Search results for: wastewater treatment plant

Authors: Nantale Prossy Nabatte, Josephat Nyagero, Elizabeth Kemigisha

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Background: Human Papilloma Virus (HPV) is a prevalent sexually transmitted infection (STI) in the world. It is important to screen for HPV so that women found positive receive early treatment to prevent the development of cervical cancer. The broad aim of the research was to explore the types, occurrence, and associated correlates of HPV infection by genotyping Human papillomavirus among a cohort of WLHIV attending an antiretroviral therapy clinic in Mukono, Uganda. Methods: A cross-sectional study was used to collect data for socio-demographic, sexual practices, and medical history factors associated with HPV genotypes using a pretested interview guide subjected to 342 WLHIV. The respondents’ results for HPV genotypes were obtained retrospectively from respective laboratory records. Data was entered in Epidata v4.6 and analysed using STATA V14. The prevalence of hr-HPV was estimated as a proportion of the entire sample size. Analysis for the correlates of hr-HPV infection was done using a modified Poisson regression model. Results: Slightly more than a half of respondents were aged below 35 years (56.7%), married (52.6%), and with a primary level of education (51.2%). The prevalence of hr-HPV was 39.8% at a 95% confidence interval (CI: 34.40- 44.78). The hr-HPV was higher among those between 30-34 years of age (n= 41, 30.2%) than those between the age of 45-49 years (n=16, 11.8%). In terms of associated correlates, age 45-49 years (aPR: 1.95, 95% CI: 1.41- 2.69), being married (aPR: 1.30, 95% CI: 1.00, 1.69), use of condoms (aPR: 1.31, 95% CI: 1.00 -1.71) and age of sexual debut (aPR: 1.42, 95% CI: 1.08-1.87) were significantly associated with Human papillomavirus genotypes. Conclusion and Recommendation: The prevalence of hr-HPV infection was high, indicative of a risk to the health of WLHIV in Mukono, Uganda, and worldwide at large. The correlates are age 45-49 years, being married, use of condoms, and age of sexual debut. Based on the results, it is recommended that the implementing teams in such projects put more emphasis on the diagnosis of hr-HPV infection and monitoring the treatment. More research is required to determine the effect of ART therapy on hr-HPV persistence.

Keywords: human papillomavirus genotypes, and their correlates, among women living with HIV, attending antiretroviral clinic

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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Authors: Brahmanage S. Rangika, Dinithi C. Peiris

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Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

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Authors: Iris Xiaohong Quan, Sharon Qi, Kelly Tianqin Shi

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This study focuses on the critical role of insurance policies in a world grappling with increasing mental health challenges, as they significantly influence the dynamics of healthcare businesses and entrepreneurial ventures. The paper utilizes the mental health sector as a case to examine the impact of insurance policies on healthcare service providers, entrepreneurs, and individuals seeking mental health support. This paper addressed the following research questions: To what extent do changes in insurance reimbursement policies affect the accessibility and affordability of mental health services for patients, and how does this impact the overall demand for such services? What are the barriers and opportunities that mental health entrepreneurs face and what strategies and adaptations do mental health businesses employ when navigating the evolving landscape of insurance reimbursement policies? How do changes in insurance reimbursement policies, specifically related to mental health services, influence the financial viability and sustainability of mental health clinics and private practices? Employing a self-designed survey aimed at autism spectrum disorder (ASD) treatment companies, alongside two in-depth case studies and an analysis of pertinent insurance policies and documents, this research aims to elucidate the multifaceted influence of insurance policies on the mental health industry. The findings from this study reveal how insurance policies shape the landscape of mental health businesses and their operations. A total of 821 autism treatment organizations or offices were contacted by telephone between November 1, 2019, and January 31, 2020. About half of the offices (53.33%) were established in the past five years, and 80% were established in the past 15 years. There is a significant increase in the establishment of ABA service centers in the recent two decades as a result of autism insurance reform, the increasing social awareness of ASD, and the redefinition of autism. In addition, almost half of the ABA service providers we surveyed had a patient size ranging from 20 to 50 in the year when the residence state passed the legislation for autism insurance coverage. On average, an ABA service provider works with 5.3 insurance companies. This research find that insurance is the main source of revenue for most ABA service providers. However, our survey reveals that clients’ out of pocket payment has been the second main revenue sources. Despite the changes of regulations and insurance policies in all states, clients still have to pay a fraction of, if not all, the ABA treatment service fees out of pocket. This research shows that some ABA service providers seek federal and government funds and grants to support their services and businesses. Our further analysis with the in-depth case studies and other secondary data also indicate the rise of entrepreneurial startups in the mental health industry. Overall, this research sheds light on both the challenges and opportunities presented by insurance policies in the mental health sector, offering insights into the new industry landscape.

Keywords: entrepreneurship, healthcare policy, insurance policy, mental health industry

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Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

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Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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Authors: Ozan Kahraman, Hao Feng

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Several models such as Weibull, Modified Gompertz, Biphasic linear, and Log-logistic models have been proposed in order to describe non-linear inactivation kinetics and used to fit non-linear inactivation data of several microorganisms for inactivation by heat, high pressure processing or pulsed electric field. First-order kinetic parameters (D-values and z-values) have often been used in order to identify microbial inactivation by non-thermal processing methods such as ultrasound. Most ultrasonic inactivation studies employed first-order kinetic parameters (D-values and z-values) in order to describe the reduction on microbial survival count. This study was conducted to analyze the E. coli O157:H7 inactivation data by using five microbial survival models (First-order, Weibull, Modified Gompertz, Biphasic linear and Log-logistic). First-order, Weibull, Modified Gompertz, Biphasic linear and Log-logistic kinetic models were used for fitting inactivation curves of Escherichia coli O157:H7. The residual sum of squares and the total sum of squares criteria were used to evaluate the models. The statistical indices of the kinetic models were used to fit inactivation data for E. coli O157:H7 by MTS at three temperatures (40, 50, and 60 0C) and three pressures (100, 200, and 300 kPa). Based on the statistical indices and visual observations, the Weibull and Biphasic models were best fitting of the data for MTS treatment as shown by high R2 values. The non-linear kinetic models, including the Modified Gompertz, First-order, and Log-logistic models did not provide any better fit to data from MTS compared the Weibull and Biphasic models. It was observed that the data found in this study did not follow the first-order kinetics. It is possibly because of the cells which are sensitive to ultrasound treatment were inactivated first, resulting in a fast inactivation period, while those resistant to ultrasound were killed slowly. The Weibull and biphasic models were found as more flexible in order to determine the survival curves of E. coli O157:H7 treated by MTS on apple-carrot juice.

Keywords: Weibull, Biphasic, MTS, kinetic models, E.coli O157:H7

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Authors: Emine Aydin, Duygu Gocmen

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In this study, pumpkin flours (PFs) were used to replace wheat flour in cookie formulation at three different levels (10%, 20% and 30% w/w). For this purpose PFs produced by two different applications (with or without metabisulfite pre-treatment) and then dried in freeze dryer. Control sample included no PFs. The total phenolic contents of the cookies supplemented with PFs were higher than that of control and gradually increased in total phenolic contents of cookies with increasing PF supplementation levels. Phenolic content makes also significant contribution on nutritional excellence of the developed cookies. Pre-treatment with metabisulfite (MS) had a positive effect on free, bound and total phenolics of cookies which are supplemented with various levels of MS-PF. This is due to a protective effect of metabisulfite pretreatment for phenolic compounds in the pumpkin flour. Phenolic antioxidants may act and absorb in a different way in humans and thus their antioxidant and health effects will be changed accordingly. In the present study phenolics’ bioavailability of cookies was investigated in order to assess PF as sources of accessible phenolics. The content of bioaccessible phenolics and phenolic bioaccessibility of cookies supplemented with PFs had higher than those of control sample. Cookies enriched with 30% MS-PF had the highest bioaccessible phenolics (597.86 mg GAE 100g-1) and phenolic bioaccessibility (41.71%). MS application in PF production caused a significant increase in phenolic bioaccessibility of cookies. According to all assay (ABTS, CUPRAC, FRAP and DPPH), antioxidant activities of cookies with PFs higher than that of control cookie. It was also observed that the cookies supplemented with MS-PF had significantly higher antioxidant activities than those of cookies including PF. In presented study, antioxidative bioaccessibilities of cookies were also determined. The cookies with PFs had significantly (p ≤ 0.05) higher antioxidative bioaccessibilities than control ones. Increasing PFs levels enhanced antioxidative bioaccessibilities of cookies. As a result, PFs addition improved the nutritional and functional properties of cookie by causing increase in antioxidant activity, total phenolic content, bioaccessible phenolics and phenolic bioaccessibilities.

Keywords: phenolic compounds, antioxidant activity, dietary fiber, pumpkin, freeze drying, cookie

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Authors: Amir Hamzeh Haghiabi

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Water resource management is of global significance as it plays a key role in the socioeconomic development of all nations. On account of the fact that Iran is situated in a highly pressurized belt in the world, precipitation is limited, so that the average annual precipitation in the country is about 250 mm, only about one third to one quarter of the world average for rainfall. Karkheh basin is located in the semiarid and arid regions of Western Iran, an area with severe water scarcity. 70 % of rainfall is directly evaporated. The potential annual evaporation of the southern and northern regions is 3,600 mm 1,800 mm, respectively. In this paper, Some aspects of water resources management for this region, the specifications of the Karkheh reservoir dam & hydroelectric power plant as the biggest dam in history of Iran with total volume of reservoir 7.3 Bm3 are illustrated. Also the situation of water availability in the basin, surface and groundwater potential are considered.

Keywords: Iran, water availability, water resources, Zagros

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Authors: Luphumlo Ncanywa, Paul Watts

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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.

Keywords: antimalarial, flow, lumefantrine, synthesis

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Authors: Sunny Arora, Meghal A. Desai

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An impetus towards green consumerism and implementation of sustainable techniques, consumption of natural products and utilization of environment friendly techniques have gained accelerated acceptance. Butein, a natural colorant, has many medicinal properties apart from its use in dyeing industries. Extraction of butein from the flowers of flame of forest was carried out using ultrasonication bath. Solid loading (2-6 g), extraction time (30-50 min), volume of solvent (30-50 mL) and types of solvent (methanol, ethanol and water) have been studied to maximize the yield of butein using the Taguchi method. The highest yield of butein 4.67% (w/w) was obtained using 4 g of plant material, 40 min of extraction time and 30 mL volume of methanol as a solvent. The present method provided a greater reduction in extraction time compared to the conventional method of extraction. Hence, the outcome of the present investigation could further be utilized to develop the method at a higher scale.

Keywords: butein, flowers of Flame of the Forest, Taguchi method, ultrasonic bath

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Authors: Nurcan Cetinkaya

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The aim of this paper is to bring about the utilization of Juncus acutus as an alternative roughage resource in ruminant nutrition. In Turkey, JA is prevailing plant of the natural grassland in Kizilirmak Delta, Samsun. Crude nutrient values such as crude protein (CP), ether extract (EE), organic matter (OM), neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin(ADL) including antioxidant activity, total phenolic and flavonoid compounds, total organic matter digestibility (OMD) and metabolisable energy (ME) values of Juncus acutus stem, seed, and also its mixture with maize silage were estimated. and published. Furthermore, the effects of JA over rumen cellulolitic bacteria were studied. The obtained results from different studies conducted on JA by our team show that Juncus acutus may be a new roughage source in ruminant nutrition.

Keywords: antioxidant activity, cellulolytic bacteria, Juncus acutus, organic matter digestibility

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: A. Sainvil, J. Mallela, L. M. Pereira

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Adolescents and young adults (AYA) diagnosed with cancer are tasked with managing their health through treatment, a time when reliance on and independence from parents may change in unexpected ways. Resilience allows patients to cope and manage their own health through treatment, promoting motivation and a healthier lifestyle. The film acts as a source of reflection through the cancer journey, which may have an impact on how patients cope. The current research investigated relationships between resilient linguistic qualities of the video narratives and attitudes toward personal health management. N=24 patients diagnosed between ages 11-18 were recruited. First, participants provided demographic information, then made a video testimonial about their cancer experience. After filming, participants then completed a questionnaire on the perceived benefits for themselves and others for making the video. Videos were transcribed and analyzed for thematic content via codebook and for linguistic qualities, indicating resilience with the use of the Linguistic Inquiry and Word Count Analysis Program (LIWC). Linear regressions were then calculated to explore relationships between resilient qualities, thematic content, and participants’ perceptions of their medical team and willingness to care for themselves. Participants who spoke with greater narrator connectedness were more likely to change their view of their medical team (β=.628 p=.034). When a participant believed that providers were likely to view their video, they were marginally more likely to want to take better care of themselves (β=.367, p=.078). Participants who spoke in depth about their health reported higher intention to take better care of themselves (β=.785, p=.033). AYAs with cancer who showcased certain resilient qualities within their narrative were more likely to consider taking better care of themselves. Additionally, the more patients reflected on their health, the more they wanted to take better care of themselves. These relationships were stronger when a patient believed that a provider would watch their video. Study findings highlight the utility of film in uncovering aspects of resilience and coping that may lead to healthier behaviors in AYAs with cancer.

Keywords: adolescents, cancer, resilience, health management

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Authors: Hawraa Zbeeb, Hala Khalifeh, Mohamad Khalil, Francesca Storace, Francesca Baldini, Giulio Lupidi, Laura Vergani

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Sarcopoterium spinosum, a widely distributed spiny shrub belonging to the Rosaceae family, is rich in essential and beneficial constituents. In fact, S. spinosum fruits and roots are traditionally used as herbal medicine in the eastern Mediterranean landscape, and this shrub is mentioned as a medicinal plant in a large number of ethnobotanical surveys. Aqueous root extracts from S. spinosum are used by traditional medicinal practitioners for weight loss treatment of diabetes and pain. Moreover, the anti-diabetic activity of S. spinosum root extract has been reported in different studies, but the beneficial effects of aerial parts, especially fruits, have not been elucidated yet. The aim of the present study was to investigate the in vitro antioxidant and lipid-lowering properties of an ethanolic extract from S. spinosum fruits using both hepatic (FaO) and endothelial (HECV) cells in an attempt to evaluate its possible employment as a nutraceutical supplement. First of all, in vitro spectrophotometric assays were employed to characterize the extract. The total phenol content (TPC) was evaluated by Folin–Ciocalteu spectrophotometric method and the radical scavenging activity was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. After that, the beneficial effects of the extract were tested on cells. FaO cells treated for 3 hours with 0.75 mM oleate/palmitate mix (1:2 molar ratio) mimic in vitro a moderate hepato-steatosis. HECV cells exposed for 1 hour to 100 µM H₂O₂ mimic an oxidative insult leading to oxidative stress conditions. After the metabolic and oxidative insult, both cell lines were treated with increasing concentrations of the S. spinosum extract (1, 10, 25 µg/mL) for 24 hours. The results showed the S. spinosum ethanolic extract is rather rich in phenols (TPC of 18.6 mgGAE/g dry extracts). Moreover, the extract showed a good scavenging ability in vitro (IC₅₀ 15.9 µg/ml and 10.9 µg/ml measured by DPPH and ABTS assays, respectively). When the extract was tested on cells, the results showed that it could ameliorate some markers of cell dysfunction. The three concentrations of the extract led to a significant decrease in the intracellular triglyceride (TG) content in steatotic FaO cells measured by spectrophotometric assay. On the other hand, HECV cells treated with increasing concentrations of the extract did not result in a significant decrease in both lipid peroxidation measured by the Thiobarbituric Acid Reactive Substances (TBARS) assay, and in reactive oxygen species (ROS) production measured by fluorometric analysis after DCF staining. Interestingly, the ethanolic extract was able to accelerate the wound repair of confluent HECV cells with respect to H₂O₂-insulted cells as measured by T-scratch assay. Taken together, these results seem to indicate that the ethanol extract from S. spinosum fruits is rich in phenol compounds and plays considerable lipid-lowering activity in vitro on steatotic hepatocytes and accelerates wound healing repair on endothelial cells. In light of that, the ethanolic extract from S. spinosum fruits could be a potential candidate for nutraceutical applications.

Keywords: antioxidant activity, ethanolic extract, lipid-lowering activity, phenolic compounds, Sarcopoterium spinosum fruits

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Authors: H. A. Jawan

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This review describes the models of environmental-related crack propagation of aluminum alloys (7xxx) during the last few decades. Acknowledge on effects of different factors on the susceptibility to SCC permits to propose valuable mechanisms on crack advancement. The reliable mechanism of cracking give a possibility to propose the optimum chemical composition and thermal treatment conditions resulting in microstructure the most suitable for real environmental condition and stress state.

Keywords: microstructure, environmental, propagation, mechanism

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Authors: Roukia Hammoudi, Chabrouk Farid, Dehak Karima, Mahfoud Hadj Mahammed, Mohamed Didi Ouldelhadj

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The objective of this study was to optimise the extraction conditions for phenolic compounds from Deverra scoparia Coss and Dur. Apiaceae plant by ultrasound assisted extraction (UAE). The effects of solvent type (acetone, ethanol and methanol), solvent concentration (%), extraction time (mins) and extraction temperature (°C) on total phenolic content (TPC) were determined. The optimum extraction conditions were found to be acetone concentration of 80%, extraction time of 25 min and extraction temperature of 25°C. Under the optimized conditions, the value for TPC was 9.68 ± 1.05 mg GAE/g of extract. The study of the antioxidant power of these oils was performed by the method of DPPH. The results showed that antioxidant activity of the Deverra scoparia essential oil was more effective as compared to ascorbic acid and trolox.

Keywords: Deverra scoparia, phenolic compounds, ultrasound assisted extraction, total phenolic content, antioxidant activity

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Authors: Roukia Hammoudi, Dehak Karima, Chabrouk Farid, Mahfoud Hadj Mahammed, Mohamed Didi Ouldelhadj

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The objective of this study was to optimise the extraction conditions for phenolic compounds from Deverra scoparia Coss and Dur. Apiaceae plant by ultrasound assisted extraction (UAE). The effects of solvent type (Acetone, Ethanol and methanol), solvent concentration (%), extraction time (mins) and extraction temperature (°C) on total phenolic content (TPC) were determined. the optimum extraction conditions were found to be acetone concentration of 80%, extraction time of 25 min and extraction temperature of 25°C. Under the optimized conditions, the value for TPC was 9.68 ± 1.05 mg GAE/g of extract. The study of the antioxidant power of these oils was performed by the method of DPPH. The results showed that antioxidant activity of the Deverra scoparia essential oil was more effective as compared to ascorbic acid and trolox.

Keywords: Deverra scoparia, phenolic compounds, ultrasound assisted extraction, total phenolic content, antioxidant activity

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Authors: F. Belkhiri, A. Baghiani, S. Boumerfeg, N. Charef, S. Khennouf, L. Arrar

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The present study was conducted to evaluate the in vitro antioxidant and antibacterial properties of methanolic extracts from roots of Tamus communis L. (TCRE), which is a plant used in traditional medicine in Algeria. The antioxidant potential of pattern was evaluated using tow complementary techniques, inhibition of free radical DPPH and the test of β-Carotene/linoleic acid. The antioxidant test indicates that non-polar fractions of TCRE (chloroform and ethyl acetate fractions) were more active than the polar fractions. Among these fractions, the chloroform extract appear in the DPPH test an IC50 of (18.89 µg/ml) comparable to that of BHT (18.6 µg/ml). This fraction was able to inhibiting the oxidation of β-Carotene with a percentage of inhibition (89.84 %). In antibacterial test, non-polar fractions showed antibacterial activity very important compared with the polar fractions. These fractions have inhibited the growth of four from nine bacterial strains, causing zones of inhibition from 08 to 23 mm of diameter.

Keywords: antioxidant activity, antibacterial activity, Tamus communis L., polar fractions

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Authors: Wiolene Montanari Nordi, Debora Botequio Moretti, Mariana Caroline Pontin, Jessica Pampolini, Raul Machado-Neto

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Gills are organs responsible for respiration and osmoregulation between the fish internal environment and water. Under stress conditions, oxidative response and gill plasticity to attempt to increase gas exchange area are noteworthy, compromising the physiological processes and therefore fish health. Colostrum is a dietary source of nutrients, immunoglobulin, antioxidant and bioactive molecules, essential for immunological protection and development of the gastrointestinal epithelium. The hypothesis of this work is that antioxidant factors present in the colostrum, unprecedentedly tested in gills, can minimize or reduce the alteration of its epithelium structure of juvenile pacu (Piaractus mesopotamicus) subjected to high stocking density. The histological changes in the gills architecture were characterized by the frequency, incidence and severity of the tissue alteration and ionic status. Juvenile (50 kg fish/m3) were fed with pelleted diets containing 0, 10, 20 or 30% of lyophilized bovine colostrum (LBC) inclusion and at 30 experimental days, gill and blood samples were collected in eight fish per treatment. The study revealed differences in the type, frequency and severity (histological alterations index – HAI) of tissue alterations among the treatments, however, no distinct differences in the incidence of alteration (mean alteration value – MAV) were observed. The main histological changes in gill were elevation of the lamellar epithelium, excessive cell proliferation of the filament and lamellar epithelium causing total or partial melting of the lamella, hyperplasia and hypertrophy of lamellar and filament epithelium, uncontrolled thickening of filament and lamellar tissues, mucous and chloride cells presence in the lamella, aneurysms, vascular congestion and presence of parasites. The MAV obtained per treatment were 2.0, 2.5, 1.8 and 2.5 to fish fed diets containing 0, 10, 20 and 30% of LBC inclusion, respectively, classifying the incidence of gill alterations as slightly to moderate. The severity of alteration of individual fish of treatment 0, 10 and 20% LBC ranged values from 5 to 40 (HAI average of 20.1, 17.5 and 17.6, respectively, P > 0.05), and differs from 30% LBC, that ranged from 6 to 129 (HAI mean of 77.2, P < 0.05). The HAI value in the treatments 0, 10 and 20% LBC reveals gill tissue with injuries classified from slightly to moderate, while in 30% LBC moderate to severe, consequence of the onset of necrosis in the tissue of two fish that compromises the normal functioning of the organ. In relation to frequency of gill alterations, evaluated according to absence of alterations (0) to highly frequent (+++), histological alterations were observed in all evaluated fish, with a trend of higher frequency in 0% LBC. The concentration of Na+, Cl-, K+ and Ca2+ did not changed in all treatments (P > 0.05), indicating similar capacity of ion exchange. The concentrations of bovine colostrum used in diets of present study did not impair the alterations observed in the gills of juvenile pacu.

Keywords: histological alterations of gill tissue, ionic status, lyophilized bovine colostrum, optical microscopy

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Authors: Fendouli Ines, Zaafrane Nesrine, Mhamdi Hana, Knani Leila, Ghorbel Mohamed

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Introduction: Ocular infiltration of leukemia can involve orbit, uveal tract, retina and optic nerve. It may result from direct ocular infiltration by leukemic cells or indirect ocular involvement resulting from secondary hematologic changes, opportunistic infections and complications of various modalities of therapy. We here in report a case of central venous retinal occlusion associated to optic nerve infiltration as presenting signs of a relapse of acute lymphoblastic leukemia. Case Report: A twelve-year-old male -patient of acute B lymphoblastic leukemia presented with headaches and bilateral blurred vision in the left ee. Ophthalmic examination showed a visual acuity reduced to counting fingers in the right eye and no light perception in the left eye. Funduscopy revealed a voluminous disc edema surrounded by retinal haemorrhages in the right eye, and venous tortusities, papillary edema, and hemorrages suggesting central retinal venous occlusion in the LE. Swept source optical coherence tomography revealed a serous retinal detachment in the RE and .hyperreflective inner layers with macular edema in the left eye. Cerebro-orbital MRI showed bilateral thickened left optic nerve. There were no radiological signs of true papillary edema due to intracranial hypertension secondary to central nervous system involvement. Myelogram and lumbar punction demonstrated blast infiltration and confirmed ocular relapse of the leukemia. Conclusion: Ocular involvement lymphoblastic acute leukemias decreased since the introduction of a systematic prophylactic treatment of central nervous system. Periodic ophthalmic examination is necessary to allow early diagnosis and treatment.

Keywords: acute leukemia, optic nerve, infiltration, relapse

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Authors: Dwi Arisandi Wijaya, Ernawati Arifin Giri-Rachman, Neni Nurainy

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Typhoid fever disease can be prevented by using a polysaccharide-based vaccine Vi which is a virulence factor of S.typhi. To produce high yield Vi polysaccharide from bacteria, it is important to know the biosynthesis of Vi polysaccharide and the regulators involved. In the In vivo condition, S. typhi faces different osmolarity, and the bacterial two-component system OmpR-EnvZ, regulate by up and down Capsular Vi polysaccharide biosynthesis. A high yielded Vi Polysaccharide strain, S. typhi strain C6524 used to study the effect of media osmolarity on Vi polysaccharide biosynthesis and the osmoregulation pattern of S. typhi strain C6524. The methods were performed by grown S. typhi strain C6524 grown on medium with 50 mM, 100 mM, and 150 mM osmolarity with the batch system. Vi polysaccharide concentration was measured by ELISA method. For further investigation of the osmoregulation pattern of strain C6524, the osmoregulator gene, OmpR, has been isolated and sequenced using the specific primer of the OmpR gene. Nucleotide sequence analysis is done with BLAST and Lallign. Amino Acid sequence analysis is done with Prosite and Multiple Sequence Alignment. The results of cultivation showed the average content of polysaccharide Vi for 50 mM, 100 mM, and 150 mM osmolarities 11.49 μg/mL, 12.06 μg/mL, and 14.53 μg/mL respectively. Analysis using Anova stated that the osmolarity treatment of 150 mM significantly affects Vi content. Analysis of nucleotide sequences shows 100% identity between S. typhi strain C6524 and Ty2. Analysis of amino acid sequences shows that the OmpR response regulator protein of the C6524 strain also has a α4-β5-α5 motif which is important for the regulatory activation system when phosphorylation occurs by domain kinase. This indicates that the regulator osmolarity response of S. typhi strain C6524 has no difference with the response regulator owned by S. typhi strain Ty2. A high Vi response rate in the 150 mM osmolarity treatment requires further research for RcsB-RcsC, another two-component system involved in Vi Biosynthesis.

Keywords: osmoregulator, OmpR, Salmonella, Vi polysaccharide

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Authors: M. A. Hamza, H. A. Bosila, M. A. Zewil, I. M. Harridy

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Silymarin is one active component extracted from milk thistle Silybum marianum; it is flavonoid recognized for its ability to benefit people with liver disorders and as a protective compound against liver damaging agents. For this reason, this research aims to study the effect of growth regulators (BA+NAA) and explant type (cotyledon, hypocotyl, and root) to increase the growth and active ingredients (silymarin) in callus of S. mariaum plant. The results showed that cotyledon explant which have been cultured in MS medium supplemented with BA 0.4 mg/l. +NAA 0.25 mg/l. Led to obtain the best results in callus fresh weight (1.847a) and callus dry weight (0.155a). On the other hand, the same explant (cotyledon) cultured in MS medium supplemented with BA 1.6 mg/l. + NAA 0.5 mg/l. The suitable condition to silymarin content (0.132 mg/100 mg dry weight). And also, it turned out, lack of importance of the use of hypocotyl and root in the production of callus and silymarin compared to cotyledon.

Keywords: silybum, callus, tissue culture, cotyledon

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Authors: Rona Lee Suelo-Calanao, Mahmoud Loubani

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Objective: Sternal wound infection (SWI) following cardiac operation has a significant impact on patient morbidity and mortality. It also contributes to longer hospital stays and increased treatment costs. SWI management is mainly focused on treatment rather than prevention. This study looks at the effect of closed incision negative pressure therapy (ciNPT) dressing to help reduce the incidence of superficial SWI in high-risk patients after cardiac surgery. The ciNPT dressing was evaluated at 3 cardiac hospitals in the United Kingdom". Methods: All patients who had cardiac surgery from 2013 to 2021 were included in the study. The patients were classed as high risk if they have two or more of the recognised risk factors: obesity, age above 80 years old, diabetes, and chronic obstructive pulmonary disease. Patients receiving standard dressing (SD) and patients using ciNPT were propensity matched, and the Fisher’s exact test (two-tailed) and unpaired T-test were used to analyse categorical and continuous data, respectively. Results: There were 766 matched cases in each group. Total SWI incidences are lower in the ciNPT group compared to the SD group (43 (5.6%) vs 119 (15.5%), P=0.0001). There are fewer deep sternal wound infections (14(1.8%) vs. 31(4.04%), p=0.0149) and fewer superficial infections (29(3.7%) vs. 88 (11.4%), p=0.0001) in the ciNPT group compared to the SD group. However, the ciNPT group showed a longer average length of stay (11.23 ± 13 days versus 9.66 ± 10 days; p=0.0083) and higher mean logistic EuroSCORE (11.143 ± 13 versus 8.094 ± 11; p=0.0001). Conclusion: Utilization of ciNPT as an approach to help reduce the incidence of superficial and deep SWI may be effective in high-risk patients requiring cardiac surgery.

Keywords: closed incision negative pressure therapy, surgical wound infection, cardiac surgery complication, high risk cardiac patients

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Authors: Ayse Pekrioglu Balkis, Sawash Mecid

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Due to continued growth and rapid development of road construction in worldwide, road sub-layers consist of soil layers, therefore, identification and recognition of type of soil and soil behavior in different condition help to us to select soil according to specification and engineering characteristic, also if necessary sometimes stabilize the soil and treat undesirable properties of soils by adding materials such as bitumen, lime, cement, etc. If the soil beneath the road is not done according to the standards and construction will need more construction time. In this case, a large part of soil should be removed, transported and sometimes deposited. Then purchased sand and gravel is transported to the site and full depth filled and compacted. Stabilization by cement or other treats gives an opportunity to use the existing soil as a base material instead of removing it and purchasing and transporting better fill materials. Classification of soil according to AASHTOO system and USCS help engineers to anticipate soil behavior and select best treatment method. In this study soil classification and the relation between soil classification and stabilization method is discussed, cement stabilization with different percentages have been selected for soil treatment based on NCHRP. There are different parameters to define the strength of soil. In this study, CBR will be used to define the strength of soil. Cement by percentages, 0%, 3%, 7% and 10% added to soil for evaluation effect of added cement to CBR of treated soil. Implementation of stabilization process by different cement content help engineers to select an economic cement amount for the stabilization process according to project specification and characteristics. Stabilization process in optimum moisture content (OMC) and mixing rate effect on the strength of soil in the laboratory and field construction operation have been performed to see the improvement rate in strength and plasticity. Cement stabilization is quicker than a universal method such as removing and changing field soils. Cement addition increases CBR values of different soil types by the range of 22-69%.

Keywords: California Bearing Ratio, cement stabilization, clayey soil, mechanical properties

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Authors: Ashwini Mohan, Haris Batley

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An orthodontic index is used to rate or categorise an individual’s occlusion using a numeric or alphanumeric score. Indexing of malocclusions and their correction is important in epidemiology, diagnosis, communication between clinicians as well as their patients and assessing treatment outcomes. Many useful indices have been put forward, but to the author’s best knowledge, no one method to this day appears to be equally suitable for the use of epidemiologists, public health program planners and clinicians. This article describes the common clinical orthodontic indices and classifications used in United Kingdom.

Keywords: classification, indices, orthodontics, validity

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Authors: Homayun Ghasemi, Mojtaba Yousefirad, Mozhgan Farzamisepehr

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Heavy metals are among soil pollutant resources that in case of accumulation in the soil and absorption by the plant, enter into the food chain and poison the plants or the people who consume those plants. This research was performed in order to examine the role of cadmium as a heavy metal in the activity of catalase and peroxidase as well as protein concentration in Trifolium resupinatum L. based on a randomized block design with three repetitions. The used treatments included consumption of Cd (NO3)2 at four levels, namely, 0, 100, 200, and 300 ppm. The plants under study were treated for 10 days. The results of the study showed that catalase activity decreased by the increase of cadmium. Moreover, peroxidase activity increased by an increase inthe consumption of cadmium. The analysis of protein level showed that plantlet protein decreased in high cadmium concentrations. The findings also demonstrated that cadmium concentration in roots was higher than in shoots.

Keywords: catalase, heavy metal, peroxidase, protein

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Authors: Paula Salazar, Rodrigo Henríquez, Pablo Zerega

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The textile, food and pharmaceutical industries are expanding daily worldwide, and they are located within the most polluting industries due to the fact that wastewater is discharged into watercourses with high concentrations of dyes and traces of drugs. Many of these compounds are stable to light and biodegradation, being considered as emerging organic contaminants. Advanced oxidation processes (AOPs) emerge as an effective alternative for the removal and elimination of this type of contaminants. Heterogeneous photocatalysis has been extensively studied as it is an efficient, low-cost and durable method. As the main photocatalyst, TiO₂ has been used for the degradation of a large number of dyes and drugs. The disadvantage of TiO₂ is its absorption in the UV region of the solar spectrum. On the other hand, quaternary chalcogenides based on Cu₂SnZnX₄ (X = S, Se) are a possible alternative due to their narrow bandgap (ca. between 0.8 to 1.5 eV depending on the phase considered), low cost, an abundance of its constituent elements in the earth's crust and its low toxicity. The objective of this research was to synthesize Cu₂SnZnS₄ (CZTS) through of a low-cost hydrothermal method and evaluate it as a potential photo-catalyst in the photo-degradation process of Congo Red. The synthesis of the nanoparticle in suspension and film onto fluorine-doped tin oxide coated glass (FTO) was carried out using a mixture of: 2 mmol CuCl₂, 1 mmol ZnCl₂, 1 mmol SnCl₂ and 4 mmol CH4N₂S in a Teflon reactor at 180⁰C for 72 h. Characterization was performed through scanning electron microscopy (SEM), X-ray diffraction (XRD) and UV VIS spectroscopy. Photo-degradation monitoring was carried out employing a UV VIS spectrophotometer. The results show that photodegradation of 55% of the dye can be obtained after 4h of exposure to polychromatic light, it should be noted that the Congo Red dye is being studied for the first time.

Keywords: CZTS, hydrothermal, photocatalysis, dye

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Authors: Mohamed Abdelfattah Meawad Hamza, H. A. Bosila, M. A. Zewil

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This research aims to study the effect of different sources of elicitors for increase growth and active ingredients in callus of Echinacea purpurea plant. Callus that have been obtained from leaf explant, was used to conduct the following studies. A study of the impact of both the phenylalanine and tyrosine (50, 100,150 and 200 mg/l.) individually and casein hydrolysate (100, 200 and 300 mg/l.) supplemented to MS medium. Results show that Casein hydrolysate 100 mg/l. has achieved the better results in both callus fresh weight 1.881 g/explant after 8 weeks of the incubation period and callus growth rate 0.398 g/explant after 6 weeks of the incubation period, while gave add 200 mg/l. The best results in total carbohydrate 2.444 mg/ 100 mg dry weight. Phenylalanine 150 mg/l. has achieved the best results in callus dry weight 0.156 g/explant after 8 weeks of incubation period. Tyrosine 200 mg/l. recorded the best result for positive production of caffeic acid 0.460 mg/ 100 mg dry weight after 4 weeks incubation period.

Keywords: tissue culture, echinacea, tyrosine, casein

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Authors: Raquel Dafouz Neus Cáceres, Javier Fernandez-Rubio, Belinda Huerta José Luis Rodríguez-Gil, Nicola Mastroianni, Miren López de Alda, Damià Barceló, Yolanda Valcárcel

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The region of Galicia, found in north-western (NW) Spain, is a national and world leader in shellfish, especially mussel production, and recognized for its fishing industry. Few studies have evaluated the presence of emerging contaminants in NW Spain, with those published mainly concerning the continental aquatic environment. The objective of this study was to identify the environmental risk posed by the presence of pharmaceuticals and drugs of abuse in this important coastal region. The presence of sixteen pharmaceuticals (benzodiazepines, anxiolytics, and caffeine), and 19 drugs of abuse (cocainics, amphetamine-like compounds, opiates and opioids, lysergic compounds, and cannabinoids) was assessed in 23 sites located in the Rías (Coastal inlets) of Muros, Arousa, and Pontevedra (NW Spain). Twenty-two of these locations were affected by waste-water treatment plant (WWTP) effluents, and one represented the effluent of one of these WWTPs. Venlafaxine was the pharmaceutical compound detected at higher concentration in the three Rías, with a maximum value of 291 ng/L at the site Porto do Son (Ría de Muros). Total concentration in the three Rías was 819,26 ng/L. Next, citalopram and lorazepam were the most prevalent compounds detected. Metabolite of cocaine benzoylecgonine was the drug of abuse with the highest concentration, measured at 972 ng/L in the Ría of Noia WWTP (no dilution). This compound was also detected at 142 ng/L in the site La Isla de Aros, Ría of Pontevedra. Total concentration for the three Rías was 1210 ng/L. Ephedrine was also detected at high level in the three Rías, with a total concentration of 579,28 ng/L. The results obtained for caffeine show maximum and average concentrations of 857 ng/L Isla de Arosa, Ría de Pontevedra the highest measured in seawater in Spain. A preliminary hazard assessment was carried out by comparing these measured environmental concentrations (MEC) to predicted no-effect concentrations (PNECs) for aquatic organisms. Six out of the 22 seawater samples resulted in a Hazard Quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. In addition, the risk was assessed on the basis of persistence, bioaccumulation, and toxicity (PBT). This work was financially supported by the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute and the program 'Proyectos de Investigacion en Salud 2015-2017' FIS (PI14/00516), the European Regional Development Fund (ERDF), the Catalan Government (Consolidated Research Groups '2014 SGR 418 - Water and Soil Quality Unit' and 2014 SGR 291 - ICRA), and the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 603437. The poster entitled 'Environmental Risk of Pharmaceuticals, Drugs of Abuse and Stimulant Caffeine in Marine Water: A Case Study in the North-Western of Spain'.

Keywords: drug of abuse, pharmaceuticals, caffeine, environmental risk, seawater

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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