Search results for: gamma stabilization
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 802

Search results for: gamma stabilization

22 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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21 Synthesis, Growth, Characterization and Quantum Chemical Investigations of an Organic Single Crystal: 2-Amino- 4-Methylpyridinium Quinoline- 2-Carboxylate

Authors: Anitha Kandasamy, Thirumurugan Ramaiah

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Interestingly, organic materials exhibit large optical nonlinearity with quick responses and having the flexibility of molecular tailoring using computational modelling and favourable synthetic methodologies. Pyridine based organic compounds and carboxylic acid contained aromatic compounds play a crucial role in crystal engineering of NCS complexes that displays admirable optical nonlinearity with fast response and favourable physicochemical properties such as low dielectric constant, wide optical transparency and large laser damage threshold value requires for optoelectronics device applications. Based on these facts, it was projected to form an acentric molecule of π-conjugated system interaction with appropriately replaced electron donor and acceptor groups for achieving higher SHG activity in which quinoline-2-carboyxlic acid is chosen as an electron acceptor and capable of acting as an acid as well as a base molecule, while 2-amino-4-methylpyridine is used as an electron donor and previously employed in numerous proton transfer complexes for synthesis of NLO materials for optoelectronic applications. 2-amino-4-mehtylpyridinium quinoline-2-carboxylate molecular complex (2AQ) is having π-donor-acceptor groups in which 2-amino-4-methylpyridine donates one of its electron to quinoline -2-carboxylic acid thereby forming a protonated 2-amino-4-methyl pyridinium moiety and mono ionized quinoline-2-carboxylate moiety which are connected via N-H…O intermolecular interactions with non-centrosymmetric crystal packing arrangement at microscopic scale is accountable to the enhancement of macroscopic second order NLO activity. The 2AQ crystal was successfully grown by a slow evaporation solution growth technique and its structure was determined in orthorhombic crystal system with acentric, P212121, space group. Hirshfeld surface analysis reveals that O…H intermolecular interactions primarily contributed with 31.0 % to the structural stabilization of 2AQ. The molecular structure of title compound has been confirmed by 1H and 13C NMR spectral studies. The vibrational modes of functional groups present in 2AQ have been assigned by using FTIR and FT-Raman spectroscopy. The grown 2AQ crystal exhibits high optical transparency with lower cut-off wavelength (275 nm) within the region of 275-1500 nm. The laser study confirmed that 2AQ exhibits high SHG efficiency of 12.6 times greater than that of KDP. TGA-DTA analysis revealed that 2AQ crystal had a thermal stability of 223 °C. The low dielectric constant and low dielectric loss at higher frequencies confirmed good crystalline nature with fewer defects of grown 2AQ crystal. The grown crystal exhibits soft material and positive photoconduction behaviour. Mulliken atomic distribution and FMOs analysis suggested that the strong intermolecular hydrogen bonding which lead to the enhancement of NLO activity. These properties suggest that 2AQ crystal is a suitable material for optoelectronic and laser frequency conversion applications.

Keywords: crystal growth, NLO activity, proton transfer complex, quantum chemical investigation

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20 Skin-to-Skin Contact Simulation: Improving Health Outcomes for Medically Fragile Newborns in the Neonatal Intensive Care Unit

Authors: Gabriella Zarlenga, Martha L. Hall

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Introduction: Premature infants are at risk for neurodevelopmental deficits and hospital readmissions, which can increase the financial burden on the health care system and families. Kangaroo care (skin-to-skin contact) is a practice that can improve preterm infant health outcomes. Preterm infants can acquire adequate body temperature, heartbeat, and breathing regulation through lying directly on the mother’s abdomen and in between her breasts. Due to some infant’s condition, kangaroo care is not a feasible intervention. The purpose of this proof-of-concept research project is to create a device which simulates skin-to-skin contact for pre-term infants not eligible for kangaroo care, with the aim of promoting baby’s health outcomes, reducing the incidence of serious neonatal and early childhood illnesses, and/or improving cognitive, social and emotional aspects of development. Methods: The study design is a proof-of-concept based on a three-phase approach; (1) observational study and data analysis of the standard of care for 2 groups of pre-term infants, (2) design and concept development of a novel device for pre-term infants not currently eligible for standard kangaroo care, and (3) prototyping, laboratory testing, and evaluation of the novel device in comparison to current assessment parameters of kangaroo care. A single center study will be conducted in an area hospital offering Level III neonatal intensive care. Eligible participants include newborns born premature (28-30 weeks of age) admitted to the NICU. The study design includes 2 groups: a control group receiving standard kangaroo care and an experimental group not eligible for kangaroo care. Based on behavioral analysis of observational video data collected in the NICU, the device will be created to simulate mother’s body using electrical components in a thermoplastic polymer housing covered in silicone. It will be designed with a microprocessor that controls simulated respiration, heartbeat, and body temperature of the 'simulated caregiver' by using a pneumatic lung, vibration sensors (heartbeat), pressure sensors (weight/position), and resistive film to measure temperature. A slight contour of the simulator surface may be integrated to help position the infant correctly. Control and monitoring of the skin-to-skin contact simulator would be performed locally by an integrated touchscreen. The unit would have built-in Wi-Fi connectivity as well as an optional Bluetooth connection in which the respiration and heart rate could be synced with a parent or caregiver. A camera would be integrated, allowing a video stream of the infant in the simulator to be streamed to a monitoring location. Findings: Expected outcomes are stabilization of respiratory and cardiac rates, thermoregulation of those infants not eligible for skin to skin contact with their mothers, and real time mother Bluetooth to the device to mimic the experience in the womb. Results of this study will benefit clinical practice by creating a new standard of care for premature neonates in the NICU that are deprived of skin to skin contact due to various health restrictions.

Keywords: kangaroo care, wearable technology, pre-term infants, medical design

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19 Isolation of Bacterial Species with Potential Capacity for Siloxane Removal in Biogas Upgrading

Authors: Ellana Boada, Eric Santos-Clotas, Alba Cabrera-Codony, Maria Martin, Lluis Baneras, Frederic Gich

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Volatile methylsiloxanes (VMS) are a group of manmade silicone compounds widely used in household and industrial applications that end up on the biogas produced through the anaerobic digestion of organic matter in landfills and wastewater treatment plants. The presence of VMS during the biogas energy conversion can cause damage on the engines, reducing the efficiency of this renewable energy source. Non regenerative adsorption onto activated carbon is the most widely used technology to remove siloxanes from biogas, while new trends point out that biotechnology offers a low-cost and environmentally friendly alternative to conventional technologies. The first objective of this research was to enrich, isolate and identify bacterial species able to grow using siloxane molecules as a sole carbon source: anoxic wastewater sludge was used as initial inoculum in liquid anoxic enrichments, adding D4 (as representative siloxane compound) previously adsorbed on activated carbon. After several months of acclimatization, liquid enrichments were plated onto solid media containing D4 and thirty-four bacterial isolates were obtained. 16S rRNA gene sequencing allowed the identification of strains belonging to the following species: Ciceribacter lividus, Alicycliphilus denitrificans, Pseudomonas aeruginosa and Pseudomonas citronellolis which are described to be capable to degrade toxic volatile organic compounds. Kinetic assays with 8 representative strains revealed higher cell growth in the presence of D4 compared to the control. Our second objective was to characterize the community composition and diversity of the microbial community present in the enrichments and to elucidate whether the isolated strains were representative members of the community or not. DNA samples were extracted, the 16S rRNA gene was amplified (515F & 806R primer pair), and the microbiome analyzed from sequences obtained with a MiSeq PE250 platform. Results showed that the retrieved isolates only represented a minor fraction of the microorganisms present in the enrichment samples, which were represented by Alpha, Beta, and Gamma proteobacteria as dominant groups in the category class thus suggesting that other microbial species and/or consortia may be important for D4 biodegradation. These results highlight the need of additional protocols for the isolation of relevant D4 degraders. Currently, we are developing molecular tools targeting key genes involved in siloxane biodegradation to identify and quantify the capacity of the isolates to metabolize D4 in batch cultures supplied with a synthetic gas stream of air containing 60 mg m⁻³ of D4 together with other volatile organic compounds found in the biogas mixture (i.e. toluene, hexane and limonene). The isolates were used as inoculum in a biotrickling filter containing lava rocks and activated carbon to assess their capacity for siloxane removal. Preliminary results of biotrickling filter performance showed 35% of siloxane biodegradation in a contact time of 14 minutes, denoting that biological siloxane removal is a promising technology for biogas upgrading.

Keywords: bacterial cultivation, biogas upgrading, microbiome, siloxanes

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18 High Purity Germanium Detector Characterization by Means of Monte Carlo Simulation through Application of Geant4 Toolkit

Authors: Milos Travar, Jovana Nikolov, Andrej Vranicar, Natasa Todorovic

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Over the years, High Purity Germanium (HPGe) detectors proved to be an excellent practical tool and, as such, have established their today's wide use in low background γ-spectrometry. One of the advantages of gamma-ray spectrometry is its easy sample preparation as chemical processing and separation of the studied subject are not required. Thus, with a single measurement, one can simultaneously perform both qualitative and quantitative analysis. One of the most prominent features of HPGe detectors, besides their excellent efficiency, is their superior resolution. This feature virtually allows a researcher to perform a thorough analysis by discriminating photons of similar energies in the studied spectra where otherwise they would superimpose within a single-energy peak and, as such, could potentially scathe analysis and produce wrongly assessed results. Naturally, this feature is of great importance when the identification of radionuclides, as well as their activity concentrations, is being practiced where high precision comes as a necessity. In measurements of this nature, in order to be able to reproduce good and trustworthy results, one has to have initially performed an adequate full-energy peak (FEP) efficiency calibration of the used equipment. However, experimental determination of the response, i.e., efficiency curves for a given detector-sample configuration and its geometry, is not always easy and requires a certain set of reference calibration sources in order to account for and cover broader energy ranges of interest. With the goal of overcoming these difficulties, a lot of researches turned towards the application of different software toolkits that implement the Monte Carlo method (e.g., MCNP, FLUKA, PENELOPE, Geant4, etc.), as it has proven time and time again to be a very powerful tool. In the process of creating a reliable model, one has to have well-established and described specifications of the detector. Unfortunately, the documentation that manufacturers provide alongside the equipment is rarely sufficient enough for this purpose. Furthermore, certain parameters tend to evolve and change over time, especially with older equipment. Deterioration of these parameters consequently decreases the active volume of the crystal and can thus affect the efficiencies by a large margin if they are not properly taken into account. In this study, the optimisation method of two HPGe detectors through the implementation of the Geant4 toolkit developed by CERN is described, with the goal of further improving simulation accuracy in calculations of FEP efficiencies by investigating the influence of certain detector variables (e.g., crystal-to-window distance, dead layer thicknesses, inner crystal’s void dimensions, etc.). Detectors on which the optimisation procedures were carried out were a standard traditional co-axial extended range detector (XtRa HPGe, CANBERRA) and a broad energy range planar detector (BEGe, CANBERRA). Optimised models were verified through comparison with experimentally obtained data from measurements of a set of point-like radioactive sources. Acquired results of both detectors displayed good agreement with experimental data that falls under an average statistical uncertainty of ∼ 4.6% for XtRa and ∼ 1.8% for BEGe detector within the energy range of 59.4−1836.1 [keV] and 59.4−1212.9 [keV], respectively.

Keywords: HPGe detector, γ spectrometry, efficiency, Geant4 simulation, Monte Carlo method

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17 The Healthcare Costs of BMI-Defined Obesity among Adults Who Have Undergone a Medical Procedure in Alberta, Canada

Authors: Sonia Butalia, Huong Luu, Alexis Guigue, Karen J. B. Martins, Khanh Vu, Scott W. Klarenbach

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Obesity is associated with significant personal impacts on health and has a substantial economic burden on payers due to increased healthcare use. A contemporary estimate of the healthcare costs associated with obesity at the population level are lacking. This evidence may provide further rationale for weight management strategies. Methods: Adults who underwent a medical procedure between 2012 and 2019 in Alberta, Canada were categorized into the investigational cohort (had body mass index [BMI]-defined class 2 or 3 obesity based on a procedure-associated code) and the control cohort (did not have the BMI procedure-associated code); those who had bariatric surgery were excluded. Characteristics were presented and healthcare costs ($CDN) determined over a 1-year observation period (2019/2020). Logistic regression and a generalized linear model with log link and gamma distribution were used to assess total healthcare costs (comprised of hospitalizations, emergency department visits, ambulatory care visits, physician visits, and outpatient prescription drugs); potential confounders included age, sex, region of residence, and whether the medical procedure was performed within 6-months before the observation period in the partial adjustment, and also the type of procedure performed, socioeconomic status, Charlson Comorbidity Index (CCI), and seven obesity-related health conditions in the full adjustment. Cost ratios and estimated cost differences with 95% confidence intervals (CI) were reported; incremental cost differences within the adjusted models represent referent cases. Results: The investigational cohort (n=220,190) was older (mean age: 53 standard deviation [SD]±17 vs 50 SD±17 years), had more females (71% vs 57%), lived in rural areas to a greater extent (20% vs 14%), experienced a higher overall burden of disease (CCI: 0.6 SD±1.3 vs 0.3 SD±0.9), and were less socioeconomically well-off (material/social deprivation was lower [14%/14%] in the most well-off quintile vs 20%/19%) compared with controls (n=1,955,548). Unadjusted total healthcare costs were estimated to be 1.77-times (95% CI: 1.76, 1.78) higher in the investigational versus control cohort; each healthcare resource contributed to the higher cost ratio. After adjusting for potential confounders, the total healthcare cost ratio decreased, but remained higher in the investigational versus control cohort (partial adjustment: 1.57 [95% CI: 1.57, 1.58]; full adjustment: 1.21 [95% CI: 1.20, 1.21]); each healthcare resource contributed to the higher cost ratio. Among urban-dwelling 50-year old females who previously had non-operative procedures, no procedures performed within 6-months before the observation period, a social deprivation index score of 3, a CCI score of 0.32, and no history of select obesity-related health conditions, the predicted cost difference between those living with and without obesity was $386 (95% CI: $376, $397). Conclusions: If these findings hold for the Canadian population, one would expect an estimated additional $3.0 billion per year in healthcare costs nationally related to BMI-defined obesity (based on an adult obesity rate of 26% and an estimated annual incremental cost of $386 [21%]); incremental costs are higher when obesity-related health conditions are not adjusted for. Results of this study provide additional rationale for investment in interventions that are effective in preventing and treating obesity and its complications.

Keywords: administrative data, body mass index-defined obesity, healthcare cost, real world evidence

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16 Assessment of Occupational Exposure and Individual Radio-Sensitivity in People Subjected to Ionizing Radiation

Authors: Oksana G. Cherednichenko, Anastasia L. Pilyugina, Sergey N.Lukashenko, Elena G. Gubitskaya

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The estimation of accumulated radiation doses in people professionally exposed to ionizing radiation was performed using methods of biological (chromosomal aberrations frequency in lymphocytes) and physical (radionuclides analysis in urine, whole-body radiation meter, individual thermoluminescent dosimeters) dosimetry. A group of 84 "A" category employees after their work in the territory of former Semipalatinsk test site (Kazakhstan) was investigated. The dose rate in some funnels exceeds 40 μSv/h. After radionuclides determination in urine using radiochemical and WBC methods, it was shown that the total effective dose of personnel internal exposure did not exceed 0.2 mSv/year, while an acceptable dose limit for staff is 20 mSv/year. The range of external radiation doses measured with individual thermo-luminescent dosimeters was 0.3-1.406 µSv. The cytogenetic examination showed that chromosomal aberrations frequency in staff was 4.27±0.22%, which is significantly higher than at the people from non-polluting settlement Tausugur (0.87±0.1%) (р ≤ 0.01) and citizens of Almaty (1.6±0.12%) (р≤ 0.01). Chromosomal type aberrations accounted for 2.32±0.16%, 0.27±0.06% of which were dicentrics and centric rings. The cytogenetic analysis of different types group radiosensitivity among «professionals» (age, sex, ethnic group, epidemiological data) revealed no significant differences between the compared values. Using various techniques by frequency of dicentrics and centric rings, the average cumulative radiation dose for group was calculated, and that was 0.084-0.143 Gy. To perform comparative individual dosimetry using physical and biological methods of dose assessment, calibration curves (including own ones) and regression equations based on general frequency of chromosomal aberrations obtained after irradiation of blood samples by gamma-radiation with the dose rate of 0,1 Gy/min were used. Herewith, on the assumption of individual variation of chromosomal aberrations frequency (1–10%), the accumulated dose of radiation varied 0-0.3 Gy. The main problem in the interpretation of individual dosimetry results is reduced to different reaction of the objects to irradiation - radiosensitivity, which dictates the need of quantitative definition of this individual reaction and its consideration in the calculation of the received radiation dose. The entire examined contingent was assigned to a group based on the received dose and detected cytogenetic aberrations. Radiosensitive individuals, at the lowest received dose in a year, showed the highest frequency of chromosomal aberrations (5.72%). In opposite, radioresistant individuals showed the lowest frequency of chromosomal aberrations (2.8%). The cohort correlation according to the criterion of radio-sensitivity in our research was distributed as follows: radio-sensitive (26.2%) — medium radio-sensitivity (57.1%), radioresistant (16.7%). Herewith, the dispersion for radioresistant individuals is 2.3; for the group with medium radio-sensitivity — 3.3; and for radio-sensitive group — 9. These data indicate the highest variation of characteristic (reactions to radiation effect) in the group of radio-sensitive individuals. People with medium radio-sensitivity show significant long-term correlation (0.66; n=48, β ≥ 0.999) between the values of doses defined according to the results of cytogenetic analysis and dose of external radiation obtained with the help of thermoluminescent dosimeters. Mathematical models based on the type of violation of the radiation dose according to the professionals radiosensitivity level were offered.

Keywords: biodosimetry, chromosomal aberrations, ionizing radiation, radiosensitivity

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15 Complete Genome Sequence Analysis of Pasteurella multocida Subspecies multocida Serotype A Strain PMTB2.1

Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar

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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.

Keywords: comparative genomics, DNA sequencing, phage, phylogenomics

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14 Structural Behavior of Subsoil Depending on Constitutive Model in Calculation Model of Pavement Structure-Subsoil System

Authors: M. Kadela

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The load caused by the traffic movement should be transferred in the road constructions in a harmless way to the pavement as follows: − on the stiff upper layers of the structure (e.g. layers of asphalt: abrading and binding), and − through the layers of principal and secondary substructure, − on the subsoil, directly or through an improved subsoil layer. Reliable description of the interaction proceeding in a system “road construction – subsoil” should be in such case one of the basic requirements of the assessment of the size of internal forces of structure and its durability. Analyses of road constructions are based on: − elements of mechanics, which allows to create computational models, and − results of the experiments included in the criteria of fatigue life analyses. Above approach is a fundamental feature of commonly used mechanistic methods. They allow to use in the conducted evaluations of the fatigue life of structures arbitrarily complex numerical computational models. Considering the work of the system “road construction – subsoil”, it is commonly accepted that, as a result of repetitive loads on the subsoil under pavement, the growth of relatively small deformation in the initial phase is recognized, then this increase disappears, and the deformation takes the character completely reversible. The reliability of calculation model is combined with appropriate use (for a given type of analysis) of constitutive relationships. Phenomena occurring in the initial stage of the system “road construction – subsoil” is unfortunately difficult to interpret in the modeling process. The classic interpretation of the behavior of the material in the elastic-plastic model (e-p) is that elastic phase of the work (e) is undergoing to phase (e-p) by increasing the load (or growth of deformation in the damaging structure). The paper presents the essence of the calibration process of cooperating subsystem in the calculation model of the system “road construction – subsoil”, created for the mechanistic analysis. Calibration process was directed to show the impact of applied constitutive models on its deformation and stress response. The proper comparative base for assessing the reliability of created. This work was supported by the on-going research project “Stabilization of weak soil by application of layer of foamed concrete used in contact with subsoil” (LIDER/022/537/L-4/NCBR/2013) financed by The National Centre for Research and Development within the LIDER Programme. M. Kadela is with the Department of Building Construction Elements and Building Structures on Mining Areas, Building Research Institute, Silesian Branch, Katowice, Poland (phone: +48 32 730 29 47; fax: +48 32 730 25 22; e-mail: m.kadela@ itb.pl). models should be, however, the actual, monitored system “road construction – subsoil”. The paper presents too behavior of subsoil under cyclic load transmitted by pavement layers. The response of subsoil to cyclic load is recorded in situ by the observation system (sensors) installed on the testing ground prepared for this purpose, being a part of the test road near Katowice, in Poland. A different behavior of the homogeneous subsoil under pavement is observed for different seasons of the year, when pavement construction works as a flexible structure in summer, and as a rigid plate in winter. Albeit the observed character of subsoil response is the same regardless of the applied load and area values, this response can be divided into: - zone of indirect action of the applied load; this zone extends to the depth of 1,0 m under the pavement, - zone of a small strain, extending to about 2,0 m.

Keywords: road structure, constitutive model, calculation model, pavement, soil, FEA, response of soil, monitored system

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13 The Plight of the Rohingyas: Design Guidelines to Accommodate Displaced People in Bangladesh

Authors: Nazia Roushan, Maria Kipti

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The sensitive issue of a large-scale entry of Rohingya refugees to Bangladesh has arisen again since August of 2017. Incited by ethnic and religious conflict, the Rohingyas—an ethnic group concentrated in the north-west state of Rakhine in Myanmar—have been fleeing to what is now Bangladesh from as early as the late 1700s in four main exoduses. This long-standing persecution has recently escalated, and accommodating the recent wave of exodus has been especially challenging due to the sheer volume of a million refugees concentrated in refugee camps in two small administrative units (upazilas) in the south-east of the country: the host area. This drastic change in the host area’s social fabric is putting a lot of strain on the country’s economic, demographic and environmental stability, and security. Although Bangladesh’s long-term experience with disaster management has enabled it to respond rapidly to the crisis, the government is failing to cope with this enormous problem and has taken insufficient steps towards improving the living conditions to inhibit the inflow of more refugees. On top of that, the absence of a comprehensive national refugee policy, and the density of the structures of the camps are constricting the upgrading of the shelters to international standards. As of December 2016, the combined number of internally displaced persons (IDPs) due to conflict and violence (stock), and new displacements due to disasters (flow) in Bangladesh had exceeded 1 million. These numbers have increased dramatically in the last few months. Moreover, by 2050, Bangladesh will have as much as 25 million climate refugees just from its coastal districts. To enhance the resilience of the vulnerable, it is crucial to methodically factorize further interventions between Disaster Risk Reduction for Resilience (DRR) and the concept of Building Back Better (BBB) in the rehabilitation-reconstruction period. Considering these points, this paper provides a palette of options for design guidelines related to the living spaces and infrastructures for refugees. This will encourage the development of national standards for refugee camps, and the national and local level rehabilitation-reconstruction practices. Unhygienic living conditions, vulnerability, and the general lack of control over life are pervasive throughout the camps. This paper, therefore, proposes site-specific strategic and physical planning and design for shelters for refugees in Bangladesh that will lead to sustainable living environments through the following: a) site survey of existing two registered and one makeshift unregistered refugee camps to document and study their physical conditions, b) questionnaires and semi-structured focus group discussions carried out among the refugees and stakeholders to understand what the lived experiences and needs are; and c) combining the findings with international minimum standards for shelter and settlement from International Federation of Red Cross and Red Crescent (IFRC), Médecins Sans Frontières (MSF), United Nations High Commissioner for Refugees (UNHCR). These proposals include temporary shelter solutions that balance between lived spaces and regimented, repetitive plans using readily available and cheap materials, erosion control and slope stabilization strategies, and most importantly, coping mechanisms for the refugees to be self-reliant and resilient.

Keywords: architecture, Bangladesh, refugee camp, resilience, Rohingya

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12 Continuity Through Best Practice. A Case Series of Complex Wounds Manage by Dedicated Orthopedic Nursing Team

Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

Abstract:

The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

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11 Nanocarriers Made of Amino Acid Based Biodegradable Polymers: Poly(Ester Amide) and Related Cationic and PEGylating Polymers

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

Abstract:

Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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10 Biomedical Application of Green Biosynthesis Magnetic Iron Oxide (Fe3O4) Nanoparticles Using Seaweed (Sargassum muticum) Aqueous Extract

Authors: Farideh Namvar, Rosfarizan Mohamed

Abstract:

In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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9 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

Abstract:

Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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8 Anti-Infective Potential of Selected Philippine Medicinal Plant Extracts against Multidrug-Resistant Bacteria

Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

Abstract:

From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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7 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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6 Improving Diagnostic Accuracy of Ankle Syndesmosis Injuries: A Comparison of Traditional Radiographic Measurements and Computed Tomography-Based Measurements

Authors: Yasar Samet Gokceoglu, Ayse Nur Incesu, Furkan Okatar, Berk Nimetoglu, Serkan Bayram, Turgut Akgul

Abstract:

Ankle syndesmosis injuries pose a significant challenge in orthopedic practice due to their potential for prolonged recovery and chronic ankle dysfunction. Accurate diagnosis and management of these injuries are essential for achieving optimal patient outcomes. The use of radiological methods, such as X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), plays a vital role in the accurate diagnosis of syndesmosis injuries in the context of ankle fractures. Treatment options for ankle syndesmosis injuries vary, with surgical interventions such as screw fixation and suture-button implantation being commonly employed. The choice of treatment is influenced by the severity of the injury and the presence of associated fractures. Additionally, the mechanism of injury, such as pure syndesmosis injury or specific fracture types, can impact the stability and management of syndesmosis injuries. Ankle fractures with syndesmosis injury present a complex clinical scenario, requiring accurate diagnosis, appropriate reduction, and tailored management strategies. The interplay between the mechanism of injury, associated fractures, and treatment modalities significantly influences the outcomes of these challenging injuries. The long-term outcomes and patient satisfaction following ankle fractures with syndesmosis injury are crucial considerations in the field of orthopedics. Patient-reported outcome measures, such as the Foot and Ankle Outcome Score (FAOS), provide essential information about functional recovery and quality of life after these injuries. When diagnosing syndesmosis injuries, standard measurements, such as the medial clear space, tibiofibular overlap, tibiofibular clear space, anterior tibiofibular ratio (ATFR), and the anterior-posterior tibiofibular ratio (APTF), are assessed through radiographs and computed tomography (CT) scans. These parameters are critical in evaluating the presence and severity of syndesmosis injuries, enabling clinicians to choose the most appropriate treatment approach. Despite advancements in diagnostic imaging, challenges remain in accurately diagnosing and treating ankle syndesmosis injuries. Traditional diagnostic parameters, while beneficial, may not capture the full extent of the injury or provide sufficient information to guide therapeutic decisions. This gap highlights the need for exploring additional diagnostic parameters that could enhance the accuracy of syndesmosis injury diagnoses and inform treatment strategies more effectively. The primary goal of this research is to evaluate the usefulness of traditional radiographic measurements in comparison to new CT-based measurements for diagnosing ankle syndesmosis injuries. Specifically, this study aims to assess the accuracy of conventional parameters, including medial clear space, tibiofibular overlap, tibiofibular clear space, ATFR, and APTF, in contrast with the recently proposed CT-based measurements such as the delta and gamma angles. Moreover, the study intends to explore the relationship between these diagnostic parameters and functional outcomes, as measured by the Foot and Ankle Outcome Score (FAOS). Establishing a correlation between specific diagnostic measurements and FAOS scores will enable us to identify the most reliable predictors of functional recovery following syndesmosis injuries. This comparative analysis will provide valuable insights into the accuracy and dependability of CT-based measurements in diagnosing ankle syndesmosis injuries and their potential impact on predicting patient outcomes. The results of this study could greatly influence clinical practices by refining diagnostic criteria and optimizing treatment planning for patients with ankle syndesmosis injuries.

Keywords: ankle syndesmosis injury, diagnostic accuracy, computed tomography, radiographic measurements, Tibiofibular syndesmosis distance

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5 Adequate Nutritional Support and Monitoring in Post-Traumatic High Output Duodenal Fistula

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

Abstract:

Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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4 A Case Study on Utility of 18FDG-PET/CT Scan in Identifying Active Extra Lymph Nodes and Staging of Breast Cancer

Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

Abstract:

Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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3 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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2 Influence of Oil Prices on the Central Caucasus State of Georgia

Authors: Charaia Vakhtang

Abstract:

Global oil prices are seeing new bottoms every day. The prices have already collapsed beneath the psychological verge of 30 USD. This tendency would be fully acceptable for the Georgian consumers, but there is one detail: two our neighboring countries (one friendly and one hostile) largely depend on resources of these hydrocarbons. Namely, the ratio of Azerbaijan in Georgia’s total FDI inflows in 2014 marked 20%. The ratio reached 40% in the January to September 2015. Azerbaijan is Georgia’s leading exports market. Namely, in 2014 Georgia’s exports to Azerbaijan constituted 544 million USD, i.e. 19% in Georgia’s total experts. In the January to November period of 2015, the ratio exceeded 11%. Moreover, Azerbaijan is Georgia’s strategic partner country as part of many regional projects that are designated for long-term perspectives. For example, the Baku-Tbilisi-Karsi railroad, the Black Sea terminal, preferential gas tariffs for Georgia and so on. The Russian economic contribution to the Georgian economy is also considerable, despite the losses the Russian hostile policy has inflicted to our country. Namely, Georgian emigrants are mainly employed in the Russian Federation and this category of Georgian citizens transfers considerable funds to Georgia every year. These transfers account for about 1 billion USD and consequently, these funds previously equalized to total FDI inflows. Moreover, despite the difficulties in the Russian market, Russia still remains a leader in terms of money transfers to Georgia. According to the last reports, money transfers from Russia to Georgia slipped by 276 million USD in 2015 compared to 2014 (-39%). At the same time, the total money transfers to Georgia in 2015 marked 1.08 billion USD, down 25% from 1.44 billion USD in 2014. This signifies the contraction in money transfers is by ¾ dependent on the Russian factor (in this case, contraction in oil prices and the Russian Ruble devaluation directly make negative impact on money transfers to Georgia). As to other countries, it is interesting that money transfers have also slipped from Italy (to 109 million USD from 121 million USD). Nevertheless, the country’s ratio in total money transfers to Georgia has increased to 10% from 8%. Money transfers to Georgia have increased by 22% (+18 million USD) from the USA. Money transfers have halved from Greece to 117 million USD from 205 million USD. As to Turkey, money transfers to Georgia from Turkey have increased by 1% to 69 million USD. Moreover, the problems with the national currencies of Russia and Azerbaijan, along with the above-mentioned developments, outline unfavorable perspectives for the Georgian economy. The depreciation of the national currencies of Azerbaijan and Russia is expected to bring unfavorable results for the Georgian economy. Even more so, the statement released by the Russian Finance Ministry on expected default is in direct relation to the welfare of the whole region and these tendencies will make direct and indirect negative impacts on Georgia’s economic indicators. Amid the economic slowdown in Armenia, Turkey and Ukraine, Georgia should try to enhance economic ties with comparatively stronger and flexible economies such as EU and USA. In other case, the Georgian economy will enter serious turbulent zone. We should make maximum benefit from the EU association agreement. It should be noted that the Russian economy slowdown that causes both regretful and happy moods in Georgia, will make negative impact on the Georgian economy. The same forecasts are made in relation to Azerbaijan. However, Georgia has many partner countries. Enhancement and development of the economic relations with these countries may maximally alleviate negative impacts from the declining economies. First of all, the EU association agreement should be mentioned as a main source for Georgia’s economic stabilization. It is the Georgian government‘s responsibility to successfully fulfill the EU association agreement requirements. In any case the imports must be replaced by domestic products and the exports should be stimulated through government support programs. The Authorities should ensure drawing more foreign investments and money resources, accumulating more tourism revenues and reducing external debts, budget expenditures should be balanced and the National Bank should carry out strict monetary policy. Moreover, the Government should develop a long-term state economic policy and carry out this policy at various Ministries. It is also of crucial importance to carry out constitutive policy and promote perspective directions on the domestic level.

Keywords: oil prices, economic growth, foreign direct investments, international trade

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1 Sustainable Agricultural and Soil Water Management Practices in Relation to Climate Change and Disaster: A Himalayan Country Experience

Authors: Krishna Raj Regmi

Abstract:

A “Climate change adaptation and disaster risk management for sustainable agriculture” project was implemented in Nepal, a Himalayan country during 2008 to 2013 sponsored jointly by Food and Agriculture Organization (FAO) and United Nations Development Programme (UNDP), Nepal. The paper is based on the results and findings of this joint pilot project. The climate change events such as increased intensity of erratic rains in short spells, trend of prolonged drought, gradual rise in temperature in the higher elevations and occurrence of cold and hot waves in Terai (lower plains) has led to flash floods, massive erosion in the hills particularly in Churia range and drying of water sources. These recurring natural and climate-induced disasters are causing heavy damages through sedimentation and inundation of agricultural lands, crops, livestock, infrastructures and rural settlements in the downstream plains and thus reducing agriculture productivity and food security in the country. About 65% of the cultivated land in Nepal is rainfed with drought-prone characteristics and stabilization of agricultural production and productivity in these tracts will be possible through adoption of rainfed and drought-tolerant technologies as well as efficient soil-water management by the local communities. The adaptation and mitigation technologies and options identified by the project for soil erosion, flash floods and landslide control are on-farm watershed management, sloping land agriculture technologies (SALT), agro-forestry practices, agri-silvi-pastoral management, hedge-row contour planting, bio-engineering along slopes and river banks, plantation of multi-purpose trees and management of degraded waste land including sandy river-bed flood plains. The stress tolerant technologies with respect to drought, floods and temperature stress for efficient utilization of nutrient, soil, water and other resources for increased productivity are adoption of stress tolerant crop varieties and breeds of animals, indigenous proven technologies, mixed and inter-cropping systems, system of rice/wheat intensification (SRI), direct rice seeding, double transplanting of rice, off-season vegetable production and regular management of nurseries, orchards and animal sheds. The alternate energy use options and resource conservation practices for use by local communities are installation of bio-gas plants and clean stoves (Chulla range) for mitigation of green house gas (GHG) emissions, use of organic manures and bio-pesticides, jatropha cultivation, green manuring in rice fields and minimum/zero tillage practices for marshy lands. The efficient water management practices for increasing productivity of crops and livestock are use of micro-irrigation practices, construction of water conservation and water harvesting ponds, use of overhead water tanks and Thai jars for rain water harvesting and rehabilitation of on-farm irrigation systems. Initiation of some works on community-based early warning system, strengthening of met stations and disaster database management has made genuine efforts in providing disaster-tailored early warning, meteorological and insurance services to the local communities. Contingent planning is recommended to develop coping strategies and capacities of local communities to adopt necessary changes in the cropping patterns and practices in relation to adverse climatic and disaster risk conditions. At the end, adoption of awareness raising and capacity development activities (technical and institutional) and networking on climate-induced disaster and risks through training, visits and knowledge sharing workshops, dissemination of technical know-how and technologies, conduct of farmers' field schools, development of extension materials and their displays are being promoted. However, there is still need of strong coordination and linkage between agriculture, environment, forestry, meteorology, irrigation, climate-induced pro-active disaster preparedness and research at the ministry, department and district level for up-scaling, implementation and institutionalization of climate change and disaster risk management activities and adaptation mitigation options in agriculture for sustainable livelihoods of the communities.

Keywords: climate change adaptation, disaster risk management, soil-water management practices, sustainable agriculture

Procedia PDF Downloads 473