Elucidating Signal Transduction Modulatory Drug Target Network of Colon Cancer: A Network Biology Approach

Latest evaluation and validation of cancer drugs and their targets has demonstrated the lack and inadequate development of new and better drugs, based on available protocols. Even though the specificity of drug targets is a great challenge in the pharmaco-proteomics field of cancer biology, for eradicating such hurdles and paving the way for the drugs of future, a novel step has been envisaged here to study the relation between drug target network and the corresponding drug network using the advanced concepts of proteomics and network biology. The literature mining was done for the collection of receptors and the ligands. About 1000 natural compounds were collected and out of those 300 molecules showed anti-cancer activity against colon cancer. Ligand Vs multiple receptor docking was done using the software Quantum 3.3.0; the results were further used for the designing of a well connected Protein Ligand Interaction (PLI) network of colon cancer. The obtained network is then extrapolated to sort out the receptors expressed in the specific cancer type. The network is then statistically analyzed and represented by the graphical interpretation, in order to ascertain the hub nodes and their locally parsed neighbours. Based on the best docking scores, the graphs obtained from the docking analysis are statistically validated with the help of VisANT. In the network three hub nodes Neutrophil cytosol factor 2, UV excision repair protein RAD23 homolog A, & Receptor-type tyrosine-protein phosphatase eta were identified, which showed the highest interaction with the ligands. Butyrate and Farnesol showed highest interaction as ligands. Multiple Sequence Alignment was done of the binding site sequence of the drug targets to find out the evolutionary closeness of the binding sites. The phylogenetic tree was also constructed to further validate the observation. Further in-vitro and in-vivo studies needs to be done to analyse the receptor specificity and anti tumor activity of these compounds in Colon cancer

Determinants of Inorganic Fertilizer Use in the Mixed Crop-Livestock Farming Systems of Central Highlands of Ethiopia

Increased use of inorganic fertilisers is believed to be fundamental to addressing the low and declining soil fertility and improving food security in sub-Sahara Africa (SSA). Despite notable improvements in the supply of inorganic fertilisers and supporting services such as extension and credit, use of inorganic fertilisers among smallholder farmers remained disappointingly low. The objective of this study was to determine key factors responsible for use of inorganic fertilisers in the mixed crop-livestock farming systems in the central highlands of Ethiopia. Heckman\u2019s two-step procedure was used to analyse the variables. Education level of the head of the household, number of livestock owned, number of plots owned, land tenure, access to credit and extension, agro-ecology and manure use influenced both the likelihood of adoption and intensity of inorganic fertiliser use. Continued land redistribution in the already degraded and land scarce highlands further undermine sustainable farming and increase nutrient mining. On the other hand, shrinking plot size as a result of repeated plot subdivisions may induce current users of inorganic fertilisers to use more nutrients per unit of land in an attempt to raise productivity. This positive effect, however, may be more than offset by the negative effects exerted by plot distance, thus leading to nutrient mining.L\u2019utilisation accrue des engrais inorganiques est reconnue \ueatre fondamentale pour addresser la baisse de la fertilit\ue9 du sol et l\u2019am\ue9lioration de la s\ue9curit\ue9 alimentaire en Afrique sub-Saharienne (SSA). Malgr\ue9 des ameliorations notables dans l\u2019approvisionnement des engrais et les services de soutien tels que la vulgarization et credit, l\u2019utilisation des engrais inorganiques par les petits expolitants est de fa\ue7on d\ue9cevante rest\ue9e basse. L\u2019objectif de cette \ue9tude \ue9tait de d\ue9terminer les faclteurs cl\ue9s reponsables pour l\u2019utilisation des engrais inorganiques dans les syst\ue8mes mixtes agro-elevages dans les hautes terres du Centre de l\u2019Ethiopie. La proc\ue9dure dite two-step de Heckman \ue9tait utilis\ue9e pour analyser les variables. Le niveau d\u2019\ue9tude du chef de m\ue9nage, le nombre de b\ue9tail poss\ue9d\ue9, le nombre de parcelle poss\ue9d\ue9, la possession de terre, l\u2019acc\ue8s au credit et les services de vulgarization, l\u2019utilisation agro-\ue9cologique et fumure organique comme influenc\ue9 par l\u2019adoption et l\u2019intensit\ue9 de l\u2019utilisation des engrais inorganiques. La redistribution des terres des hautes terres d\ue9j\ue0 d\ue9grad\ue9es et rares compromet toute tentative de leur exploitation durable et acc\ue9l\ue8re l\u2019appauvrissement du sol en \ue9lements min\ue9raux. D\u2019autre part, la r\ue9duction de la taille des parcelles comme r\ue9sultat des subdivisions r\ue9p\ue9t\ue9es des parcelles pourrait induire une utilisation plus accrue des engrais inorganiques par unit\ue9 de terre dans la tentative d\u2019accro\ueetre la productivit\ue9. Cet effet positif, par ailleur, pourrait \ueatre plus que contre-balanc\ue9 par les effets n\ue9gatifs tels qu\u2019 influenc\ue9s par la distance, ainsi, conduisant \ue0 la perte d\u2019\ue9lements min\ue9raux du sol

The Moment Problem in Hypercomplex Systems

This paper is devoted to give the necessary and sufficient conditions guarantees that the product of two generalized moment functions defined in a hypercomplex system L1(Q,m) is also generalized moment function in L1(Q,m) . Also, we prove that a bounded continuous function  in a hypercomplex system L1(Q,m) is conditionally positive definite if and only if is generalized moment functions defined in L1(Q,m) . Moreover, we will give the integral representations of a generalized moment functions defined in L1 (Q, m)

Non-urgent emergency department attendances in children : a retrospective observational analysis

Introduction: A significant proportion of ED attendances in children may be non-urgent attendances (NUAs), which could be better managed elsewhere. This study aimed to quantify NUAs and urgent attendances (UAs) in children to ED and determine which children present in this way and when. Methods: Dataset extracted from the CUREd research database containing linked data on the provision of care in Yorkshire and Humber. Analysis focused on children’s ED attendances (April 2014–March 2017). Summary statistics and odds ratios (OR) comparing NUAs and UAs were examined by: age, mode and time of arrival and deprivation alongside comparing summary statistics for waiting, treatment and total department times. Results: NUAs were more likely in younger children: OR for NUA in children aged 1–4 years, 0.82 (95% CI: 0.80 to 0.83), age 15 years, 0.39 (95% CI: 0.38 to 0.40), when compared with those under 1 year. NUAs were more likely to arrive out of hours (OOHs) compared with in hours: OR 1.19 (95% CI 1.18 to 1.20), and OOHs arrivals were less common in older children compared with those under 1 year: age 1–4 years, 0.87 (95% CI: 0.84 to 0.89) age 15 years, 0.66 (95% CI: 0.63 to 0.69). NUAs also spent less total time in the ED, with a median (IQR) of 98 min (60–147) compared with 127 min (80–185) for UAs. Conclusion: A substantial proportion of ED attendances in children are NUAs. Our data suggest there are particular groups of children for whom targeted interventions would be most beneficial. Children under 5 years would be such a group, particularly in providing accessible, timely care outside of usual community care opening hours

PREPARATION AND FLAVOUR EVALUATION OF HIGH QUALITY FREEZE DRIED SEASONING BLEND

Combinations of different spices were used at variable concentrations in the preparation of vari-ous curry blends. The sample showed the highest sensory attributes in comparison with control cur-ry sample was compounded with different spices, onion and garlic at variable concentrations in cor-responding seasoning blend. The oleoresin of the seasoning blend that possessed the highest quality scores was prepared and subjected to freeze drying process after dispersion on suitable carrier. The flavour contribution percentages of the character-istic notes; light sweet top, medium aromatic, full boiled spicy and pungent spicy were calculated for each curry and seasoning blends. The hydro dis-tilled (HD) oils of the selected curry and its con-stituents were subjected to GC-MS analysis. The results revealed the high contribution of the com-ponents possess spicy note in the raw curry sam-ple. The components possess pungent notes showed less representation. β-Caryophellene was the major compounds in the HD oil of raw season-ing blends followed by δ-carene and ar-turmenone. The qualitative and quantitative varia-tion in the volatile compounds separated from the HD oil of the freeze dried sample may be attribut-ed to the interaction between such components and the used carrier (10% maltodextrin in water)

Evaluation of the physical, chemical, bacteriological and trace metals concentrations in different brands of packaged drinking water

—Human survival largely depends on potable water quality. This study used current analytical procedures and compared with the National Agency for Food and Drug Administration Control (NAFDAC) drinking water specification to evaluate the physio-chemical and microbiological characteristics of fifteen packaged water brands that are available locally. Atomic absorption spectroscopy was used to determine trace metals while instrumental techniques determined the physical and chemical parameters. The evaluation focused on the pH, colour, total dissolved solids, turbidity, dissolved oxygen, fluoride, chloride, iron, zinc, magnesium, calcium, potassium, and sodium. In all the samples examined, chromium, manganese, cadmium, and copper were not detected. However, total bacterial counts were discovered in samples (S1, S2, S3, B1 and B2) with values of 2, 3, 5, 3 and 1 cfu/100 ml, respectively. Packaged water containing these type and quantity of bacteria are not fit for consumption by human beings. It requires the most appropriate techniques for processing

Perspective Chapter: The Toxic Silver (Hg)

In the late 1950s, residents of a Japanese fishing village known as “Minamata” began falling ill and dying at an alarming rate. The Japanese authorities stated that methyl-mercury-rich seafood and shellfish caused the sickness. Burning fossil fuels represent ≈52.7% of Hg emissions. The majorities of mercury’s compounds are volatile and thus travel hundreds of miles with wind before being deposited on the earth’s surface. High acidity and dissolved organic carbon increase Hg-mobility in soil to enter the food chain. Additionally, Hg is taken up by areal plant parts via gas exchange. Mercury has no identified role in plants while exhibiting high affinity to form complexes with soft ligands such as sulfur and this consequently inactivates amino acids and sulfur-containing antioxidants. Long-term human exposure to Hg leads to neurotoxicity in children and adults, immunological, cardiac, and motor reproductive and genetic disorders. Accordingly, remediating contaminated soils has become an obligation. Mercury, like other potentially toxic elements, is not biodegradable, and therefore, its remediation should encompass either removal of Hg from soils or even its immobilization. This chapter discusses Hg’s chemical behavior, sources, health dangers, and soil remediation methods to lower Hg levels

Soil: the great connector of our lives now and beyond COVID-19

Open Access Journal; Published online: 05 Nov 2020Humanity depends on the existence of healthy soils, both for the production of food and for ensuring a healthy, biodiverse environment, among other functions. COVID-19 is threatening food availability in many places of the world due to the disruption of food chains, lack of workforce, closed borders and national lockdowns. As a consequence, more emphasis is being placed on local food production, which may lead to more intensive cultivation of vulnerable areas and to soil degradation. In order to increase the resilience of populations facing this pandemic and future global crises, transitioning to a paradigm that relies more heavily on local food production on soils that are carefully tended and protected through sustainable management is necessary. To reach this goal, the Intergovernmental Technical Panel on Soils (ITPS) of the Food and Agriculture Organization of the United Nations (FAO) recommends five active strategies: improved access to land, sound land use planning, sustainable soil management, enhanced research, and investments in education and extension. The soil is the great connector of lives, the source and destination of all. It is the healer and restorer and resurrector, by which disease passes into health, age into youth, death into life. Without proper care for it we can have no community, because without proper care for it we can have no life

Association between the magnitude of intravenous busulfan exposure and development of hepatic veno-occlusive disease in children and young adults undergoing myeloablative allogeneic hematopoietic cell transplantation

Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious clinical problem observed with busulfan-based conditioning HCT. The development of VOD/SOS may be associated with busulfan exposure. Getting more insight into the association between busulfan exposure and the development of VOD/SOS enables further optimization of dos-ing and treatment strategies. The objective of this study was to assess the association between the magnitude of busulfan exposure and the occurrence of VOD/SOS in children and young adults undergoing myeloablative con-ditioning with a busulfan-containing regimen before allogeneic HCT. In this observational study we included all patients who underwent allogeneic HCT with intravenous busulfan as part of the conditioning regimen at 15 pediatric transplantation centers between 2000 and 2015. The endpoint was the development of VOD/SOS. The magnitude of busulfan exposure was estimated using nonlinear mixed effect modeling and expressed as the maximal concentration (Cmax; day 1 and day 1 to 4 Cmax), cumulative area under the curve (AUC; day 1, high-est 1-day AUC in 4 days, and 4-day cumulative AUC), cumulative time above a concentration of 300 mg/L, and clearance on day 1. A total of 88 out of 697 patients (12.6%) developed VOD/SOS. The number of alkylators in the conditioning regimen was a strong effect modifier; therefore we stratified the regression analysis for the number of alkylators. For patients receiving only busulfan as one alkylator (36.3%, n = 253), cumulative busulfan exposure (>78 mg x h/L) was associated with increased VOD/SOS risk (12.6% versus 4.7%; odds ratio [OR] = 2.95, 95% confidence interval [CI] 1.13 to 7.66). For individuals receiving busulfan with one or two addi-tional alkylators (63.7%, n = 444), cumulative busulfan exposure (78 mg x h/L) did not further increase the risk of VOD/SOS (15.4% versus 15.2%; OR = 1.03, 95% CI 0.61 to 1.75). The effect of the magnitude of busulfan exposure on VOD/SOS risk in children and young adults undergoing HCT is dependent on the number of alkylators. In patients receiving busulfan as the only alkylator, higher cumulative busulfan exposure increased the risk of VOD/SOS, whereas in those receiving multiple alkylators, the magnitude of busulfan expo-sure did not further increase this risk. Transplantation and immunomodulatio

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000–18: a geospatial modelling study

Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation