Search results for: cell-free protein expression

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Krithika Lakshmi Sathiya Moorthy

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Introduction: Young people’s attitude towards Intimate partner violence (IPV) is likely to influence their indulgence in or abstinence from IPV in future. We aimed to assess the knowledge and attitudes of college students in a south Indian city regarding IPV, its associated factors and redressal mechanisms. Methods: A convenient sample of 247 students, pursuing medicine and engineering, participated in this analytical cross sectional study. They responded to a self-administered questionnaire developed and pretested for this study. The questionnaire comprises statements from a third person’s perspective and vignettes to reduce social desirability bias. Clearance was obtained from the Institute Ethical Committee of Velammal Medical College Hospital and Research Institute, Madurai, India. Data were entered in Epidata Entry v3.1, Odense, Denmark and analysed using SPSS v20.0. Results: Among 247 students, 116 (47%) were males and 59 (24.9%) hailed from rural areas. About 18% (43) of students believed that IPV was a problem only among females. Almost half of the students had witnessed IPV; at home between their parents (9.7%), other family members (13.4%), in their neighbourhood (13%) or public places (15%). Only 118 (47.8%) were aware that a law was in place in India to address IPV. The perceived risk factors for IPV were alcoholic spouse (78.9%), low income families (53.8%), personality traits (52.2%) and dowry system (51%). A sizeable number of students (38.4%) believed that some amount of physical violence was allowable in a marital relationship while 57.6% even considered IPV as an expression of love. Males as compared to females were more in agreement with negative gender stereotypes such as husband can– ‘threaten wife to ensure welfare of family’ (55% vs. 34%, p < 0.001), ‘spy on wife to check fidelity’ (41% vs. 27%, p < 0.001), ‘financially deprive housewife to punish’ (13% vs. 3.8%, p=0.001) and agreed with the statement that it is ‘duty of wife to comply with demands for sex from the husband’ (9.5% vs 4.6%, p=0.3). About 32% males and 25.6% females foresaw themselves as perpetrators of IPV in future. Conclusion: Knowledge about IPV and the associated risk factors among the study population was satisfactory. However, there was widespread acceptance of negative societal gender stereotypes, more so among males and some degrees of IPV were acceptable between married couples. The study advocates the need to halt the propagation of negative gender stereotypes in the impressionable young minds and the necessity to spread the awareness that no degree of IPV is acceptable. This knowledge is also required to plan the content and choose the appropriate media to effectively communicate the awareness about IPV among young persons.

Keywords: attitude, India, intimate partner violence, knowledge, students

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Authors: Begum Rokeya, Rahelee Zinnat, Fatema Jebunnesa, Israt Ara Hossain, A. Rahman

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Background and Aims: Arsenic in drinking water is a global environmental health problem, and the exposure may increase dyslipidemia and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of lipid metabolism, atherosclerosis formation, arsenic exposure and impact in pregnancy is still unclear. Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and Dyslipidemia. However, the exact mechanism of this arsenic-mediated increase in atherosclerosis risk factors remains enigmatic. We explore the association of the effect of arsenic on serum lipid profile in pregnant subjects. Methods: A total 200 pregnant mother screened in this study from arsenic exposed area. Our study group included 100 exposed subjects were cases and 100 Non exposed healthy pregnant were controls requited by a cross-sectional study. Clinical and anthropometric measurements were done by standard techniques. Lipidemic status was assessed by enzymatic endpoint method. Urinary As was measured by inductively coupled plasma-mass spectrometry and adjusted with specific gravity and Arsenic exposure was assessed by the level of urinary arsenic level > 100 μg/L was categorized as arsenic exposed and < 100 μg/L were categorized as non-exposed. Multivariate logistic regression and Student’s t - test was used for statistical analysis. Results: Systolic and diastolic blood pressure both were significantly higher in the Arsenic exposed pregnant subjects compared to the Non-exposed group (p<0.001). Arsenic exposed subjects had 2 times higher chance of developing hypertensive pregnancy (Odds Ratio 2.2). In parallel to the findings in Ar exposed subjects showed significantly higher proportion of triglyceride and total cholesterol and low density of lipo protein when compare to non- arsenic exposed pregnant subjects. Significant correlation of urinary arsenic level was also found with SBP, DBP, TG, T chol and serum LDL-Cholesterol. On multivariate logistic regression showed urinary arsenic had a positive association with DBP, SBP, Triglyceride and LDL-c. Conclusion: In conclusion, arsenic exposure may induce dyslipidemia like atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.

Keywords: Arsenic Exposure, Dyslipidemia, Gestational Diabetes Mellitus, Serum lipid profile

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Authors: Ghada Abo-Zaid

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The main objective of this study was to examine the association between the elevated level of CRP and incidence of hypertension before and after adjusting by age, BMI, gender, SES, smoking, diabetes, cholesterol LDL and cholesterol HDL and to determine whether the association were differ by race. Method: Cross sectional data for participations from age 17 to age 74 years who included in The National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were analysed. CRP level was classified into three categories ( > 3mg/L, between 1mg/LL and 3mg/L, and < 3 mg/L). Blood pressure categorization was done using JNC 7 algorithm Hypertension defined as either systolic blood pressure (SBP) of 140 mmHg or more and disystolic blood pressure (DBP) of 90mmHg or greater, otherwise a self-reported prior diagnosis by a physician. Pre-hypertension was defined as (139 > SBP > 120 or 89 > DPB > 80). Multinominal regression model was undertaken to measure the association between CRP level and hypertension. Results: In univariable models, CRP concentrations > 3 mg/L were associated with a 73% greater risk of incident hypertension compared with CRP concentrations < 1 mg/L (Hypertension: odds ratio [OR] = 1.73; 95% confidence interval [CI], 1.50-1.99). Ethnic comparisons showed that American Mexican had the highest risk of incident hypertension (odds ratio [OR] = 2.39; 95% confidence interval [CI], 2.21-2.58).This risk was statistically insignificant, however, either after controlling by other variables (Hypertension: OR = 0.75; 95% CI, 0.52-1.08,), or categorized by race [American Mexican: odds ratio [OR] = 1.58; 95% confidence interval [CI], 0,58-4.26, Other Hispanic: odds ratio [OR] = 0.87; 95% confidence interval [CI], 0.19-4.42, Non-Hispanic white: odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.50-1.59, Non-Hispanic Black: odds ratio [OR] = 0.44; 95% confidence interval [CI], 0.22-0,87]. The same results were found for pre-hypertension, and the Non-Hispanic black showed the highest significant risk for Pre-Hypertension (odds ratio [OR] = 1.60; 95% confidence interval [CI], 1.26-2.03). When CRP concentrations were between 1.0-3.0 mg/L, in an unadjusted models prehypertension was associated with higher likelihood of elevated CRP (OR = 1.37; 95% CI, 1.15-1.62). The same relationship was maintained in Non-Hispanic white, Non-Hispanic black, and other race (Non-Hispanic white: OR = 1.24; 95% CI, 1.03-1.48, Non-Hispanic black: OR = 1.60; 95% CI, 1.27-2.03, other race: OR = 2.50; 95% CI, 1.32-4.74) while the association was insignificant with American Mexican and other Hispanic. In the adjusted model, the relationship between CRP and prehypertension were no longer available. In contrary, Hypertension was not independently associated with elevated CRP, and the results were the same after grouped by race or adjusted by the confounder variables. The same results were obtained when SBP or DBP were on a continuous measure. Conclusions: This study confirmed the existence of an association between hypertension, prehypertension and elevated level of CRP, however this association was no longer available after adjusting by other variables. Ethic group differences were statistically significant at the univariable models, while it disappeared after controlling by other variables.

Keywords: CRP, hypertension, ethnicity, NHANES, blood pressure

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Authors: Ana L. Gonzalez-Celis, Edgardo Ruiz-Carrillo, Karina Reyes-Jarquin, Margarita Chavez-Becerra

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Since recent decades, the aging has been viewed from a more positive perspective, where is not only about losses and damage, but also about being on a stage where you can enjoy life and live with well-being and quality of life. The challenge to feel better is to find those resources that seniors have. For that reason, psychological well-being has shown interest in the study of the affect and life satisfaction (hedonic well-being), while from a more recent tradition, focus on the development of capabilities and the personal growth, considering both as the main indicators of the quality of life. A resource that can be used in the later age is generativity, which refers to the ability of older people to develop and grow through activities that contribute with the improvement of the context in which they live and participate. In this way the generative interest is understood as a favourable attitude that contribute to the common benefit while strengthening and enriching the social institutions, to ensure continuity between generations and social development. On the other hand, generative behavior, differentiating from generative interest, is the expression of that attitude reflected in activities that make a social contribution and a benefit for generations to come. Hence the purpose of the research was to test if there is an association between the generative behaviour type and the psychological well-being with their dimensions. For this reason 188 Mexican adults from 60 to 94 years old (M = 69.78), 67% women, 33% men, completed two instruments: The Ryff’s Well-Being Scales to measure psychological well-being with 39 items with two dimensions (Hedonic and Eudaimonic well-being), and the Loyola’s Generative Behaviors Scale, grouped in five categories: Knowledge transmitted to the next generation, things to be remember, creativity, be productive, contribution to the community, and responsibility of other people. In addition, the socio-demographic data sheet was tested, and self-reported health status. The results indicated that the psychological well-being and its dimensions were significantly associated with the presence of generative behavior, where the level of well-being was higher when the frequency of some generative behaviour excelled; finding that the behavior with greater psychological well-being (M = 81.04, SD = 8.18) was "things to be remembered"; while with greater hedonic well-being (M = 73.39, SD = 12.19) was the behavior "responsibility of other people"; and with greater Eudaimonic well-being (M = 84.61, SD = 6.63), was the behavior "things to be remembered”. The most important findings highlight the importance of generative behaviors in adulthood, finding empirical evidence that the generativity in the last stage of life is associated with well-being. However, by finding differences in the types of generative behaviors at the level of well-being, is proposed the idea that generativity is not situated as an isolated construct, but needs other contextualized and related constructs that can simultaneously operate at different levels, taking into account the relationship between the environment and the individual, encompassing both the social and psychological dimension.

Keywords: eudaimonic well-being, generativity, hedonic well-being, Mexican elders, psychological well-being

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Authors: Nurdan Olguncelik Kaplan, Aysen Akay

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Nowadays soil pollution has become a global problem. External added polluters to the soil are destroying and changing the structure of the soil and the problems are becoming more complex and in this sense the correction of these problems is going to be harder and more costly. Cadmium has got a fast mobility in the soil and plant system because of that cadmium can interfere very easily to the human and animal food chain and in the same time this can be very dangerous. The cadmium which is absorbed and stored by the plants is causing to many metabolic changes of the plants like; protein synthesis, nitrogen and carbohydrate metabolism, enzyme (nitrate reductase) activation, photo and chlorophyll synthesis. The biological function of cadmium is not known over the plants and it is not a necessary element. The plant is generally taking in small amounts the cadmium and this element is competing with the zinc. Cadmium is causing root damages. Buckwheat (Fagopyrum esculentum) is an important nutraceutical because of its high content of flavonoids, minerals and vitamins, and their nutritionally balanced amino-acid composition. Buckwheat has relatively high biomass productivity, is adapted to many areas of the world, and can flourish in sterile fields; therefore buckwheat plants are widely used for the phytoremediation process.The aim of this study were to evaluate the phytoremediation capacity of the high-yielding plant Buckwheat (Fagopyrum esculentum) in soils contaminated with Cd and Zn. The soils were applied to differrent doses cd(0-12.5-25-50-100 mg Cd kg−1 soil in the form of 3CdSO4.8H2O ) and Zn (0-10-30 mg Zn kg−1 soil in the form of ZnSO4.7H2O) and incubated about 60 days. Later buckwheat seeds were sown and grown for three mounth under greenhouse conditions. The test plants were irrigated by using pure water after the planting process. Buckwheat seeds (Gunes and Aktas species) were taken from Bahri Dagdas International Agricultural Research. After harvest, Cd and Zn concentrations of plant biomass and grain, yield and translocation factors (TFs) for Cd and Cd were determined. Cadmium accumulation in biomass and grain significantly increased in dose-dependent manner. Long term field trials are required to further investigate the potential of buckwheat to reclaimed the soil. But this could be undertaken in conjunction with actual remediation schemes. However, the differences in element accumulation among the genotypes were affected more by the properties of genotypes than by the soil properties. Gunes genotype accumulated higher lead than Aktas genotypes.

Keywords: buckwheat, cadmium, phytoremediation, zinc

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Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Yi Li, Yinan Zheng, Ya Ke, Yungwing Ho

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Motor learning is a process that frequently happens among humans and rodents, which is defined as the changes in the capability to perform a skill that is conformed to have a relatively permanent improvement through practice or experience. There are many ways to learn a behavior, among which is observational learning. Observational learning is the process of learning by watching the behaviors of others, for example, a child imitating parents, learning a new sport by watching the training videos or solving puzzles by watching the solutions. Many research explores observational learning in humans and primates. However, the neuronal mechanism of which, especially observational motor learning, was uncertain. It’s well accepted that mirror neurons are essential in the observational learning process. These neurons fire when the primate performs a goal-directed action and sees someone else demonstrating the same action, which suggests they have high firing activity both completing and watching the behavior. The mirror neurons are assumed to mediate imitation or play a critical and fundamental role in action understanding. They are distributed in many brain areas of primates, i.e., posterior parietal cortex (PPC), premotor cortex (M2), and primary motor cortex (M1) of the macaque brain. However, few researchers report the existence of mirror neurons in rodents. To verify the existence of mirror neurons and the possible role in motor learning in rodents, we performed customised string-pulling behavior combined with multiple behavior analysis methods, photometry, electrophysiology recording, c-fos staining and optogenetics in healthy mice. After five days of training, the demonstrator (demo) mice showed a significantly quicker response and shorter time to reach the string; fast, steady and accurate performance to pull down the string; and more precisely grasping the beads. During three days of observation, the mice showed more facial motions when the demo mice performed behaviors. On the first training day, the observer reduced the number of trials to find and pull the string. However, the time to find beads and pull down string were unchanged in the successful attempts on the first day and other training days, which indicated successful action understanding but failed motor learning through observation in mice. After observation, the post-hoc staining revealed that the c-fos expression was increased in the cognitive-related brain areas (medial prefrontal cortex) and motor cortices (M1, M2). In conclusion, this project indicated that the observation led to a better understanding of behaviors and activated the cognitive and motor-related brain areas, which suggested the possible existence of mirror neurons in these brain areas.

Keywords: observation, motor learning, string-pulling behavior, prefrontal cortex, motor cortex, cognitive

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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Authors: Elizabeth Laguaite, Alexandria Purdy

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Heart transplant recipients face psycho-physiological stressors, including pain, lengthy hospitalizations, delirium, and existential crises. They pose an increased risk for Post Traumatic Stress Disorder (PTSD) and can be a predictor of poorer mental and physical Health-Related Quality of Life (HRQOL) outcomes and increased mortality. There is limited research on the prevention of Post Traumatic Stress Symptoms (PTSS) in transplant patients. This case report focuses on a collaborative Music and Art Therapy intervention used to improve outcomes for HMH transplant recipient John (Alias). John, a 58-year-old man with congestive heart failure, was admitted to HMH in February of 2021 with cardiogenic shock, cannulated with an Intra-aortic Balloon Pump, Impella 5.5, and Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) as a bridge to heart and kidney transplant. He was listed as status 1 for transplant. Music Therapy and Art Therapy (MT and AT) were ordered by the physician for mood regulation, trauma processing and anxiety management. During MT/AT sessions, John reported a history of anxiety and depression exacerbated by medical acuity, shortness of breath, and lengthy hospitalizations. He expressed difficulty sleeping, pain, and existential questions. Initially seen individually by MT/AT, it was determined he could benefit from a collaborative approach due to similar thematic content within sessions. A Life Review intervention was developed by MT/AT. The purpose was for him to creatively express, reflect and process his medical narrative, including the identification of positive and negative events leading up to admission at HMH, the journey to transplant, and his hope for the future. Through this intervention, he created artworks that symbolized each event and paired them with songs, two of which were composed with the MT during treatment. As of September 2023, John has not been readmitted to the hospital and expressed that this treatment is what “got him through transplant”. MT and AT can provide opportunities for a patient to reminisce through creative expression, leading to a shift in the personal meaning of these experiences, promoting resolution, and ameliorating associated trauma. The closer to trauma it is processed, the less likely to develop PTSD. This collaborative MT/AT approach could improve long-term outcomes by reducing mortality and readmission rates for transplant patients.

Keywords: art therapy, music therapy, critical care, PTSD, trauma, transplant

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Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

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Authors: S. Fazelifar, M. Ghasemi

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Aim: Recent studies on cardiovascular risk factors have been focused on the new markers of inflammatory diseases such as C-reactive protein (CRP). Research evidence shows that physical activity along with other factors such as reduced smoking, controlling blood pressure, control blood lipids TC, LDL-c, HDL-c and having a healthy weight can reduce the risk of chronic heart disease (CHD) .Therefore, the aim of this study was to determine the effect of twelve weeks aerobic exercise and consumption of apple vinegar on cardiovascular risk factor in older women. Methodology: 28 inactive women (mean body weight 72.13 ± 8.6 kg, height 157 ± 7.4cm, age 48.06 ± 5.18 years and BMI 28.2 ± 3.2 kg/m2) by recall and notice of investigation, among of the eligible voters recruited and randomly divided in 4 groups: control, apple vinegar, exercise, exercise + apple vinegar. The training program includes a 20-minute warm-up and stretching, running for 15 minutes in the first session with an intensity of 80% of maximum heart rate and an increase in one-minute run time in next training session. Also, subjects in experimental groups received daily specified amount of 50 ml apple vinegar. Blood samples were collected from the brachial vein in before and after training to measure CRP and blood lipids (cholesterol, HDL, VLDL, LDL). The levels of CRP were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results indicated that individual characteristics including height, weight, age, and body mass index were not significantly different among the four groups. The results showed that levels of CRP and LDL cholesterol were significantly reduced in all groups at post-test compared to the pre-test. The HDL levels increased significantly in all groups in post-test compared to the pre-test. Analysis of the data indicates that levels of CRP, TC, and LDL were significantly reduced in all groups compared to the control group, while the changes in the other groups were not significant relative to each other. Conclusion: Results of this study showed that twelve weeks of aerobic exercise with apple vinegar cause a significant decrease in CRP, cholesterol, LDL, and significantly increased HDL levels. According to the results of this study, it is possible that aerobic exercise with apple vinegar can inhibit CRP and undesirable fats. Considering the strong association between the inflammatory indices and the prevalence of cardiovascular diseases, every factor that decreases these indices can reduce the cardiovascular complications.

Keywords: aerobic exercise, apple vinegar, CRP, older women

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Authors: Orsolya Horvath, Laszlo Deres, Krisztian Eros, Katalin Ordog, Tamas Habon, Balazs Sumegi, Kalman Toth, Robert Halmosi

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Introduction: Oxidative stress induces an imbalance in mitochondrial fusion and fission processes, finally leading to cell death. The two antioxidant molecules, BGP-15 and L2286 have beneficial effects on mitochondrial functions and on cellular oxidative stress response. In this work, we studied the effects of these compounds on the processes of mitochondrial quality control. Methods: We used H9c2 cardiomyoblast and isolated neonatal rat cardiomyocytes (NRCM) for the experiments. The concentration of stressors and antioxidants was beforehand determined with MTT test. We applied 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) in 125 µM, 400 µM and 800 µM concentrations for 4 and 8 hours on H9c2 cells. H₂O₂ was applied in 150 µM and 300 µM concentration for 0.5 and 4 hours on both models. L2286 was administered in 10 µM, while BGP-15 in 50 µM doses. Cellular levels of the key proteins playing role in mitochondrial dynamics were measured in Western blot samples. For the analysis of mitochondrial network dynamics, we applied electron microscopy and immunocytochemistry. Results: Due to MNNG treatment the level of fusion proteins (OPA1, MFN2) decreased, while the level of fission protein DRP1 elevated markedly. The levels of fusion proteins OPA1 and MNF2 increased in the L2286 and BGP-15 treated groups. During the 8 hour treatment period, the level of DRP1 also increased in the treated cells (p < 0.05). In the H₂O₂ stressed cells, administration of L2286 increased the level of OPA1 in both H9c2 and NRCM models. MFN2 levels in isolated neonatal rat cardiomyocytes raised considerably due to BGP-15 treatment (p < 0.05). L2286 administration decreased the DRP1 level in H9c2 cells (p < 0.05). We observed that the H₂O₂-induced mitochondrial fragmentation could be decreased by L2286 treatment. Conclusion: Our results indicated that the PARP-inhibitor L2286 has beneficial effect on mitochondrial dynamics during oxidative stress scenario, and also in the case of directly induced DNA damage. We could make the similar conclusions in case of BGP-15 administration, which, via reducing ROS accumulation, propagates fusion processes, this way aids preserving cellular viability. Funding: GINOP-2.3.2-15-2016-00049; GINOP-2.3.2-15-2016-00048; GINOP-2.3.3-15-2016-00025; EFOP-3.6.1-16-2016-00004; ÚNKP-17-4-I-PTE-209

Keywords: H9c2, mitochondrial dynamics, neonatal rat cardiomyocytes, oxidative stress

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Hortènsia Curell, Ana Fernández-Montraveta

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This paper presents the creation, development, and analysis of a corpus designed to study the presence of attitude markers and author’s stance in research articles in two different areas of linguistics (theoretical linguistics and sociolinguistics). These two disciplines are expected to behave differently in this respect, given the disparity in their discursive conventions. Attitude markers in this work are understood as the linguistic elements (adjectives, nouns and verbs) used to convey the writer's stance towards the content presented in the article, and are crucial in understanding writer-reader interaction and the writer's position. These attitude markers are divided into three broad classes: assessment, significance, and emotion. In addition to them, we also consider first-person singular and plural pronouns and possessives, modal verbs, and passive constructions, which are other linguistic elements expressing the author’s stance. The corpus, Corpus of Attitude in Academic Writing (CAAW), comprises a collection of 21 articles, collected from six journals indexed in JCR. These articles were originally written in English by a single native-speaker author from the UK or USA and were published between 2022 and 2023. The total number of words in the corpus is approximately 222,400, with 106,422 from theoretical linguistics (Lingua, Linguistic Inquiry and Journal of Linguistics) and 116,022 from sociolinguistics journals (International Journal of the Sociology of Language, Language in Society and Journal of Sociolinguistics). Together with the corpus, we present the tool created for the creation and storage of the corpus, along with a tool for automatic annotation. The steps followed in the compilation of the corpus are as follows. First, the articles were selected according to the parameters explained above. Second, they were downloaded and converted to txt format. Finally, examples, direct quotes, section titles and references were eliminated, since they do not involve the author’s stance. The resulting texts were the input for the annotation of the linguistic features related to stance. As for the annotation, two articles (one from each subdiscipline) were annotated manually by the two researchers. An existing list was used as a baseline, and other attitude markers were identified, together with the other elements mentioned above. Once a consensus was reached, the rest of articles were annotated automatically using the tool created for this purpose. The annotated corpus will serve as a resource for scholars working in discourse analysis (both in linguistics and communication) and related fields, since it offers new insights into the expression of attitude. The tools created for the compilation and annotation of the corpus will be useful to study author’s attitude and stance in articles from any academic discipline: new data can be uploaded and the list of markers can be enlarged. Finally, the tool can be expanded to other languages, which will allow cross-linguistic studies of author’s stance.

Keywords: academic writing, attitude, corpus, english

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Authors: Kersch-Counet C., Fransen K. H. S., Broyd M., Nyakayiru J. D. O. A., Schoemaker M. H., Mallee L. F., Bovee-Oudenhoven I. M. J.

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Background: Around one third of people, including athletes, suffer from feelings of gut discomfort. Fermentation of dairy is a process that has been associated with products that can improve gut health. However, insight in (potential) health benefits of most fermented foods is limited to chemical analyses and in-vitro models. Objective: The aim of this open-label, single-arm explorative trial was to investigate in a real life setting the effect of consumption of a fermented whey product for 3 weeks on self-perceived physical and mental wellbeing and digestive issues in 150 US recreational athletes (20-50 years of age) with self-reported gut complaints at enrolment. Methods: Participants living at the West-Coast of the US received for 3 weeks a daily powder of 15 g of BiotisTM Fermentis to be mixed in water using a supplied shaker. Weekly questionnaires were conducted by MMR research to study the effect on physical/mental health issues and self-perceived gut complaints. Non-parametric tests (e.g., Friedman test) were used to assess statistical differences over time while the Kruskal-Wallis and Wilcoxon signed-rank tests were used for sub-groups analysis. Results: Bloating, stress and anxiety were the top 3 issues of the US recreational athletes. Satisfaction of physical wellbeing increased significantly throughout the 3-weeks of fermented whey product consumption (p<0.0005). Combined digestive issues decreased significantly after 2- and 3-weeks of product consumption, with bloating showing a significant reduction (p<0.05). There was a trend that self-reported stress levels reduced after 3 weeks and participants said to significantly feel more active, energetic, and vital (p<0.05). Subgroup analysis showed that gender and habitual protein supplement consumption were associated with specific health issues and modulated the response to the fermented dairy product. Conclusion: Daily consumption of the fermented BiotisTM Fermentis product is associated with a reduction in self-perceived gastrointestinal symptoms and improved overall wellbeing and mood state in US recreational athletes. This large nutrition and health consumer study brings valuable insights in self-reported gut complaints of recreational athletes in the US and their response to a fermented dairy product. A controlled clinical trial in a targeted population is recommended to scientifically substantiate the product effect as observed in this explorative study.

Keywords: real-life study, digestive health, fermented whey, sports

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Authors: Amnah M. A. Alsuhaibani, Amal N. Al-Kuraieef

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Introduction: In the recent decades, production of low-calorie jams is needed for diabetics that comprise low calorie fruits and low calorie sweeteners. Object: the research aimed to prepare low calorie formulated pumpkin jams (fructose, stevia and aspartame) incorporated with soy bean and evaluate the jams through chemical analysis and sensory evaluation after storage for six month. Moreover, the possible effect of consumption of low calorie jams on diabetic rats was investigated. Methods: Five formulas of pumpkin jam with different sucrose, fructose, stevia and aspartame sweeteners and soy bean were prepared and stored at 10 oC for six month compared to ordinary pumpkin jam. Chemical composition and sensory evaluation of formulated jams were evaluated at zero time, 3 month and 6 month of storage. The best three acceptable pumpkin jams were taken for biological study on diabetic rats. Rats divided into group (1) served as negative control and streptozotocin induce diabetes four rat groups that were positive diabetic control (group2), rats fed on standard diet with 10% sucrose soybean jam, fructose soybean jam and stevia soybean jam (group 3, 4&5), respectively. Results: The content of protein, fat, ash and fiber were increased but carbohydrate was decreased in low calorie formulated pumpkin jams compared to ordinary jam. Production of aspartame soybean pumpkin jam had lower score of all sensory attributes compared to other jam then followed by stevia soybean Pumpkin jam. Using non nutritive sweeteners (stevia & aspartame) with soybean in processing jam could lower the score of the sensory attributes after storage for 3 and 6 months. The highest score was recorded for sucrose and fructose soybean jams followed by stevia soybean jam while aspartame soybean jam recorded the lowest score significantly. The biological evaluation showed a significant improvement in body weight and FER of rats after six weeks of consumption of standard diet with jams (Group 3,4&5) compared to Group1. Rats consumed 10% low calorie jam with nutrient sweetener (fructose) and non nutrient sweetener (stevia) soybean jam (group 4& 5) showed significant decrease in glucose level, liver function enzymes activity, and liver cholesterol & total lipids in addition of significant increase of insulin and glycogen compared to the levels of group 2. Conclusion: low calorie pumpkin jams can be prepared by low calorie sweeteners and soybean and also storage for 3 months at 10oC without change sensory attributes. Consumption of stevia pumpkin jam fortified with soybean had positive health effects on streptozoticin induced diabetes in rats.

Keywords: pumpkin jam, HFCS, aspartame, stevia, storage

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Authors: Nelson R. Osungbemiro, O. A. Bello-Olusoji, M. Oladipupo

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This study was carried out to determine the effects of probiotics Pseudomonas fluorescens on the growth performance, histology examination and immune modulation of African Catfish, (Clarias gariepinus) challenged with Clostridium botulinum. P. fluorescens, and C. botulinum isolates were removed from the gut, gill and skin organs of procured adult samples of Clarias gariepinus from commercial fish farms in Akure, Ondo State, Nigeria. The physical and biochemical tests were performed on the bacterial isolates using standard microbiological techniques for their identification. Antibacterial activity tests on P. fluorescens showed inhibition zone with mean value of 3.7 mm which indicates high level of antagonism. The experimental diets were prepared at different probiotics bacterial concentration comprises of five treatments of different bacterial suspension, including the control (T1), T2 (10³), T3 (10⁵), T4 (10⁷) and T5 (10⁹). Three replicates for each treatment type were prepared. Growth performance and nutrients utilization indices were calculated. The proximate analysis of fish carcass and experimental diet was carried out using standard methods. After feeding for 70 days, haematological values and histological test were done following standard methods; also a subgroup from each experimental treatment was challenged by inoculating Intraperitonieally (I/P) with different concentration of pathogenic C. botulinum. Statistically, there were significant differences (P < 0.05) in the growth performance and nutrient utilization of C. gariepinus. Best weight gain and feed conversion ratio were recorded in fish fed T4 (10⁷) and poorest value obtained in the control. Haematological analyses of C. gariepinus fed the experimental diets indicated that all the fish fed diets with P. fluorescens had marked significantly (p < 0.05) higher White Blood Cell than the control diet. The results of the challenge test showed that fish fed the control diet had the highest mortality rate. Histological examination of the gill, intestine, and liver of fish in this study showed several histopathological alterations in fish fed the control diets compared with those fed the P. fluorescens diets. The study indicated that the optimum level of P. fluorescens required for C. gariepinus growth and white blood cells formation is 10⁷ CFU g⁻¹, while carcass protein deposition required 10⁵ CFU g⁻¹ of P. fluorescens concentration. The study also confirmed P. fluorescens as efficient probiotics that is capable of improving the immune response of C. gariepinus against the attack of a virulent fish pathogen, C. botulinum.

Keywords: Clarias gariepinus, Clostridium botulinum, probiotics, Pseudomonas fluorescens

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Authors: A. B. Moldes, X. Vecino, L. Rodriguez-López, J. M. Dominguez, J. M. Cruz

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The concept of the circular economy is focus on the importance of providing goods and services sustainably. Thus, in a future it will be necessary to respond to the environmental contamination and to the use of renewables substrates by moving to a more restorative economic system that drives towards the utilization and revalorization of residues to obtain valuable products. During its evolution our industrial economy has hardly moved through one major characteristic, established in the early days of industrialization, based on a linear model of resource consumption. However, this industrial consumption system will not be maintained during long time. On the other hand, there are many industries, like the corn milling industry, that although does not consume high amount of non renewable substrates, they produce valuable streams that treated accurately, they could provide additional, economical and environmental, benefits by the extraction of interesting commercial renewable products, that can replace some of the substances obtained by chemical synthesis, using non renewable substrates. From this point of view, the use of streams from corn milling industry to obtain surface-active compounds will decrease the utilization of non-renewables sources for obtaining this kind of compounds, contributing to a circular and global economy. However, the success of the circular economy depends on the interest of the industrial sectors in the revalorization of their streams by developing relevant and new business models. Thus, it is necessary to invest in the research of new alternatives that reduce the consumption of non-renewable substrates. In this study is proposed the utilization of a corn milling industry stream to obtain an extract with surfactant capacity. Once the biosurfactant is extracted, the corn milling stream can be commercialized as nutritional media in biotechnological process or as animal feed supplement. Usually this stream is combined with other ingredients obtaining a product namely corn gluten feed or may be sold separately as a liquid protein source for beef and dairy feeding, or as a nutritional pellet binder. Following the productive scheme proposed in this work, the corn milling industry will obtain a biosurfactant extract that could be incorporated in its productive process replacing those chemical detergents, used in some point of its productive chain, or it could be commercialized as a new product of the corn manufacture. The biosurfactants obtained from corn milling industry could replace the chemical surfactants in many formulations, and uses, and it supposes an example of the potential that many industrial streams could offer for obtaining valuable products when they are manage properly.

Keywords: biosurfactantes, circular economy, corn, sustainability

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Authors: B. K. Manjunatha Goud, Aruna Chanu Oinam

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The undergraduate medical curriculum is oriented towards training the students to undertake the responsibilities of a physician. During the training period, adequate emphasis is placed on inculcating logical and scientific habits of thought; clarity of expression and independence of judgment; and ability to collect and analyze information and to correlate them. At Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Biochemistry a basic medical science subject is taught in the 1st year of 5 years medical course with vertical interdisciplinary interaction with all subjects, which needs to be taught and learned adequately by the students to be related to clinical case or clinical problem in medicine and future diagnostics so that they can practice confidently and skillfully in the community. Based on these facts study was done to know the extent of usage of library resources by the students and the impact of study materials on their preparation for examination. It was a comparative cross sectional study included 100 and 80 1st and 2nd-year students who had successfully completed Biochemistry course. The purpose of the study was explained to all students [participants]. Information was collected on a pre-designed, pre-tested and self-administered questionnaire. The questionnaire was validated by the senior faculties and pre tested on students who were not involved in the study. The study results showed that 80.30% and 93.15% of 1st and 2nd year students have the clear idea of course outline given in course handout or study guide. We also found a statistically significant number of students agreed that they were benefited from the practical session and writing notes in the class hour. A high percentage of students [50% and 62.02%] disagreed that that reading only the handouts is enough for their examination as compared to other students. The study also showed that only 35% and 41% of students visited the library on daily basis for the learning process, around 65% of students were using lecture notes and text books as a tool for learning and to understand the subject and 45% and 53% of students used the library resources (recommended text books) compared to online sources before the examinations. The results presented here show that students perceived that e-learning resources like power point presentations along with text book reading using SQ4R technique had made a positive impact on various aspects of their learning in Biochemistry. The use of library by students has overall positive impact on learning process especially in medical field enhances the outcome, and medical students are better equipped to treat the patient. But it’s also true that use of library use has been in decline which will impact the knowledge aspects and outcome. In conclusion, a student has to be taught how to use the library as learning tool apart from lecture handouts.

Keywords: medical education, learning resources, study guide, biochemistry

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Authors: Steven G. Sclan

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Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.

Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research

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Authors: Ghada Mahmoud El Kassas, Maged Atta El Wakeel

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Background: Environmental enteric dysfunction (EED) is impending trouble that flared up in the last decades to be pervasive in infants and children. EED is asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. Evidence has suggested that supplementary zinc might ameliorate this damage by reducing gastrointestinal inflammation and may also benefit cognitive development. Objective: We tested whether zinc supplementation improves intestinal integrity, growth, and cognitive function in stunted children predicted to have EED. Methodology: This case–control prospective interventional study was conducted on 120 Egyptian Stunted children aged 1-10 years who recruited from the Nutrition clinic, the National research center, and 100 age and gender-matched healthy children as controls. At the primary phase of the study, Full history taking, clinical examination, and anthropometric measurements were done. Standard deviation score (SDS) for all measurements were calculated. Serum markers as Zonulin, Endotoxin core antibody (EndoCab), highly sensitive C-reactive protein (hsCRP), alpha1-acid glycoprotein (AGP), Tumor necrosis factor (TNF), and fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) (as predictors of EED) were measured. Cognitive development was assessed (Bayley or Wechsler scores). Oral zinc at a dosage of 20 mg/d was supplemented to all cases and followed up for 6 months, after which the 2ry phase of the study included the previous clinical, laboratory, and cognitive assessment. Results: Serum and fecal inflammatory markers were significantly higher in cases compared to controls. Zonulin (P < 0.01), (EndoCab) (P < 0.001) and (AGP) (P < 0.03) markedly decreased in cases at the end of 2ry phase. Also (MPO), (NEO), and (AAT) showed a significant decline in cases at the end of the study (P < 0.001 for all). A significant increase in mid-upper arm circumference (MUAC) (P < 0.01), weight for age z-score, and skinfold thicknesses (P< 0.05 for both) was detected at end of the study, while height was not significantly affected. Cases also showed significant improvement of cognitive function at phase 2 of the study. Conclusion: Intestinal inflammatory state related to EED showed marked recovery after zinc supplementation. As a result, anthropometric and cognitive parameters showed obvious improvement with zinc supplementation.

Keywords: stunting, cognitive function, environmental enteric dysfunction, zinc

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Authors: Arkadiusz Gut, Robert Mirski

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The nativist-constructivist debate constitutes a considerable part of current research on mindreading. Peter Carruthers and his colleagues are known for their nativist position in the debate and take issue with constructivist views proposed by other researchers, with Henry Wellman, Alison Gopnik, and Ian Apperly at the forefront. More specifically, Carruthers together with Evan Westra propose a nativistic explanation of Theory of Mind Scale study results that Wellman et al. see as supporting constructivism. While allowing for development of the innate mindreading system, Westra and Carruthers base their argumentation essentially on a competence-performance gap, claiming that cross-cultural differences in Theory of Mind Scale progression as well as discrepancies between infants’ and toddlers’ results on verbal and non-verbal false-belief tasks are fully explainable in terms of acquisition of other, pragmatic, cognitive developments, which are said to allow for an expression of the innately present Theory of Mind understanding. The goal of the present paper is to bring together arguments against the view offered by Westra and Carruthers. It will be shown that even though Carruthers et al.’s interpretation has not been directly controlled for in Wellman et al.’s experiments, there are serious reasons to dismiss such nativistic views which Carruthers et al. advance. The present paper discusses the following issues that undermine Carruthers et al.’s nativistic conception: (1) The concept of innateness is argued to be developmentally inaccurate; it has been dropped in many biological sciences altogether and many developmental psychologists advocate for doing the same in cognitive psychology. Reality of development is a complex interaction of changing elements that is belied by the simplistic notion of ‘the innate.’ (2) The purported innate mindreading conceptual system posited by Carruthers ascribes adult-like understanding to infants, ignoring the difference between first- and second-order understanding, between what can be called ‘presentation’ and ‘representation.’ (3) Advances in neurobiology speak strongly against any inborn conceptual knowledge; neocortex, where conceptual knowledge finds its correlates, is said to be largely equipotential at birth. (4) Carruthers et al.’s interpretations are excessively charitable; they extend results of studies done with 15-month-olds to conclusions about innateness, whereas in reality at that age there has been plenty of time for construction of the skill. (5) Looking-time experiment paradigm used in non-verbal false belief tasks that provide the main support for Carruthers’ argumentation has been criticized on methodological grounds. In the light of the presented arguments, nativism in theory of mind research is concluded to be an untenable position.

Keywords: development, false belief, mindreading, nativism, theory of mind

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Authors: Gleb Fomin, Kairat Tabynov, Nurkeldy Turebekov, Dinara Turegeldiyeva, Rinat Islamov

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The level of major cytokines in the blood of patients with COVID-19 varies greatly depending on age, gender, duration and severity of infection, and comorbidity. There are two clinically significant cytokines, IL-6 and TNF-α, which increase in levels in patients with severe COVID-19. However, in a model of COVID-19 in hamsters, TNF-α levels are unchanged or reduced, while the expression of other cytokines reflects the profile of cytokines found in patients’ plasma. The aim of our study was to evaluate the relationship between the level of cytokines in the blood, lungs, and lung damage in the model of the Syrian hamster (Mesocricetus auratus) infected with the SARS-CoV-2 strain. The study used outbred female and male Syrian hamsters (n=36, 4 groups) weighing 80-110 g and 5 months old (protocol IACUC, #4, 09/22/2020). Animals were infected intranasally with the hCoV-19/Kazakhstan/KazNAU-NSCEDI-481/2020 strain and euthanized at 3 d.p.i. The level of cytokines IL-6, TNF-α, IFN-α, and IFN-γ was determined by ELISA MyBioSourse (USA) for hamsters. Lung samples were subjected to histological processing. The presence of pathological changes in histological preparations was assessed on a 3-point scale. The work was carried out in the ABSL-3 laboratory. The data were analyzed in GraphPad Prism 6.00 (GraphPad Software, La Jolla, California, USA). The work was supported by the MES RK grant (AP09259865). In the blood, the level of TNF-α increased in males (p=0.0012) and IFN-γ in males and females (p=0.0001). On the contrary, IFN-α production decreased (p=0.0006). Only TNF-α level increased in lung tissues (p=0.0011). Correlation analysis showed a negative relationship between the level of IL-6 in the blood and lung damage in males (r -0.71, p=0.0001) and females (r-0.57, p=0.025). On the contrary, in males, the level of IL-6 in the lungs and score is positively correlated (r 0.80, p=0.01). The level of IFN-γ in the blood (r -0.64, p=0.035) and lungs (r-0.72, p=0.017) in males has a negative correlation with lung damage. No links were found for TNF-α and IFN-α. The study showed a positive association between lung injury and tissue levels of IL-6 in male hamsters. It is known that in humans, high concentrations of IL-6 in the lungs are associated with suppression of cellular immunity and, as a result, with an increase in the severity of COVID-19. TNF-α and IFN-γ play a key role in the pathogenesis of COVID-19 in hamsters. However, the mechanisms of their activity require more detailed study. IFN-α plays a lesser role in direct lung injury in a Syrian hamster model. We have shown the significance of tissue IL-6 and IFN-γ as predictors of the severity of lung damage in COVID-19 in the Syrian hamster model. Changes in the level of cytokines in the blood may not always reflect pathological processes in the lungs with COVID-19.

Keywords: syrian hamster, COVID-19, cytokines, biological model

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Authors: Ratna Sharma, Kaveri Dutta

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Assam (India), the gate way to the Northeast India is mainly known for its exquisite silks, the art and craft. The state has a rich collection of traditional jewellery which is unique and exclusive to the state. These jewelleries hold a special place in the heart of the Assamese women. Similarly handloom industry of Assam is basically silk oriented. Among the wild silk, Eri silk fabric has remained as “the poor man’s silk” but it is closely attached to the assamese society, dress for it's warm quality. In view of the changing market trends, fashion and consumer demands, Silk is emerging as a fashion fabric both in India and abroad. In case of Eri silk fabric it has limited use in clothing and accessories. Hence the restructured and redesigned traditional jewellery motifs of Assam (India) over Eri silk products will have greater potential in reviving the decline of art, generate revenue, self employment towards craftsmen and also recognition of the art. The information incorporated in the paper is primary and the data have been collected by purposive sampling method. This work of art was expressed on Eri silk fabric in the form of traditional hand embroidery as it is closely connected with the era of the individual in history of mankind and reflects the personal expression of an entity. For this study selected traditional motifs of Assamese ornaments was used. Some of the popular traditional Assamese jewellery include earrings with exquisite Lokaparo, Keru, Thuriya, Jangphai, etc. An array of necklaces including Golpata, Satsori, Jon biri, Bena, Gejera, Dhol biri, Doog doogi, Biri Moni, Mukuta Moni, Poalmoni, Silikha Moni and Magardana and diversified rings including Senpata, Horinsakua, Jethinejia, bakharpata and others. Selected two motifs each from necklace, earring and finger ring designs. Selected motifs were further developed into 3 categories- the border, the main motif and all over butta followed by placement of developed patterns on products. Products developed were stoles, scarf’s, purses, brooch pins, skirts for women and ties, handkerchief, jackets for men. The developed products were surveyed by selected respondents. From the present study it can be observed that the embellished traditional jewellery motifs resulted in fresh and colourful pattern on developed Eri silk products. Moreover the motifs which were gradually fading among the community itself showed a very good recognition towards art. The embroidered Eri silk fabric also created a huge change in a positive way among craftsman.

Keywords: Art and craft of Assam, eri silk, hand embroidery, traditional Assamese jewellery motifs

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Authors: Hooriya Sadr Dadras, Shiva Seyed Erfani

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Speaking skills merit meticulous attention both on the side of the learners and the teachers. In particular, accuracy is a critical component to guarantee the messages to be conveyed through conversation because a wrongful change may adversely alter the content and purpose of the talk. Different types of tasks have served teachers to meet numerous educational objectives. Besides, negotiation of meaning and the use of different strategies have been areas of concern in socio-cultural theories of SLA. Negotiation of meaning is among the conversational processes which have a crucial role in facilitating the understanding and expression of meaning in a given second language. Conversational strategies are used during interaction when there is a breakdown in communication that leads to the interlocutor attempting to remedy the gap through talk. Therefore, this study was an attempt to investigate if there was any significant difference between the effect of reasoning gap tasks and information gap tasks on the frequency of conversational strategies used in negotiation of meaning in classrooms on one hand, and on the accuracy in speaking of Iranian intermediate EFL learners on the other. After a pilot study to check the practicality of the treatments, at the outset of the main study, the Preliminary English Test was administered to ensure the homogeneity of 87 out of 107 participants who attended the intact classes of a 15 session term in one control and two experimental groups. Also, speaking sections of PET were used as pretest and posttest to examine their speaking accuracy. The tests were recorded and transcribed to estimate the percentage of the number of the clauses with no grammatical errors in the total produced clauses to measure the speaking accuracy. In all groups, the grammatical points of accuracy were instructed and the use of conversational strategies was practiced. Then, different kinds of reasoning gap tasks (matchmaking, deciding on the course of action, and working out a time table) and information gap tasks (restoring an incomplete chart, spot the differences, arranging sentences into stories, and guessing game) were manipulated in experimental groups during treatment sessions, and the students were required to practice conversational strategies when doing speaking tasks. The conversations throughout the terms were recorded and transcribed to count the frequency of the conversational strategies used in all groups. The results of statistical analysis demonstrated that applying both the reasoning gap tasks and information gap tasks significantly affected the frequency of conversational strategies through negotiation. In the face of the improvements, the reasoning gap tasks had a more significant impact on encouraging the negotiation of meaning and increasing the number of conversational frequencies every session. The findings also indicated both task types could help learners significantly improve their speaking accuracy. Here, applying the reasoning gap tasks was more effective than the information gap tasks in improving the level of learners’ speaking accuracy.

Keywords: accuracy in speaking, conversational strategies, information gap tasks, reasoning gap tasks

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Authors: Hsiao-Lin Fang

Abstract:

The Patient Self-Determination Act is based on the belief that each life is unique. The act regards each patient as an autonomous entity and explicitly protects the patient’s rights to know and make decisions and choices while ensuring that the patient’s wish for a peaceful end is granted. Even when the patient is unconscious and unable to express himself/herself, the patient’s self-determination and its exercise are still protected under the law. The act also ensures that healthcare professionals (HCPs) have a specific set of rules to follow and complete legal protection when their patients are unable to express themselves clearly. This report is about a 55-year-old female patient who weighed 110 kg and was diagnosed with acute type A aortic dissection. The case was that the patient suddenly felt backache and nausea during sleep before daybreak and was therefore transferred to this hospital from the original one. After the doctor explained the patient’s conditions, it was concluded that surgery was necessary. However, the patient’s family was immediately against the surgery after having heard its possible complications. Nevertheless, the patient was still willing to receive the surgery. Being at odds with her family, the patient decided to sign the surgery agreement herself and agreed to receive the two surgical procedures: (1) ascending aorta replacement and (2) innominate artery debranching. After the surgery, the patient did not regain consciousness and therefore received computed tomography scanning of the brain, which revealed false lumen involving proximal left common carotid artery, left subclavian artery and innominate artery, and severe compression of the true lumen with total/subtotal occlusion in the left common carotid artery. On the following day, the doctor discussed two further surgical procedures: (1) endografting for descending aorta and (2) endografting for left common carotid artery and subclavian artery with the family. However, as the patient’s postoperative recovery of consciousness only reached the level of stupor and her family had no intention of subsequent healthcare for the patient, the family made the joint decision three days later to have the endotracheal tube removed from the patient and let her die a natural death. Suggestion: An advance directive (AD) can be created beforehand. Once the patient is in a special clinical state (e.g., terminal illness, permanent vegetative state, etc.), the AD can determine whether to sustain the patient’s life through ‘medical intervention’ or to respect the patient’s rights to choose a peaceful end and receive palliative care. Through the expression of self-determination, it is possible to respect the patient’s medical practice autonomy and protect the patient’s dignity and right to a peaceful end, thereby respecting and supporting the patient’s decision. This also allows the three sides: the patient, the family and the medical team to understand the patient’s true wish in the process of advance care planning (ACP) and thereby promote harmony in the HCP-patient relationship.

Keywords: intensive care unit patient, cardiovascular surgery, self-determination, advance directive

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Authors: Ewelina Musielak, Agnieszka Feliczak-Guzik, Izabela Nowak

Abstract:

Based on the latest data, it is expected that the substances of therapeutic interest used will be as natural as possible. Therefore, active substances with the highest possible efficacy and low toxicity are sought. Among natural substances with therapeutic effects, those of plant origin stand out. Curcumin isolated from the Curcuma longa plant has proven to be particularly important from a medical point of view. Due to its ability to regulate many important transcription factors, cytokines, and protein kinases, curcumin has found use as an anti-inflammatory, antioxidant, antiproliferative, antiangiogenic, and anticancer agent. The unfavorable properties of curcumin, such as low solubility, poor bioavailability, and rapid degradation under neutral or alkaline pH conditions, limit its clinical application. These problems can be solved by combining curcumin with suitable carriers such as hierarchical zeolites. This is a new class of materials that exhibit several advantages. Hierarchical zeolites used as drug carriers enable delayed release of the active ingredient and promote drug transport to the desired tissues and organs. In addition, hierarchical zeolites play an important role in regulating micronutrient levels in the body and have been used successfully in cancer diagnosis and therapy. To apply curcumin to hierarchical zeolites synthesized from commercial FAU zeolite, solutions containing curcumin, carrier and acetone were prepared. The prepared mixtures were then stirred on a magnetic stirrer for 24 h at room temperature. The curcumin-filled hierarchical zeolites were drained into a glass funnel, where they were washed three times with acetone and distilled water, after which the obtained material was air-dried until completely dry. In addition, the effect of piperine addition to zeolite carrier containing a sufficient amount of curcumin was studied. The resulting products were weighed and the percentage of pure curcumin in the hierarchical zeolite was calculated. All the synthesized materials were characterized by several techniques: elemental analysis, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, Fourier transform infrared (FT-IR), N2 adsorption, and X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The aim of the presented study was to improve the biological activity of curcumin by applying it to hierarchical zeolites based on FAU zeolite. The results showed that the loading efficiency of curcumin into hierarchical zeolites based on commercial FAU-type zeolite is enhanced by modifying the zeolite carrier itself. The hierarchical zeolites proved to be very good and efficient carriers of plant-derived active ingredients such as curcumin.

Keywords: carriers of active substances, curcumin, hierarchical zeolites, incorporation

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Authors: S. G. Vasantharaju, Viswanath Guptha, Raghavendra Shetty

Abstract:

Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.

Keywords: Aminophyllin, preclinical pharmacokinetics, rat plasma, RPHPLC

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