Search results for: spread of drugs

Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

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Stroke is associated with a significant risk of morbidity and mortality. There is scarcity of research on the long-term survival after first-ever ischaemic stroke (IS) events in England with regards to effects of different medical therapies and comorbidities. The objective of this study was to model the all-cause mortality after an IS diagnosis in the adult population of England. Using a retrospective case-control design, we extracted the electronic medical records of patients born prior to or in year 1960 in England with a first-ever ischaemic stroke diagnosis from January 1986 to January 2017 within the Health and Improvement Network (THIN) database. Participants with a history of ischaemic stroke were matched to 3 controls by sex and age at diagnosis and general practice. The primary outcome was the all-cause mortality. The hazards of the all-cause mortality were estimated using a Weibull-Cox survival model which included both scale and shape effects and a shared random effect of general practice. The model included sex, birth cohort, socio-economic status, comorbidities and medical therapies. 20,250 patients with a history of IS (cases) and 55,519 controls were followed up to 30 years. From 2008 to 2015, the one-year all-cause mortality for the IS patients declined with an absolute change of -0.5%. Preventive treatments to cases increased considerably over time. These included prescriptions of statins and antihypertensives. However, prescriptions for antiplatelet drugs decreased in the routine general practice since 2010. The survival model revealed a survival benefit of antiplatelet treatment to stroke survivors with hazard ratio (HR) of 0.92 (0.90 – 0.94). IS diagnosis had significant interactions with gender and age at entry and hypertension diagnosis. IS diagnosis was associated with high risk of all-cause mortality with HR= 3.39 (3.05-3.72) for cases compared to controls. Hypertension was associated with poor survival with HR = 4.79 (4.49 - 5.09) for hypertensive cases relative to non-hypertensive controls, though the detrimental effect of hypertension has not reached significance for hypertensive controls, HR = 1.19(0.82-1.56). This study of English primary care data showed that between 2008 and 2015, the rates of prescriptions of stroke preventive treatments increased, and a short-term all-cause mortality after IS stroke declined. However, stroke resulted in poor long-term survival. Hypertension, a modifiable risk factor, was found to be associated with poor survival outcomes in IS patients. Antiplatelet drugs were found to be protective to survival. Better efforts are required to reduce the burden of stroke through health service development and primary prevention.

Keywords: general practice, hazard ratio, health improvement network (THIN), ischaemic stroke, multiple imputation, Weibull-Cox model.

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Authors: Quervin Zacary M. Roldan, Gwyneth Gabrielle M. Fajardo, Carmela M. Maciar

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Alcohol in the Philippines is regarded as a part of their culture however, it is also stigmatized, as alcohol addiction is prevalent among Filipino Males leading them to develop Alcohol Use Disorder. With this, Discourses of alcohol consumption from Individuals recovering from AUD from different rehabilitation centers in the Philippines were analyzed in the study to explore how they ‘talk’ about their alcohol consumption. By utilizing the Foucauldian Discourse Analysis following the six steps by Carla Willig, four (4) major discourses were major construed by the recovering individuals of AUD which are: (1) Being alcohol-free was a dream, (2) Drinking alcohol turns you into a demon that will destroy your life, (3) Drinking alcohol as ‘doing’ drugs and (4) Alcohol is a temporary solution. These discourses construct alcohol consumption as something that is being referred to as a 'bad' substance which is both normalized and stigmatized in Philippine society.

Keywords: alcohol, alcohol consumption, alcohol-based beverages, psychological effects, discourse, alcohol use disorder, stigma

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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: Djehich Mohamed Yousri

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In this paper, we explore the extent to which states seek to promote regional foreign policy. More specifically, the analytical feasibility is to find out exactly what countries seek to export, and how they have used their relations and foreign policies to enhance cooperation with other countries. The first part discusses the development of regional interests and theoretical approaches that attempted to explain the push for regionalism in the field of foreign policy. The second part of the paper presents the motives and mechanisms through which states spread the idea of regionalism in making foreign policy. Finally, we assess the implications of regionalism for the nature and practice of foreign policy, particularly with regard to the gains or constraints to which various actors are exposed in their regional endeavors. We conclude with some considerations that indicate that strengthening regionalism has become an additional and real program in the field of foreign policy analysis.

Keywords: foreign policy, collective foreign policy, regionalization and foreign policy, regional foreign policy, foreign affairs

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Authors: Rajesh A. Rane, Shital S. Naphade, Rajshekhar Karpoormath

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Thiozolidin-4-one, a mimic of thiazolobenzimidazole (TBZ) has drawn many attentions due to its potent and selective inhibition against the HIV-1 and low toxicity by binding to the allosteric site of the reverse transcriptase (RT) as a non-nucleoside RT inhibitor (NNRTI). Similarly, marine bromopyrrole alkaloids are well known for their diverse array of anti-infective properties. Hence, we have reported synthesis and in vitro HIV-1 RT inhibitory activity of a series of 4-thiazolidinone-bromopyrrole alkaloid hybrids tethered with amide linker. The results of in vitro HIV-1 RT kit assay showed that some of the compounds, such as 4c, 4d, and 4i could effectively inhibit RT activity. Among them, compounds 4c having 4-chlorophenyl substituted 4-thiazolidione ring was the best one with the IC50 value of 0.26 µM. The sturdy emerges with key structure-activity relationship that pyrrole-NH-free core benefited inhibition against HIV-1 RT inhibition. This study identified conjugate 4c with potent activity and selectivity as promising compound for further drug development to HIV.

Keywords: antiviral drugs, bromopyrrole alkaloids, HIV-1 RT inhibition, 4-thiazolidinone

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Authors: A. Sathiya Susuman, N. Wilson

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Background: The sexual behaviour of youths is believed to play an important role in the spread of sexually transmitted infections (STIs). Method: The data from the Malawi Demographic and Health Survey 2010 and a sample of 16,217 youth’s age 15 to 24 years (with each household 27.2% female and 72.8% male) was the basis for analysis. Bivariate and logistic regression analysis was performed. Results: The result shows married youth were not interested in condom use (94.2%, p<0.05). Those who were living together were 69 times (OR=1.69, 95% CI, 1.26–2.26) more likely to be involved in early sexual activity compared to those who were not living together. Conclusion: This scientific paper will help other researchers, policy makers, and planners to create strategies to encourage these youths to make use of contraception.

Keywords: sexually transmitted infections (STIs), reproductive tract infections (RTIs), condom use, sexual partners, early sexual debut, youths

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Authors: Karima Merchant

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The aim of this study was to analyze the impact of the Writing Eight Exercise, an exercise from the Brain Integration Therapy, with Kindergartners who are struggling with writing tasks in school. With the help of this exercise, children were able to cross the midline, an invisible line running from our brain to our feet, which separates the body’s right from left. Crossing the midline integrates the brain hemispheres, thus encouraging bilateral movement. The study was spread over 15 weeks where the children were required to do the Writing Eight Exercise 4 times a week. The data collection methods included observations, student work samples and feedback from teachers and parents. Based on the results of this study, it can be concluded that the Writing Eight Exercise had a positive impact on students’ approach towards writing tasks, letter formation, and fine motor skills.

Keywords: crossing the midline, fine motor skills, letter formation, writing

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Authors: M. Mohammed Raoof, A. Enkhtaivan, H. Aljuaid

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This study follows the design science research methodology to design and implement a smartphone application artifact. The developed artifact was evaluated through three phases. The System Usability Scale (SUS) metric was used for the evaluation. The designed artifact aims to spread awareness about reducing air pollution, decreasing lung cancer development, and checking the air quality status in Southern California Counties. Participants have been drawn for a pilot study to facilitate awareness of air pollution. The study found that smartphone applications have a beneficial effect on the study’s aims.

Keywords: air pollution, design science research, indoor air pollution, lung cancer, outdoor air pollution, smartphone application

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Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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Authors: Weena Eiamprapai

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The growth of Thai society in western style in the middle of Rattanakosin period can be defined as modernization /civilization. These terms had an influence on the development of the country in the reign of King Rama V owing to the governance reform, and cultures influenced by the West. Those were passed on until the reign of King Rama VI. The preference was not only for the renovation of architecture and arts based on Thai customs reflecting the prosperity and beauty of handicrafts but also for the acceptance of westernization. The remain of this acceptance includes the concept of such value as gentlemanly behavior like that in Victorian Era of the United Kingdom, and the support of women’s status. Moreover, the wide spread of modernization leads to the movement to change the country’s governance system from absolute monarchy to democracy by a group of people called Rattanakosin Era (R.E.) 130 party.

Keywords: art, culture, development period, modernization, King Rama VI

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Authors: Takashi Sakai, Itaru Kumisawa

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Because die drawing requires insertion of a die, a plug, or a mandrel, higher precision and efficiency are demanded for drawing equipment for a tube having smaller diameter. Manufacturing of such tubes is also accompanied by problems such as cracking and fracture. We specifically examine dieless drawing, which is less affected by these drawing-related difficulties. This deformation process is governed by a similar principle to that of reduction in diameter when pulling a heated glass tube. We conducted dieless drawing of SUS304 stainless steel microtubes under various conditions with three factor parameters of heating temperature, area reduction, and drawing speed. We used SEM-EBSD to observe the processing condition effects on microstructural elements. As the result of this study, crystallographic orientation of microtube is clear by using SEM-EBSD analysis.

Keywords: microtube, dieless drawing, IPF (inverse pole figure), GOS (grain orientation spread), crystallographic analysis

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Authors: S. A. Kondratyev, O. I. Ibragimova

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The authors discuss the collecting abilities of desorbable species (DS) of saturated fatty acids. The DS species of the reagent are understood as species capable of moving from the surface of the mineral particle to the bubble at the moment of the rupture of the interlayer of liquid separating these objects of interaction. DS species of carboxylic acids (molecules and ionic-molecular complexes) have the ability to spread over the surface of the bubble. The rate of their spreading at pH 7 and 10 over the water surface is determined. The collectibility criterion of saturated fatty acids is proposed. The values of forces exerted by the spreading DS species of reagents on liquid in the interlayer and the liquid flow rate from the interlayer are determined.

Keywords: criterion of action of physically adsorbed reagent, flotation, saturated fatty acids, surface pressure

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Authors: Imbesat Daudi

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Islamophobia, which is a billion-dollar industry, is widespread, especially in the United States, Europe, India, Israel, and countries that have Muslim minorities at odds with their governmental policies. Hatred of Islam in the West did not evolve spontaneously; it was methodically created. Islamophobia's current format has been designed to spread on its own, find a space in the Western psyche, and resist its eradication. Hatred has been sustained by neoconservative ideologues and their allies, which are supported by the mainstream media. Social scientists have evaluated how ideas spread, why any idea can go viral, and where new ideas find space in our brains. This was possible because of the advances in the computational power of software and computers. Spreading of ideas, including Islamophobia, follows a sine curve; it has three phases: An initial exploratory phase with a long lag period, an explosive phase if ideas go viral, and the final phase when ideas find space in the human psyche. In the initial phase, the ideas are quickly examined in a center in the prefrontal lobe. When it is deemed relevant, it is sent for evaluation to another center of the prefrontal lobe; there, it is critically examined. Once it takes a final shape, the idea is sent as a final product to a center in the occipital lobe. This center cannot critically evaluate ideas; it can only defend them from its critics. Counterarguments, no matter how scientific, are automatically rejected. Therefore, arguments that could be highly effective in the early phases are counterproductive once they are stored in the occipital lobe. Anti-Islamophobic intellectuals have done a very good job of countering Islamophobic arguments. However, they have not been as effective as neoconservative ideologues who have promoted anti-Muslim rhetoric that was based on half-truths, misinformation, or outright lies. The failure is partly due to the support pro-war activists receive from the mainstream media, state institutions, mega-corporations engaged in violent conflicts, and think tanks that provide Islamophobic arguments. However, there are also scientific reasons why anti-Islamophobic thinkers have been less effective. There are different dynamics of spreading ideas once they are stored in the occipital lobe. The human brain is incapable of evaluating further once it accepts ideas as its own; therefore, a different strategy is required to be effective. This paper examines 1) why anti-Islamophobic intellectuals have failed in changing the minds of non-Muslims and 2) the steps of countering hatred. Simply put, a new strategy is needed that can effectively counteract hatred of Islam and Muslims. Islamophobia is a disease that requires strong measures. Fighting hatred is always a challenge, but if we understand why Islamophobia is taking root in the twenty-first century, one can succeed in challenging Islamophobic arguments. That will need a coordinated effort of Intellectuals, writers and the media.

Keywords: islamophobia, Islam and violence, anti-islamophobia, demonization of Islam

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Authors: Rekha Vijayvergia

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Around seven percent of tribal population of India lives in Rajasthan. Rajasthan has rich cultural diversity and biodiversity. Ethno-botany can be defined as the total natural and traditional relationship and the interactions between man and his surrounding plant wealth from times immemorial, due to sheer, necessity, intuition, observation, and experimentation. Medicinal plants are valuable and are used for the production of various drugs. These plants produce a high diversity of natural products or secondary metabolites like Mahanimbicine, Andrographine, murrayaline, lupeol, and limonin etc. with a prominent function in the protection against diseases like diabetes, kidney stones, osteoporosis, tumours, opthalmia, leucorrhoea, bronchial asthma, diarrhea, cancer, etc. The present report gives an account of traditional medicinal uses of common medicinal plants of Rajasthan. A total of 18 plant species belonging to 13 families are reported, that are being used for various purposes.

Keywords: ethno botany, Rajasthan, secondary metabolites, traditional medicines

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Authors: Bader Alkandari, Jamal Y. Madouh, Ahmad M. Alkandari, Anwar A. Alnaqi

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A new formulation of fuzzy linear estimation problem is presented. It is formulated as a linear programming problem. The objective is to minimize the spread of the data points, taking into consideration the type of the membership function of the fuzzy parameters to satisfy the constraints on each measurement point and to insure that the original membership is included in the estimated membership. Different models are developed for a fuzzy triangular membership. The proposed models are applied to different examples from the area of fuzzy linear regression and finally to different examples for estimating the electrical load on a busbar. It had been found that the proposed technique is more suited for electrical load estimation, since the nature of the load is characterized by the uncertainty and vagueness.

Keywords: fuzzy regression, load estimation, fuzzy linear parameters, electrical load estimation

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Authors: Boukari Nassim

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This paper describes the use of odd pair autoregressive coefficients (Yule _Walker and Burg) for the feature extraction of electroencephalogram (EEG) signals. In the classification: the radial basis function neural network neural network (RBFNN) is employed. The RBFNN is described by his architecture and his characteristics: as the RBF is defined by the spread which is modified for improving the results of the classification. Five types of EEG signals are defined for this work: Set A, Set B for normal signals, Set C, Set D for interictal signals, set E for ictal signal (we can found that in Bonn university). In outputs, two classes are given (AC, AD, AE, BC, BD, BE, CE, DE), the best accuracy is calculated at 99% for the combined odd pair autoregressive coefficients. Our method is very effective for the diagnosis of epileptic EEG signals.

Keywords: epilepsy, EEG signals classification, combined odd pair autoregressive coefficients, radial basis function neural network

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Authors: C. E. Madubueze, S. C. Madubueze, S. Ajama

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Cholera is a disease that is predominately common in developing countries due to poor sanitation and overcrowding population. In this paper, a deterministic model for the dynamics of cholera is developed and control measures such as health educational message, therapeutic treatment, and vaccination are incorporated in the model. The effective reproduction number is computed in terms of the model parameters. The existence and stability of the equilibrium states, disease free and endemic equilibrium states are established and showed to be locally and globally asymptotically stable when R0 < 1 and R0 > 1 respectively. The existence of backward bifurcation of the model is investigated. Furthermore, numerical simulation of the model developed is carried out to show the impact of the control measures and the result indicates that combined control measures will help to reduce the spread of cholera in the population

Keywords: backward bifurcation, cholera, equilibrium, dynamics, stability

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Authors: Francesco La Torre, Angela Di Cesare, Donato Traversa

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The mosquito-transmitted nematode Dirofilaria repens is the causative agent of subcutaneous filariosis in dogs, other animals and humans. Adults and circulating microfilariae may cause different forms of skin conditions, and various allergic reactions. The infection is distributed in several countries and spreading in several areas of Europe. The control of D. repens is pivotal to reduce the transmission in dogs and to minimize the risk of infection in humans, but only few information is available for the chemoprevention of subcutaneous filariosis of dogs. A recent clinical field study showed the efficacy and safety of a monthly administration of an oral formulation containing milbemycin oxime (Milbemax®, Novartis Animal Health) in the chemoprevention of D. repens infection in dogs. Most recent and focused insights into epidemiology and control of zoonotic canine subcutaneous filariosis are here discussed.

Keywords: Dirofilaria repens, epidemiology, zoonosis, control

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Authors: Shashank Tiwari, S. P. Mahapatra

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The aim of this technique is to reduce the steps of process scales up, save time & cost of the industries. This technique will minimise the steps of process scale up. The new steps are, Novel Lab Scale, Novel Lab Scale Trials, Novel Trial Batches, Novel Exhibit Batches, Novel Validation Batches. In these steps, it is not divided to validation batches in three parts but the data of trials batches, Exhibit Batches and Validation batches are use and compile for production and used for validation. It also increases the batch size of the trial, exhibit batches. The new size of trials batches is not less than fifty Thousand, the exhibit batches increase up to two lack and the validation batches up to five lack. After preparing the batches all their data & drugs use for stability & maintain the validation record and compile data for the technology transfer in production department for preparing the marketed size batches.

Keywords: batches, technique, preparation, scale up, validation

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Authors: Okunola Oluseye Ademola

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The study investigated various socio-cultural factors influencing adherence to antiretroviral drugs among people living with HIV in a University Teaching Hospital in South-western Nigeria. The objectives are to examine the perception of people living with HIV/AIDS (PLWHA) of antiretroviral therapy (ART) in Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, investigate the influence of socio-cultural factors on adherence of PLWHA to treatment regimen in the study area and assess the prevalence of adherence to ART among PLWHA in the study area. It was a cross-sectional where both qualitative and quantitative research methods were adopted. The participants were HIV diagnosed patients attending clinic at the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife between the ages of 18 and 60 years. Also three healthcare delivery personnel working in the clinic were interviewed. Out of the 3007 patients receiving treatment, using Fischer’s formula of sampling technique, 336 patients living with HIV/AIDS were selected for the study. These participants had been on antiretroviral drugs for more than six months prior to the study and were selected using simple random sampling technique. Two focus group discussion sessions comprising of 10 male and 10 female living with HIV and currently on ART were conducted. These groups were purposively selected based on their being on ART for more than one year. Also in-depth interviews were conducted among three purposively selected healthcare givers (an experienced nurse, a doctor and a pharmacist) who are working in this clinic. All the participants were interviewed at the clinic on the various clinic days. Data were collected using a structured questionnaire, an interview guide and tape-recorder. The quantitative data were analysed using descriptive and inferential statistics. Content analysis was employed to analyse responses from IDI and FGD sessions. The findings from the study revealed a very positive perception to ART among PLWHA which was about 86.3% while the level of adherence to ART was 89.0% among the respondents. There was a very strong relationship between social and family supports and the degree of adherence to ART in the PLWHA. Nutrition, polygamy, difficulty in financing transportation fare to the clinic, unemployment, drug hawkers, religion, excuse duty from work and waking up very early were highlighted as socio-cultural barriers to adherence to ART. Fear of death, strong family support, religion belief, not seeking alternative treatment, absence of rituals and perceived improved health status were identified as very strong facilitators to adherence. The study concluded that to achieve a very optimal outcome in the management of HIV among PLWHA, various social and cultural contexts should be taken into consideration as this study was able to ascertain the influence of various socio-cultural factors militating and facilitating adherence to ART.

Keywords: ART, HIV, PLWHA, socio-cultural

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Zhenzhong Yang

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Herbal medicines are important supplements to chemical drugs and usually consist of a complex mixture of constituents. The current quality control strategy of herbal medicines is mainly based on chemical markers, which largely failed to owe to the markers, not reflecting the herbal medicines’ multiple mechanisms of action. Herein, a bioactive chemical markers based strategy was proposed and applied to the quality assessment and control of herbal medicines. This strategy mainly includes the comprehensive chemical characterization of herbal medicines, bioactive chemical markers identification, and related quantitative analysis methods development. As a proof-of-concept, this strategy was applied to a Panax notoginseng derived herbal medicine. The bioactive chemical markers based strategy offers a rational approach for quality assessment and control of herbal medicines.

Keywords: bioactive chemical markers, herbal medicines, quality assessment, quality control

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Authors: Yasmin Tantawi, Mary Beth Rosson

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In response to the dearth of information about emoji use for different purposes in different settings, this paper investigates the paralinguistic function of emojis within Twitter communication in the United States. To conduct this investigation, the Twitter feeds from 16 population centers spread throughout the United States were collected from the Twitter public API. One hundred tweets were collected from each population center, totaling to 1,600 tweets. Tweets containing emojis were next extracted using the “emot” Python package; these were then analyzed via the IBM Watson API Natural Language Understanding module to identify the topics discussed. A manual content analysis was then conducted to ascertain the paralinguistic and emotional features of the emojis used in these tweets. We present our characterization of emoji usage in Twitter and discuss implications for the design of Twitter and other text-based communication tools.

Keywords: computer-mediated communication, content analysis, paralinguistics, sociology

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: Olfat Mohamed Hussien Yousef

Abstract:

Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).

Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure

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Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

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Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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Authors: Ajay Aggarwal, Kamal Saroha, Sanju Nanda

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Niosomes or non-ionic surfactant vesicles are microscopic lamellar structures formed on admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs. Entrapment efficiency was found to be higher in case of niosome prepared with span60 than niosome prepared with tween. The amount of release was found to be in order of Span20>Tween60>Tween20>Span60. As the concentration of surfactant is increased in vitro release was increased due to high entrapment. The stability study of optimized batch revealed that particle size was increased after 3months on increasing the temperature. On the other hand entrapment efficiency was decreased on increasing the temperature.

Keywords: niosomes, vesicles, span, tween, in vitro release

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Authors: Zhiyong Shan, Preethi Santhanam, Vinod Namboodiri, Rajiv Bagai

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In recent years, the emerging network worms and attacks have distributive characteristics, which can spread globally in a very short time. Security management crossing networks to co-defense network-wide attacks and improve the efficiency of security administration is urgently needed. We propose a hierarchical distributed network security management system (HD-NSMS), which can integrate security management across multiple networks. First, we describe the system in macrostructure and microstructure; then discuss three key problems when building HD-NSMS: device model, alert mechanism, and emergency response mechanism; lastly, we describe the implementation of HD-NSMS. The paper is valuable for implementing NSMS in that it derives from a practical network security management system (NSMS).

Keywords: network security management, device organization, emergency response, cross-network

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Authors: Belkacem Benadda, Adil Benabdellah, Boutheyna Souna

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The Internet of Things (IoT) is an unprecedented creation. Electronics objects are now able to interact, share, respond and adapt to their environment on a much larger basis. Actual spread of these modern means of connectivity and solutions with high data volume exchange are affecting our ways of life. Accommodation is becoming an intelligent living space, not only suited to the people circumstances and desires, but also to systems constraints to make daily life simpler, cheaper, increase possibilities and achieve a higher level of services and luxury. In this paper we are as Internet access, teleworking, consumption monitoring, information search, etc.). This paper addresses the design and integration of a smart home, it also purposes an IoT solution that allows smart power consumption based on measurements from power-grid and deep learning analysis.

Keywords: array sensors, IoT, power grid, FPGA, embedded

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

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

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

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