized, one group, measured pre- and post-intervention. Participants: Thirty-six hospitalized patients admitted to the orthopedics unit of a general hospital in South Korea. Methods. First, a smartphone application to enhance patients’ knowledge of surgery-related adverse events was developed through an iterative process, which included a literature review, expert consultation, and pilot testing. The application was installed on participants’ smartphones, and research assistants taught the participants to use it. Twenty-five true/false questions were used to assess patients’ knowledge of preoperative precautions (eight items), surgical site infection (five items), Foley catheter management (four items), drainage management (four items), and anesthesia-related complications (four items). Results: Overall, the percentage of correct answers increased significantly, from 57.02% to 73.82%, although answers related to a few specific topics did not increase that much. Although the patients’ understanding of drainage management and the Foley catheter did increase substantially after they used the smartphone application, it was still relatively low. Conclusions: The smartphone application developed during this study enhanced the patients’ knowledge of surgery-related adverse events during hospitalization. However, nurses must make an additional effort to help patients to understand certain topics, including drainage and Foley catheter management. Relevance to clinical practice: Insufficient patient knowledge increases the risk of adverse events during hospitalization. Nurses should take active steps to enhance patients’ knowledge of a range of safety issues during hospitalization, in order to decrease the number of surgery-related adverse events.

Keywords: patient education, patient participation, patient safety, smartphone application, surgical errors

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Malab Sana Balouch, Meenakshi Nayar

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Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.

Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist

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Authors: Joe Voshall, Leigha Shoup

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In 2022, the Ohio Peace Officer Training Council and the Attorney General required officers to complete a minimum of 24 hours of continued professional training for the year. Much of the training was based on Mental Health or similarly related topics. This includes Officer Wellness and Officer Mental Health. It is becoming clearer that the stigma of Officer / First Responder Mental Health is a topic that is becoming more prevalently faced. To assist officers and first responders in facing mental health issues, we are developing new training. This training will aid in recognizing mental health-related issues in officers/first responders and citizens, as well as further using the same information to better respond and interact with one another and the public. In general, society has many varying views of mental health, much of which is largely over-sensationalized by television, movies, and other forms of entertainment. There has also been a stigma in law enforcement / first responders related to mental health and being weak as a result of on-the-job-related trauma-induced struggles. It is our hope this new training will assist officers and first responders in not only positively facing and addressing their mental health but using their own experience and education to recognize signs and symptoms of mental health within individuals in the community. Further, we hope that through this recognition, officers and first responders can use their experiences and more in-depth understanding to better interact within the field and with the public. Through recognition and better understanding of mental health issues and more positive interaction with the public, additional achievements are likely to result. This includes in the removal of bias and stigma for everyone.

Keywords: law enforcement, mental health, officer related mental health, trauma

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Mokhtar Kouki Inès Rekik

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This paper focuses on the assessment of the air pollution and morbidity relationship in Tunisia. Air pollution is measured by ozone air concentration and the morbidity is measured by the number of respiratory-related restricted activity days during the 2-week period prior to the interview. Socioeconomic data are also collected in order to adjust for any confounding covariates. Our sample is composed by 407 Tunisian respondents; 44.7% are women, the average age is 35.2, near 69% are living in a house built after the 1980, and 27.8% have reported at least one day of respiratory-related restricted activity. The model consists on the regression of the number of respiratory-related restricted activity days on the air quality measure and the socioeconomic covariates. In order to correct for zero-inflation and heterogeneity, we estimate several models (Poisson, Negative binomial, Zero inflated Poisson, Poisson hurdle, Negative binomial hurdle and finite mixture Poisson models). Bootstrapping and post-stratification techniques are used in order to correct for any sample bias. According to the Akaike information criteria, the hurdle negative binomial model has the greatest goodness of fit. The main result indicates that, after adjusting for socioeconomic data, the ozone concentration increases the probability of positive number of restricted activity days.

Keywords: bootstrapping, hurdle negbin model, overdispersion, ozone concentration, respiratory-related restricted activity days

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Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

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Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

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Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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Authors: William Wong Xiu Shun, Yoonjin Hyun, Mingyu Kim, Seongi Choi, Namgyu Kim

Abstract:

Recently, the demand of extracting the R&D keywords from the issues and using them in retrieving R&D information is increasing rapidly. But it is hard to identify the related issues or to distinguish them. Although the similarity between the issues cannot be identified, but with the R&D lexicon, the issues that always shared the same R&D keywords can be determined. In details, the R&D keywords that associated with particular issue is implied the key technology elements that needed to solve the problem of the particular issue. Furthermore, the related issues that sharing the same R&D keywords can be showed in a more systematic way through the issue clustering constructed from the perspective of R&D. Thus, sharing of the R&D result and reusable of the R&D technology can be facilitated. Indirectly, the redundancy of investment on the same R&D can be reduce as the R&D information can be shared between those corresponding issues and reusability of the related R&D can be improved. Therefore, a methodology of constructing an issue clustering from the perspective of common R&D keywords is proposed to satisfy the demands mentioned.

Keywords: clustering, social network analysis, text mining, topic analysis

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