Search results for: resistant gene expression

Authors: Gary J. Pickering, Sarah Lucas, Catherine E. Klodnicki, Nicole J. Gaudette

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Two taste pheno types that are of interest in the study of habitual diet-related risk factors and disease are 6-n-propylthiouracil (PROP) responsiveness and thermal tasting. Individuals differ considerable in how intensely they experience the bitterness of PROP, which is partially explained by three major single nucleotide polymorphisms associated with the TAS2R38 gene. Importantly, this variable responsiveness is a useful proxy for general taste responsiveness, and links to diet-related disease risk, including body mass index, in some studies. Thermal tasting - a newly discovered taste phenotype independent of PROP responsiveness - refers to the capacity of many individuals to perceive phantom tastes in response to lingual thermal stimulation, and is linked with TRPM5 channels. Thermal tasters (TTs) also experience oral sensations more intensely than thermal non-tasters (TnTs), and this was shown to associate with differences in self-reported food preferences in a previous survey from our lab. Here we report on two related studies, where we sought to determine whether PROP responsiveness and thermal tasting would associate with perceptual differences in the oral sensations elicited by sampled energy-dense foods, and whether in turn this would influence liking. We hypothesized that hyper-tasters (thermal tasters and individuals who experience PROP intensely) would (a) rate sweet and high-fat foods more intensely than hypo-tasters, and (b) would differ from hypo-tasters in liking scores. (Liking has been proposed recently as a more accurate measure of actual food consumption). In Study 1, a range of energy-dense foods and beverages, including table cream and chocolate, was assessed by 25 TTs and 19 TnTs. Ratings of oral sensation intensity and overall liking were obtained using gVAS and gDOL scales, respectively. TTs and TnTs did not differ significantly in intensity ratings for most stimuli (ANOVA). In a 2nd study, 44 female participants sampled 22 foods and beverages, assessing them for intensity of oral sensations (gVAS) and overall liking (9-point hedonic scale). TTs (n=23) rated their overall liking of creaminess and milk products lower than did TnTs (n=21), and liked milk chocolate less. PROP responsiveness was negatively correlated with liking of food and beverages belonging to the sweet or sensory food grouping. No other differences in intensity or liking scores between hyper- and hypo-tasters were found. Taken overall, our results are somewhat unexpected, lending only modest support to the hypothesis that these taste phenotypes associate with energy-dense food liking and consumption through differences in the oral sensations they elicit. Reasons for this lack of concordance with expectations and some prior literature are discussed, and suggestions for future research are advanced.

Keywords: taste phenotypes, sensory evaluation, PROP, thermal tasting, diet-related health risk

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Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

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Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

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Authors: Evgenia Iakovleva, Juha Koivisto, Pasi Karppinen, J. Inkinen, Mikko Alava

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Preventing the spread of infectious diseases throughout the worldwide is one of the most important tasks of modern health care. Infectious diseases not only account for one fifth of the deaths in the world, but also cause many pathological complications for the human health. Touch surfaces pose an important vector for the spread of infections by varying microorganisms, including antimicrobial resistant organisms. Further, antimicrobial resistance is reply of bacteria to the overused or inappropriate used of antibiotics everywhere. The biggest challenges in bacterial detection by existing methods are non-direct determination, long time of analysis, the sample preparation, use of chemicals and expensive equipment, and availability of qualified specialists. Therefore, a high-performance, rapid, real-time detection is demanded in rapid practical bacterial detection and to control the epidemiological hazard. Among the known methods for determining bacteria on the surfaces, Hyperspectral methods can be used as direct and rapid methods for microorganism detection on different kind of surfaces based on fluorescence without sampling, sample preparation and chemicals. The aim of this study was to assess the relevance of such systems to remote sensing of surfaces for microorganisms detection to prevent a global spread of infectious diseases. Bacillus subtilis and Escherichia coli with different concentrations (from 0 to 10x8 cell/100µL) were detected with hyperspectral camera using different filters as visible visualization of bacteria and background spots on the steel plate. A method of internal standards was applied for monitoring the correctness of the analysis results. Distances from sample to hyperspectral camera and light source are 25 cm and 40 cm, respectively. Each sample is optically imaged from the surface by hyperspectral imaging system, utilizing a JAI CM-140GE-UV camera. Light source is BeamZ FLATPAR DMX Tri-light, 3W tri-colour LEDs (red, blue and green). Light colors are changed through DMX USB Pro interface. The developed system was calibrated following a standard procedure of setting exposure and focused for light with λ=525 nm. The filter is ThorLabs KuriousTM hyperspectral filter controller with wavelengths from 420 to 720 nm. All data collection, pro-processing and multivariate analysis was performed using LabVIEW and Python software. The studied human eye visible and invisible bacterial stains clustered apart from a reference steel material by clustering analysis using different light sources and filter wavelengths. The calculation of random and systematic errors of the analysis results proved the applicability of the method in real conditions. Validation experiments have been carried out with photometry and ATP swab-test. The lower detection limit of developed method is several orders of magnitude lower than for both validation methods. All parameters of the experiments were the same, except for the light. Hyperspectral imaging method allows to separate not only bacteria and surfaces, but also different types of bacteria, such as Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. Developed method allows skipping the sample preparation and the use of chemicals, unlike all other microbiological methods. The time of analysis with novel hyperspectral system is a few seconds, which is innovative in the field of microbiological tests.

Keywords: Escherichia coli, Bacillus subtilis, hyperspectral imaging, microorganisms detection

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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: Supriya Ambawat, Subaran Singh, C. Tara Satyavathi, B. S. Rajpurohit, Ummed Singh, Balraj Singh

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Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important staple food of the arid and semiarid tropical regions of Asia, Africa, and Latin America. It is rightly termed as nutricereal as it has high nutrition value and a good source of carbohydrate, protein, fat, ash, dietary fiber, potassium, magnesium, iron, zinc, etc. Pearl millet has low prolamine fraction and is gluten free which is useful for people having a gluten allergy. It has several health benefits like reduction in blood pressure, thyroid, diabe¬tes, cardiovascular and celiac diseases but its direct consumption as food has significantly declined due to several reasons. Keeping this in view, it is important to reorient the ef¬forts to generate demand through value-addition and quality improvement and create awareness on the nutritional merits of pearl millet. In India, through Indian Council of Agricultural Research-All India Coordinated Research Project on Pearl millet, multilocational coordinated trials for developed hybrids were conducted at various centers. The gene banks of pearl millet contain varieties with high levels of iron and zinc which were used to produce new pearl millet varieties with elevated iron levels bred with the high‐yielding varieties. Thus, using breeding approaches and biochemical analysis, a total of 167 hybrids and 61 varieties were identified and released for cultivation in different agro-ecological zones of the country which also includes some biofortified hybrids rich in Fe and Zn. Further, using several biotechnological interventions such as molecular markers, next-generation sequencing (NGS), association mapping, nested association mapping (NAM), MAGIC populations, genome editing, genotyping by sequencing (GBS), genome wide association studies (GWAS) advancement in millet improvement has become possible by identifying and tagging of genes underlying a trait in the genome. Using DArT markers very high density linkage maps were constructed for pearl millet. Improved HHB67 has been released using marker assisted selection (MAS) strategies, and genomic tools were used to identify Fe-Zn Quantitative Trait Loci (QTL). The draft genome sequence of millet has also opened various ways to explore pearl millet. Further, genomic positions of significantly associated simple sequence repeat (SSR) markers with iron and zinc content in the consensus map is being identified and research is in progress towards mapping QTLs for flour rancidity. The sequence information is being used to explore genes and enzymatic pathways responsible for rancidity of flour. Thus, development and application of several biotechnological approaches along with biofortification can accelerate the genetic gain targets for pearl millet improvement and help improve its quality.

Keywords: Biotechnological approaches, genomic tools, malnutrition, MAS, nutricereal, pearl millet, sequencing.

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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: 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: 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: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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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: Nourhan Hussein Fanaki, Hoda Mohamed Gamal El-Din Omar, Nihal Kadry Moussa, Eva Adel Edward Farid

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The resistance of staphylococci to various antibiotics has become a major concern for health care professionals. The efficacy of the combinations of selected glycopeptides (vancomycin and teicoplanin) with gentamicin or rifampicin, as well as that of gentamicin/rifampicin combination, was studied against selected pathogenic staphylococcus isolated from Egypt. The molecular distribution of genes conferring resistance to these four antibiotics was detected among tested clinical isolates. Antibiotic combinations were studied using the checkerboard technique and the time-kill assay (in both the stationary and log phases). Induction of resistance to glycopeptides in staphylococci was tried in the absence and presence of diclofenac sodium as inducer. Transmission electron microscopy was used to study the effect of glycopeptides on the ultrastructure of the cell wall of staphylococci. Attempts were made to cure gentamicin resistance plasmids and to study the transfer of these plasmids by conjugation. Trials for the transformation of the successfully isolated gentamicin resistance plasmid to competent cells were carried out. The detection of genes conferring resistance to the tested antibiotics was performed using the polymerase chain reaction. The studied antibiotic combinations proved their efficacy, especially when tested during the log phase. Induction of resistance to glycopeptides in staphylococci was more promising in presence of diclofenac sodium, compared to its absence. Transmission electron microscopy revealed the thickening of bacterial cell wall in staphylococcus clinical isolates due to the presence of tested glycopeptides. Curing of gentamicin resistance plasmids was only successful in 2 out of 9 tested isolates, with a curing rate of 1 percent for each. Both isolates, when used as donors in conjugation experiments, yielded promising conjugation frequencies ranging between 5.4 X 10-2 and 7.48 X 10-2 colony forming unit/donor cells. Plasmid isolation was only successful in one out of the two tested isolates. However, low transformation efficiency (59.7 transformants/microgram plasmid DNA) of such plasmids was obtained. Negative regulators of autolysis, such as arlR, lytR and lrgB, as well as cell-wall associated genes, such as pbp4 and/or pbp2, were detected in staphylococcus isolates with reduced susceptibility to the tested glycopeptides. Concerning rifampicin resistance genes, rpoBstaph was detected in 75 percent of the tested staphylococcus isolates. It could be concluded that in vitro studies emphasized the usefulness of the combination of vancomycin or teicoplanin with gentamicin or rifampicin, as well as that of gentamicin with rifampicin, against staphylococci showing varying resistance patterns. However, further in vivo studies are required to ensure the safety and efficacy of such combinations. Diclofenac sodium can act as an inducer of resistance to glycopeptides in staphylococci. Cell-wall thickness is a major contributor to such resistance among them. Gentamicin resistance in these strains could be chromosomally or plasmid mediated. Multiple mutations in the rpoB gene could mediate staphylococcus resistance to rifampicin.

Keywords: glycopeptides, combinations, induction, diclofenac, transmission electron microscopy, polymerase chain reaction

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Authors: L. Abubakar, B. M. Sokoto, I. U. Mohammed, M. S. Na’allah, A. Mohammad, A. N. Garba, T. S. Bubuche

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Onion (Allium cepa var. cepa L.) is the most important species of the Allium group belonging to family Alliaceae and genus Allium. It can be regarded as the single important vegetable species in the world after tomatoes. Despite the similarities, which bring the species together, the genus is a strikingly diverse one, with more than five hundred species, which are perennial and mostly bulbous plants. Out of these, only seven species are in cultivation, and five are the most important species of the cultivated Allium. However, Allium cepa (onion) and Allium sativum (Garlic) are the two major cultivated species grown all over the world of which the onion crop is the most important. North Western Nigeria (Sokoto, Kebbi and Zamfara States) constitute the major onion producing zone in Nigeria, which is primarily during the dry season. However, onion production in the zone is seriously affected by two main factors i.e. diseases and storage losses, in addition to other constraints that limits the cultivation of the crop during the rainy season which include lack of prolonged rainy season to allow for proper maturation of the crop. The major onion disease in this zone is purple blotch caused by a fungus Alternaria porri and currently efforts are on to develop onion hybrids resistant to the disease. Genetic diversity plays an important role in plant breeding either to exploit heterosis or to generate productive recombinants. Assessment of a large number of genotypes for a genetic diversity is the first step in this direction. The objective of this research therefore is to evaluate the genetic potentials of the onion cultivars of North Western Nigeria, with a view of developing new cultivars that address the major production challenges to onion cultivation in North Western, Nigeria. Thirteen onion cultivars were collected during an expedition covering North western Nigeria and Southern part of Niger Republic during 2013, which are areas noted for onion production. The cultivars were evaluated at two locations; Sokoto, in Sokoto State and Jega in Kebbi State all in Nigeria during the 2013/14 onion season (dry season) under irrigation. The objective of the research was to determine the genetic potentials of onion cultivars of north western Nigeria as a basis for breeding purposes. Combined analysis of the results revealed highly significant variation between the cultivars across the locations with respect to plant height, number of leaves/plant, bolting %, bulb height, bulb weight, mean bulb yield and cured bulb weight, with significant variation in terms of bulb diameter. Tasa from Warra Local Government Area of Kebbi State (V4) recorded the greatest mean fresh bulb yield with Jar Albasa (V8) from Illela Local Government Area of Sokoto State recording the least. Similarly Marsa (V5) from Silame Local Government Area recorded the greatest mean cured bulb yield (marketable bulb)with Kiba (V11) from Goronyo Local Government of Sokoto State recording the least. Significant variation was recorded between the locations with respect to all characters, with Sokoto being better in terms of plant height, number of leaves/plant, bolting % and bulb diameter. Jega was better in terms of bulb height, bulb yield and cured bulb weight. Significant variation was therefore observed between the cultivars.

Keywords: evaluation, genetic, onions, North Western Nigeria

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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: 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: 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: Zakia Hbellaq

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The Mediterranean region is considered a hotbed for climate change. Morocco is a semi-arid Mediterranean country facing water shortages and poor water quality. Its limited water resources limit the activities of various economic sectors. Most of Morocco's territory is in arid and desert areas. The potential water resources are estimated at 22 billion m3, which is equivalent to about 700 m3/inhabitant/year, and Morocco is in a state of structural water stress. Strictly speaking, the Kingdom of Morocco is one of the “very riskiest” countries, according to the World Resources Institute (WRI), which oversees the calculation of water stress risk in 167 countries. The surprising results of the Institute (WRI) rank Morocco as one of the riskiest countries in terms of water scarcity, ranking 3.89 out of 5, thus occupying the 23rd place out of a total of 167 countries, which indicates that the demand for water exceeds the available resources. Agriculture with a score of 3.89 is most affected by water stress from irrigation and places a heavy burden on the water table. Irrigation is an unavoidable technical need and has undeniable economic and social benefits given the available resources and climatic conditions. Irrigation, and therefore the agricultural sector, currently uses 86% of its water resources, while industry uses 5.5%. Although its development has undeniable economic and social benefits, it also contributes to the overfishing of most groundwater resources and the surprising decline in levels and deterioration of water quality in some aquifers. In this context, REUSE is one of the proposed solutions to reduce the water footprint of the agricultural sector and alleviate the shortage of water resources. Indeed, wastewater reuse, also known as REUSE (reuse of treated wastewater), is a step forward not only for the circular economy but also for the future, especially in the context of climate change. In particular, water reuse provides an alternative to existing water supplies and can be used to improve water security, sustainability, and resilience. However, given the introduction of organic trace pollutants or, organic micro-pollutants, the absorption of emerging contaminants, and decreasing salinity, it is possible to tackle innovative capabilities to overcome these problems and ensure food and health safety. To this end, attention will be paid to the adoption of an integrated and attractive approach, based on the reinforcement and optimization of the treatments proposed for the elimination of the organic load with particular attention to the elimination of emerging pollutants, to achieve this goal. , membrane bioreactors (MBR) as stand-alone technologies are not able to meet the requirements of WHO guidelines. They will be combined with heterogeneous Fenton processes using persulfate or hydrogen peroxide oxidants. Similarly, adsorption and filtration are applied as tertiary treatment In addition, the evaluation of crop performance in terms of yield, productivity, quality, and safety, through the optimization of Trichoderma sp strains that will be used to increase crop resistance to abiotic stresses, as well as the use of modern omics tools such as transcriptomic analysis using RNA sequencing and methylation to identify adaptive traits and associated genetic diversity that is tolerant/resistant/resilient to biotic and abiotic stresses. Hence, ensuring this approach will undoubtedly alleviate water scarcity and, likewise, increase the negative and harmful impact of wastewater irrigation on the condition of crops and the health of their consumers.

Keywords: water scarcity, food security, irrigation, agricultural water footprint, reuse, emerging contaminants

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

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

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: 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

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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: Robert Miller, Fred Soltero, Sandra Allan, Denise Bonilla

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The Tropical Bont Tick (TBT), Amblyomma variegatum, was introduced to the Caribbean in the mid-1700s. Since it has spread throughout the Caribbean dispersed by cattle egrets (Bubulcus ibis). Tropical Bont Ticks vector many pathogens to livestock and humans. However, only the livestock diseases heartwater, Ehrlichia (Cowdria) ruminantium, and dermatophilosis, Dermatophilus congolensis, are associated with TBT in the Caribbean. African tick bite fever (Rickettsia africae) is widespread in Caribbean TBT but human cases are rare. The Caribbean Amblyomma Programme (CAP) was an effort led by the Food and Agricultural Organization to eradicate TBTs from participating islands. This 10-year effort successfully eradicated TBT from many islands. However, most are reinfested since its termination. Pheromone technology has been developed to aid in TBT control. Although not part of the CAP treatment scheme, this research established that pheromones in combination with pesticide greatly improves treatment efficiencies. Additionally, pheromone combined with CO₂ traps greatly improves active surveillance success. St. Croix has a history of TBT outbreaks. Passive surveillance detected outbreaks in 2016 and in May of 2021. Surveillance efforts are underway to determine the extent of TBT on St Croix. Puerto Rico is the next island in the archipelago and is at a greater risk of re-infestation due to active outbreaks in St Croix. Tropical Bont Ticks were last detected in Puerto Rico in the 1980s. The infestation started on the small Puerto Rican island of Vieques, the closest landmass to St Croix, and spread to the main island through cattle movements. This infestation was eradicated with the help of the Tropical Cattle Tick (TCT), Rhipicephalus (Boophilus) microplus, eradication program. At the time, large percentages of Puerto Rican cattle were treated for ticks along with the necessary material and manpower mobilized for the effort. Therefore, a shift of focus from the TCT to TBT prevented its establishment in Puerto Rico. Currently, no large-scale treatment of TCTs occurs in Puerto Rico. Therefore, the risk of TBT establishment is now greater than it was in the 1980s. From Puerto Rico, the risk of TBT movement to the American continent increases significantly. The establishment of TBTs in the Americas would cause $1.2 billion USD in losses to the livestock industry per year. The USDA Agricultural Research Service recently worked with the USDA Animal Health Inspection Service and the Puerto Rican Department of Agriculture to modernize the management of the TCT. This modernized program uses safer pesticides and has successfully been used to eradicate pesticide-susceptible and -resistant ticks throughout the island. The objective of this work is to prevent the infestation of Puerto Rico by TBTs by combining the current TCT management efforts with TBT surveillance in Vieques. The combined effort is designed to eradicate TCT from Vieques while using the treated cattle as trap animals for TBT using pheromone impregnated tail tags attached to treated animals. Additionally, active surveillance using CO₂-baited traps combined with pheromone will be used to actively survey the environment for free-living TBT. Knowledge gained will inform TBT control efforts in St. Croix.

Keywords: Amblyomma variegatum, caribbean, eradication, Rhipicephalus (boophilus) microplus, pheromone

Procedia PDF Downloads 150

Authors: Mohamed Elmogbail

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The present study aimed at investigating difficulties those Translators encounter in understanding idiomatic expressions between Arabic and English languages. To achieve this goal, the researcher raised the three questions are:(1) What are the major difficulties that translators encounter in translating idiomatic expressions? (2) What factors cause such difficulties that translators encountered in translating idiomatic expressions? (3) What are the possible techniques that should be followed to overcome these difficulties? To answer these questions, the researcher designed questionnaire Table (2) and mentioned tables related to Test Show the second question in the study is about the factors that stand behind the challenges. Translators encounter while translating idiomatic expressions. The translators asked Provided the following factors:1- Because of lack of exposure to the source culture, they do not know the connotations of the cultural words that are related to the environment, food, folklore 2- Misusing dictionaries made the participants unable to find a proper target language idiomatic expression. 3-Lack of using idiomatic expressions in daily life. Table (3): (Questionnaire) Results to the table (3) Questions Of the study are About suggestions that can be inferred to handle these challenges. The questioned translators provided the following solutions:1- translators must be exposed to source language culture, including religion, habits, and traditions.2- translators should also be exposed to source language idiomatic expressions by introducing English culture in textbooks and through participating in extensive English culture courses.3- translators should be familiar with the differences between source and target language cultures.4- translators should avoid literal translation that results in most cases in wrong or poor translation.5- Schools, universities, and institutions should introduce translators to English culture.6- translators should participate in cultural workshops at universities.7- translators should try to use idiomatic expressions in everyday situations.8- translators should read more idiomatic expressions books. And researcher also designed a translation test consisted of 40 excerpts given to a random sample of 100 Translators in Khartoum capital of Sudan to translate them. After Collected data for the study, the researcher proceeded to a more detailed analysis, the methodology used in the analysis of idiomatic expressions Is empirical and descriptive. This study is qualitative by nature, but the quantitative method used the analysis of the data. Some figure and statistics are used, such as (statistical package for the social sciences). The researcher calculated the percentage proportion of each translation expressions. And compared them to each other. The finding of the study showed that most translations are inadequate as the translators faced difficulties while communication, these difficulties were mostly due to their unfamiliarity with idiomatic expressions producing improper equivalence in the communication, and not being able to use translation techniques as required, and resorted to literal translation, furthermore, the study recommended that more comprehensive studies to executed on translating idiomatic expressions to enrich the translation field.

Keywords: translation, translators, idioms., expressions

Procedia PDF Downloads 126

Authors: Ana Paula Almeida Castaldelli Maciel, Gabriela Medeiros, Amanda de Souza Machado, Maria Clara Pilatti, Ralpho Rinaldo dos Reis, Silvio Cesar Sampaio

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Sustainable agricultural systems are crucial to ensuring global food security and the long-term production of nutritious food. Comprehensive soil and water management practices, including nutrient management, balanced fertilizer use, and appropriate waste management, are essential for sustainable agriculture. Swine wastewater (SWW) treatment has become a significant focus due to environmental concerns related to heavy metals, antibiotics, resistant pathogens, and nutrients. In South America, small farms use soil to dispose of animal waste, a practice that is expected to increase with global pork production. The potential of SWW as a nutrient source is promising, contributing to global food security, nutrient cycling, and mineral fertilizer reduction. Short- and long-term studies evaluated the effects of SWW on soil and plant parameters, such as nutrients, heavy metals, organic matter (OM), cation exchange capacity (CEC), and pH. Although promising results have been observed in short- and medium-term applications, long-term applications require more attention due to heavy metal concentrations. Organic soil amendment strategies, due to their economic and ecological benefits, are commonly used to reduce the bioavailability of heavy metals. However, the rate of degradation and initial levels of OM must be monitored to avoid changes in soil pH and release of metals. The study aimed to evaluate the long-term effects of SWW application on soil fertility parameters, focusing on calcium (Ca), magnesium (Mg), and potassium (K), in addition to CEC and OM. Experiments were conducted at the Universidade Estadual do Oeste do Paraná, Brazil, using 24 drainage lysimeters for nine years, with different application rates of SWW and mineral fertilization. Principal Component Analysis (PCA) was then conducted to summarize the composite variables, known as principal components (PC), and limit the dimensionality to be evaluated. The retained PCs were then correlated with the original variables to identify the level of association between each variable and each PC. Data were interpreted using Analysis of Variance - ANOVA for general linear models (GLM). As OM was not measured in the 2007 soybean experiment, it was assessed separately from PCA to avoid loss of information. PCA and ANOVA indicated that crop type, SWW, and mineral fertilization significantly influenced soil nutrient levels. Soybeans presented higher concentrations of Ca, Mg, and CEC. The application of SWW influenced K levels, with higher concentrations observed in SWW from biodigesters and higher doses of swine manure. Variability in nutrient concentrations in SWW due to factors such as animal age and feed composition makes standard recommendations challenging. OM levels increased in SWW-treated soils, improving soil fertility and structure. In conclusion, the application of SWW can increase soil fertility and crop productivity, reducing environmental risks. However, careful management and long-term monitoring are essential to optimize benefits and minimize adverse effects.

Keywords: contamination, water research, biodigester, nutrients

Procedia PDF Downloads 31

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

Procedia PDF Downloads 138

Authors: Milica Lilic, Marina Rosales Martínez

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Academic research cannot be oblivious to social problems and needs, so projects that have the capacity for transformation and impact should have the opportunity to go beyond the University circles and bring benefit to society. Apart from patents and R&D research contracts, this opportunity can be achieved through entrepreneurship as one of the most direct tools to turn knowledge into a tangible product. Thus, as an example of good practices, it is intended to analyze the case of an institutional entrepreneurship program carried out at the University of Seville, aimed at researchers interested in assessing the business opportunity of their research and expanding their knowledge on procedures for the commercialization of technologies used at academic projects. The program is based on three pillars: training, teamwork sessions and networking. The training includes aspects such as product-client fit, technical-scientific and economic-financial feasibility of a spin-off, institutional organization and decision making, public and private fundraising, and making the spin-off visible in the business world (social networks, key contacts, corporate image and ethical principles). On the other hand, the teamwork sessions are guided by a mentor and aimed at identifying research results with potential, clarifying financial needs and procedures to obtain the necessary resources for the consolidation of the spin-off. This part of the program is considered to be crucial in order for the participants to convert their academic findings into a business model. Finally, the networking part is oriented to workshops about the digital transformation of a project, the accurate communication of the product or service a spin-off offers to society and the development of transferable skills necessary for managing a business. This blended program results in the final stage where each team, through an elevator pitch format, presents their research turned into a business model to an experienced jury. The awarded teams get a starting capital for their enterprise and enjoy the opportunity of formally consolidating their spin-off company at the University. Studying the results of the program, it has been shown that many researchers have basic or no knowledge of entrepreneurship skills and different ways to turn their research results into a business model with a direct impact on society. Therefore, the described program has been used as an example to highlight the importance of knowledge transfer at the University and the role that this institution should have in providing the tools to promote entrepreneurship within it. Keeping in mind that the University is defined by three main activities (teaching, research and knowledge transfer), it is safe to conclude that the latter, and the entrepreneurship as an expression of it, is crucial in order for the other two to comply with their purpose.

Keywords: good practice, knowledge transfer, a spin-off company, university

Procedia PDF Downloads 120

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

Procedia PDF Downloads 329