Search results for: renal fibrosis signaling pathway

Authors: JiYoung Park, SueGoo Rhee, HyunAe Woo

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In liver regeneration, quiescent hepatocytes need to be primed to fully respond to growth factors such as hepatocyte growth factor. To understand the priming process, it is necessary to analyze patterns of gene expression that occur during liver regeneration after partial hepatectomy (PHx). Recently, tyrosine phosphorylation of signal transducer and activator of transcription 3 (pYSTAT3) has been shown to play an important role in initiating liver regeneration. In order to evaluate the role of pYSTAT3 on liver regeneration after PHx, we used an intrabody which can selectively inhibit pYSTAT3. In our previous studies, an intrabody had been shown that it bound specifically to the pYSTAT3. Adenovirus-mediated expression of the intrabody in HepG2 cells, as well as mouse liver, blocked both accumulation of pYSTAT3 in the nucleus and downstream target of pYSTAT3. In this study, PHx was performed on intrabody-expressing mice and the expression levels of liver regeneration-related genes were analyzed. We also measured liver/body weight ratios and the related cellular signaling pathways were analyzed. Acute phase response genes were reduced in an intrabody-expressing mice during liver regeneration than in control virus-injected mice. However, the time course of liver mass restoration in intrabody-expressing mice was similar to that observed in control virus-injected mice. We also observed that the expression levels of anti-apoptotic genes, such as Bcl2 and Bcl-xL were decreased in intrabody-expressing mice whereas the expression of cell cycle-related genes such as cyclin D1, and c-myc was increased. Liver regeneration after PHx was partially impaired by the selective inhibition of pYSTAT3 with a phosphorylation site-specific intrabody and these results indicated that pYSTAT3 might have limited role in liver mass recovery.

Keywords: STAT3, pYSTAT3, liver regeneration, intrabody

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Authors: Sónia Ribeiro, Diana Farinha, Hélia Sales, Rita Pontes, João Nunes

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The demand and commitment to sustainability in the agrifood sector introduce news opportunities for new composite materials. Composite materials are emerging as a vital entity for the sustainable development. Polylactic acid (PLA) has been recognized as a potential polymer with attractive characteristics for agrifood sector applications. PLA that can be beneficial for the development of composites, biocomposites, films, porous gels, and so on. The production of PLA from lignocellulosic biomass residues matrix is a key option towards a sustainable and circular bioeconomy and a non-competitive application with feed and food sector. The Flui and BeirInov projects presents news developments in the production of PLA composites to value the Portuguese forest ecosystem, with high amount of lignocellulosic biomass residues and available. A performance production of lactic acid from lignocellulosic biomass undergoes a process of autohydrolysis, saccharification and fermentation, originating a lactic acid fermentation medium with a 72.27g.L-1 was obtained and a final purification of 72%. The high purification PLA from multi lignocellulosic residues representing one economic expensive process, and a new materials and application for the polymers and a combination with others types of composites matrix characteristic is the drive-up for this green market.

Keywords: polylactic acid, lignocellulosic biomass, agrifood, composite materials

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Authors: Imme Petersen, Wiebke Sick, Regine Kollek

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In systems medicine, high-throughput technologies produce large amounts of data on different biological and pathological processes, including (disturbed) gene expressions, metabolic pathways and signaling. The large volume of data of different types, stored in separate databases and often located at different geographical sites have posed new challenges regarding data handling and processing. Tools based on bioinformatics have been developed to resolve the upcoming problems of systematizing, standardizing and integrating the various data. However, the heterogeneity of data gathered at different levels of biological complexity is still a major challenge in data analysis. To build multilayer disease modules, large and heterogeneous data of disease-related information (e.g., genotype, phenotype, environmental factors) are correlated. Therefore, a great deal of attention in systems medicine has been put on data standardization, primarily to retrieve and combine large, heterogeneous datasets into standardized and incorporated forms and structures. However, this data-centred concept of standardization in systems medicine is contrary to the debate in science and technology studies (STS) on standardization that rather emphasizes the dynamics, contexts and negotiations of standard operating procedures. Based on empirical work on research consortia that explore the molecular profile of diseases to establish systems medical approaches in the clinic in Germany, we trace how standardized data are processed and shaped by bioinformatics tools, how scientists using such data in research perceive such standard operating procedures and which consequences for knowledge production (e.g. modeling) arise from it. Hence, different concepts and meanings of standardization are explored to get a deeper insight into standard operating procedures not only in systems medicine, but also beyond.

Keywords: data, science and technology studies (STS), standardization, systems medicine

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Authors: Munir Majdalawieh, Adam Marks

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In today’s very competitive higher education industry (HEI), HEIs are faced with the primary concern of developing, deploying, and sustaining high quality academic programs. Today, the HEI has well-established accreditation systems endorsed by a country’s legislation and institutions. The accreditation system is an educational pathway focused on the criteria and processes for evaluating educational programs. Although many aspects of the accreditation process highlight both the past and the present (prove), the “program review” assessment is "forward-looking assessment" (improve) and thus transforms the process into a continuing assessment activity rather than a periodic event. The purpose of this study is to propose a conceptual measurement framework for program review to be used by HEIs to undertake a robust and targeted approach to proactively and continuously review their academic programs to evaluate its practicality and effectiveness as well as to improve the education of the students. The proposed framework consists of two main components: program review principles and the program review measurement matrix.

Keywords: academic program, program review principles, curriculum development, accreditation, evaluation, assessment, review measurement matrix, program review process, information technologies supporting learning, learning/teaching methodologies and assessment

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Authors: Chloe T. Cohen, Sarah Johnson

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Psychoanalytic literature has traditionally focused on the theoretical explanations of psychological phenomena rather than empirical research to support those ideas. Many clinicians assume a lack of empirical verification of the theories that underpin psychoanalytic treatment disqualifies psychoanalytic psychotherapy as an effective clinical technique. One such theory is Lacan’s ‘Name of the Father’, which extended Freud’s idea of the importance of a successful resolution of the Oedipal problem, situating it even earlier in psychological development. Lacan posited that the Name of the Father construct (establishing psychological structure and preventing psychosis) was best represented in language use, metaphor, and linguistic structure. However, no study to date has empirically examined the Name of the Father construct. The current study attempts to measure Lacan’s ‘Name of the Father’ construct through linguistic structure and metaphor use and to compare it with Freud’s ‘original introject’. We will then investigate whether they relate to adult personality functioning (measured using the Rorschach Inkblot Test). We aim to contribute to the empirical study of psychoanalytic concepts by operationalizing and validating the Name of the Father empirically. We also aim to examine the relationship of the Name of the Father construct to Freud’s concept of the original introject and to adult pathology. We hypothesize that measures of the original introject will mediate the pathway between linguistic indicators of Lacan’s Name of the Father construct and personality functioning.

Keywords: Lacan, Name of the Father, original introject, personality functioning, psychoanalysis

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Authors: Harminder Kaur, Manpreet Kaur, Akanksha Kapila, Reenu

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Schiff base with general formula H₂L was derived from condensation of o-vanillin and 3-nitro-o-phenylenediamine. This Schiff base was used for the synthesis of organotin(IV) complexes with general formula R₂SnL [R=Phenyl or n-octyl] using equimolar quantities. Elemental analysis UV-Vis, FTIR, and multinuclear spectroscopic techniques (¹H, ¹³C, and ¹¹⁹Sn) NMR were carried out for the characterization of the synthesized complexes. These complexes were coloured and soluble in polar solvents. Computational studies have been performed to obtain the details of the geometry and electronic structures of ligand as well as complexes. Geometry of the ligands and complexes have been optimized at the level of Density Functional Theory with B3LYP/6-311G (d,p) and B3LYP/MPW1PW91 respectively followed by vibrational frequency analysis using Gaussian 09. Observed ¹¹⁹Sn NMR chemical shifts of one of the synthesized complexes showed tetrahedral geometry around Tin atom which is also confirmed by DFT. HOMO-LUMO energy distribution was calculated. FTIR, ¹HNMR and ¹³CNMR spectra were also obtained theoretically using DFT. Further IRC calculations were employed to determine the transition state for the reaction and to get the theoretical information about the reaction pathway. Moreover, molecular docking studies can be explored to ensure the anticancer activity of the newly synthesized organotin(IV) complexes.

Keywords: DFT, molecular docking, organotin(IV) complexes, o-vanillin, 3-nitro-o-phenylenediamine

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Authors: Khaled S. Al Salhen

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Aldehyde oxidase is molybdo-flavoenzyme involved in the oxidation of hundreds of endogenous and exogenous and N-heterocyclic compounds and environmental pollutants. Uncharged N-heterocyclic aromatic compounds such phenanthridine are commonly distributed pollutants in soil, air, sediments, surface water and groundwater, and in animal and plant tissues. Phenanthridine as uncharged N-heterocyclic aromatic compound was incubated with partially purified aldehyde oxidase from rainbow trout fish liver. Reversed-phase HLPC method was used to separate the oxidation products from phenanthridine and the metabolite was identified. The 6(5H)-phenanthridinone was identified the major metabolite by partially purified aldehyde oxidase from fish liver. Kinetic constant for the oxidation reactions were determined spectrophotometrically and showed that this substrate has a good affinity (Km = 78 ± 7.6 µM) for hepatic aldehyde oxidase, coupled with a relatively high oxidation rate (0.77± 0.03 nmol/min/mg protein). In addition, the kinetic parameters of hepatic fish aldehyde oxidase towards the phenanthridine substrate indicate that in vitro biotransformation by hepatic fish aldehyde oxidase will be a significant pathway. This study confirms that partially purified aldehyde oxidase from fish liver is indeed the enzyme responsible for the in vitro production 6(5H)-phenanthridinone metabolite as it is a major metabolite by mammalian aldehyde oxidase.

Keywords: aldehyde oxidase, fish, phenanthridine, specificity

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Authors: Kazui Sasakii, Seira Mormune-Moriya, Hiroaki Tanahashi, Shigeji Kongaya

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Poly (3.4-ethylenedioxythiophene) doped with poly (4-styrene sulfonate) (PEDOT: PSS) attracted a great deal of attention because of its unique characteristics of flexibility, optical properties, heat resistance and colloidal dispersion in water. It is well known that when high boiling solvents such as ethylene glycol or dimethyl sulfoxide are added as a secondary dopant to the micellar structure, PEDOT microcrystallizes and becomes highly conductive. In previous study bis(4-hydroxyphenyl) sulfone (BPS) was used as a secondary dopant for PEDOT:PSS and the enhancement of the conductivity was revealed. However, ductility is one of the serious issues which limited the application of PEDOT:PSS/BPS. So far, the composition with polymer binders has been conducted, however, polymer binders decrease the conductivity of the materials. In this study, PEDOT: PSS composites with polyester (PEs) were prepared by a simple aqueous process using PEs emulsion. The structural studies revealed that PEDOT:PSS and PEs were homogeneously distributed in the composites. It was found that the properties of PEDOT:PSS were remarkably enhanced by the incorporation of PEs. According to the tensile test, the ductility of PEDOT:PSS was remarkably improved. Interestingly, the conductivity of PEDOT:PSS/PEs composites was higher than that of neat PEDOT:PSS. For example, the conductivity increased by 8% at PEs content of 25 wt%. Since PEDOT:PSS were homogeneously dispersed on the surface of PEs particles, it was assumed that the conductive pathway was constructed by PEs particles in the nanocomposites. Therefore, a significant increase in conductivity was achieved.

Keywords: polymer composites, conductivity, PEDOT:PSS, polyester

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Authors: Ayeshmanthe Rathnayake, Siew Goh, Carmel Fenton, Ashutosh Hardikar

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Post-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accident, heart failure, renal dysfunction, infection and length of stay, and hospital costs. Cardiac tamponade, although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a left posterior pericardiotomy aims to shunt blood from the pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade. 2118 patients had undergone isolated Coronary Artery Bypass Graft (CABG) at Royal Hobart Hospital from 2008-2021. They were divided into pericardiotomy vs control group. Patient baseline demographics, intraoperative data, and post-operative outcomes were reviewed retrospectively. Total incidence of new POAF and cardiac tamponade was 26.1% and 0.75%, respectively. Primary outcome of both the incidence of POAF(22.9% vs27.8%OR 0.77 p<0.05) and Cardiac Tamponade (0% vs 1.1% OR 0.85 p<0.05) were less in the pericardiotomy group.Increasing age, BMI, poor left ventricular function (EF <30%), and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal. Left posterior pericardiotomy is associated with a significant reduction in the incidence of POAFand cardiac tamponade and issafe and efficient.

Keywords: cardiac surgery, pericardiotomy, post-operative atrial fibrillation, cardiac tamponade

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Authors: Christos Bouras, Eirini Stergiou, Charitini Karakostaki, Vasileios Tzanos, Vasileios Kokkinos

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Wind power represents a major pathway to curtailing greenhouse gas emissions and thus reducing the rate of climate change. A wind turbine runs practically emission-free for 20 years, representing one of the most environmentally sustainable sources of energy. Nevertheless, environmental and biodiversity concerns can often slow down or halt the deployment of wind farms due to local public opposition. This opposition is often fueled by poor relationships between wind energy stakeholders and civil society, which in many cases led to conflictual protests and property damage. In this context, addressing these concerns is essential in order to facilitate the proliferation of wind farms in Europe and the phase-out of fossil fuels from the energy mix. The aim of this study is to identify a number of good practices and cases to avoid increasing biodiversity protection at all stages of wind farms’ lifecycle in three participating countries, namely Greece, Latvia, and Poland. The results indicate that although available technological solutions are already being exploited worldwide, in these countries, there is still room for improvement. To address this gap, a set of policy recommendations is proposed to accomplish the wind energy targets in the near future while simultaneously mitigating the pertinent biodiversity risks.

Keywords: biodiversity protection, environmental impact, social acceptance, wind energy

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Authors: Kimuli Ismail, Michael Lubwama, John Baptist Kirabira, Adam Sebbit

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This study develops 4 energy scenarios for Greater Kampala Metropolitan Area (GKMA). GKMA is Uganda’s capital with a population of 4.1million and a GDP growth rate of 5.8 with a nonsustainable energy management system. The study uses TIMES-VEDA to examine the energy impacts of business as usual (BAU), Kabejja, Carbon-Tax, and Lutta scenarios in commercial, industrial, transportation, residential, agricultural, and electricity generation activities. BAU is the baseline scenario with limited CO2 emissions restrictions against which Kabejja with 20% CO2 emissions restriction, a carbon tax of $100/ton imposed in 2050 for Carbon-Tax scenario, and Lutta with 95% CO2 emissions restriction is made. The analysis suggests that if the current policy trends continue as BAU, consumption would increase from 139.6PJ to 497.42PJ and CO2 emissions will increase from 4.6mtns to 7mtns. However, consumption would decrease by 2.3% in Kabejja, 3.4% in Carbon-Tax, and 3.3 % in Lutta compared to BAU. The CO2 emissions would decrease by 8.57% in Kabejja, 55.14% in Carbon-Tax, and 60% in Lutta compared to BAU. Sustainability is achievable when low-carbon electricity is increased by 53.68% in the EMS, and setting up an electrified Kampala metro. The study recommends Lutta as the sustainable pathway to a lowcarbon 2050.

Keywords: Sustainability, Scenario Plannnig, Times-Veda Modelling, Energy Policy Development

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Authors: Mariem Meddeb Sidhom, Souhayel Hedfi, Rjaibia Houda, Mehdi Dridi, Mohamed Ali Yousfi, Sâadia Gargouri

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Considering the important increase in costs of caspofungin treatments and ahead the evolution of its indication, pharmacy department was prompted to realize a review of the adequacy of prescriptions in the medical intensive care units (ICU). A retrospective observational study was conducted in Tunis military hospital concerning ICU prescriptions of caspofungin from 2008 until 2013. A pharmacist had returned to the patient’s medical records to collect data and to the microbiology department for parasitological results. The adequacy of prescriptions was evaluated by a pharmacist and an infectiologist parasitologist, referring to predefined scale of criteria resuming the indications of the marketing authorization (MA) and grade AI-AII of the guidelines of the Infectious Diseases Society of America (IDSA). Sixty two ICU patients have been treated with caspofungin during the period of study; however, 8 files were lost. Thus, 54 patients were included in the study having received 55 prescriptions of caspofungin. Males were a majority with 64.8% of the population. Mean age was 51 years. Caspofungin was indicated in accordance with the IDSA recommendations in 43.6% of the cases. The most case of non respect to the guidelines was the indication of caspofungin as empirical treatment in non neutropenic patients. Caspofungin was utilized as a first line treatment in 9 cases where it was possible to give fluconazole first, as germs were fluconazole- sensitive. Caspofungin was indicated in 2 patients with good renal function and in which nor amphotericin B, liposomal ampho B neither itraconazole had been previously used, as indicates the MA. The posology of caspofungin was respected in all prescriptions with a loading dose of 70 mg in the first day and a maintenance dose of 50 mg daily. Seven patients had received a daily dose of 70 mg, the recommended dose for people weighing more than 80 Kg. Caspofungin prescriptions are far to be adequately done. There is a clear need of optimization in indicating this molecule and that must be done in collaboration between the pharmacy department, the ICUs and parasitology department.

Keywords: caspofungin, prescription, intensive care units, marketing authorization, Tunisian hospital cohort

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Authors: Said Ghalem

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Honey is primarily composed of sugars: glucose and fructose. Depending honey, it's either fructose or glucose predominates. More the fructose concentration and the less the glycemic index (GI) is high. Thus, changes in the insulin response shows a decrease of the amount of insulin secreted at an increased fructose honey. Honey is also a compound that can reduce the lipid in the blood. Several studies on animals, but which remain to be checked in humans, have shown that the honey can have interesting effects when combined with other molecules: associated with Metformin (a medicine taken by diabetics), it shows the benefits and effects of diabetes preserves the tissue; associated ginger, it increases the antioxidant activity and thus avoids neurologic complications, neuropathic. Molecular modeling techniques are widely used in chemistry, biology, and the pharmaceutical industry. Most of the currently existing drugs target enzymes. Inhibition of DPP-4 is an important approach in the treatment of type 2 diabetes. We have chosen for the inhibition of DPP-4 the following molecules: Linagliptin (BI1356), Sitagliptin (Januvia), Vildagliptin, Saxagliptin, Alogliptin, and Metformin (Glucophage), that are involved in the disease management of type 2 diabetes and added to honey. For this, we used software Molecular Operating Environment. A Wistar rat study was initiated in our laboratory with a well-studied protocol; after sacrifice, according to international standards and respect for the animal This theoretical approach predicts the mode of interaction of a ligand with its target. The honey can have interesting effects when combined with other molecules, it shows the benefits and effects of honey preserves the tissue, it increases the antioxidant activity, and thus avoids neurologic complications, neuropathic or macrovascular. The organs, especially the kidneys of Wistar, shows that the parameters to renal function let us conclude that damages caused by diabetes are slightly perceptible than those observed without the addition of a high concentration of fructose honey.

Keywords: honey, molecular modeling, DPP4 enzyme, metformin

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

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Authors: Mohammad Aladwan

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Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Ahmed Shaboub, Yusuf Jasim Althawadi, Shadi Alaa Abdelaal, Mohamed Hussein Abdalla, Hatem Amr Elzahaby, Mohamed Mohamed, Hazem S. Ghaith, Ahmed Negida

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Objectives: We aimed to compare the safety and outcomes of the minimally invasive approaches versus conventional sternotomy procedures for aortic valve replacement. Methods: We conducted a PRISMA-compliant systematic review and meta-analysis. We ran an electronic search of PubMed, Cochrane CENTRAL, Scopus, and Web of Science to identify the relevant published studies. Data were extracted and pooled as standardized mean difference (SMD) or risk ratio (RR) using StataMP version 17 for macOS. Results: Forty-one studies with a total of 15,065 patients were included in this meta-analysis (minimally invasive approaches n=7231 vs. conventional sternotomy n=7834). The pooled effect size showed that minimally invasive approaches had lower mortality rate (RR 0.76, 95%CI [0.59 to 0.99]), intensive care unit and hospital stays (SMD -0.16 and -0.31, respectively), ventilation time (SMD -0.26, 95%CI [-0.38 to -0.15]), 24-h chest tube drainage (SMD -1.03, 95%CI [-1.53 to -0.53]), RBCs transfusion (RR 0.81, 95%CI [0.70 to 0.93]), wound infection (RR 0.66, 95%CI [0.47 to 0.92]) and acute renal failure (RR 0.65, 95%CI [0.46 to 0.93]). However, minimally invasive approaches had longer operative time, cross-clamp, and bypass times (SMD 0.47, 95%CI [0.22 to 0.72], SMD 0.27, 95%CI [0.07 to 0.48], and SMD 0.37, 95%CI [0.20 to 0.45], respectively). There were no differences between the two groups in blood loss, endocarditis, cardiac tamponade, stroke, arrhythmias, pneumonia, pneumothorax, bleeding reoperation, tracheostomy, hemodialysis, or myocardial infarction (all P>0.05). Conclusion: Current evidence showed higher safety and better operative outcomes with minimally invasive aortic valve replacement compared to the conventional approach. Future RCTs with long-term follow-ups are recommended.

Keywords: aortic replacement, minimally invasive, sternotomy, mini-sternotomy, aortic valve, meta analysis

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Authors: Ashish Kumar Pathak, Ritika Sharma, Vishal Nath, Sudhir Pratap Singh, Rakesh Tuli

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Litchi is a sub-tropical fruit crop with genotypes bearing delicious juicy fruits with variable seed size (bold to rudimentary size). Small seed size is a desirable trait in litchi, as it increases consumer acceptance and fruit processing. The biochemical activities in mid- stage ovules (e.g. 16, 20, 24 and 28 days after anthesis) determine the fate of seed and fruit development in litchi. Comprehensive ovule-specific transcriptome analysis was performed in two litchi genotypes with contrasting seed size to gain molecular insight on determinants of seed fates in litchi fruits. The transcriptomic data was de-novo assembled in 1,39,608 trinity transcripts, out of which 6,325 trinity transcripts were differentially expressed between the two contrasting genotypes. Differential transcriptional pattern was found among ovule development stages in contrasting litchi genotypes. The putative genes for salicylic acid, jasmonic acid and brassinosteroid pathway were down-regulated in ovules of small-seeded litchi. Embryogenesis, cell expansion, seed size and stress related trinity transcripts exhibited altered expression in small-seeded genotype. The putative regulators of seed maturation and seed storage were down-regulated in small-seed genotype.

Keywords: Litchi, seed, transcriptome, defence

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Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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Authors: Pui Shan Wong, Kosuke Tashiro, Satoru Kuhara, Sachiyo Aburatani

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Functional genomics and gene regulation inference has readily expanded our knowledge and understanding of gene interactions with regards to expression regulation. With the advancement of transcriptome sequencing in time-series comes the ability to study the sequential changes of the transcriptome. This method presented here works to augment existing regulation networks accumulated in literature with transcriptome data gathered from time-series experiments to construct a sequential representation of transcription factor activity. This method is applied on a time-series RNA-Seq data set from Escherichia coli as it transitions from growth to stationary phase over five hours. Investigations are conducted on the various metabolic activities in gene regulation processes by taking advantage of the correlation between regulatory gene pairs to examine their activity on a dynamic network. Especially, the changes in metabolic activity during phase transition are analyzed with focus on the pagP gene as well as other associated transcription factors. The visualization of the sequential transcriptional activity is used to describe the change in metabolic pathway activity originating from the pagP transcription factor, phoP. The results show a shift from amino acid and nucleic acid metabolism, to energy metabolism during the transition to stationary phase in E. coli.

Keywords: Escherichia coli, gene regulation, network, time-series

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Karolis Leonavičius, Dalius Kučiauskas, Dangiras Lukošius, Arnoldas Jasiūnas, Kostas Zdanys, Rokas Stanislovas, Emilis Gegevičius, Žana Kapustina, Juozas Nainys

Abstract:

Screening throughput is a common bottleneck in many research areas, including functional genomics, drug discovery, and directed evolution. High-throughput screening techniques can be classified into two main categories: (i) affinity-based screening and (ii) functional screening. The first one relies on binding assays that provide information about the affinity of a test molecule for a target binding site. Binding assays are relatively easy to establish; however, they reveal no functional activity. In contrast, functional assays show an effect triggered by the interaction of a ligand at a target binding site. Functional assays might be based on a broad range of readouts, such as cell proliferation, reporter gene expression, downstream signaling, and other effects that are a consequence of ligand binding. Screening of large cell or gene libraries based on direct activity rather than binding affinity is now a preferred strategy in many areas of research as functional assays more closely resemble the context where entities of interest are anticipated to act. Droplet sorting is the basis of high-throughput functional biological screening, yet its applicability is limited due to the technical complexity of integrating high-performance droplet analysis and manipulation systems. As a solution, the Droplet Genomics Styx platform enables custom droplet sorting workflows, which are necessary for the development of early-stage or complex biological therapeutics or industrially important biocatalysts. The poster will focus on the technical design considerations of Styx in the context of its application spectra.

Keywords: functional screening, droplet microfluidics, droplet sorting, dielectrophoresis

Procedia PDF Downloads 135

Authors: Boshra Mozaffar, Arash Ardavani, Iskandar Idris

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Food taste and flavor affect food choice and acceptance, which are essential to maintain good health and quality of life. Reduced circulating zinc levels have been shown to adversely affect taste which can result in reduced appetite, weight loss and psychological problems, but the efficacy of Zinc supplementation to treat disorders of taste remains unclear. In this systematic review and meta-analysis, we aimed to examine the efficacy of zinc supplementation in the treatment of taste disorders. We searched four electronic bibliographical databases; Ovid MEDLINE, Ovid Embase, Ovid AMAD and PubMed. Article bibliographies were also searched, which yielded additional relevant studies. To facilitate the collection and identification of all available and relevant articles published before 7 December 2020, there were no restrictions on the publication date. We performed a systematic review and meta-analysis according to the PRISMA Statement. This review was registered at PROSPERO and given the identification number CRD42021228461. In total, we included 12 randomized controlled trials with 938 subjects. Intervention includes zinc (sulfate, gluconate, picolinate, polaprezinc and acetate); the pooled results of the meta-analysis indicate that improvements in taste disorder occurred more frequently in the intervention group compared to the control group (RR = 1.8; 95% CI:1.27 -2.57, p=0.009). The doses are equivalent to 17 mg- 86.7 mg of elemental zin for three to six months. Zinc supplementation is an effective treatment for taste disorders in patients with zinc deficiency or idiopathic taste disorders when given in high doses ranging from 68–86.7 mg/d for up to three months. However, we did not find sufficient evidence to determine the effectiveness of zinc supplementation in patients with taste disorders induced by chronic renal failure.

Keywords: taste change, taste disorder, zinc, zinc sulfate or Zn, deficiency, supplementation.

Procedia PDF Downloads 263

Authors: A. Duncan, A. Blake, A. O'Gara, J. Fitzgerald

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Introduction: Acute traumatic rib fractures have significant morbidity and mortality and are a commonly seen injury in trauma patients. Rib fracture pain can often be acute and can prove challenging to manage. We performed an audit on patients with acute traumatic rib fractures with the aim of composing a referral and treatment pathway for such patients. Methods: From January 2021 to January 2022, the pain medicine service encouraged early referral of all traumatic rib fractures to the pain service for a multi-modal management approach. A retrospective audit of analgesic management was performed on a select cohort of 24 patients, with a mean age of 67, of which 19 had unilateral rib fractures. Results: 17 of 24 patients (71%) underwent local, regional block as part of a multi-modal analgesia regime. Only one regional complication was observed, seen with hypotension occurring in one patient with a thoracic epidural. The group who did not undergo regional block had a length of stay (LOS) 17 days longer than those who did (27 vs. 10) and higher rates of pneumonia (29% vs. 18%). Conclusion: Early referral to pain specialists is an important component of the effective management of acute traumatic rib fractures. From our audit, it is evident that regional blocks can be effectively used in these cases as part of a multi-modal analgesia regime and may confer benefits in terms of respiratory complications and length of stay.

Keywords: rib fractures, regional blocks, thoracic epidural, erector spina block

Procedia PDF Downloads 75

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

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Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Saroj Poudel, Joshua Mancini, Douglas Pike, Jennifer Timm, Alexei Tyryshkin, Vikas Nanda, Paul Falkowski

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On the early Earth, protein-metal complexes likely harvested energy from a reduced environment. These complexes would have been precursors to the metabolic enzymes of ancient organisms. Hydrogenase is an essential enzyme in most anaerobic organisms for the reduction and oxidation of hydrogen in the environment and is likely one of the earliest evolved enzymes. To attempt to reinvent a precursor to modern hydrogenase, we computationally designed a short thirteen amino acid peptide that binds the often-required catalytic transition metal Nickel in hydrogenase. This simple complex can achieve hundreds of hydrogen evolution cycles using light energy in a broad range of temperature and pH. Biophysical and structural investigations strongly indicate the peptide forms a di-nickel active site analogous to Acetyl-CoA synthase, an ancient protein central to carbon reduction in the Wood-Ljungdahl pathway and capable of hydrogen evolution. This work demonstrates that prior to the complex evolution of multidomain enzymes, early peptide-metal complexes could have catalyzed energy transfer from the environment on the early Earth and enabled the evolution of modern metabolism

Keywords: hydrogenase, prebiotic enzyme, metalloenzyme, computational design

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Authors: Debatosh Das, Moxian Chen, Jianhua Zhang, Caroline Gutjahr

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Arbuscular mycorrhiza (AM) is a mutualistic symbiosis between plant roots and Glomeromycotina fungi, which is activated under low but inhibited by high phosphate. The effect of phosphate on AM development has been observed for many years, but mechanisms regulating it under contrasting phosphate levels remain unknown. Based on previous observations that promoters of several AM functional genes contain PHR binding motifs, we hypothesized that PHR2, a master regulator of phosphate starvation response in rice, was recruited to regulate AM symbiosis development. We observed a drastic reduction in root colonization and significant AM transcriptome modulation in phr2. PHR2 targets genes required for root colonization and AM signaling. The role of PHR2 in improving root colonization, mycorrhizal phosphate uptake, and growth response was confirmed in field soil. In conclusion, rice PHR2, which is considered a master regulator of phosphate starvation responses, acts as a positive regulator of AM symbiosis between Glomeromycotina fungi and rice roots. PHR2 directly targets the transcription of plant strigolactone and AM genes involved in the establishment of this symbiosis. Our work facilitates an understanding of ways to enhance AMF propagule populations introduced in field soils (as a biofertilizer) in order to restore the natural plant-AMF networks disrupted by modern agricultural practices. We show that PHR2 is required for AM-mediated improvement of rice yield in low phosphate paddy field soil. Thus, our work contributes knowledge for rational application of AM in sustainable agriculture. Our data provide important insights into the regulation of AM by the plant phosphate status, which has a broad significance in agriculture and terrestrial ecosystems.

Keywords: biofertilizer, phosphate, mycorrhiza, rice, sustainable, symbiosis

Procedia PDF Downloads 133

Authors: Abdelgawad, Salah El-Tahawy

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This paper aimed to establish econometrical equation models for the Nile delta region in Egypt, which will represent a basement for future predictions of Lumpy skin disease outbreaks and its pathway in relation to climate change. Data of lumpy skin disease (LSD) outbreaks were collected from the cattle farms located in the provinces representing the Nile delta region during 1 January, 2015 to December, 2015. The obtained results indicated that there was a significant association between the degree of the LSD outbreaks and the investigated climate factors (temperature, wind speed, and humidity) and the outbreaks peaked during the months of June, July, and August and gradually decreased to the lowest rate in January, February, and December. The model obtained depicted that the increment of these climate factors were associated with evidently increment on LSD outbreaks on the Nile Delta of Egypt. The model validation process was done by the root mean square error (RMSE) and means bias (MB) which compared the number of LSD outbreaks expected with the number of observed outbreaks and estimated the confidence level of the model. The value of RMSE was 1.38% and MB was 99.50% confirming that this established model described the current association between the LSD outbreaks and the change on climate factors and also can be used as a base for predicting the of LSD outbreaks depending on the climatic change on the future.

Keywords: LSD, climate factors, Nile delta, modeling

Procedia PDF Downloads 288