Search results for: extremely drug- resistant

Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Tanyaporn Chairoch

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Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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Authors: Samuel Faboyede, Obiamaka Nwobu, Samuel Fakile, Dickson Mukoro

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In the present dynamic business environment of corporate governance and regulations, financial reporting is an inevitable and extremely significant process for every business enterprise. Several financial elements such as Annual Reports, Quarterly Reports, ad-hoc filing, and other statutory/regulatory reports provide vital information to the investors and regulators, and establish trust and rapport between the internal and external stakeholders of an organization. Investors today are very demanding, and emphasize greatly on authenticity, accuracy, and reliability of financial data. For many companies, the Internet plays a key role in communicating business information, internally to management and externally to stakeholders. Despite high prominence being attached to external reporting, it is disconnected in most companies, who generate their external financial documents manually, resulting in high degree of errors and prolonged cycle times. Chief Executive Officers and Chief Financial Officers are increasingly susceptible to endorsing error-laden reports, late filing of reports, and non-compliance with regulatory acts. There is a lack of common platform to manage the sensitive information – internally and externally – in financial reports. The Internet financial reporting language known as eXtensible Business Reporting Language (XBRL) continues to develop in the face of challenges and has now reached the point where much of its promised benefits are available. This paper looks at the emergence of this revolutionary twenty-first century language of digital reporting. It posits that today, the world is on the brink of an Internet revolution that will redefine the ‘business reporting’ paradigm. The new Internet technology, eXtensible Business Reporting Language (XBRL), is already being deployed and used across the world. It finds that XBRL is an eXtensible Markup Language (XML) based information format that places self-describing tags around discrete pieces of business information. Once tags are assigned, it is possible to extract only desired information, rather than having to download or print an entire document. XBRL is platform-independent and it will work on any current or recent-year operating system, or any computer and interface with virtually any software. The paper concludes that corporate stakeholders and the government cannot afford to ignore the XBRL. It therefore recommends that all must act locally and think globally now via the adoption of XBRL that is changing the face of worldwide business reporting.

Keywords: XBRL, financial reporting, internet, internal and external reports

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Authors: Carlos M. Goncalves, Luisa Duarte, Teresa Cartaxo

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The aim of this work was to understand the reasons behind the underutilization of electroconvulsive therapy (ECT) in the younger population and raise possible solutions. We conducted a non-systematic review of literature throughout a search on PubMed, using the terms ‘children’, ‘adolescents’ and ‘electroconvulsive’, ‘therapy’. Candidate articles written in languages other than English were excluded. Articles were selected according to title and/or abstract’s content relevance, resulting in a total of 5 articles. ECT is a recognized effective treatment in adults for several psychiatric conditions. As in adults, ECT in children and adolescents is proven most beneficial in the treatment of severe mood disorders, catatonia, and, to a lesser extent, schizophrenia. ECT in adults has also been used to treat autism’s self-injurious behaviours, Tourette’s syndrome and resistant first-episode schizophrenia disorder. Despite growing evidence on its safety and effectiveness in children and adolescents, like those found in adults, ECT remains a controversial and underused treatment in patients this age, even when it is clearly indicated. There are various possible reasons to this; limited awareness among professionals (lack of knowledge and experience among child psychiatrists), stigmatic public opinion (despite positive feedback from patients and families, there is an unfavourable and inaccurate representation in the media, contributing to a negative public opinion), legal restrictions and ethical controversies (restrictive regulations such as a minimum age for administration), lack of randomized trials (the currently available studies are retrospective, with small size samples, and most of the publications are either case reports or case series). This shows the need to raise awareness and knowledge, not only for mental health professionals, but also to the general population, through the media, regarding indications, methods and safety of ECT in order to provide reliable information to the patient and families. Large-scale longitudinal studies are also useful to further demonstrate the efficacy and safety of ECT and can aid in the formulation of algorithms and guidelines as without these changes, the availability of ECT to the younger population will remain restricted by regulations and social stigma. In conclusion, these results highlight that lack of adequate knowledge and accurate information are the most important factors behind the underutilization of ECT in younger population. Mental healthcare professionals occupy a cornerstone position; if data is given by a well-informed healthcare professional instead of the media, general population (including patients and their families) will probably regard the procedure in a more favourable way. So, the starting point should be to improve health care professional’s knowledge and experience on this choice of treatment.

Keywords: adolescents, children, electroconvulsive, therapy

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Authors: Meszár Tárik

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The aim of the study is to introduce the minority groups living in Iraq and to shed light on their current situation. The Middle East is a rather heterogeneous region in ethnic terms. It includes many ethnic, national, religious, linguistic, or ethnoreligious groups. The relationship between the majority and minority is the main cause of various conflicts in the region. It seems that most of the post-Ottoman states have not yet developed a unified national identity capable of integrating their multi-ethnic societies. The issue of minorities living in the Middle East is highly politicized and controversial, as the various Arab states consider the treatment of minorities as their internal affair, do not recognize discrimination or even deny the existence of any kind of minorities on their territory. This attitude of the Middle Eastern states may also be due to the fact that the minority issue can be abused and can serve as a reference point for the intervention policies of Western countries at any time. Methodologically, the challenges of these groups are perceived through the manifestos of prominent individuals and organizations belonging to minorities. The basic aim is to present the minorities’ own history in dealing with the issue. It also introduces the different ethnic and religious minorities in Iraq and analyzes their situation during the operation of the terrorist organization „Islamic State” and in the aftermath. It is clear that the situation of these communities deteriorated significantly with the advance of ISIS, but it is also clear that even after the expulsion of the militant group, we cannot necessarily report an improvement in this area, especially in terms of the ability of minorities to assert their interests and physical security. The emergence of armed militias involved in the expulsion of ISIS sometimes has extremely negative effects on them. Until the interests of non-Muslims are adequately represented at the local level and in the legislature, most experts and advocates believe that little will change in their situation. When conflicts flare, many Iraqi citizens usually leave Iraq, but because of the poor public security situation (threats from terrorist organizations, interventions by other countries), emigration causes serious problems not only outside the country’s borders but also within the country. Another ominous implication for minorities is that their communities are very slow if ever, to return to their homes after fleeing their own settlements. An important finding of the study is that this phenomenon is changing the face of traditional Iraqi settlements and threatens to plunge groups that have lived there for thousands of years into the abyss of history. Therefore, we not only present the current situation of minorities living in Iraq but also discuss their future possibilities.

Keywords: Middle East, Iraq, Islamic State, minorities

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Authors: Daniel R. McDougall, Martin D. de Jonge, Gordon M. Miskelly, Duncan J. McGillivray, Andrew G. Jeffs

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The chelating agent ethylenediaminetetraacetic acid (EDTA) is commonly added as a cure-all to seawater in aquaculture hatcheries around the world to reduce heavy metal toxicity, significantly improve the survival of larval shellfish, and to therefore improve the overall production efficiency of the aquaculture industry. However, EDTA is not a biodegradable chemical and is considered to be a persistent organic pollutant, which will accumulate in the environment over time. This makes the use of EDTA unsustainable environmentally, and therefore alternatives should be considered. Ethylenediaminedisuccinic acid (EDDS) is a biodegradable alternative to EDTA with very similar metal chelation properties. This study investigates the effect of EDTA and EDDS at two different concentrations, on metal concentrations found within developing New Zealand green-lipped mussel (Perna canaliculus) larvae. P. canaliculus is New Zealand’s main shellfish aquaculture species, providing a major export for New Zealand’s economy, with excellent potential for increased production in the near future. It is well known that the early stages of bivalve development are the most vulnerable to metal toxicity and P. canaliculus is no exception. The commercially used concentration (12 µmol L⁻¹) of EDTA added to P. canaliculus larval rearing tanks often increases the yield of D-larvae by over 80%. This concentration of EDTA and EDDS will be tested in this study, along with a lower concentration (3 µmol L⁻¹). After 48 hours of larval development, the D-larvae will be analyzed for heavy metal content with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and heavy metal distribution with synchrotron X-ray Fluorescence Microscopy (XFM). In this study, we found that EDDS also improves the yield of P. canaliculus larvae and could be a viable alternative to EDTA in aquaculture. Furthermore, results suggest a higher concentration of chelating agent is more effective for improving the yield of developing P. canaliculus larvae. Metals with significant differences in concentration with the addition of EDTA were Cr, Cu, Zn, Cd and Pb (P < 0.05). We observed for the first time to the author’s best knowledge, metal distribution within 100 µm P. canaliculus D-larvae using synchrotron XFM and found changes in the distribution of metals with the addition of EDTA. XFM also has the potential to provide information about the chemical state of the metals within mussel larvae. This research provides greater insight into the reasons for the effectiveness of adding the chelating agent to aquaculture culture water, and a more environmentally conscious alternative to the currently used EDTA, which could be extremely valuable for the aquaculture industry.

Keywords: EDDS, EDTA, heavy metals, P. canaliculus, toxicity, water treatment

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Authors: Naohiro Nakamura, Takuya Kinoshita, Hiroshi Fukuyama

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The 2011 off The Pacific Coast of Tohoku Earthquake caused considerable damage to wide areas of eastern Japan. A large number of earthquake observation records were obtained at various places. To design more earthquake-resistant buildings and improve earthquake disaster prevention, it is necessary to utilize these data to analyze and evaluate the behavior of a building during an earthquake. This paper presents an earthquake response simulation analysis (hereafter a seismic response analysis) that was conducted using data recorded during the main earthquake (hereafter the main shock) as well as the earthquakes before and after it. The data were obtained at a high-rise steel-reinforced concrete (SRC) building in the bay area of Tokyo. We first give an overview of the building, along with the characteristics of the earthquake motion and the building during the main shock. The data indicate that there was a change in the natural period before and after the earthquake. Next, we present the results of our seismic response analysis. First, the analysis model and conditions are shown, and then, the analysis result is compared with the observational records. Using the analysis result, we then study the effect of soil-structure interaction on the response of the building. By identifying the characteristics of the building during the earthquake (i.e., the 1st natural period and the 1st damping ratio) by the Auto-Regressive eXogenous (ARX) model, we compare the analysis result with the observational records so as to evaluate the accuracy of the response analysis. In this study, a lumped-mass system SR model was used to conduct a seismic response analysis using observational data as input waves. The main results of this study are as follows: 1) The observational records of the 3/11 main shock put it between a level 1 and level 2 earthquake. The result of the ground response analysis showed that the maximum shear strain in the ground was about 0.1% and that the possibility of liquefaction occurring was low. 2) During the 3/11 main shock, the observed wave showed that the eigenperiod of the building became longer; this behavior could be generally reproduced in the response analysis. This prolonged eigenperiod was due to the nonlinearity of the superstructure, and the effect of the nonlinearity of the ground seems to have been small. 3) As for the 4/11 aftershock, a continuous analysis in which the subject seismic wave was input after the 3/11 main shock was input was conducted. The analyzed values generally corresponded well with the observed values. This means that the effect of the nonlinearity of the main shock was retained by the building. It is important to consider this when conducting the response evaluation. 4) The first period and the damping ratio during a vibration were evaluated by an ARX model. Our results show that the response analysis model in this study is generally good at estimating a change in the response of the building during a vibration.

Keywords: ARX model, response analysis, SRC building, the 2011 off the Pacific Coast of Tohoku Earthquake

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Authors: Irina Belozerova

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In the recent years, the number of crimes against peace and humanity has constantly been increasing. The development of the international community is inseparably connected to the compliance with the law which protects the rights and interests of citizens in all of their manifestations. The provisions of the law of criminal procedure are no exception. The rights of the victims of genocide, of the war crimes and the crimes against humanity, require particular attention. These crimes fall within the jurisdiction of the International Criminal Court governed by the Rome Statute of the International Criminal Court. These crimes have the following features. First, any such crime has a mass character and therefore requires specific regulation in the international criminal law and procedure and the national criminal law and procedure of different countries. Second, the victims of such crimes are usually children, women and old people; the entire national, ethnic, racial or religious groups are destroyed. These features influence the classification of victims by the age criterion. Article 68 of the Rome Statute provides for protection of the safety, physical and psychological well-being, dignity and privacy of victims and witnesses and thus determines the procedural status of these persons. However, not all the persons whose rights have been violated by the commission of these crimes acquire the status of victims. This is due to the fact that such crimes affect a huge number of persons and it is impossible to mention them all by name. It is also difficult to assess the entire damage suffered by the victims. While assessing the amount of damages it is essential to take into account physical and moral harm, as well as property damage. The procedural status of victims thus gains an exclusive character. In order to determine the full extent of the damage suffered by the victims it is necessary to collect sufficient evidence. However, it is extremely difficult to collect the evidence that would ensure the full and objective protection of the victims’ rights. While making requests for the collection of evidence, the International Criminal Court faces the problem of protection of national security information. Religious beliefs and the family life of victims are of great importance. In some Islamic countries, it is impossible to question a woman without her husband’s consent which affects the objectivity of her testimony. Finally, the number of victims is quantified by hundreds and thousands. The assessment of these elements demands time and highly qualified work. These factors justify the creation of a mechanism that would help to collect the evidence and establish the truth in the international criminal proceedings. This mechanism will help to impose a just and appropriate punishment for the persons accused of having committed a crime, since, committing the crime, criminals could not misunderstand the outcome of their criminal intent.

Keywords: crimes against humanity, evidence in international criminal proceedings, international criminal proceedings, protection of victims

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Authors: Cetin Balanuye

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The present study aims to accomplish two tasks: First, it critically reinterprets the actual relationship between democracy and the modern state in order to show that it is responsible for most of our current political problems and dilemmas. Second, it is argued that this relationship can be reimagined for better, and Spinozistic notions such as ‘conatus’, ‘power’ and ‘virtue’ are crucial in this pursuit. The significance of the present study lies in several interrelated observations: The world has never been a more heterogeneous place than today. People from different religious, cultural and historical backgrounds do equally have 'good reasons' to hold that their world views are the best ones. We have almost no authority to be respected equally by all these different world views. We no longer have gods at once we had in our ancient times. We have three big monotheistic religions, yet the God of which is significantly different from each other. The worse is that the believers of these religions do not seem eager to perform a duet, but rather tend to fight a duel with each other. Thanks to post-modernism, neither reason nor science is any longer seen as universally value-neutral guide to be employed in our search for a common ground. In sum, the question 'how should I live?' has never generated this much diversity before in terms of answers and the answers have never been this much away from a fairly objective evaluation. Our so-called liberal democracies are supposed to perform against this heterogenous, antagonistic and self-sustained web of discursive background. It is argued that our conception of 'State' with a weak emphasis on democracy is not a solution, if not itself the source of this topsy-turvy. Weak emphasis on democracy should be understood here as a kind of liberal democracy which operates in a partisan State, one which takes sides among rivals either for this or against that world view. This conception of State rests on a misleading understanding of the concept of power, and it is argued that it can only be corrected by means of a Spinoza-informed ontology of politics. The role of State in such an ontology is no longer a partisanship of any kind, nor is it representative of all-encompassing authority to favor any world view. State in this Spinozistic ontology equally encourages world views and their discursive practices to let them increase the power of acting and have more power to affect rules and regulations. World views can enhance every medium -in the sense of nonviolence ethology- to increase their power of acting. The more active a world view is, the more powerful and the more virtuous it is in terms of its effective power on the State. Though Spinoza has provided us with a limited guideline to understand what kind of democracy, he actually had in his mind, his ontology developed in Ethics is rich enough to imagine and inspire a better democratic practice to help us sustain the modern State in our extremely pluralistic contemporary societies.

Keywords: democracy, Islam, power, Spinoza

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Authors: C. Puangsawat, C. Limotai, P. Srikhachin

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Bio-psycho-social caring was required for promoting the quality of life of the patients with epilepsy (PWE), despite controlled seizures. Multifaceted issues emerge at the epilepsy clinic. Unpredicted seizures, antiepileptic drug compliance problems/adverse effects, psychiatric, and social problems are all needed to be explored and managed. The Nursing Service System (NSS) at the tertiary epilepsy clinic (TEC) was consequently developed for improving the clinical care for PWE. Case manager concept was integrated as the framework guiding the processes and strategies used for developing the NSS as well as the roles of the multidisciplinary team at the clinic. This study aimed to report the outcomes of the developed NSS integrated case manager concept. The processes of our developed NSS program included 1) screening for patient’s problems using questionnaire prior to seeing epileptologists i.e., assessing the patient’s risk to develop acute seizures at the clinic, issues related to medication use, and uncovered psychiatric and social problems; and 2) assigning the patients at risk to be evaluated and managed by appropriate team. Nurses specializing in epilepsy in coordination with the multidisciplinary team implemented the NSS to promote coordinated work among the team which consists of epileptologists, nurses, pharmacists, psychologists, and social workers. Determination of the role of each person and their responsibilities along with joint care plan were clearly established. One year after implementation, the rate of acute seizure occurrence at the clinic was decreased, and satisfactory feedback from the patients was received. In order to achieve an optimal goal to promote self-management behaviors in PWE, continuing the NSS and systematic assessment of its effectiveness is required.

Keywords: case manager concept, nursing service system, patients with epilepsy, quality of life

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Authors: Arjun Prakash, Vinutha H., Karthik N.

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BACKGROUND: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy with an estimated prevalence of 0.6 - 5.8% in the general adult population. It is caused by compression of the Median Nerve (MN) at the wrist as it passes through a narrow osteofibrous canal. Presently, the diagnosis is established by the clinical symptoms and physical examination and Nerve conduction study (NCS) is used to assess its severity. However, it is considered to be painful, time consuming and expensive, with a false-negative rate between 16 - 34%. Ultrasonography (USG) is now increasingly used as a diagnostic tool in CTS due to its non-invasive nature, increased accessibility and relatively low cost. Elastography is a newer modality in USG which helps to assess stiffness of tissues. However, there is limited available literature about its applications in peripheral nerves. OBJECTIVES: Our objectives were to measure the Cross-Sectional Area (CSA) and elasticity of MN at the carpal tunnel using Grey scale Ultrasonography (USG), Strain Elastography (SE) and Shear Wave Elastography (SWE). We also made an attempt to independently evaluate the role of Gray scale USG, SE and SWE in grading the severity of CTS, keeping NCS as the gold standard. MATERIALS AND METHODS: After approval from the Institutional Ethics Review Board, we conducted a comparative cross sectional study for a period of 18 months. The participants were divided into two groups. Group A consisted of 54 patients with clinically diagnosed CTS who underwent NCS, and Group B consisted of 50 controls without any clinical symptoms of CTS. All Ultrasound examinations were performed on SAMSUNG RS 80 EVO Ultrasound machine with 2 - 9 Mega Hertz linear probe. In both groups, CSA of the MN was measured on Grey scale USG, and its elasticity was measured at the carpal tunnel (in terms of Strain ratio and Shear Modulus). The variables were compared between both groups by using ‘Independent t test’, and subgroup analyses were performed using one-way analysis of variance. Receiver operating characteristic curves were used to evaluate the diagnostic performance of each variable. RESULTS: The mean CSA of the MN was 13.60 + 3.201 mm2 and 9.17 + 1.665 mm2 in Group A and Group B, respectively (p < 0.001). The mean SWE was 30.65 + 12.996 kPa and 17.33 + 2.919 kPa in Group A and Group B, respectively (p < 0.001), and the mean Strain ratio was 7.545 + 2.017 and 5.802 + 1.153 in Group A and Group B respectively (p < 0.001). CONCLUSION: The combined use of Gray scale USG, SE and SWE is extremely useful in grading the severity of CTS and can be used as a painless and cost-effective alternative to NCS. Early diagnosis and grading of CTS and effective treatment is essential to avoid permanent nerve damage and functional disability.

Keywords: carpal tunnel, ultrasound, elastography, nerve conduction study

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Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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

Keywords: readiness, maturity, system, integration

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Authors: Ismail I. Abo-Ghanema, Faheim E. Wehaish, Rasha M. Saleh , Walaa F. Awadin, Mohamed F. Elshal

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The antidiabetic activity of myrrh and ginseng ethanolic extracts were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male albino rats were divided into five groups, each consisted of six rats. The first group (G1) is the negative control that was fed basal diet, the second group (G2) was injected with STZ and received no treatment, the third group (G3) injected with STZ and received metformin (50 mg/kg, b.wt) as standard anti-diabetic drug, the fourth group (G4) injected with STZ and ginseng (50 mg/kg, b.wt), the fifth group (G5) injected with STZ and received myrrh (500 mg/kg, b.wt). As compared with G1-group, STZ injection increased blood concentrations of glucose (6.2 fold), glycated hemoglobin (HbA1c) (2.51 fold), aspartateaminotransferase (AST), and alanine aminotransferase (ALT) (2.64, 4.60 fold respectively), creatinine (2.91 fold), cholesterol (1.79 fold), triglycerides (2.06 fold), low density lipoprotein-cholesterol (LDL) (2.92 fold), nitric oxide (NO) (20.18 fold), and malondialdehyde (MDA) (2.25 fold), whereas it decreased blood insulin (0.40 fold), albumin (0.60 fold), high density lipoprotein-cholesterol (HDL) (0.33 fold), and reduced glutathione (GSH) (0.49 fold). Vascular permeability index (VPI as measured by Evan's Blue; EB extravasations test) was significantly increased in the skin of diabetic animals (9.6 fold) when compared with the G1-group. In addition, histological alterations in liver, pancreas, kidneys and heart were observed. After 4 weeks of treatment, rats in G4 and G5 showed significant corrections in the all measured parameters and indices. In conclusions, the ethanolic extracts of ginseng and myrrh exhibited promising and safe anti-diabetic activity especially on peripheral circulation as manifested by decreased vascular permeability and improved histopathological alterations of examined organs and insulin secretion. Hence, it may be pursued for their clinical usefulness in the management of diabetes mellitus (DM) and associated vascular complications.

Keywords: diabetic rats, peripheral circulation, natural plants, myrrh, ginseng

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Authors: Meera Tandan, Mohan Timilsina, Martin Cormican, Akke Vellinga

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Background: In general practice, many infections are treated empirically without microbiological confirmation. Understanding susceptibility of antimicrobials during empirical prescribing can be helpful to reduce inappropriate prescribing. This study aims to apply a prediction model using a decision tree approach to predict the antimicrobial resistance (AMR) of urinary tract infections (UTI) based on non-clinical features of patients over 65 years. Decision tree models are a novel idea to predict the outcome of AMR at an initial stage. Method: Data was extracted from the database of the microbiological laboratory of the University Hospitals Galway on all antimicrobial susceptibility testing (AST) of urine specimens from patients over the age of 65 from January 2011 to December 2014. The primary endpoint was resistance to common antimicrobials (Nitrofurantoin, trimethoprim, ciprofloxacin, co-amoxiclav and amoxicillin) used to treat UTI. A classification and regression tree (CART) model was generated with the outcome ‘resistant infection’. The importance of each predictor (the number of previous samples, age, gender, location (nursing home, hospital, community) and causative agent) on antimicrobial resistance was estimated. Sensitivity, specificity, negative predictive (NPV) and positive predictive (PPV) values were used to evaluate the performance of the model. Seventy-five percent (75%) of the data were used as a training set and validation of the model was performed with the remaining 25% of the dataset. Results: A total of 9805 UTI patients over 65 years had their urine sample submitted for AST at least once over the four years. E.coli, Klebsiella, Proteus species were the most commonly identified pathogens among the UTI patients without catheter whereas Sertia, Staphylococcus aureus; Enterobacter was common with the catheter. The validated CART model shows slight differences in the sensitivity, specificity, PPV and NPV in between the models with and without the causative organisms. The sensitivity, specificity, PPV and NPV for the model with non-clinical predictors was between 74% and 88% depending on the antimicrobial. Conclusion: The CART models developed using non-clinical predictors have good performance when predicting antimicrobial resistance. These models predict which antimicrobial may be the most appropriate based on non-clinical factors. Other CART models, prospective data collection and validation and an increasing number of non-clinical factors will improve model performance. The presented model provides an alternative approach to decision making on antimicrobial prescribing for UTIs in older patients.

Keywords: antimicrobial resistance, urinary tract infection, prediction, decision tree

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Authors: Maria Bercea, Monica Diana Olteanu

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Investigation of polymer systems able to change inside of the body into networks represent an attractive approach, especially when there is a minimally invasive and patient friendly administration. Pharmaceutical formulations based on Pluronic F127 [poly (oxyethylene) (PEO) blocks (70%) and poly(oxypropylene) (PPO) blocks (30%)] present an excellent potential as drug delivery systems. The use of Pluronic F127 alone as gel-forming solution is limited by some characteristics, such as poor mechanical properties, short residence time, high permeability, etc. Investigation of the interactions between the natural and synthetic polymers and surfactants in solution is a subject of great interest from both scientific and practical point of view. As for example, formulations based on Pluronics and chitosan could be used to obtain dual phase transition hydrogels responsive to temperature and pH changes. In this study, different materials were prepared by using poly(vinyl alcohol), chitosan solutions mixed with aqueous solutions of Pluronic F127. The rheological properties of different formulations were investigated in temperature sweep experiments as well as at a constant temperature of 37oC for exploring in-situ gel formation in the human body conditions. In addition, some viscometric investigations were carried out in order to understand the interactions which determine the complex behaviour of these systems. Correlation between the thermodynamic and rheological parameters and phase separation phenomena observed for the investigated systems allowed the dissemination the constitutive response of polymeric materials at different external stimuli, such as temperature and pH. The rheological investigation demonstrated that the viscoelastic moduli of the hydrogels can be tuned depending on concentration of different components as well as pH and temperature conditions and cumulative contributions can be obtained.

Keywords: hydrogel, polymer mixture, stimuli responsive, biomedical applications

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Authors: Vasiliki Kolake, Christos Kavalaris, Sofia Megoudi, Maria Maxouri, Panagiotis A. Karas, Aris Kyparissis, Efi Levizou

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Conservation agriculture (CA), is a production system approach that can tackle the challenges of climate change mainly through facilitating carbon storage into the soil and increasing crop resilience. This is extremely important for the vulnerable Mediterranean agroecosystems, which already face adverse environmental conditions. The agronomic practices used in CA, i.e. permanent soil cover and no-tillage, result in reduced soil erosion and increased soil organic matter, preservation of water and improvement of quality and fertility of the soil in the long-term. Thus the functional characteristics and processes of the soil are considerably affected by the implementation of CA. The aim of the present work was to assess the effects of CA on soil nitrification potential and mycorrhizal colonization about the above-ground production in a wheat field. Two adjacent but independent field sites of 1.5ha each were used (Thessaly plain, Central Greece), comprising the no-till and conventional tillage treatments. The no-tillage site was covered by residues of the previous crop (cotton). Potential nitrification and the nitrate and ammonium content of the soil were measured at two different soil depths (3 and 15cm) at 20-days intervals throughout the growth period. Additionally, the leaf area index (LAI) was monitored at the same time-course. The mycorrhizal colonization was measured at the commencement and end of the experiment. At the final harvest, total yield and plant biomass were also recorded. The results indicate that wheat yield was considerably favored by CA practices, exhibiting a 42% increase compared to the conventional tillage treatment. The superior performance of the CA crop was also depicted in the above-ground plant biomass, where a 26% increase was recorded. LAI, which is considered a reliable growth index, did not show statistically significant differences between treatments throughout the growth period. On the contrary, significant differences were recorded in endomycorrhizal colonization one day before the final harvest, with CA plants exhibiting 20% colonization, while the conventional tillage plants hardly reached 1%. The on-going analyses of potential nitrification measurements, as well as nitrate and ammonium determination, will shed light on the effects of CA on key processes in the soil. These results will integrate the assessment of CA impact on certain below and above-ground processes during wheat cultivation under the Mediterranean climate.

Keywords: conservation agriculture, LAI, mycorrhizal colonization, potential nitrification, wheat, yield

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Authors: Feras Darwish Elhajji, Alberto Berardi, Manal Ayyash, Iman Basheti

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The concept of the use of probiotics for humans now has been known for decades however, their intake by the Jordanian population seems to be less common when compared to population in the developed countries. Community pharmacy is the main supplier of probiotics, however, after conducting an extensive literature review, not any published research article could be found talking about the role, knowledge, and practice of the pharmacists in the area of probiotics. The main aim of this study was to evaluate the level of knowledge about probiotics and their dispensing practice in community pharmacies in Jordan. Community pharmacy staff (pharmacists and technicians) in Amman and north of Jordan were randomly selected to complete an anonymous questionnaire that had been pre-tested and validated. Ethical approval was obtained from the university ethics committee. The questionnaire included the following sections: demographics, knowledge and perceptions about probiotics, and role of the pharmacist Pharmacists and technicians were visited and interviewed in 281 community pharmacies. Asking about probiotics, 90.4% of them said that they know what probiotics are, although only 29.5% agreed that pharmacy staff in Jordan have good knowledge about probiotics, and 88.3% agreed that pharmacy staff in Jordan need more training and knowledge about probiotics. Variables that were significantly related to knowledge about probiotics were being a pharmacist (ρ= 0.012), area of the community pharmacy (ρ= 0.019), and female staff (ρ= 0.031) after conducting logistic regression statistical analysis. More than two-thirds of the participants thought that probiotics are classified as dietary supplements by Jordan Food and Drug Administration (JFDA). Of those who knew probiotics, the majority of them – 76.8% and 91.7% – agreed that probiotics are effective and safe, respectively. Believing in efficacy of the probiotics was significantly associated with answering their use to be with or after antibiotic administration and to increase normal flora gut population (ρ= 0.007). Efficacy was also significantly associated with recommending probiotics to consumers by the pharmacist (ρ< 0.001) and by the doctor (ρ= 0.041). At the same time, the concept of safety was mainly associated with their use for flatulence and gases (ρ= 0.048). Level of knowledge about probiotics and their uses, efficacy and safety amongst community pharmacy staff in Jordan is found to be good. However, this level can be raised in the future, especially knowledge about uses of probiotics.

Keywords: community pharmacy, Jordan, prebiotics, probiotics

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Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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Authors: Ronel Solis, Leonardo Collado

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Migration law in the Republic of Panama has been regulated mainly by the executive branch. This has created a crisis not only institutional but also social because the evolution of these norms has rested greatly from the discretion of the government in office. This has created instability in immigration regulation and more now, with the migration crisis of which Panama is also part. Different migration policies have been established. The most recent is that of the controlled migration flow, in which, for humanitarian reasons, migrants move from the border with Colombia to the border with Costa Rica. Unfortunately, such control is not enough, and in some cases, unprotected migrants have been confined for months, their passports have been withheld, and no recognition of their rights is offered. The Inter-American Court of Human Rights has condemned Panama for the unfair detention of an irregular migrant, who was detained for two years in Panamanian prisons, without having committed a crime and without accessing a just defense. This is the case Vélez Loor vs. the Republic of Panama. Uncontrollable migration has been putting pressure on Panamanian public health services. The recent denunciation of HIV-related NGOs that warns that there are hundreds of foreigners who receive expensive antiretroviral therapy in Panama is serious, and several of them are irregular migrants. On the other hand, there are no border control posts with the Republic of Colombia, because it is a jungle area and migrants are exposed to arms and drug trafficking, and unfortunately, also to prostitution. Government entities such as the border police service have provided humanitarian support to migrants on the border with Colombia, although it is not their administrative function, and various entities discuss who should address this crisis. However, few economic resources are allocated by the government to solve this problem, especially with the recent mass migration of Venezuelans who have fled their country. The establishment of a migratory normative code is necessary to establish uniformity in the recognition and application of migratory rights. In this way, dependence on the changing migration policies of the different Panamanian governments would be eliminated, and the rights of migrants and nationals would be guaranteed.

Keywords: executive branch, irregular migration, migration code, Republic of Panama

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Authors: Jessica A. Hellings, Piyushkumar Jani

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Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

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Authors: Naveeda Akhtar Qureshi, Wajiha

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Coccidiosis is a protozoan parasitic disease of genus Eimeria. It is an avian infection causing a great economic loss of 3 billion USD per year globally. A number of anticoccidial drugs are in use however many of them have side effects and cost effective. With increase in poultry demand throughout the world there is a need of more drugs and vaccines against coccidiosis. The present study is based upon the use of F. racemosa a medicinal plant to be a potential source of anticoccidial agents. The methanolic leaves extract was fractionated by column and thin layer chromatography and got nineteen fractions. Each fraction different concentrations was evaluated for its anticoccidial properties in an invitro experiment against E. tenella, E. necatrix and E. mitis. The anticoccidial active fractions were further characterized by spectroscopy (UV-Vis, FTIR) and GC-MS analysis. The in silico molecular docking of active fractions identified compounds were carried out. Among all fractions significantly maximum sporulation inhibition efficacy was shown by F-19 (67.11±2.18) followed by F-15 (65.21±1.34) at concentration of 30mg/ml against E. tenella. The significantly highest sporozoites viability inhibition was shown by F-19 (69.23±2.11) followed by F-15 (67.14±1.52) against E. necatrix at concentration 30mg/ml. Anticoccidial active fractions 15 and 19 showed peak spectrum at 207 and 202nm respectively by UV analysis. Their FTIR analysis confirmed the presence of carboxylic acid, amines, phenols, etc. Anticoccidial active compounds like Cyclododecane methanol, oleic acid, Octadecanoic acid, etc were identified by GC-MS analysis. Identified compounds in silico molecular docking study showed that cyclododecane methanol of F-19 and oleic acid of F-15 showed highest binding affinity with target S-Adenosylmethionine synthase. Hence for further authentication in vivo anticoccidial studies are recommended.

Keywords: ficus racemosa, cluster fig, column chromatography, anticoccidial fractions, GC-MS, molecular docking., s-adenosylmethionine synthase

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Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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Deer antler, traditionally used as a tonic and valuable drug in oriental medicine, has been considered to possess bone-strengthening activity. The upper section, mid section, and base of the antler has been known to exhibit different biological properties. Present study was performed to examine the effects of different parts of deer antler extract (DH) on osteogenic gene expressions in MG-63 cells and longitudinal bone growth in adolescent male rats. The expressions of osteogenic genes, collagen, alkaline phosphatase, osteocalcin, and osteopontin, were measured by quantitative real-time PCR. Longitudinal bone growth was measured in 3-week-old male Sprague-Dawley rats using fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and bone morphogenetic protein-2 (BMP-2) were measured. Collagen and osteocalcin mRNA expressions were increased by all three parts of the DH treatment while osteopontin gene expression was not affected by any of the DH treatment. Alkaline phosphatase gene expression was increased by upper and mid part of DH while base part of DH fails to affect alkaline phosphatase gene expression. The upper and mid parts of the DH treatment enhanced longitudinal bone growth and total height of growth plate. The induction of BMP-2 protein expression in growth plate assessed by immunostaining was also promoted by upper and mid parts of the DH treatment. These results suggest that DH, especially upper and mid parts, stimulate osteogenic gene expressions and have the effect on bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

Keywords: bone morphogenetic protein-2, deer antler, longitudinal bone growth, osteogenic genes

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: Amira Abdelrasoul

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This study aimed to ascertain the controlled permeability of biomimetic cellulose triacetate (CTA) membranes by investigating the electrical oscillatory behavior across impregnated membranes (IM). The biomimetic CTA membranes were infused with a fatty acid to induce electrical oscillatory behavior and, hence, to ensure controlled permeability. In situ synchrotron radiation micro-computed tomography (SR-μCT) at the BioMedical Imaging and Therapy (BMIT) Beamline at the Canadian Light Source (CLS) was used to evaluate the main morphology of IMs compared to neat CTA membranes to ensure fatty acid impregnation inside the pores of the membrane matrices. A monochromatic beam at 20 keV was used for the visualization of the morphology of the membrane. The X-ray radiographs were recorded by means of a beam monitor AA-40 (500 μm LuAG scintillator, Hamamatsu, Japan) coupled with a high-resolution camera, providing a pixel size of 5.5 μm and a field of view (FOV) of 4.4 mm × 2.2 mm. Changes were evident in the phase transition temperatures of the impregnated CTA membrane at the melting temperature of the fatty acid. The pulsations of measured voltages were related to changes in the salt concentration of KCl in the vicinity of the electrode. Amplitudes and frequencies of voltage pulsations were dependent on the temperature and concentration of the KCl solution, which controlled the permeability of the biomimetic membranes. The presented smart biomimetic membrane successfully combined porous polymer support and impregnating liquid not only imitate the main barrier properties of the biological membranes but could be easily modified to achieve some new properties, such as facilitated and active transport, regulation by chemical, physical and pharmaceutical factors. These results open new frontiers for the facilitation and regulation of active transport and permeability through biomimetic smart membranes for a variety of biomedical and drug delivery applications.

Keywords: biomimetic, membrane, synchrotron, permeability, morphology

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Authors: Ghaneshree Moonsamy, Nodumo N. Zulu, Rajesh Lalloo, Suren Singh, Santosh O. Ramchuran

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The abalone industry of South Africa is under severe pressure due to illegal harvesting and poaching of this seafood delicacy. These abalones are harvested excessively; as a result, these animals do not have a chance to replace themselves in their habitats, ensuing in a drastic decrease in natural stocks of abalone. Abalone has an extremely slow growth rate and takes approximately four years to reach a size that is market acceptable; therefore, it was imperative to investigate methods to boost the overall growth rate and immunity of the animal. The University of Cape Town (UCT) began to research, which resulted in the isolation of two microorganisms, a yeast isolate Debaryomyces hansenii and a bacterial isolate Vibrio midae, from the gut of the abalone and characterised them for their probiotic abilities. This work resulted in an internationally competitive concept technology that was patented. The next stage of research was to develop a suitable bioprocess to enable commercial production. Numerous steps were taken to develop an efficient production process for V. midae, one of the isolates found by UCT. The initial stages of research involved the development of a stable and robust inoculum and the optimization of physiological growth parameters such as temperature and pH. A range of temperature and pH conditions were evaluated, and data obtained revealed an optimum growth temperature of 30ᵒC and a pH of 6.5. Once these critical growth parameters were established further media optimization studies were performed. Corn steep liquor (CSL) and high test molasses (HTM) were selected as suitable alternatives to more expensive, conventionally used growth medium additives. The optimization of CSL (6.4 g.l⁻¹) and HTM (24 g.l⁻¹) concentrations in the growth medium resulted in a 180% increase in cell concentration, a 5716-fold increase in cell productivity and a 97.2% decrease in the material cost of production in comparison to conventional growth conditions and parameters used at the onset of the study. In addition, a stable market-ready liquid probiotic product, encompassing the viable but not culturable (VBNC) state of Vibrio midae cells, was developed during the downstream processing aspect of the study. The demonstration of this technology at a full manufacturing scale has further enhanced the attractiveness and commercial feasibility of this production process.

Keywords: probiotics, abalone aquaculture, bioprocess technology, manufacturing scale technology development

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Authors: Nassima Elyebdri, Asma Boumediou, Soumia Addoun

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Traditional medicine has been part of the Algerian culture for decades. In particular, the city of Tlemcen still retains practices based on phytotherapy to the present day, as this kind of medicine fulfills the needs of its followers among the local population. The toxic plants contain diverse natural substances which supplied a lot of medicine in the pharmaceutical industry. In order to explore new medicinal sources among toxic plants, an ethnobotanical study was carried out on the use of these plants by the population, at Emir Abdelkader Square of the city of Tlemcen, a rather busy place with a high number of traditional health practitioners and herbalists. This is a descriptive and transversal study aimed at estimating the frequency of using toxic plants among the studied population, for a period of 4 months. The information was collected, using self-anonymous questionnaires, and analyzed by the IBM SPSS Statistics software used for statistical analysis. A sample of 200 people, including 120 women and 80 men, were interviewed. The mean age was 41 ± 16 years. Among those questioned, 83.5% used plants; 8% of them used toxic plants and 35% used plants that can be toxic under certain conditions. Some improvements were observed in 88% of the cases where toxic plants were used. 80 medicinal plants, belonging to 36 botanical families, were listed, identified and classified. The most frequent indications for these plants were for respiratory diseases in 64.7% of cases, and for digestive disorders in 51.5% of cases. 11% of these plants are toxic, 26% could be toxic under certain conditions. Among toxics plants, the most common ones are Berberis vulgaris with 5.4%, indicated in the treatment of uterine fibroids and thyroid, Rhamnus alaternus with 4.8% for hepatic jaundice, Nerium oleander with 3% for hemorrhoids, Ruta chalepensis with 1.2%, indicated for digestive disorders and dysmenorrhea, and Viscum album with 1.2%, indicated for respiratory diseases. The most common plants that could be toxic are Mentha pulegium (15.6%), Eucalyptus globulus (11.4%), and Pimpinella anisum (10.2%). This study revealed interesting results on the use of toxic plants, which are likely to serve as a basis for further ethno-pharmacological investigations in order to get new drug sources.

Keywords: ethnobotany, phytotherapy, Tlemcen, toxic plants

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Authors: Scholastic Nangila Adeli, Francisca Mbutitia Ngithi

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Stigma is commonly associated with mental health patients and may act as a barrier to individuals who may seek or engage in treatment services. Stigmatization among university students is common whether they know someone with a mental health problem, or have a good knowledge and experience of mental health issues. The objective of this study was to establish the various barriers that prevent university students who have mental health challenges from seeking treatment and care. The study was a descriptive in nature where 320 respondents helped to establish the barriers to treatment or participation in mental health care among university students. A questionnaire was used to help establish the barriers and attitude towards mental illness among the respondents. Results from this study revealed that mental illnesses are common among university students and they are manifested in different forms like; anxiety and panic attacks, mood and eating disorders, Impulse control leading to gambling, alcohol and drug addictions, anger and depression leading to loneliness. Mental stigma (both social and self) was the major barrier with 62% of the respondents stating that social stigma was worse than self-stigma. This is because of the social discrimination towards the victim of mental challenges. On issues of attitude, 71% of the respondents said that they can never admit that they have a mental issue and would rather secretly seek clinical or psychological help for fear of being discriminated or excluded by peers. This view is informed by the societal belief that people with mental health challenges were dangerous (associating them with criminal behavior) and hard to socialize with or help. From the findings of this study, it is concluded that mental health problems are real among university students in Kenya and it is important for the university environment to minimize or eradicate stigma within the social circles. Stigma can be minimized or eradicated by creating awareness among university students and fostering social inclusion so that the students who have mental health challenges can experience a sense of belonging and acceptance hence build their self-esteem.

Keywords: disorders, impulse control, mental health problems, stigma

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Authors: J.R.S.S. Kumara, M.A.R.M. Fernando, S.Venkatesh, D.K. Jayaratne

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Protection of heritage monuments against lightning has become extremely important as far as their historical values are concerned. When such structures are large and tall, the risk of lightning initiated from both cloud and ground can be high. This paper presents a lightning risk analysis of three giant stupas in Anuradhapura era (fourth century BC onwards) in Sri Lanka. The three stupas are Jethawaaramaya (269-296 AD), Abayagiriya (88-76 BC) and Ruwanweliseya (161-137 BC), the third, fifth and seventh largest ancient structures in the world. These stupas are solid brick structures consisting of a base, a near hemispherical dome and a conical spire on the top. The ancient stupas constructed with a dielectric crystal on the top and connected to the ground through a conducting material, was considered as the hypothesis for their original lightning protection technique. However, at present, all three stupas are protected with Franklin rod type air termination systems located on top of the spire. First, a risk analysis was carried out according to IEC 62305 by considering the isokeraunic level of the area and the height of the stupas. Then the standard protective angle method and rolling sphere method were used to locate the possible touching points on the surface of the stupas. The study was extended to estimate the critical current which could strike on the unprotected areas of the stupas. The equations proposed by (Uman 2001) and (Cooray2007) were used to find the striking distances. A modified version of rolling sphere method was also applied to see the effects of upward leaders. All these studies were carried out for two scenarios: with original (i.e. ancient) lightning protection system and with present (i.e. new) air termination system. The field distribution on the surface of the stupa in the presence of a downward leader was obtained using finite element based commercial software COMSOL Multiphysics for further investigations of lightning risks. The obtained results were analyzed and compared each other to evaluate the performance of ancient and new lightning protection methods and identify suitable methods to design lightning protection systems for stupas. According to IEC standards, all three stupas with new and ancient lightning protection system has Level IV protection as per protection angle method. However according to rolling sphere method applied with Uman’s equation protection level is III. The same method applied with Cooray’s equation always shows a high risk with respect to Uman’s equation. It was found that there is a risk of lightning strikes on the dome and square chamber of the stupa, and the corresponding critical current values were different with respect to the equations used in the rolling sphere method and modified rolling sphere method.

Keywords: Stupa, heritage, lightning protection, rolling sphere method, protection level

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