Search results for: therapeutic agents

Authors: Komal Vig

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Cardiovascular disease (CVD)-related deaths occur in 17.3 million people globally each year, accounting for 30% of all deaths worldwide, with a predicted annual incidence of deaths to reach 23.3 million globally by 2030. Autologous bypass grafts remain an important therapeutic option for the treatment of CVD, but the poor quality of the donor patient’s blood vessels, the invasiveness of the resection surgery, and postoperative movement restrictions create issues. The present study is aimed to improve the endothelialization of intimal surface of graft by using low temperature plasma (LTP) to increase the cell attachment and proliferation. Polytetrafluoroethylene (PTFE) was treated with LTP. Air was used as the feed-gas, and the pressure in the plasma chamber was kept at 800 mTorr. Scaffolds were also modified with gelatin and collagen by dipping method. Human umbilical vein endothelial cells (HUVEC) were plated on the developed scaffolds, and cell proliferation was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and by microscopy. mRNA expressions levels of different cell markers were investigated using quantitative real-time PCR (qPCR). XPS confirmed the introduction of oxygenated functionalities from LTP. HUVEC cells showed 80% seeding efficiency on the scaffold. Microscopic and MTT assays indicated increase in cell viability in LTP treated scaffolds, especially when treated with gelatin or collagen, compared to untreated scaffolds. Gene expression studies shows enhanced expression of cell adhesion marker Integrin- α 5 gene after LTP treatment. LTP treated scaffolds exhibited better cell proliferation and viability compared to untreated scaffolds. Protein treatment of scaffold increased cell proliferation. Based on our initial results, more scaffolds alternatives will be developed and investigated for cell growth and vascularization studies. Acknowledgments: This work is supported by the NSF EPSCoR RII-Track-1 Cooperative Agreement OIA-2148653.

Keywords: LTP, HUVEC cells, vascular graft, endothelialization

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Authors: Sanja O. Podunavac-Kuzmanović, Strahinja Z. Kovačević, Lidija R. Jevrić

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Prion is a protein substance whose certain form is considered as infectious agent. It is presumed to be the cause of the transmissible spongiform encephalopathies (TSEs). The protein it is composed of, called PrP, can fold in structurally distinct ways. At least one of those 3D structures is transmissible to other prion proteins. Prions can be found in brain tissue of healthy people and have certain biological role. The structure of prions naturally occurring in healthy organisms is marked as PrPc, and the structure of infectious prion is labeled as PrPSc. PrPc may play a role in synaptic plasticity and neuronal development. Also, it may be required for neuronal myelin sheath maintenance, including a role in iron uptake and iron homeostasis. PrPSc can be considered as an environmental pollutant. The main aim of this study was to carry out the molecular modeling and calculation of molecular descriptors (lipophilicity, physico-chemical and topological descriptors) of structurally diverse compounds which can be considered as anti-prion agents. Molecular modeling was conducted applying ChemBio3D Ultra version 12.0 software. The obtained 3D models were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. The Austin Model 1 (AM-1) was used for full geometry optimization of all structures. The obtained set of molecular descriptors is applied in analysis of similarities and dissimilarities among the tested compounds. This study is an important step in further development of quantitative structure-activity relationship (QSAR) models, which can be used for prediction of anti-prion activity of newly synthesized compounds.

Keywords: chemometrics, molecular modeling, molecular descriptors, prions, QSAR

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Authors: B. M. Pardeshi

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Introduction: Minerals and trace elements are chemical elements required by our bodies for numerous biological and physiological processes that are necessary for the maintenance of health. Medicinal plants are highly beneficial for the maintenance of good health and prevention of diseases. They are known as potential sources of minerals and vitamins. 30 to 40% of today’s conventional drugs used in the medicinal and curative properties of various plants are employed in herbal supplement botanicals, nutraceuticals and drug. Aim: The authors explored the mineral element content of some herbs, because mineral elements may have significant role in the development and treatment of gastrointestinal diseases, and a close connection between the presence or absence of mineral elements and inflammatory mediators was noted. Methods: Present study deals with the elemental analysis of medicinal plants by Instrumental Neutron activation Analysis and Atomic Absorption Spectroscopy. Medicinal herbals prescribed for skin diseases were purchased from markets and were analyzed by Instrumental Neutron Activation Analysis (INAA) using 252Cf Californium spontaneous fission neutron source (flux* 109 n s-1) and the induced activities were counted by γ-ray spectrometry and Atomic Absorption Spectroscopy (AAS) techniques (Perkin Elmer 3100 Model) available at Department of Chemistry University of Pune, India, was used for the measurement of major, minor and trace elements. Results: 15 elements viz. Al, K, Cl, Na, Mn by INAA and Cu, Co, Pb Ni, Cr, Ca, Fe, Zn, Hg and Cd by AAS were analyzed from different medicinal plants from India. A critical examination of the data shows that the elements Ca , K, Cl, Al, and Fe are found to be present at major levels in most of the samples while the other elements Na, Mn, Cu, Co, Pb, Ni, Cr, Ca, Zn, Hg and Cd are present in minor or trace levels. Conclusion: The beneficial therapeutic effect of the studied herbs may be related to their mineral element content. The elemental concentration in different medicinal plants is discussed.

Keywords: instrumental neutron activation analysis, atomic absorption spectroscopy, medicinal plants, trace elemental analysis, mineral contents

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Authors: James Ladzekpo

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Background: The urgent need to identify new pharmacological targets for diabetes treatment and prevention has been amplified by the disease's extensive impact on individuals and healthcare systems. A deeper insight into the biological underpinnings of diabetes is crucial for the creation of therapeutic strategies aimed at these biological processes. Current predictive models based on genetic variations fall short of accurately forecasting diabetes. Objectives: Our study aims to pinpoint key epigenetic factors that predispose individuals to diabetes. These factors will inform the development of an advanced predictive model that estimates diabetes risk from genetic profiles, utilizing state-of-the-art statistical and data mining methods. Methodology: We have implemented a recursive feature elimination with cross-validation using the support vector machine (SVM) approach for refined feature selection. Building on this, we developed six machine learning models, including logistic regression, k-Nearest Neighbors (k-NN), Naive Bayes, Random Forest, Gradient Boosting, and Multilayer Perceptron Neural Network, to evaluate their performance. Findings: The Gradient Boosting Classifier excelled, achieving a median recall of 92.17% and outstanding metrics such as area under the receiver operating characteristics curve (AUC) with a median of 68%, alongside median accuracy and precision scores of 76%. Through our machine learning analysis, we identified 31 genes significantly associated with diabetes traits, highlighting their potential as biomarkers and targets for diabetes management strategies. Conclusion: Particularly noteworthy were the Gradient Boosting Classifier and Multilayer Perceptron Neural Network, which demonstrated potential in diabetes outcome prediction. We recommend future investigations to incorporate larger cohorts and a wider array of predictive variables to enhance the models' predictive capabilities.

Keywords: diabetes, machine learning, prediction, biomarkers

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Authors: Sharmi Mukherjee, Anindita Chakraborty

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Cellular irradiation incites complex responses including arrest of cell cycle progression. This article accentuates the effects of radiation on cell cycle status of radiation non-targeted cells. Human Hepatoma HepG2 cells were exposed to increasing doses of γ radiations (1, 2, 4, 6 Gy) and their cell culture media was transferred to non-targeted HepG2 cells cultured in other Petri plates. These radiation non-targeted cells cultured in the ICCM (Irradiated cell conditioned media) were the bystander cells on which cell cycle analysis was performed using flow cytometry. An apparent decrease in the distribution of bystander cells at G0/G1 phase was observed with increased radiation doses upto 4 Gy representing a linear relationship. This was accompanied by a gradual increase in cellular distribution at G2/M phase. Interestingly the number of cells in G2/M phase at 1 and 2 Gy irradiation was not significantly different from each other. However, the percentage of G2 phase cells at 4 and 6 Gy doses were significantly higher than 2 Gy dose indicating the IC50 dose to be between 2 and 4 Gy. Cell cycle arrest is an indirect indicator of genotoxic damage in cells. In this study, bystander stress signals through the cell culture media of irradiated cells disseminated the radiation induced DNA damages in the non-targeted cells which resulted in arrest of the cell cycle progression at G2/M phase checkpoint. This implies that actual radiation biological effects represent a penumbra with effects encompassing a larger area than the actual beam. This article highlights the existence of genotoxic damages as bystander effects of γ rays in human Hepatoma cells by cell cycle analysis and opens up avenues for appraisal of bystander stress communications between tumor cells. Contemplation of underlying signaling mechanisms can be manipulated to maximize damaging effects of radiation with minimum dose and thus has therapeutic applications.

Keywords: bystander effect, cell cycle, genotoxic damage, hepatoma

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Authors: Shirin Ghatrehsamani

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Higher efficiency and lower environmental impact are the consequence of using advanced technology in farming. They also help to decrease yield variability by diminishing weather variability impact, optimizing nutrient and pest management as well as reducing competition from weeds. A better understanding of the pros and cons of applying technology and finding the main reason for preventing the utilization of the technology has a significant impact on developing technology adoption among farmers and producers in the digital agriculture era. The results from two surveys carried out in 2019 and 2021 were used to investigate whether the crop types had an impact on the willingness to utilize technology on the farms. The main focus of the questionnaire was on utilizing precision agriculture (PA) technologies among farmers in some parts of the united states. Collected data was analyzed to determine the practical application of various technologies. The survey results showed more similarities in the main reason not to use PA between the two crop types, but the present application of using technology in specialty crops is generally five times larger than in row crops. GPS receiver applications were reported similar for both types of crops. Lack of knowledge and high cost of data handling were cited as the main problems. The most significant difference was among using variable rate technology, which was 43% for specialty crops while was reported 0% for row crops. Pest scouting and mapping were commonly used for specialty crops, while they were rarely applied for row crops. Survey respondents found yield mapping, soil sampling map, and irrigation scheduling were more valuable for specialty crops than row crops in management decisions. About 50% of the respondents would like to share the PA data in both types of crops. Almost 50 % of respondents got their PA information from retailers in both categories, and as the second source, using extension agents were more common in specialty crops than row crops.

Keywords: precision agriculture, smart farming, digital agriculture, technology adoption

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Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

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Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Maryam Jaberi, Siavosh Shayan, Mojtaba Yamani

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Habble-Rud River basin (HR), up to 100 km length, one of the largest watersheds which drain into deserts to the north of Central Iran (Dasht-e Kavir). This stream is oblique with the NE-SW trending, flow in the southern range of central Alborz Mountains and the northern border of Central Iran. The end of the ~17 km suddenly change direction and with the southern trending to have a morphology which meanders passes through the Alborz Mountain ridge and flows into the Garmsar plain where it forms one of the largest alluvial fans in Iran, i.e. the vast Garmsar alluvial fan with an area of 476 km2. This study was carried out through morphometric analyses, longitudinal river profiles, and study of geomorpholic evidence such as fluvial terraces, gypsum-salt domes, seismic data, and satellite images. This study aimed to investigate the changes in the pattern of rivers in the southern part of the HR river basin. The southern part of HR river basin located at the southern foothills of the Central Alborz is characterized the thrust faults (Sorkheh-Kalut and Garmsar faults), folds,diapirs and arid climate. The activity of more than 10 salt domes that belong to the Oligocene-Miocene period has considerably influenced the pattern of streams in this region. Dissolution of these domes has not only reduced the quality of water and soil resources, but also has led to the formation of badlands and gullies.Our results indicated that the pattern of rivers in the southern part of HR river basin was influenced by discharge of the HR river in Quaternary, geological structure, subsidence of Central Iran and vertical uplift of Alborz mountain. These agents caused the formation meanders in the southern part of the HR River and evaluation of the seasonal rivers like Shoor-Darre and Garmabsar.

Keywords: geomorphologic evaluation, rivers pattern, Habble-Rud River basin, seasonal rivers

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Authors: Zaida Perez-Bassart, Berta Polanco-Estibalez, Maria Jose Fabra, Amparo Lopez-Rubio, Antonio Martinez-Abad

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Mushroom production has enormously increased in recent years, not only as food products but also for applications in pharmaceuticals, nutraceuticals, and cosmetics. Consequently, interest in its chemical composition, nutritional value, and therapeutic properties has also increased. Fungi are rich in bioactive compounds such as polysaccharides, polyphenols, glycopeptides, and ergosterol, of great medicinal value, but within polysaccharides, β-glucans are the most prominent molecules. They are formed by D-glucose monomers, linked by β-glucosidic bonds β-(1,3) with side chains linked by β-(1,6) bonds. The number and position of the β-(1,6) branches strongly influence the arrangement of the tertiary structure, which, together with the molecular weight, determine the different attributed bioactivities (immunostimulating, anticancer, antimicrobial, prebiotic, etc.) and physico-chemical properties (solubility, bioaccessibility, viscosity or emulsifying). On the other hand, there is a growing interest in the study of fungi as an alternative source of chitin obtained from the by-products of the fungal industry. In this work, a cascade extraction process using aqueous neutral and alkaline treatments was carried out for Grifola frondosa and Lentinula edodes, and the compositional analysis and functional properties of each fraction were characterized. Interestingly, the first fraction obtained by using aqueous treatment at room temperature was the richest in polysaccharides, proteins, and polyphenols, thus obtaining a greater antioxidant capacity than in the other fractions. In contrast, the fractions obtained by alkaline treatments showed a higher degree of β-glucans purification compared to aqueous extractions but a lower extraction yield. Results revealed the different structural recalcitrance of β-glucans, preferentially linked to proteins or chitin depending on the fungus type, which had a direct impact on the functionalities and bioactivities of each fraction.

Keywords: fungi, mushroom, β-glucans, chitin

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Authors: Hanin Suleiman Alqam

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The knowledge-based economy, as its name implies relies on knowledge, information and high levels of skills made available for all economic agents. Delving a bit more deeply, the concept of a knowledge-based economy is showcasing four main pillars, which are: Education and Training, Information and Communication Technology, Economic incentives and Institutional regimes, and Research and Development (R&D) and Innovation system. A good number of researches are showing its positive contribution to economic diversification underpinning sustainable development and growth. The present paper aimed at assessing the role of SMEs in moving Oman’s economy from a traditional economy to a knowledge-based economy. To lay down a groundwork that should lead to future studies, the methodology selected is based on exploratory research. Hence, the interview was conducted as a data collection tool. Based on a purposive sampling technique, seven handpicked experts have partaken in the study as they are working in different key organizations considered to be directly or indirectly the backbone of the Omani national economy. A thematic approach is employed for the purpose of data analysis. Results of the study showed that SMEs are not really contributing in the knowledge-based economy due to a lack of awareness about its importance to the country and to the enterprise within SMEs in Oman. However, it was shown that SMEs owners are interested in innovation and are trying to support innovative individuals by attracting them to their enterprises. On the other hand, the results revealed that SMEs' performance in e-solution is still not up to the level as 32% of SMEs only are using e-solutions in their internal processes and procedures like accounting systems. It is recommended to SMEs owners to use new and modern technologies in marketing and customer relation, encourage creativity, research and development, and allow the youth to have opportunities and facilitate the procedure in terms of innovation so that their role in contributing to the knowledge-based economy could be improved.

Keywords: knowledge-based economy, SMEs, ICT pillars, research and innovation

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Authors: Ramanish Ravishankar, Azar Hussain, Mahmoud Loubani, Mubarak Chaudhry

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Background and Aims: Currently, there are no strict guidelines in cardiopulmonary bypass temperature management in cardiac surgery not involving the aortic arch. This study aims to compare patient outcomes undergoing mild hypothermia and normothermia. The aim of this study was to compare patient outcomes between mild hypothermia and normothermia undergoing on-pump cardiac surgery not involving the aortic arch. Methods: This was a retrospective cohort study from January 2015 until May 2023. Patients who underwent cardiac surgery with cardiopulmonary bypass temperatures ≥32oC were included and stratified into mild hypothermia (32oC – 35oC) and normothermia (>35oC) cohorts. Propensity matching was applied through the nearest neighbour method (1:1) using the risk factors detailed in the EuroScore using RStudio. The primary outcome was mortality. Secondary outcomes included post-op stay, intensive care unit readmission, re-admission, stroke, and renal complications. Patients who had major aortic surgery and off-pump operations were excluded. Results: Each cohort had 1675 patients. There was a significant increase in overall mortality with the mild hypothermia cohort (3.59% vs. 2.32%; p=0.04912). There was also a greater stroke incidence (2.09% vs. 1.13%; p=0.0396) and transient ischaemic attack (TIA) risk (3.1% vs. 1.49%; p=0.0027). There was no significant difference in renal complications (9.13% vs. 7.88%; p=0.2155). Conclusions: Patient’s who underwent mild hypothermia during cardiopulmonary bypass have a significantly greater mortality, stroke, and transient ischaemic attack incidence. Mild hypothermia does not appear to provide any benefit over normothermia and does not appear to provide any neuroprotective benefits. This shows different results to that of other major studies; further trials and studies need to be conducted to reach a consensus.

Keywords: cardiac surgery, therapeutic hypothermia, neuroprotection, cardiopulmonary bypass

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Authors: Fikiru Temesgen Gelata

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Food security, adaptation, and climate change mitigation are all problems that can be resolved simultaneously with Climate-Smart Agriculture (CSA). This study examines determinants of climate-smart agriculture (CSA) practices among smallholder farmers, aiming to understand the factors guiding adoption decisions and evaluate the impact of CSA on smallholder farmer income in the study areas. For this study, three-stage sampling techniques were applied to select 230 smallholders randomly. Mann-Kendal test and multinomial endogenous switching regression model were used to analyze trends of decrease or increase within long-term temporal data and the impact of CSA on the smallholder farmer income, respectively. Findings revealed education level, household size, land ownership, off-farm income, climate information, and contact with extension agents found to be highly adopted CSA practices. On the contrary, erosion exerted a detrimental impact on all the agricultural practices examined within the study region. Various factors such as farming methods, the size of farms, proximity to irrigated farmlands, availability of extension services, distance to market hubs, and access to weather forecasts were recognized as key determinants influencing the adoption of CSA practices. The multinomial endogenous switching regression model (MESR) revealed that joint adoption of crop rotation and soil and water conservation practices significantly increased farm income by 1,107,245 ETB. The study recommends that counties and governments should prioritize addressing climate change in their development agendas to increase the adoption of climate-smart farming techniques.

Keywords: climate-smart practices, food security, Oincome, MERM, Ethiopia

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Authors: Zahra R. Almansoor

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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.

Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions

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Authors: P. Susheela, Mary Rosaline, R. Radha

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This research was designed to determine the bioactive compounds present in the nest samples of the mud dauber wasp, Sceliophron caementarium. Insects and insect-based products have been used for the treatment of various ailments from a very long time. It has been found that all over the world including the western societies and the indigenous populations, the usage of insect-based medicine plays an important role in various healing practices and magic rituals. Studies on the therapeutic usage of insects are negligible when compared to plants, the. In the present scenario, it is important to explore bioactive compounds from natural sources rather than depending on synthetic drugs that have adverse effects on human body. Keeping this in view, an attempt was made to analyze and identify bioactive components from the nest sample of the mud dauber wasp, Sceliophron caementarium. The nests of the mud dauber wasp, Sceliophron caementarium were collected from Coimbatore, Tamil Nadu, India. The nest sample was extracted with ethanol for 6-8 hours using Soxhlet apparatus. The final residue was obtained by filtering the extract through Whatman filter paper No.41. The GCMS analysis of the nest sample was performed using Perkin Elmer Elite - 5 capillary column. The resultant compounds were compared with the database of National Institute Standard and Technology (NIST), WILEY8, FAME. The GC-MS analysis of the concentrated ethanol extract revealed the presence of eight constituents like Methylene chloride, Eicosanoic acid, 1, 1’:3’, 1’’-Terphenyl, 5'-Phenyl, Di-N-Decylsulfone, 1, 2-Bis (Trimethylsilyl) Benzene, Androstane-11, 17-Dione, 3-[(Trimethylsilyl) Oxy]-, 17-[O-(Phenylmethyl) O. Most of the identified compounds were reported as having biological activities viz. anti-inflammatory, antibacterial and antifungal properties that can be of pharmaceutical importance and further study of these isolated compounds may prove their medicinal importance in future.

Keywords: Sceliophron caementarium, Gas chromatography-mass spectrometry, ethanol extract, bioactive compounds

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Authors: Michele Catalano, Jacopo Di Domenico, Luca Riccetti, Andrea Teglio

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We develop a data-driven agent based model (ABM) for the Italian economy. We calibrate the model for the initial condition and parameters. As a preliminary step, we replicate the Monte-Carlo simulation for the Austrian economy. Then, we evaluate the dynamic properties of the model: the long-run equilibrium and the allocative efficiency in terms of disequilibrium patterns arising in the search and matching process for final goods, capital, intermediate goods, and credit markets. In this perspective, we use a randomized initial condition approach. We perform a robustness analysis perturbing the system for different parameter setups. We explore the empirical properties of the model using a rolling window forecast exercise from 2010 to 2022 to observe the model’s forecasting ability in the wake of the COVID-19 pandemic. We perform an analysis of the properties of the model with a different number of agents, that is, with different scales of the model compared to the real economy. The model generally displays transient dynamics that properly fit macroeconomic data regarding forecasting ability. We stress the model with a large set of shocks, namely interest policy, fiscal policy, and exogenous factors, such as external foreign demand for export. In this way, we can explore the most exposed sectors of the economy. Finally, we modify the technology mix of the various sectors and, consequently, the underlying input-output sectoral interdependence to stress the economy and observe the long-run projections. In this way, we can include in the model the generation of endogenous crisis due to the implied structural change, technological unemployment, and potential lack of aggregate demand creating the condition for cyclical endogenous crises reproduced in this artificial economy.

Keywords: agent-based models, behavioral macro, macroeconomic forecasting, micro data

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Authors: Da-Eun Kim, Heon-Seock Cynn, Sil-Ah Choi, A-Reum Shin

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Bridging exercise in supine position with the hips and knees flexed have been commonly performed as one of the therapeutic exercises and is a comfortable and pain-free position to most individuals with chronic low back pain (CLBP). Many previous studies have investigated the beneficial way of performing bridging exercises to improve activation of abdominal and gluteal muscle and reduce muscle activity of hamstrings (HAM) and erector spinae (ES) and compensatory lumbopelvic motion. The purpose of this study was to compare the effects of three different bridging exercises on the HAM, ES, gluteus maximus (Gmax), gluteus medius (Gmed), and transverse abdominis/internal abdominis oblique (TrA/IO) activities and anterior pelvic tilt angle in subjects with CLBP. Seventeen subjects with CLBP participated in this study. They performed bridging under three different conditions (with 30° hip abduction, isometric hip abduction, and isometric hip adduction). Surface electromyography was used to measure muscle activity, and the ImageJ software was used to calculate anterior pelvic tilt angle. One-way repeated-measures analysis of variance was used to assess the statistical significance of the measured variables. HAM activity was significantly lower in bridging with 30° hip abduction and isometric hip abduction than in bridging with isometric hip adduction. Gmax and Gmed activities were significantly greater in bridging with isometric hip abduction than in bridging with 30° hip abduction and isometric hip adduction. TrA/IO muscle activity was significantly greater and anterior pelvic tilt angle was significantly lower in bridging with isometric hip adduction than in bridging with 30° hip abduction and isometric hip abduction. Bridging with isometric hip abduction using Thera-Band can effectively reduce HAM activity, and increase Gmax and Gmed activities in subjects with CLBP. Bridging with isometric hip adduction using a pressure biofeedback unit can be a beneficial exercise to improve TrA/IO activity and minimize anterior pelvic tilt in subjects with CLBP.

Keywords: bridging exercise, electromyography, low back pain, lower limb exercise

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Authors: Eli Buchbinder

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Introduction. Language is the basis to our experience as human being. We use language in describing our experiences and construct meaning and narratives from experiences. Metaphors are a valuable linguistic tool commonly use. Metaphors link two domains that are ordinarily not related. Metaphors achieve simultaneously multi-level integration: abstract and concrete, rational and imaginative, familiar and the unfamiliar, conscious and preconscious/unconscious. As such, metaphors epistemological and ontological tool that are important in social work in every field and domain. Goals and Methods The presentation’s aim is to validate the value of metaphors through the first psychiatric breakdown is a traumatic for families. The presentation is based on two pooled qualitative studies. The first study focused on 12 spouses: 7 women and 5 men, between the ages of 22 and 57, regarding their experiences and meanings of the first psychiatric hospitalization of their partners diagnosed with affective disorders. The second study focused on 10 parents, between the ages of 47 and 62, regarding their experiences and meanings following their child's first psychotic breakdown during young adulthood. Results Two types of major metaphors evolved from the interviews in farming the trauma of the first mental breakdown. The first mode - orientation (spatial) metaphors, reflect symbolic expression of the loss of a secure base, represented in the physical environment, e.g., describing hospitalization as "falling into an abyss." The second mode- ontological metaphors, reflect how parents and spouses present their traumatic experiences of hospitalization in terms of discrete, powerful and coherent entities, e.g., describing the first hospitalization as "swimming against the tide." The two metaphors modes reflect the embodiment of the unpredictability, being mired in distress, shock, intense pain and the experience the collapse of continuity on the life course and cuts off the experience of control. Conclusions Metaphors are important and powerful guide in assessing individuals and families’ phenomenological reality. As such, metaphors are useful for understanding and orientated therapeutic intervening, in the studies above, with the first psychiatric hospitalization experienced, as well as in others social workers’ interventions.

Keywords: first mental breakdown, metaphors, family perspective, qualitative research

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Authors: Sam Yurdakul, Nick Baverstock, Jim Mills

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TDT 064 (FLEXISEQ®) is a drug-free gel used to treat osteoarthritis (OA)-associated pain and joint stiffness. It contains ultra-deformable phospholipid Sequessome™ vesicles, which can pass through the skin barrier intact. In six randomized OA studies, topical TDT 064 was well tolerated and improved joint pain, physical function and stiffness. In the largest study, these TDT 064-mediated effects were statistically significantly greater than oral placebo and equivalent to celecoxib. To understand the therapeutic effects of TDT 064, we investigated the localisation of the drug-free vesicles within rat synovial joints. TDT 064 containing DiO-labelled Sequessome™ vesicles was applied to the knees of four 6-week-old CD® hairless rats (10 mg/kg/ joint), 2–3 times/day, for 3 days (representing the recommended clinical dose). Eighteen hours later, the animals and one untreated control were sacrificed, and the knee joints isolated, flash frozen and embedded in Acrytol Mounting Media™. Approximately 15 sections (10 µm) from each joint were analysed by fluorescence microscopy. To investigate whether the localisation of DiO fluorescence was associated with intact vesicles, an anti-PEG monoclonal antibody (mAb) was used to detect Tween, a constituent of Sequessome™ vesicles. Sections were visualized at 484 nm (DiO) and 647 nm (anti-PEG mAb) and analysed using inForm 1.4 (Perkin Elmer, Inc.). Significant fluorescence was observed at 484 nm in sections from TDT 064-treated animals. No non-specific fluorescence was observed in control sections. Fluorescence was detected as discrete vesicles on the cartilage surfaces, inside the cartilaginous matrix and within the synovial space. The number of DiO-labelled vesicles in multiple fields of view was consistent and >100 in sections from four different treated knees. DiO and anti-PEG mAb co-localised within the collagenous tissues in four different joint sections. Under higher magnification (40x), vesicles were seen in the intercellular spaces of the synovial joint tissue, but no fluorescence was seen inside cells. These data suggest that the phospholipid vesicles in TDT 064 localize at the surface of the joint cartilage; these vesicles may therefore be supplementing the phospholipid deficiency reported in OA and acting as a biolubricant within the synovial joint.

Keywords: joint pain, osteoarthritis, phospholipid vesicles, TDT 064

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: X. Han, S. Duan, C. Liu, C. Zhou, W. Zhu, L. Kong

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The ionic imprinting technique refers to the three-dimensional rigid structure with the fixed pore sizes, which was formed by the binding interactions of ions and functional monomers and used ions as the template, it has a high level of recognition to the ionic template. The preparation of monolithic column by the in-situ polymerization need to put the compound of template, functional monomers, cross-linking agent and initiating agent into the solution, dissolve it and inject to the column tube, and then the compound will have a polymerization reaction at a certain temperature, after the synthetic reaction, we washed out the unread template and solution. The monolithic columns are easy to prepare, low consumption and cost-effective with fast mass transfer, besides, they have many chemical functions. But the monolithic columns have some problems in the practical application, such as low-efficiency, quantitative analysis cannot be performed accurately because of the peak shape is wide and has tailing phenomena; the choice of polymerization systems is limited and the lack of theoretical foundations. Thus the optimization of components and preparation methods is an important research direction. During the preparation of ionic imprinted monolithic columns, pore-forming agent can make the polymer generate the porous structure, which can influence the physical properties of polymer, what’ s more, it can directly decide the stability and selectivity of polymerization reaction. The compounds generated in the pre-polymerization reaction could directly decide the identification and screening capabilities of imprinted polymer; thus the choice of pore-forming agent is quite critical in the preparation of imprinted monolithic columns. This article mainly focuses on the research that when using different pore-forming agents, the impact of zinc ion imprinted monolithic column on the enrichment performance of zinc ion.

Keywords: high performance liquid chromatography (HPLC), ionic imprinting, monolithic column, pore-forming agent

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Authors: Maiko Kiyohara, Toshiki Ito

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In this study, we used a psychotherapy process for patient with dissociative disorder and the graphic Rorschach (Digital version) (GRD). A dissociative disorder is a type of dissociation characterized by multiple alternating personalities (also called alternate identity or another identity). "dissociation" is a state in which consciousness, memory, thinking, emotion, perception, behavior, body image, and so on are divided and experienced. Dissociation symptoms, such as lack of memory, are seen, and the repetition of blanks in daily events causes serious problems in life. Although the pathological mechanism of dissociation has not yet been fully elucidated, it is said that it is caused by childhood abuse or shocking trauma. In case of Japan, no reliable data has been reported on the number of patients and prevalence of dissociative disorders, no drug is compatible with dissociation symptoms, and no clear treatment has been established. GRD is a method that the author revised in 2017 to a Graphic Rorschach, which is a special technique for subjects to draw language responses when enforce Rorschach. GRD reduces the burden on both the subject and the examiner, reduces the complexity of organizing data, improves the simplicity of organizing data, and improves the accuracy of interpretation by introducing a tablet computer during the drawing reaction. We are conducting research for the purpose. The patient in this case is a woman in her 50s, and has multiple personalities since childhood. At present, there are about 10 personalities whose main personality is just grasped. The patients is raising her junior high school sons as single parent, but personal changes often occur at home, which makes the home environment inferior and economically oppressive, and has severely hindered daily life. In psychotherapy, while a personality different from the main personality has appeared, I have also conducted psychotherapy with her son. In this case, the psychotherapy process and the GRD were performed to understand the personality characteristics, and the possibility of therapeutic significance to personality integration is reported.

Keywords: GRD, dissociative disorder, a case study of psychotherapy process, dissociation

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Authors: Ezedin Geta Seid

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Slope failures are among the common geo-environmental natural hazards in the hilly and mountainous terrain of the world causing damages to human life and destruction of infrastructures. In Ethiopia, the demand for the construction of infrastructures, especially highways and railways, has increased to connect the developmental centers. However, the failure of roadside slopes formed due to the difficulty of geographical locations is the major difficulty for this development. As a result, a comprehensive site-specific investigation of destabilizing agents and a suitable selection of slope profiles are needed during design. Hence, this study emphasized the stability analysis and performance evaluation of slope profiles (single slope, multi-slope, and benched slope). The analysis was conducted for static and dynamic loading conditions using limit equilibrium (slide software) and finite element method (Praxis software). The analysis results in selected critical sections show that the slope is marginally stable, with FS varying from 1.2 to 1.5 in static conditions, and unstable with FS below 1 in dynamic conditions. From the comparison of analysis methods, the finite element method provides more valuable information about the failure surface of a slope than limit equilibrium analysis. Performance evaluation of geometric profiles shows that geometric modification provides better and more economical slope stability. Benching provides significant stability for cut slopes (i.e., the use of 2m and 3m bench improves the factor of safety by 7.5% and 12% from a single slope profile). The method is more effective on steep slopes. Similarly, the use of a multi-slope profile improves the stability of the slope in stratified soil with varied strength. The performance is more significant when it is used in combination with benches. The study also recommends drainage control and slope reinforcement as a remedial measure for cut slopes.

Keywords: slope failure, slope profile, bench slope, multi slope

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Authors: Nicholas C. Rose, Christopher D. Spicer

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The regeneration of damaged or diseased tissues would provide an invaluable therapeutic tool in biological research and medicine. Cells must be provided with a number of different biochemical signals in order to form mature tissue through complex signaling networks that are difficult to recreate in synthetic materials. The ability to attach and detach bioactive proteins from material in an iterative and dynamic manner would therefore present a powerful way to mimic natural biochemical signaling cascades for tissue growth. We propose to reversibly attach these bioactive proteins using ortho-boronoimine (oBI) linkages and related derivatives formed by the reaction of an ortho-boronobenzaldehyde with a nucleophilic amine derivative. To enable the use of oBIs for biomaterial modification, we have studied binding and cleavage processes with precise detail in the context of small molecule models. A panel of oBI complexes has been synthesized and screened using a novel Förster resonance energy transfer (FRET) assay, using a cyanine dye FRET pair (Cy3 and Cy5), to identify the most reactive boron-aldehyde/amine nucleophile pairs. Upon conjugation of the dyes, FRET occurs under Cy3 excitation and the resultant ratio of Cy3:Cy5 emission directly correlates to conversion. Reaction kinetics and equilibria can be accurately quantified for reactive pairs, with dissociation constants of oBI derivatives in water (KD) found to span 9-orders of magnitude (10⁻²-10⁻¹¹ M). These studies have provided us with a better understanding of oBI linkages that we hope to exploit to reversibly attach bioconjugates to materials. The long-term aim of the project is to develop a modular biomaterial platform that can be used to help combat chronic diseases such as osteoarthritis, heart disease, and chronic wounds by providing cells with potent biological stimuli for tissue engineering.

Keywords: dynamic, bioconjugation, bornoimine, rapid, physiological

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Authors: Nino KItoshvili

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The family is an integral part of society, which plays a major role in the socialization and the formation of a person as a full member of society. The marital conflict even harms family members and finds a different effect on each member of the family, especially on children. There is a significant difference in the behavior of adolescents in conflict and non-conflict families. In times of marital conflict, adolescent psycho-social well-being is significantly dependent on socio-cultural mediating variables such as; Family income; Parenting style; The functioning of the family, and the existence of psycho-social support. In a family with low economic performance, low psychosocial harassment, family dysfunction, and bad parenting style, marital conflict significantly increases the risk of deteriorating adolescent psycho-social well-being. At this time, to support the well-being of the child, a special role is played by improving the marital relationship, which must be supported by state and community services. There are very few family studies in this field in Georgia, the therapeutic direction of the family is at an early stage, and there are no family-supporting psycho-social programs. This increases the chances of adolescent psycho-social well-being deteriorating amd socialization problems. The study will examine the mediating variables of marital conflict and adolescent psycho-social well-being and will attempt to determine their mediating and moderating role. Research suggests that an increase in the rate of marital conflict is associated with a decrease in child well-being. The well-being of children in conflict families is lower than that of children in non-conflict families and depends on the variables of mediating variables. Quantitative research will be conducted to study this phenomenon through a questionnaire developed and standardized in the research process. The study will be attended by families living in Georgia - spouses (married) and their adolescent children. By analyzing the data obtained from the research, we will be able to determine in which cases the intensity of the relationship between the marital conflict and the well-being of the adolescent increases or decreases; To conclude the mediating and moderating role of mediating variables and also to make relevant recommendations to reduce the negative impact on the psycho-social well-being of a child of marital conflict.

Keywords: adolescent, mediation, moderation, conflict, couple, well-being

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Authors: Raana Babadi Fathipour

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Biofilms, those intricate structures of microbial aggregation that emerge as microorganisms adhere to animate or inanimate surfaces, possess an innate capacity to shield their inhabitants from adversities within the environment whilst fortifying their endurance against antimicrobial agents. This remarkable aspect facilitates the persistence and virulence of said microorganisms, establishing biofilm formation as an integral component of bacterial survival mechanisms. However, should foodborne pathogens adopt this mode of existence, the potentiality for foodborne disease infections becomes alarmingly intensified—an alarming prospect that harbors significant public health hazards and engenders deleterious economic ramifications. Thus, due to these consequences lurking on the horizon, extensive research concentrating upon comprehending biofilms and devising efficacious removal strategies assumes a position imbued with paramount importance within the realm of the food industry. The problem of food waste resulting from spoilage in the food industry continues to present a widespread challenge to both environmental sustainability and the security of our food supplies. In this comprehensive analysis, we delve into the formation of bacterial biofilms, highlighting the specific issues they pose within the realm of food production. Additionally, we provide an overview of various types of common foodborne pathogens that tend to thrive in these biofilms. Furthermore, we summarize existing strategies aimed at tackling or managing detrimental bacterial biofilm growth. We also introduce contemporary approaches that show promise in terms of controlling this issue and highlight their potential for further advancement. Ultimately, our focus lies on outlining prospects for future development as they pertain specifically to combatting bacterial biofilms within the field.

Keywords: foodborne pathogens, food safety, biofilm, resistance, quorum-sensing

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Authors: Mohammed Khalil Ur Rahman, Khanita Aammatullh

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Rasayana is one of the eight clinical specialities of classical Ayurveda The disease preventive and health promotive approach of ‘Ayurveda’, which takes into consideration the whole body, mind and spirit while dealing with the maintenance of health, promotion of health and treating ailments is holistic and finds increasing acceptability in many regions of the world. Ancient Ayurvedic physicians had developed certain dietary and therapeutic measures to arrest/delay ageing and rejuvenating whole functional dynamics of the body system. This revitalization and rejuvenation is known as the ‘Rasayan chikitsa’ (rejuvenation therapy). Traditionally, Rasayana drugs are used against a plethora of seemingly diverse disorders with no pathophysiological connections according to modern medicine. Though, this group of plants generally possesses strong antioxidant activity, only a few have been investigated in detail. Over about 100 disorders like rheumatoid arthritis, hemorrhagic shock, CVS disorders, cystic fibrosis, metabolic disorders, neurodegenerative diseases, gastrointestinal ulcerogenesis and AIDS have been reported as reactive oxygen species mediated. In this review, the role of free radicals in these diseases has been briefly reviewed. ‘Rasayana’ plants with potent antioxidant activity have been reviewed for their traditional uses, and mechanism of antioxidant action. Fifteen such plants have been dealt with in detail and some more plants with less work have also been reviewed briefly The Rasayanas are rejuvenators, nutritional supplements and possess strong antioxidant activity. They also have antagonistic actions on the oxidative stressors, which give rise to the formation of different free radicals. Ocimum sanctum, Tinospora cordifolia, Emblica officinalis, Convolvulus pluricaulis, Centella asiatica, Bacopa monniera, Withania somnifera, Triphala rasayana, Chyawanprash, Brahma rasayana are very important rasayanas which are described in ayurveda and proved by new researches.

Keywords: rasayana, antioxidant activity, Bacopa monniera, Withania somnifera Triphala, chyawanprash

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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