Search results for: anti-tubercular therapy induced hepatotoxicity

Authors: M. M. Wickramasinghe

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Cholesterol and triglycerides are lipids, mainly essential to maintain the cellular structure of the human body. Cholesterol is also important for hormone production, vitamin D production, proper digestion functions, and strengthening the immune system. Excess fats in the blood circulation, known as hyperlipidemia, become harmful leading to arterial clogging and causing atherosclerosis. Aim of this research is to develop a treatment protocol to efficiently break down and maintain circulatory lipids by improving blood circulation without strenuous physical exercises while immersed in a tub of water. To achieve the target of strong exercise effect, this method involves generating powerful ozone bubbles to spin, collide, and burst in the water. Powerful emission of air into water is capable of transferring locked energy of the water molecules and releasing energy. This method involves water and air-based impact generated by pumping ozone at the speed of 46 lts/sec with a concentration of 0.03-0.05 ppt according to safety standards of The Federal Institute for Drugs and Medical Devices, BfArM, Germany. The direct impact of ozone bubbles on the muscular system and skin becomes the main target and is capable of increasing the heart rate while immersed in water. A total time duration of 20 minutes is adequate to exert a strong exercise effect, improve blood circulation, and stimulate the nervous and endocrine systems. Unstable ozone breakdown into oxygen release onto the surface of the water giving additional benefits and supplying high-quality air rich in oxygen required to maintain efficient metabolic functions. The breathing technique was introduced to improve the efficiency of lung functions and benefit the air exchange mechanism. The temperature of the water is maintained at 39c to 40c to support arterial dilation and enzyme functions and efficiently improve blood circulation to the vital organs. The buoyancy of water and natural hydrostatic pressure release the tension of the body weight and relax the mind and body. Sufficient hydration (3lts of water per day) is an essential requirement to transport nutrients and remove waste byproducts to process through the liver, kidney, and skin. Proper nutritional intake is an added advantage to optimize the efficiency of this method which aids in a fast recovery process. Within 20-30 days of daily treatment, triglycerides, low-density lipoproteins (LDL), and total cholesterol reduction were observed in patients with abnormal levels of lipid profile. Borderline patients were cleared within 10–15 days of treatment. This is a highly efficient system that provides many benefits and is able to achieve a successful reduction of triglycerides, LDL, and total cholesterol within a short period of time. Supported by proper hydration and nutritional balance, this system of natural treatment maintains healthy levels of lipids in the blood and avoids the risk of cerebral stroke, high blood pressure, and heart attacks.

Keywords: atherosclerosis, cholesterol, hydrotherapy, hyperlipidemia, lipid management, ozone therapy, triglycerides

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Authors: Rawan Hakawati, Beatrice Smyth, David Rooney, Geoffrey McCullough

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Targets have been set in the EU to increase the share of renewable energy consumption to 20% by 2020, but developments have not occurred evenly across the member states. Northern Ireland is almost 90% dependent on imported fossil fuels. With such high energy dependency, Northern Ireland is particularly susceptible to the security of supply issues. Linked to fossil fuels are greenhouse gas emissions, and the EU plans to reduce emissions by 20% by 2020. The use of indigenously produced biomass could reduce both greenhouse gas emissions and external energy dependence. With a wide range of both crop and waste feedstock potentially available in Northern Ireland, anaerobic digestion has been put forward as a possible solution for renewable energy production, waste management, and greenhouse gas reduction. Not all feedstock, however, is the same, and an understanding of feedstock suitability is important for both plant operators and policy makers. The aim of this paper is to investigate biomass suitability for anaerobic digestion in Northern Ireland. It is also important that decisions are based on solid scientific evidence. For this reason, the methodology used is multi-criteria decision matrix analysis which takes multiple criteria into account simultaneously and ranks alternatives accordingly. The model uses the weighted sum method (which follows the Entropy Method to measure uncertainty using probability theory) to decide on weights. The Topsis method is utilized to carry out the mathematical analysis to provide the final scores. Feedstock that is currently available in Northern Ireland was classified into two categories: wastes (manure, sewage sludge and food waste) and energy crops, specifically grass silage. To select the most suitable feedstock, methane yield, feedstock availability, feedstock production cost, biogas production, calorific value, produced kilowatt-hours, dry matter content, and carbon to nitrogen ratio were assessed. The highest weight (0.249) corresponded to production cost reflecting a variation of £41 gate fee to 22£/tonne cost. The weights calculated found that grass silage was the most suitable feedstock. A sensitivity analysis was then conducted to investigate the impact of weights. The analysis used the Pugh Matrix Method which relies upon The Analytical Hierarchy Process and pairwise comparisons to determine a weighting for each criterion. The results showed that the highest weight (0.193) corresponded to biogas production indicating that grass silage and manure are the most suitable feedstock. Introducing co-digestion of two or more substrates can boost the biogas yield due to a synergistic effect induced by the feedstock to favor positive biological interactions. A further benefit of co-digesting manure is that the anaerobic digestion process also acts as a waste management strategy. From the research, it was concluded that energy from agricultural biomass is highly advantageous in Northern Ireland because it would increase the country's production of renewable energy, manage waste production, and would limit the production of greenhouse gases (current contribution from agriculture sector is 26%). Decision-making methods based on scientific evidence aid policy makers in classifying multiple criteria in a logical mathematical manner in order to reach a resolution.

Keywords: anaerobic digestion, biomass as feedstock, decision matrix, renewable energy

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Authors: Deepanwita Deka, Dhruva Kumar Jha

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Endophytes are the microbes that colonize living, internal tissues of plants without causing any immediate, overt negative effects. Endophytes are rich source of therapeutic substances like antimicrobial, anticancerous, herbicidal, insecticidal, immunomodulatory compounds. Brucea mollis, commonly known as Quinine in Assam, belonging to the family Simaroubaceae, is a shrub or small tree, recorded as endangered species in North East India by CAMP survey in 2003. It is traditionally being used as antimalarial and antimicrobial agent and has antiplasmodial, cytotoxic, anticancer, diuretic, cardiovascular effect etc. Being endangered and medicinal; this plant may host certain noble endophytes which need to be studied in depth. The aim of the present study was isolation and identification of potent endophytic fungi from Brucea mollis, an endangered medicinal plant, to protect it from extinction due to over use for medicinal purposes. Aseptically collected leaves, barks and roots samples of healthy plants were washed and cut into a total of 648 segments of about 2 cm long and 0.5 cm broad with sterile knife, comprising 216 segments each from leaves, barks and roots. These segments were surface sterilized using ethanol, mercuric chloride (HgCl2) and aqueous solution of sodium hypochlorite (NaClO). Different media viz., Czapeck-Dox-Agar (CDA, Himedia), Potato-Dextrose-Agar (PDA, Himedia), Malt Extract Agar (MEA, Himedia), Sabourad Dextrose Agar (SDA, Himedia), V8 juice agar, nutrient agar and water agar media and media amended with plant extracts were used separately for the isolation of the endophytic fungi. A total of 11 fungal species were recovered from leaf, bark and root tissues of B. mollis. The isolates were screened for antimicrobial, antioxidant and enzymatic activities using certain protocols. Cochliobolus geniculatus was identified as the most dominant species. The mycelia sterilia (creamy white) showing highest inhibitory activity against Candida albicans (MTCC 183) was induced to sporulate using modified PDA media. The isolate was identified as Geosmithia pallida. The internal transcribed spacer of rDNA was sequenced for confirmation of the taxonomic identity of the sterile mycelia (creamy white). The internal transcribed spacer r-DNA sequence was submitted to the NCBI (KU693285) for the first time from India. G. pallida and Penicillium showed highest antioxidant activity among all the isolates. The antioxidant activity of G. pallida and Penicillium didn’t show statistically significant difference (P˃0.05). G. pallida, Cochliobolus geniculatus and P. purpurogenum respectively showed highest cellulase, amylase and protease activities. Thus, endopytic fungal isolates may be used as potential natural resource of pharmaceutical importance. The endophytic fungi, Geosmithia pallida, may be used for synthesis of pharmaceutically important natural products and consequently can replace plants hitherto used for the same purpose. This study suggests that endophytes should be investigated more aggressively to better understand the endophyte biology of B. mollis.

Keywords: Antimicrobial activity, antioxidant activity, Brucea mollis, endophytic fungi, enzyme activity, Geosmithia pallida

Procedia PDF Downloads 156

Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: Mamert Mbonimpa, Ousseynou Kanteye, Élysée Tshibangu Ngabu, Rachid Amrou, Abdelkabir Maqsoud, Tikou Belem

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The management of mine wastes (waste rocks and tailings) containing sulphide minerals such as pyrite and pyrrhotite represents the main environmental challenge for the mining industry. Indeed, acid mine drainage (AMD) can be generated when these wastes are exposed to water and air. AMD is characterized by low pH and high concentrations of heavy metals, which are toxic to plants, animals, and humans. It affects the quality of the ecosystem through water and soil pollution. Different techniques involving soil materials can be used to control AMD generation, including impermeable covers (compacted clays) and oxygen barriers. The latter group includes covers with capillary barrier effects (CCBE), a multilayered cover that include the moisture retention layer playing the role of an oxygen barrier. Once AMD is produced at a mine site, it must be treated so that the final effluent at the mine site complies with regulations and can be discharged into the environment. Active neutralization with lime is one of the treatment methods used. This treatment produces sludge that is usually stored in sedimentation ponds. Other sludge management alternatives have been examined in recent years, including sludge co-disposal with tailings or waste rocks, disposal in underground mine excavations, and storage in technical landfill sites. Considering the ability of AMD neutralization sludge to maintain an alkaline to neutral pH for decades or even centuries, due to the excess alkalinity induced by residual lime within the sludge, valorization of sludge in specific applications could be an interesting management option. If done efficiently, the reuse of sludge could free up storage ponds and thus reduce the environmental impact. It should be noted that mixtures of sludge and soils could potentially constitute usable materials in CCBE for the rehabilitation of acid-generating mine sites, while sludge alone is not suitable for this purpose. The high sludge water content (up to 300%), even after sedimentation, can, however, constitute a geotechnical challenge. Adding lime to the mixtures can reduce the water content and improve the geotechnical properties. The objective of this paper is to investigate the impact of the sludge content (30, 40 and 50%) in sand-sludge mixtures (SSM) on their hydrogeotechnical properties (compaction, shrinkage behaviour, saturated hydraulic conductivity, and water retention curve). The impact of lime addition (dosages from 2% to 6%) on the moisture content, dry density after compaction and saturated hydraulic conductivity of SSM was also investigated. Results showed that sludge adding to sand significantly improves the saturated hydraulic conductivity and water retention capacity, but the shrinkage increased with sludge content. The dry density after compaction of lime-treated SSM increases with the lime dosage but remains lower than the optimal dry density of the untreated mixtures. The saturated hydraulic conductivity of lime-treated SSM after 24 hours of cure decreases by 3 orders of magnitude. Considering the hydrogeotechnical properties obtained with these mixtures, it would be possible to design CCBE whose moisture retention layer is made of SSM. Physical laboratory models confirmed the performance of such CCBE.

Keywords: mine waste, AMD neutralization sludge, sand-sludge mixture, hydrogeotechnical properties, mine site reclamation, CCBE

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: Vaso K. Kapnopoulou, Piero Caridis

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The fatigue of ship structural details is of major concern in the maritime industry as it can generate fracture issues that may compromise structural integrity. In the present study, a fatigue analysis of the lower hopper knuckle connection of a bulk carrier was conducted using the Finite Element Method by means of ABAQUS/CAE software. The fatigue life was calculated using Miner’s Rule and the long-term distribution of stress range by the use of the two-parameter Weibull distribution. The cumulative damage ratio was estimated using the fatigue damage resulting from the stress range occurring at each load condition. For this purpose, a cargo hold model was first generated, which extends over the length of two holds (the mid-hold and half of each of the adjacent holds) and transversely over the full breadth of the hull girder. Following that, a submodel of the area of interest was extracted in order to calculate the hot spot stress of the connection and to estimate the fatigue life of the structural detail. Two hot spot locations were identified; one at the top layer of the inner bottom plate and one at the top layer of the hopper plate. The IACS Common Structural Rules (CSR) require that specific dynamic load cases for each loading condition are assessed. Following this, the dynamic load case that causes the highest stress range at each loading condition should be used in the fatigue analysis for the calculation of the cumulative fatigue damage ratio. Each load case has a different effect on ship hull response. Of main concern, when assessing the fatigue strength of the lower hopper knuckle connection, was the determination of the maximum, i.e. the critical value of the stress range, which acts in a direction normal to the weld toe line. This acts in the transverse direction, that is, perpendicularly to the ship's centerline axis. The load cases were explored both theoretically and numerically in order to establish the one that causes the highest damage to the location examined. The most severe one was identified to be the load case induced by beam sea condition where the encountered wave comes from the starboard. At the level of the cargo hold model, the model was assumed to be simply supported at its ends. A coarse mesh was generated in order to represent the overall stiffness of the structure. The elements employed were quadrilateral shell elements, each having four integration points. A linear elastic analysis was performed because linear elastic material behavior can be presumed, since only localized yielding is allowed by most design codes. At the submodel level, the displacements of the analysis of the cargo hold model to the outer region nodes of the submodel acted as boundary conditions and applied loading for the submodel. In order to calculate the hot spot stress at the hot spot locations, a very fine mesh zone was generated and used. The fatigue life of the detail was found to be 16.4 years which is lower than the design fatigue life of the structure (25 years), making this location vulnerable to fatigue fracture issues. Moreover, the loading conditions that induce the most damage to the location were found to be the various ballasting conditions.

Keywords: dynamic load cases, finite element method, high cycle fatigue, lower hopper knuckle

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Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

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Authors: Chia-Pei Chen, Yu-Ju Chen, Yu-Juei Hsu

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The prevalence and incidence of end-stage renal disease in Taiwan ranks the highest in the world. According to the statistical survey of the Ministry of Health and Welfare in 2019, kidney disease is the ninth leading cause of death in Taiwan. It leads to autonomic dysfunction, inflammatory response and symptom distress, and further increases the damage to the structure and function of the kidneys, leading to increased demand for renal replacement therapy and risks of cardiovascular disease, which also has medical costs for the society. If we can intervene in a feasible manual to effectively regulate the autonomic nerve function of CKD patients, reduce the inflammatory response and symptom distress. To prolong the progression of the disease, it will be the main goal of caring for CKD patients. This study aims to test the effect of heart rate variability biofeedback (HRVBF) on improving autonomic nerve function (Heart Rate Variability, HRV), inflammatory response (Interleukin-6 [IL-6], C reaction protein [CRP] ), symptom distress (Piper fatigue scale, Pittsburgh Sleep Quality Index [PSQI], and Beck Depression Inventory-II [BDI-II] ) in patients with chronic kidney disease. This study was experimental research, with a convenience sampling. Participants were recruited from the nephrology clinic at a medical center in northern Taiwan. With signed informed consent, participants were randomly assigned to the HRVBF or control group by using the Excel BINOMDIST function. The HRVBF group received four weekly hospital-based HRVBF training, and 8 weeks of home-based self-practice was done with StressEraser. The control group received usual care. We followed all participants for 3 months, in which we repeatedly measured their autonomic nerve function (HRV), inflammatory response (IL-6, CRP), and symptom distress (Piper fatigue scale, PSQI, and BDI-II) on their first day of study participation (baselines), 1 month, and 3 months after the intervention to test the effects of HRVBF. The results were analyzed by SPSS version 23.0 statistical software. The data of demographics, HRV, IL-6, CRP, Piper fatigue scale, PSQI, and BDI-II were analyzed by descriptive statistics. To test for differences between and within groups in all outcome variables, it was used by paired sample t-test, independent sample t-test, Wilcoxon Signed-Rank test and Mann-Whitney U test. Results: Thirty-four patients with chronic kidney disease were enrolled, but three of them were lost to follow-up. The remaining 31 patients completed the study, including 15 in the HRVBF group and 16 in the control group. The characteristics of the two groups were not significantly different. The four-week hospital-based HRVBF training combined with eight-week home-based self-practice can effectively enhance the parasympathetic nerve performance for patients with chronic kidney disease, which may against the disease-related parasympathetic nerve inhibition. In the inflammatory response, IL-6 and CRP in the HRVBF group could not achieve significant improvement when compared with the control group. Self-reported fatigue and depression significantly decreased in the HRVBF group, but they still failed to achieve a significant difference between the two groups. HRVBF has no significant effect on improving the sleep quality for CKD patients.

Keywords: heart rate variability biofeedback, autonomic nerve function, inflammatory response, symptom distress, chronic kidney disease

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Abiodun Afolabi, Rufus Adesoji Adedoyin

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This study investigated and compared the effects of gym-based exercise programme (GEBP) and audio-visual guided home-based exercise programme (AVGHBEP) on selected Anthropometric variables (Weight (W), Body Mass Index (BMI), Waist Circumference (WC), Hip Circumference (HC), Thigh Circumference (TC), Waist-Hip-Ratio (WHR), Waist-Height-Ratio (WHtR), Waist-Thigh-Ratio (WTR), Biceps Skinfold Thickness (BSFT), Triceps Skinfold Thickness (TSFT), Suprailliac Skinfold Thickness (SISFT), Subscapular Skinfold Thickness (SSSFT) and Percent Body Fat (PBF)); and Cardiovasular variables (Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Heart Rate (HR)) of overweight and obese students of Federal College of Education (Special), Oyo, Oyo State, Nigeria, with a view to providing information and evidence for GBEP and AVGHBEP in reducing overweight and obesity for promoting cardiovascular fitness. Eighty overweight and obese students (BMI ≥ 25 Kg/m²) were involved in this pretest-posttest quasi experimental study. Participants were randomly assigned into GBEP (n = 40) and AVGBBEP (n = 40) groups. Anthropometric and cardiovascular variables were measured using a weighing scale, height meter, tape measure, skinfold caliper and electronic sphygmomanometer following standard protocols. GBEP and AVGHBEP were implemented following a circuit training (aerobic and resistance training) pattern with a duration of 40-60 minutes, thrice weekly for twelve weeks. GBEP consisted of gymnasium supervised exercise programme while AVGHBEP is a Visual Display guided exercise programme conducted at the home setting. Data were analyzed by Descriptive and Inferential Statistics. The mean ages of the participants were 22.55 ± 2.55 and 23.65 ± 2.89 years for the GBEP group and AVGHBEP group, respectively. Findings showed that in the GBEP group, there were significant reductions in anthropometric variables and adiposity measures of Weight, BMI, BSFT, TSFT, SISFT, SSSFT, WC, HC, TC, WHtR, and PBF at week 12 of the study. Similarly, in the AVGHBEP group, there were significant reductions in Weight, BMI, BSFT, TSFT, SISFT, SSSFT, WC, HC, TC, WHtR and PBF at the 12th week of intervention. Comparison of the effects of GEBP and AVGHBEP on anthropometric variables and measures of adiposity showed that there was no significant difference between the two groups in weight, BMI, BSFT, TSFT, SISFT, SSSFT, WC, HC, TC, WHR, WHtR, WTR and PBF between the two groups at week 12 of the study. Furthermore, findings on the effects of exercise on programmes on cardiovascular variables revealed that significant reductions occurred in SBP in GBEP group and AVGHBEP group respectively. Comparison of the effects of GBEP and AVGHBEP on cardiovascular variables showed that there was no significant difference in SBP, DBP and HR between the two groups at week 12 of the study. It was concluded that the Audio-Visual Guided Home-based Exercise Programme was as effective as the Gym-Based Exercise Programme in causing a significant reduction in anthropometric variables and body fat among college students who are overweight and obese over a period of twelve weeks. Both Gymnasium-Based Exercise Programme and Audio-Visual Guided Home-Based Exercise Programme led to significant reduction in Systolic Blood Pressure over a period of weeks. Audio-Visual Guided Home-Based Exercise Programme can, therefore, be used as an alternative therapy in the non-pharmacological management of people who are overweight and obese.

Keywords: gym-based exercises, audio-visual guided home-based exercises, anthropometric parameters, cardiovascular parameters, overweight students, obese students

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Authors: Dmitry Yu. Korulkin, Raissa A. Muzychkina

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Bioactive substances of plant origin can be one of the advanced means of solution to the issue of combined therapy to inflammation. The main advantages of medical plants are softness and width of their therapeutic effect on an organism, the absence of side effects and complications even if the used continuously, high tolerability by patients. Moreover, medial plants are often the only and (or) cost-effective sources of natural biologically active substances and medicines. Along with other biologically active groups of chemical compounds, essential oils with wide range of pharmacological effects became very ingrained in medical practice. Essential oil was obtained by the method hydrodistillation air-dry aerial part of Polygonum L. plants using Clevenger apparatus. Qualitative composition of essential oils was analyzed by chromatography-mass-spectrometry method using Agilent 6890N apparatus. The qualitative analysis is based on the comparison of retention time and full mass-spectra with respective data on components of reference oils and pure compounds, if there were any, and with the data of libraries of mass-spectra Wiley 7th edition and NIST 02. The main components of essential oil are for: Polygonum amphibium L. - γ-terpinene, borneol, piperitol, 1,8-cyneole, α-pinene, linalool, terpinolene and sabinene; Polygonum minus Huds. Fl. Angl. – linalool, terpinolene, camphene, borneol, 1,8-cyneole, α-pinene, 4-terpineol and 1-octen-3-ol; Polygonum alpinum All. – camphene, sabinene, 1-octen-3-ol, 4-carene, p- and o-cymol, γ-terpinene, borneol, -terpineol; Polygonum persicaria L. - α-pinene, sabinene, -terpinene, 4-carene, 1,8-cyneole, borneol, 4-terpineol. Antibacterial activity was researched relating to strains of gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Streptococcus agalacticae, relating to gram-negative strain Escherichia coli and to yeast fungus Сandida albicans using agar diffusion method. The medicines of comparison were gentamicin for bacteria and nystatin for yeast fungus Сandida albicans. It has been shown that Polygonum L. essential oils has moderate antibacterial effect to gram-positive microorganisms and weak antifungal activity to Candida albicans yeast fungus. At the second stage of our researches wound healing properties of ointment form of 3% essential oil was researched on the model of flat dermal wounds. To assess the influence of essential oil on healing processes the model of flat dermal wound. The speed of wound healing on rats of different groups was judged based on assessment the area of a wound from time to time. During research of wound healing properties disturbance of integral in neither group: general condition and behavior of animals, food intake, and excretion. Wound healing action of 3% ointment on base of Polygonum L. essential oil and polyethyleneglycol is comparable with the action of reference substances. As more favorable healing dynamics was observed in the experimental group than in control group, the tested ointment can be deemed more promising for further detailed study as wound healing means.

Keywords: antibacterial, antifungal, bioactive substances, essential oils, isolation, Polygonum L.

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Authors: Sophia El Ouazzani, Amer M. Burhan, Mary Wickenden

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Background: Despite improvements in recent years, the Moroccan mental healthcare system still face disparity between available resources and the current population’sneeds. The societal stigma, and limited economic, political, and human resources are all factors in shaping the psychiatric system, exacerbating the discontinuity of services for users after discharged from the hospital. As a result, limited opportunities for social inclusion and meaningful community engagement undermines human rights and recovery potential for people with mental health problems, especially those with psychiatric disabilities from serious mental illness (SMI). Recovery-oriented practice, such as mental health rehabilitation, addresses the complex needs of patients with SMI and support their community inclusion. The cultural acceptability of recovery-oriented practice is an important notion to consider for a successful implementation. Exploring the extent to which recovery-oriented practices are used in Morocco is a necessary first step to assess the cultural relevance of such a practice model. Aims: This study aims to explore understanding and knowledge, perception, and perspective about core concepts in mental health rehabilitation, including psychiatric disability, recovery, and engagement in meaningful occupations for people with SMI in Morocco. Methods: A pilot qualitative study was undertaken. Data was collected via semi-structured interviews and focusgroup discussions with healthcare professional students. Questions were organised around the following themes: 1) students’ perceptions, understanding, and expectations around concepts such as SMI, mental health disability, and recovery, and 2) changes in their views and expectations after starting their professional training. Further analysis of students’ perspectives on the concept of ‘meaningful occupation’ and how is this viewed within the context of the research questions was done. The data was extracted using an inductive thematic analysis approach. This is a pilot stage of a doctoral project, further data will be collected and analysed until saturation is reached. Results: A total of eight students were included in this study which included occupational therapy and mental health nursing students receiving training in Morocco. The following themes emerged as influencing students’ perceptions and views around the main concepts: 1) Stigma and discrimination, 2) Fatalism and low expectations, 3) Gendered perceptions, 4) Religious causation, 5) Family involvement, 6) Professional background, 7) Inaccessibility of services and treatment. Discussion/Contribution: Preliminary analysis of the data suggests that students’ perceptions changed after gaining more clinical experiences and being exposed to people with psychiatric disabilities. Prior to their training, stigma shaped greatly how they viewed people with SMI. The fear, misunderstanding, and shame around SMI and their functional capacities may contribute to people with SMI being stigmatizedand marginalised from their family and their community. Religious causations associated to SMIsare understood as further deepening the social stigma around psychiatric disability. Perceptions are influenced by gender, with women being doubly discriminated against in relation to recovery opportunities. Therapeutic pessimism seems to persist amongst students and within the mental healthcare system in general and regarding the recovery potential and opportunities for people with SMI. The limited resources, fatalism, and stigma all contribute to the low expectations for recovery and community inclusion. Implications and future directions will be discussed.

Keywords: disability, mental health rehabilitation, recovery, serious mental illness, transcultural psychiatry

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Authors: Carolyn Hatch, Laurent Simon

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Urban mobility and the transportation industry are undergoing a transformation, shifting from an auto production-consumption model that has dominated since the early 20th century towards new forms of personal and shared multi-modality [1]. This is shaped by key forces such as climate change, which has induced a shift in production and consumption patterns and efforts to decarbonize and improve transport services through, for instance, the integration of vehicle automation, electrification and mobility sharing [2]. Advanced innovation practices and platforms for experimentation and validation of new mobility products and services that are increasingly complex and multi-stakeholder-oriented are shaping this new world of mobility. Transportation hubs – such as airports - are emblematic of these disruptive forces playing out in the mobility industry. Airports are emerging as the core of innovation ecosystems on and around contemporary mobility issues, and increasingly recognized as complex public/private nodes operating in many societal dimensions [3,4]. These include urban development, sustainability transitions, digital experimentation, customer experience, infrastructure development and data exploitation (for instance, airports generate massive and often untapped data flows, with significant potential for use, commercialization and social benefit). Yet airport innovation practices have not been well documented in the innovation literature. This paper addresses this gap by proposing a model of airport innovation that aims to equip airport stakeholders to respond to these new and complex innovation needs in practice. The methodology involves: 1 – a literature review bringing together key research and theory on airport innovation management, open innovation and innovation ecosystems in order to evaluate airport practices through an innovation lens; 2 – an international benchmarking of leading airports and their innovation practices, including such examples as Aéroports de Paris, Schipol in Amsterdam, Changi in Singapore, and others; and 3 – semi-structured interviews with airport managers on key aspects of organizational practice, facilitated through a close partnership with the Airport Council International (ACI), a major stakeholder in this research project. Preliminary results find that the most successful airports are those that have shifted to a multi-stakeholder, platform ecosystem model of innovation. The recent entrance of new actors in airports (Google, Amazon, Accor, Vinci, Airbnb and others) have forced the opening of organizational boundaries to share and exchange knowledge with a broader set of ecosystem players. This has also led to new forms of governance and intermediation by airport actors to connect complex, highly distributed knowledge, along with new kinds of inter-organizational collaboration, co-creation and collective ideation processes. Leading airports in the case study have demonstrated a unique capacity to force traditionally siloed activities to “think together”, “explore together” and “act together”, to share data, contribute expertise and pioneer new governance approaches and collaborative practices. In so doing, they have successfully integrated these many disruptive change pathways and forced their implementation and coordination towards innovative mobility outcomes, with positive societal, environmental and economic impacts. This research has implications for: 1 - innovation theory, 2 - urban and transport policy, and 3 - organizational practice - within the mobility industry and across the economy.

Keywords: airport management, ecosystem, innovation, mobility, platform, transport hubs

Procedia PDF Downloads 157

Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

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Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

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Introduction: This study explores the potential applications of autologous pedal fat pad grafting as a minimally invasive therapeutic strategy for addressing pedal fat pad loss. Without adequate shock absorbing tissue, a patient can experience functional deficits, ulcerations, loss of quality of life, and significant limitations with ambulation. This study details a novel technique involving autologous adipose grafting from the abdomen to enhance plantar fat pad thickness in a patient involved in a severe motor vehicle accident which resulted in total fat pad loss of the heel. Autologous adipose grafting (AAG) was used following adipose allografting in an effort to recreate a normal shock absorbing surface to allow return to activities of daily living and painless ambulation. Methods: A 46-year-old male sustained multiple open pedal fractures and necrosis to the heel fat pad after a motorcycle accident, which resulted in complete loss of the calcaneal fat pad. The patient underwent serial debridement’s, utilization of wound vac therapy and split thickness skin grafting to accomplish complete closure, despite complete loss of adipose to area. Patient presented with complaints of pain on ambulation, inability to bear weight on the heel, recurrent ulcerations, admitted had not been ambulating for two years. Clinical exam demonstrated complete loss of the plantar fat pad with a thin layer of epithelial tissue overlying the calcaneal bone, allowing visibility of the osseous contour of the calcaneus. Scar tissue had formed in place of the fat pad, with thickened epithelial tissue extending from the midfoot to the calcaneus. After conservative measures were exhausted, the patient opted for initial management by adipose allograft matrix (AAM) injections. Post operative X-ray imaging revealed noticeable improvement in calcaneal fat pad thickness. At 1 year follow up, the patient was able to ambulate without assistive devices. The fat pad at this point was significantly thicker than it was pre-operatively, but the thickness did not restore to pre-accident thickness. In order to compare the take of allograft versus autografting of adipose tissue, the decision to use adipose autograft through abdominal liposuction harvesting was deemed suitable. A general surgeon completed harvesting of adipose cells from the patient’s abdomen via liposuction, and a podiatric surgeon performed the AAG injection into the heel. Total of 15 cc’s of autologous adipose tissue injected to the calcaneus. Results: There was a visual increase in the calcaneal fat pad thickness both clinically and radiographically. At the 6-week follow up, imaging revealed retention of the calcaneal fat pad thickness. Three months postop, patient returned to activities of daily living and increased quality of life due to their increased ability to ambulate. Discussion: AAG is a novel treatment for pedal fat pad loss. These treatments may be viable and reproducible therapeutic choices for patients suffering from fat pad atrophy, fat pad loss, and/or plantar ulcerations. Both treatments of AAM and AAG exhibited similar therapeutic results by providing pain relief for ambulation and allowing for patients to return to their quality of life.

Keywords: podiatry, wound, adipose, allograft, autograft, wound care, limb reconstruction, injection, limb salvage

Procedia PDF Downloads 50

Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

Procedia PDF Downloads 147

Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

Procedia PDF Downloads 156

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

Procedia PDF Downloads 356

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

Procedia PDF Downloads 361

Authors: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

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Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Philip A. Szlosek, M. Susan Guyer, Mary G. Barnum, Elizabeth M. Mullin

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In the United States, athletic training is a healthcare profession that encompasses the prevention, examination, diagnosis, treatment, and rehabilitation of injuries and medical conditions. Athletic trainers work under the direction of or in collaboration with a physician and are recognized by the American Medical Association as allied healthcare professionals. Internationally, this profession is often known as athletic therapy. As healthcare professionals, athletic trainers must be prepared for autonomous practice immediately after graduation. However, new athletic trainers have been shown to have clinical areas of strength and weakness.To better assess professional readiness and improve the preparedness of new athletic trainers, the factors of athletic training professional readiness must be defined. Limited research exists defining the holistic aspects of professional readiness needed for athletic trainers. Confirming the factors of professional readiness in athletic training could enhance the professional preparation of athletic trainers and result in more highly prepared new professionals. The objective of this study was to further explore and confirm the factors of professional readiness in athletic training. Authors useda qualitative design based in grounded theory. Participants included athletic trainers with greater than 24 months of experience from a variety of work settings from each district of the National Athletic Trainer’s Association. Participants took the demographic questionnaire electronically using Qualtrics Survey Software (Provo UT). After completing the demographic questionnaire, 20 participants were selected to complete one-on-one interviews using GoToMeeting audiovisual web conferencing software. IBM Statistical Package for the Social Sciences (SPSS, v. 21.0) was used to calculate descriptive statistics for participant demographics. The first author transcribed all interviews verbatim and utilized a grounded theory approach during qualitative data analysis. Data were analyzed using a constant comparative analysis and open and axial coding. Trustworthiness was established using reflexivity, member checks, and peer reviews. Analysis revealed four overarching themes, including management, interpersonal relations, clinical decision-making, and confidence. Management was categorized as athletic training services not involving direct patient care and was divided into three subthemes, including administration skills, advocacy, and time management. Interpersonal Relations was categorized as the need and ability of the athletic trainer to properly interact with others. Interpersonal relations was divided into three subthemes, including personality traits, communication, and collaborative practice. Clinical decision-making was categorized as the skills and attributes required by the athletic trainer whenmaking clinical decisions related to patient care. Clinical decision-making was divided into three subthemes including clinical skills, continuing education, and reflective practice. The final theme was confidence. Participants discussed the importance of confidence regarding relationships building, clinical and administrative duties, and clinical decision-making. Overall, participants explained the value of a well-rounded athletic trainer and emphasized that athletic trainers need communication and organizational skills, the ability to collaborate, and must value self-reflection and continuing education in addition to having clinical expertise. Future research should finalize a comprehensive model of professional readiness for athletic training, develop a holistic assessment instrument for athletic training professional readiness, and explore the preparedness of new athletic trainers.

Keywords: autonomous practice, newly certified athletic trainer, preparedness for professional practice, transition to practice skills

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Jonas Volungevicius, Kristina Amaleviciute, Rimantas Vaisvalavicius, Alvyra Slepetiene, Darijus Veteikis

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Lithuanian territory is characterized by landscape with prevailing morain hills and clayey lowlands. The largest part of it has endured agrogenization of various degrees which was the cause of changes both in the structure of landscape and soil cover, transformations of soil profile and degradation of natural background soils. These changes influence negatively geoecological potential of landscape and soil and contribute to the weakening of the sustainability of agroecosystems. Research objective: to reveal the landscape agrogenization induced alterations of catenae and their appendant soil profiles in Lithuanian morain hills and clayey lowlands. Methods: Soil cover analysis and catenae charting was conducted using landscape profiling; soil morphology detected and soil type identified following WRB 2014. Granulometric composition of soil profiles was obtained by laser diffraction method (lazer diffractometer Mastersizer 2000). pH was measured in H2O extraction using potentiometric titration; SOC was determined by the Tyurin method modified by Nikitin, measuring with spectrometer Cary 50 (VARIAN) in 590 nm wavelength using glucose standards. Results: analysis showed that the decrease of forest vegetation and the other natural landscape components following the agrogenization of the research area influenced differently but significantly the structural alterations in soil cover and vertical soil profile. The research detected that due to landscape agrogenization, the suppression of zone-specific processes and the intensification of inter-zone processes determined by agrogenic factors take place in Lithuanian agroecosystems. In forested hills historically prevailing Retisols and Histosols territorial complex is transforming into the territorial complex of Regosols, Deluvial soils and drained Histosols. Processes taking place are simplification of vertical profile structure, intensive rejuvenation of profile, disappearance of the features of zone-specific soil-forming processes (podzolization, lessivage, gley formation). Erosion and deluvial processes manifest more intensively and weakly accumulating organic material more intensively spread in a vertical soil profile. The territorial soil complex of Gleyic Luvisols and Gleysols dominating in forested clayey lowlands subjected to agrogenization is transformed into the catena of drained Luvisols and pseudo Cambisols. The best expressed are their changes in moisture regime (morphological features of gley and stagnic properties are on decline) together with alterations of pH and distribution and intensity of accumulation of organic matter in profile. A specific horizon, antraquic, uncharacteristic to natural soil formation is appearing. Important to note that due to deep ploughing and other agrotechnical measures, the natural vertical differentiation of clay particles in a soil profile is destroyed which leads not only to alterations of physical qualities of soil, but also encumbers the identification of Luvisols by creating presumptions to misidentify them as Cambisols. The latter have never developed in these ecosystems under the present climatic conditions. Acknowledgements: This work was supported by the National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: agroecosystems, landscape agrogenization, luvisols, retisols, transformation of soil profile

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

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

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

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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