Search results for: respiratory diseases
68 Health Risk Assessment from Potable Water Containing Tritium and Heavy Metals
Authors: Olga A. Momot, Boris I. Synzynys, Alla A. Oudalova
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Obninsk is situated in the Kaluga region 100 km southwest of Moscow on the left bank of the Protva River. Several enterprises utilizing nuclear energy are operating in the town. A special attention in the region where radiation-hazardous facilities are located has traditionally been paid to radioactive gas and aerosol releases into the atmosphere; liquid waste discharges into the Protva river and groundwater pollution. Municipal intakes involve 34 wells arranged 15 km apart in a sequence north-south along the foot of the left slope of the Protva river valley. Northern and southern water intakes are upstream and downstream of the town, respectively. They belong to river valley intakes with mixed feeding, i.e. precipitation infiltration is responsible for a smaller part of groundwater, and a greater amount is being formed by overflowing from Protva. Water intakes are maintained by the Protva river runoff, the volume of which depends on the precipitation fallen out and watershed area. Groundwater contamination with tritium was first detected in a sanitary-protective zone of the Institute of Physics and Power Engineering (SRC-IPPE) by Roshydromet researchers when realizing the “Program of radiological monitoring in the territory of nuclear industry enterprises”. A comprehensive survey of the SRC-IPPE’s industrial site and adjacent territories has revealed that research nuclear reactors and accelerators where tritium targets are applied as well as radioactive waste storages could be considered as potential sources of technogenic tritium. All the above sources are located within the sanitary controlled area of intakes. Tritium activity in water of springs and wells near the SRC-IPPE is about 17.4 – 3200 Bq/l. The observed values of tritium activity are below the intervention levels (7600 Bq/l for inorganic compounds and 3300 Bq/l for organically bound tritium). The risk has being assessed to estimate possible effect of considered tritium concentrations on human health. Data on tritium concentrations in pipe-line drinking water were used for calculations. The activity of 3H amounted to 10.6 Bq/l and corresponded to the risk of such water consumption of ~ 3·10-7 year-1. The risk value given in magnitude is close to the individual annual death risk for population living near a NPP – 1.6·10-8 year-1 and at the same time corresponds to the level of tolerable risk (10-6) and falls within “risk optimization”, i.e. in the sphere for planning the economically sound measures on exposure risk reduction. To estimate the chemical risk, physical and chemical analysis was made of waters from all springs and wells near the SRC-IPPE. Chemical risk from groundwater contamination was estimated according to the EPA US guidance. The risk of carcinogenic diseases at a drinking water consumption amounts to 5·10-5. According to the classification accepted the health risk in case of spring water consumption is inadmissible. The compared assessments of risk associated with tritium exposure, on the one hand, and the dangerous chemical (e.g. heavy metals) contamination of Obninsk drinking water, on the other hand, have confirmed that just these chemical pollutants are responsible for health risk.Keywords: radiation-hazardous facilities, water intakes, tritium, heavy metal, health risk
Procedia PDF Downloads 23567 Potential of Polyphenols from Tamarix Gallica towards Common Pathological Features of Diabetes and Alzheimer’s Diseases
Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori
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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica
Procedia PDF Downloads 27266 Isolation and Identification of Low-Temperature Tolerant-Yeast Strains from Apple with Biocontrol Activity
Authors: Lachin Mikjtarnejad, Mohsen Farzaneh
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Various microbes, such as fungi and bacteria species, are naturally found in the fruit microbiota, and some of them act as a pathogen and result in fruit rot. Among non-pathogenic microbes, yeasts (single-celled microorganisms belonging to the fungi kingdom) can colonize fruit tissues and interact with them without causing any damage to them. Although yeasts are part of the plant microbiota, there is little information about their interactions with plants in comparison with bacteria and filamentous fungi. According to several existing studies, some yeasts can colonize different plant species and have the biological control ability to suppress some of the plant pathogens. It means those specific yeast-colonized plants are more resistant to some plant pathogens. The major objective of the present investigation is to isolate yeast strains from apple fruit and screen their ability to control Penicillium expansum, the causal agent of blue mold of fruits. In the present study, psychrotrophic and epiphytic yeasts were isolated from apple fruits that were stored at low temperatures (0–1°C). Totally, 42 yeast isolates were obtained and identified by molecular analysis based on genomic sequences of the D1/D2 and ITS1/ITS4 regions of their rDNA. All isolated yeasts were primarily screened by' in vitro dual culture assay against P. expansum by measuring the fungus' relative growth inhibition after 10 days of incubation. The results showed that the mycelial growth of P. expansum was reduced between 41–53% when challenged by promising yeast strains. The isolates with the strongest antagonistic activity belonged to Metschnikowia pulcherrima A13, Rhodotorula mucilaginosa A41, Leucosporidium Scottii A26, Aureobasidium pullulans A19, Pichia guilliermondii A32, Cryptococcus flavescents A25, and Pichia kluyveri A40. The results of seven superior isolates to inhibit blue mold decay on fruit showed that isolates A. pullulans A19, L. scottii A26, and Pi. guilliermondii A32 could significantly reduce the fruit rot and decay with 26 mm, 22 mm and 20 mm zone diameter, respectively, compared to the control sample with 43 mm. Our results show Pi. guilliermondii strain A13 was the most effective yeast isolates in inhibiting P. expansum on apple fruits. In addition, various biological control mechanisms of promising biological isolates against blue mold have been evaluated to date, including competition for nutrients and space, production of volatile metabolites, reduction of spore germination, production of siderophores and production of extracellular lytic enzymes such as chitinase and β-1,3-glucanase. However, the competition for nutrients and the ability to inhibit P. expansum spore growth have been introduced as the prevailing mechanisms among them. Accordingly, in our study, isolates A13, A41, A40, A25, A32, A19 and A26 inhibited the germination of P. expansum, whereas isolates A13 and A19 were the strongest inhibitors of P. expansum mycelia growth, causing 89.13% and 81.75 % reduction in the mycelial surface, respectively. All the promising isolates produced chitinase and β-1,3-glucanase after 3, 5 and 7 days of cultivation. Finally, based on our findings, we are proposing that, Pi. guilliermondiias as an effective biocontrol agent and alternative to chemical fungicides to control the blue mold of apple fruit.Keywords: yeast, yeast enzymes, biocontrol, post harvest diseases
Procedia PDF Downloads 11965 Nephrotoxicity and Hepatotoxicity Induced by Chronic Aluminium Exposure in Rats: Impact of Nutrients Combination versus Social Isolation and Protein Malnutrition
Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh
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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations
Procedia PDF Downloads 24364 Magneto-Luminescent Biocompatible Complexes Based on Alloyed Quantum Dots and Superparamagnetic Iron Oxide Nanoparticles
Authors: A. Matiushkina, A. Bazhenova, I. Litvinov, E. Kornilova, A. Dubavik, A. Orlova
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Magnetic-luminescent complexes based on superparamagnetic iron oxide nanoparticles (SPIONs) and semiconductor quantum dots (QDs) have been recognized as a new class of materials that have high potential in modern medicine. These materials can serve for theranostics of oncological diseases, and also as a target agent for drug delivery. They combine the qualities characteristic of magnetic nanoparticles, that is, magneto-controllability and the ability to local heating under the influence of an external magnetic field, as well as phosphors, due to luminescence of which, for example, early tumor imaging is possible. The complexity of creating complexes is the energy transfer between particles, which quenches the luminescence of QDs in complexes with SPIONs. In this regard, a relatively new type of alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs is used in our work. The presence of a sufficiently thick gradient semiconductor shell in alloyed QDs makes it possible to reduce the probability of energy transfer from QDs to SPIONs in complexes. At the same time, Forster Resonance Energy Transfer (FRET) is a perfect instrument to confirm the formation of complexes based on QDs and different-type energy acceptors. The formation of complexes in the aprotic bipolar solvent dimethyl sulfoxide is ensured by the coordination of the carboxyl group of the stabilizing QD molecule (L-cysteine) on the surface iron atoms of the SPIONs. An analysis of the photoluminescence (PL) spectra has shown that a sequential increase in the SPIONs concentration in the samples is accompanied by effective quenching of the luminescence of QDs. However, it has not confirmed the formation of complexes yet, because of a decrease in the PL intensity of QDs due to reabsorption of light by SPIONs. Therefore, a study of the PL kinetics of QDs at different SPIONs concentrations was made, which demonstrates that an increase in the SPIONs concentration is accompanied by a symbatic reduction in all characteristic PL decay times. It confirms the FRET from QDs to SPIONs, which indicates the QDs/SPIONs complex formation, rather than a spontaneous aggregation of QDs, which is usually accompanied by a sharp increase in the percentage of the QD fraction with the shortest characteristic PL decay time. The complexes have been studied by the magnetic circular dichroism (MCD) spectroscopy that allows one to estimate the response of magnetic material to the applied magnetic field and also can be useful to check SPIONs aggregation. An analysis of the MCD spectra has shown that the complexes have zero residual magnetization, which is an important factor for using in biomedical applications, and don't contain SPIONs aggregates. Cell penetration, biocompatibility, and stability of QDs/SPIONs complexes in cancer cells have been studied using HeLa cell line. We have found that the complexes penetrate in HeLa cell and don't demonstrate cytotoxic effect up to 25 nM concentration. Our results clearly demonstrate that alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs can be successfully used in complexes with SPIONs reached new hybrid nanostructures, which combine bright luminescence for tumor imaging and magnetic properties for targeted drug delivery and magnetic hyperthermia of tumors. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and was financially supported by Government of Russian Federation, Grant 08-08.Keywords: alloyed quantum dots, magnetic circular dichroism, magneto-luminescent complexes, superparamagnetic iron oxide nanoparticles
Procedia PDF Downloads 10863 Quantified Metabolomics for the Determination of Phenotypes and Biomarkers across Species in Health and Disease
Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette
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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment
Procedia PDF Downloads 33362 The Prevalence of Soil Transmitted Helminths among Newly Arrived Expatriate Labors in Jeddah, Saudi Arabia
Authors: Mohammad Al-Refai, Majed Wakid
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Introduction: Soil-transmitted diseases (STD) are caused by intestinal worms that are transmitted via various routes into the human body resulting in various clinical manifestations. The intestinal worms causing these infections are known as soil transmitted helminths (STH), including Hook worms, Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), and Strongyloides sterocoralis (S. sterocoralis). Objectives: The aim of this study was to investigate the prevalence of STH among newly arrived expatriate labors in Jeddah city, Saudi Arabia, using three different techniques (direct smears, sedimentation concentration, and real-time PCR). Methods: A total of 188 stool specimens were collected and investigated at the parasitology laboratory in the Special Infectious Agents Unit at King Fahd Medical Research Center, King Abdulaziz University in Jeddah, Saudi Arabia. Microscopic examination of wet mount preparations using normal saline and Lugols Iodine was carried out, followed by the formal ether sedimentation method. In addition, real-time PCR was used as a molecular tool to detect several STH and hookworm speciation. Results: Out of 188 stool specimens analyzed, in addition to STH parasite, several other types were detected. 9 samples (4.79%) were positive for Entamoeba coli, 7 samples (3.72%) for T. trichiura, 6 samples (3.19%) for Necator americanus, 4 samples (2.13%) for S. sterocoralis, 4 samples (2.13%) for A. lumbricoides, 4 samples (2.13%) for E. histolytica, 3 samples (1.60%) for Blastocystis hominis, 2 samples (1.06%) for Ancylostoma duodenale, 2 samples (1.06%) for Giardia lamblia, 1 sample (0.53%) for Iodamoeba buetschlii, 1 sample (0.53%) for Hymenolepis nana, 1 sample (0.53%) for Endolimax nana, and 1 sample (0.53%) for Heterophyes heterophyes. Out of the 35 infected cases, 26 revealed single infection, 8 with double infections, and only one triple infection of different STH species and other intestinal parasites. Higher rates of STH infections were detected among housemaids (11 cases) followed by drivers (7 cases) when compared to other occupations. According to educational level, illiterate participants represent the majority of infected workers (12 cases). The majority of workers' positive cases were from the Philippines. In comparison between laboratory techniques, out of the 188 samples screened for STH, real-time PCR was able to detect the DNA in (19/188) samples followed by Ritchie sedimentation technique (18/188), and direct wet smear (7/188). Conclusion: STH infections are a major public health issue to healthcare systems around the world. Communities must be educated on hygiene practices and the severity of such parasites to human health. As far as drivers and housemaids come to close contact with families, including children and elderlies. This may put family members at risk of developing serious side effects related to STH, especially as the majority of workers were illiterate, lacking the basic hygiene knowledge and practices. We recommend the official authority in Jeddah and around the kingdom of Saudi Arabia to revise the standard screening tests for newly arrived workers and enforce regular follow-up inspections to minimize the chances of the spread of STH from expatriate workers to the public.Keywords: expatriate labors, Jeddah, prevalence, soil transmitted helminths
Procedia PDF Downloads 14161 Gendered Water Insecurity: a Structural Equation Approach for Female-Headed Households in South Africa
Authors: Saul Ngarava, Leocadia Zhou, Nomakhaya Monde
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Water crises have the fourth most significant societal impact after weapons of mass destruction, climate change, and extreme weather conditions, ahead of natural disasters. Intricacies between women and water are central to achieving the 2030 Sustainable Development Goals (SDGs). The majority of the 1.2 billion poor people worldwide, with two-thirds being women, and mostly located in Sub Sahara Africa (SSA) and South Asia, do not have access to safe and reliable sources of water. There exist gendered differences in water security based on the division of labour associating women with water. Globally, women and girls are responsible for water collection in 80% of the households which have no water on their premises. Women spend 16 million hours a day collecting water, while men and children spend 6 million and 4 million per day, respectively, which is time foregone in the pursuit of other livelihood activities. Due to their proximity and activities concerning water, women are vulnerable to water insecurity through exposures to water-borne diseases, fatigue from physically carrying water, and exposure to sexual and physical harassment, amongst others. Proximity to treated water and their wellbeing also has an effect on their sensitivity and adaptive capacity to water insecurity. The great distances, difficult terrain and heavy lifting expose women to vulnerabilities of water insecurity. However, few studies have quantified the vulnerabilities and burdens on women, with a few taking a phenomenological qualitative approach. Vulnerability studies have also been scanty in the water security realm, with most studies taking linear forms of either quantifying exposures, sensitivities or adaptive capacities in climate change studies. The current study argues for the need for a water insecurity vulnerability assessment, especially for women into research agendas as well as policy interventions, monitoring, and evaluation. The study sought to identify and provide pathways through which female-headed households were water insecure in South Africa, the 30th driest country in the world. This was through linking the drinking water decision as well as the vulnerability frameworks. Secondary data collected during the 2016 General Household Survey (GHS) was utilised, with a sample of 5928 female-headed households. Principal Component Analysis and Structural Equation Modelling were used to analyse the data. The results show dynamic relationships between water characteristics and water treatment. There were also associations between water access and wealth status of the female-headed households. Association was also found between water access and water treatment as well as between wealth status and water treatment. The study concludes that there are dynamic relationships in water insecurity (exposure, sensitivity, and adaptive capacity) for female-headed households in South Africa. The study recommends that a multi-prong approach is required in tackling exposures, sensitivities, and adaptive capacities to water insecurity. This should include capacitating and empowering women for wealth generation, improve access to water treatment equipment as well as prioritising the improvement of infrastructure that brings piped and safe water to female-headed households.Keywords: gender, principal component analysis, structural equation modelling, vulnerability, water insecurity
Procedia PDF Downloads 11760 Prospects of Low Immune Response Transplants Based on Acellular Organ Scaffolds
Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen
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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants
Procedia PDF Downloads 27359 Promotion of Healthy Food Choices in School Children through Nutrition Education
Authors: Vinti Davar
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Introduction: Childhood overweight increases the risk for certain medical and psychological conditions. Millions of school-age children worldwide are affected by serious yet easily treatable and preventable illnesses that inhibit their ability to learn. Healthier children stay in school longer, attend more regularly, learn more and become healthier and more productive adults. Schools are an important setting for nutrition education because one can reach most children, teachers and parents. These years offer a key window for shaping their lifetime habits, which have an impact on their health throughout life. Against this background, an attempt was made to impart nutrition education to school children in Haryana state of India to promote healthy food choices and assess the effectiveness of this program. Methodology: This study was completed in two phases. During the first phase, pre-intervention anthropometric and dietary survey was conducted; the teaching materials for nutrition intervention program were developed and tested; and the questionnaire was validated. In the second phase, an intervention was implemented in two schools of Kurukshetra, Haryana for six months by personal visits once a week. A total of 350 children in the age group of 6-12 years were selected. Out of these, 279 children, 153 boys and 126 girls completed the study. The subjects were divided into four groups namely: underweight, normal, overweight and obese based on body mass index-for-age categories. A power point colorful presentation to improve the quality of tiffin, snacks and meals emphasizing inclusion of all food groups especially vegetables every day and fruits at least 3-4 days per week was used. An extra 20 minutes of aerobic exercise daily was likewise organized and a healthy school environment created. Provision of clean drinking water by school authorities was ensured. Selling of soft drinks and energy-dense snacks in the school canteen as well as advertisements about soft drink and snacks on the school walls were banned. Post intervention, anthropometric indices and food selections were reassessed. Results: The results of this study reiterate the critical role of nutrition education and promotion in improving the healthier food choices by school children. It was observed that normal, overweight and obese children participating in nutrition education intervention program significantly (p≤0.05) increased their daily seasonal fruit and vegetable consumption. Fat and oil consumption was significantly reduced by overweight and obese subjects. Fast food intake was controlled by obese children. The nutrition knowledge of school children significantly improved (p≤0.05) from pre to post intervention. A highly significant increase (p≤0.00) was noted in the nutrition attitude score after intervention in all four groups. Conclusion: This study has shown that a well-planned nutrition education program could improve nutrition knowledge and promote positive changes in healthy food choices. A nutrition program inculcates wholesome eating and active life style habits in children and adolescents that could not only prevent them from chronic diseases and early death but also reduce healthcare cost and enhance the quality of life of citizens and thereby nations.Keywords: children, eating habits healthy food, obesity, school going, fast foods
Procedia PDF Downloads 20358 Role of Functional Divergence in Specific Inhibitor Design: Using γ-Glutamyltranspeptidase (GGT) as a Model Protein
Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel
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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design
Procedia PDF Downloads 26457 Oil and Proteins of Sardine (Sardina Pilchardus) Compared with Casein or Mixture of Vegetable Oils Improves Dyslipidemia and Reduces Inflammation and Oxidative Stress in Hypercholesterolemic and Obese Rats
Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel
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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense
Procedia PDF Downloads 6056 Enhancing Early Detection of Coronary Heart Disease Through Cloud-Based AI and Novel Simulation Techniques
Authors: Md. Abu Sufian, Robiqul Islam, Imam Hossain Shajid, Mahesh Hanumanthu, Jarasree Varadarajan, Md. Sipon Miah, Mingbo Niu
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Coronary Heart Disease (CHD) remains a principal cause of global morbidity and mortality, characterized by atherosclerosis—the build-up of fatty deposits inside the arteries. The study introduces an innovative methodology that leverages cloud-based platforms like AWS Live Streaming and Artificial Intelligence (AI) to early detect and prevent CHD symptoms in web applications. By employing novel simulation processes and AI algorithms, this research aims to significantly mitigate the health and societal impacts of CHD. Methodology: This study introduces a novel simulation process alongside a multi-phased model development strategy. Initially, health-related data, including heart rate variability, blood pressure, lipid profiles, and ECG readings, were collected through user interactions with web-based applications as well as API Integration. The novel simulation process involved creating synthetic datasets that mimic early-stage CHD symptoms, allowing for the refinement and training of AI algorithms under controlled conditions without compromising patient privacy. AWS Live Streaming was utilized to capture real-time health data, which was then processed and analysed using advanced AI techniques. The novel aspect of our methodology lies in the simulation of CHD symptom progression, which provides a dynamic training environment for our AI models enhancing their predictive accuracy and robustness. Model Development: it developed a machine learning model trained on both real and simulated datasets. Incorporating a variety of algorithms including neural networks and ensemble learning model to identify early signs of CHD. The model's continuous learning mechanism allows it to evolve adapting to new data inputs and improving its predictive performance over time. Results and Findings: The deployment of our model yielded promising results. In the validation phase, it achieved an accuracy of 92% in predicting early CHD symptoms surpassing existing models. The precision and recall metrics stood at 89% and 91% respectively, indicating a high level of reliability in identifying at-risk individuals. These results underscore the effectiveness of combining live data streaming with AI in the early detection of CHD. Societal Implications: The implementation of cloud-based AI for CHD symptom detection represents a significant step forward in preventive healthcare. By facilitating early intervention, this approach has the potential to reduce the incidence of CHD-related complications, decrease healthcare costs, and improve patient outcomes. Moreover, the accessibility and scalability of cloud-based solutions democratize advanced health monitoring, making it available to a broader population. This study illustrates the transformative potential of integrating technology and healthcare, setting a new standard for the early detection and management of chronic diseases.Keywords: coronary heart disease, cloud-based ai, machine learning, novel simulation techniques, early detection, preventive healthcare
Procedia PDF Downloads 5755 Mineralized Nanoparticles as a Contrast Agent for Ultrasound and Magnetic Resonance Imaging
Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee
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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging
Procedia PDF Downloads 23154 Molecular Characterization of Chicken B Cell Marker (ChB6) in Native Chicken of Poonch Region from International Borders of India and Pakistan
Authors: Mandeep Singh Azad.Dibyendu Chakraborty, Vikas Vohra
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Introduction: Poonch is one of the remotest districts of the Jammu and Kashmir (UT) and situated on international borders. This native poultry population in these areas is quite hardy and thrives well in adverse climatic conditions. Till date, no local breed from this area (Jammu Province) has been characterized thus present study was undertaken with the main objectives of molecular characterization of ChB6 gene in local native chicken of Poonch region located at international borders between India and Pakistan. The chicken B-cell marker (ChB6) gene has been proposed as a candidate gene in regulating B-cell development. Material and Method: RNA was isolated by Blood RNA Purification Kit (HiPura) and Trizol method from whole blood samples. Positive PCR products with size 1110 bp were selected for further purification, sequencing and analysis. The amplified PCR product was sequenced by Sangers dideoxy chain termination method. The obtained sequence of ChB6 gene of Poonchi chicken were compared by MEGAX software. BioEdit software was used to construct phylogenic tree, and Neighbor Joining method was used to infer evolutionary history. In order to compute evolutionary distance Maximum Composite Likelihood method was used. Results: The positively amplified samples of ChB6 genes were then subjected to Sanger sequencing with “Primer Walking. The sequences were then analyzed using MEGA X and BioEdit software. The sequence results were compared with other reported sequence from different breed of chicken and with other species obtained from the NCBI (National Center for Biotechnology Information). ClustalW method using MEGA X software was used for multiple sequence alignment. The sequence results of ChB6 gene of Poonchi chicken was compared with Centrocercus urophasianus, G. gallus mRNA for B6.1 protein, G. gallus mRNA for B6.2, G. gallus mRNA for B6.3, Gallus gallus B6.1, Halichoeres bivittatus, Miniopterus fuliginosus Ferringtonia patagonica, Tympanuchus phasianellus. The genetic distances were 0.2720, 0.0000, 0.0245, 0.0212, 0.0147, 1.6461, 2.2394, 2.0070 and 0.2363 for ChB6 gene of Poonchi chicken sequence with other sequences in the present study respectively. Sequencing results showed variations between different species. It was observed that AT content were higher then GC content for ChB6 gene. The lower AT content suggests less thermostable. It was observed that there was no sequence difference within the Poonchi population for ChB6 gene. The high homology within chicken population indicates the conservation of ChB6 gene. The maximum difference was observed with Miniopterus fuliginosus (Eastern bent-wing bat) followed by Ferringtonia patagonica and Halichoeres bivittatus. Conclusion: Genetic variation is the essential component for genetic improvement. The results of immune related gene Chb6 shows between population genetic variability. Therefore, further association studies of this gene with some prevalent diseases in large population would be helpful to identify disease resistant/ susceptible genotypes in the indigenous chicken population.Keywords: ChB6, sequencing, ClustalW, genetic distance, poonchi chicken, SNP
Procedia PDF Downloads 6053 Diabetic Screening in Rural Lesotho, Southern Africa
Authors: Marie-Helena Docherty, Sion Edryd Williams
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The prevalence of diabetes mellitus is increasing worldwide. In Sub-Saharan Africa, type 2 diabetes represents over 90% of all types of diabetes with the number of diabetic patients expected to rise. This represents a huge economic burden in an area already contending with high rates of other significant diseases, including the highest worldwide prevalence of HIV. Diabetic complications considerably impact on morbidity and mortality. The epidemiological data for the region quotes high rates of retinopathy (7-63%), neuropathy (27-66%) and microalbuminuria (10-83%). It is therefore imperative that diabetic screening programmes are established. It is recognised that in many parts of the developing world the implementation and management of such programmes is limited by a lack of available resources. The International Diabetes Federation produced guidelines in 2012 taking these limitations into account suggesting that all diabetic patients should have access to basic screening. These guidelines are consistent with the national diabetic guidelines produced by the Lesotho Medical Council. However, diabetic care in Lesotho is delivered at the local level, with variable levels of quality. A cross sectional study was performed in the outpatient department of Maluti Hospital in Mapoteng, Lesotho, a busy rural hospital in the Berea district. Demographic data on gender, age and modality of treatment were collected over a six-week time period. Information regarding 3 basic screening parameters was obtained. These parameters included eye screening (defined as a documented ophthalmology review within the last 12 months), foot screening (defined as a documented foot health assessment by any health care professional within the last 12 months) and secondary prevention (defined as a documented blood pressure and lipid profile reading within the last 12 months). These parameters were selected on the basis of the absolute minimum level of resources in Maluti Hospital. Renal screening was excluded, as the hospital does not have access to reliable renal profile checks or urinalysis. There is however a fully functioning on-site ophthalmology department run by a senior ophthalmologist with the ability to provide retinal photography, retinal surgery and photocoagulation therapy. Data was collected on 183 type 2 diabetics. 112 patients were male and 71 were female. The average age was 43 years. 4 patients were diet controlled, 140 patients were on oral hypoglycaemic agents (metformin and/or glibenclamide), and 39 patients were on a combination of insulin and oral hypoglycaemics. In the preceding 12 months, 5 patients had undergone eye screening (3%), 24 patients had undergone foot screening (13%), and 31 patients had lipid profile testing (17%). All patients had a documented blood pressure reading (100%). Our results show that screening is poorly performed in the basic indicators suggested by the IDF and the Lesotho Medical Council. On the basis of these results, a screening programme was developed using the mnemonic SaFE; secondary prevention, foot and eye care. This is simple, memorable and transferable between healthcare professionals. In the future, the expectation would be to expand upon this current programme to include renal screening, and to further develop screening pertaining to secondary prevention.Keywords: Africa, complications, rural, screening
Procedia PDF Downloads 28052 A Cluster Randomised Controlled Trial Investigating the Impact of Integrating Mass Drug Administration Treating Soil Transmitted Helminths with Mass Dog Rabies Vaccination in Remote Communities in Tanzania
Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer
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Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths
Procedia PDF Downloads 17251 Calpains; Insights Into the Pathogenesis of Heart Failure
Authors: Mohammadjavad Sotoudeheian
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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte
Procedia PDF Downloads 6350 Decrease in Olfactory Cortex Volume and Alterations in Caspase Expression in the Olfactory Bulb in the Pathogenesis of Alzheimer’s Disease
Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham
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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction
Procedia PDF Downloads 25149 Formulation of a Submicron Delivery System including a Platelet Lysate to Be Administered in Damaged Skin
Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero
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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration
Procedia PDF Downloads 16748 The Knowledge, Attitude, and Practice About Health Information Technology Among First-Generation Muslim Immigrant Women in Atlanta City During the Pandemic
Authors: Awatef Ahmed Ben Ramadan, Aqsa Arshad
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Background: There is a huge Muslim migration movement to North America and Europe for several reasons, primarily refuge from war areas and partly to search for better work and educational chances. There are always concerns regarding first-Generation Immigrant women's health and computer literacy, an adequate understanding of the health systems, and the use of the existing healthcare technology and services effectively and efficiently. Language proficiency level, preference for cultural and traditional remedies, socioeconomic factors, fear of stereotyping, limited accessibility to health services, and general unfamiliarity with the existing health services and resources are familiar variables among these women. Aims: The current study aims to assess the health and digital literacy of first-generation Muslim women in Atlanta city. Also, the study aims to examine how the COVID-19 pandemic has encouraged the use of health information technology and increased technology awareness among the targeted women. Methods: The study design is cross-sectional correlational research. The study will be conducted to produce preliminary results that the investigators want to have to supplement an NIH grant application about leveraging information technology to reduce the health inequalities amongst the first-generation immigrant Muslim women in Atlanta City. The investigators will collect the study data in two phases using different tools. Phase one was conducted in June 2022; the investigators used tools to measure health and digital literacy amongst 42 first-generation immigrant Muslim women. Phase two was conducted in November 2022; the investigators measured the Knowledge, Attitude, and Practice (KAP) of using health information technology such as telehealth from a sample of 45 first-generation Muslim immigrant women in Atlanta; in addition, the investigators measured how the current pandemic has affected their KAP to use telemedicine and telehealth services. Both phases' study participants were recruited using convenience sampling methodology. The investigators collected around 40 of 18 years old or older first-generation Muslim immigrant women for both study phases. The study excluded Immigrants who hold work visas and second-generation immigrants. Results: At the point of submitting this abstract, the investigators are still analyzing the study data to produce preliminary results to apply for an NIH grant entitled "Leveraging Health Information Technology (Health IT) to Address and Reduce Health Care Disparities (R01 Clinical Trial Optional)". This research will be the first step of a comprehensive research project to assess and measure health and digital literacy amongst a vulnerable community group. The targeted group might have different points of view from the U.S.-born inhabitants on how to: promote their health, gain healthy lifestyles and habits, screen for diseases, adhere to health treatment and follow-up plans, perceive the importance of using available and affordable technology to communicate with their providers and improve their health, and help in making serious decisions for their health. The investigators aim to develop an educational and instructional health mobile application considering the language and cultural factors that affect immigrants' ability to access different health and social support sources, know their health rights and obligations in their communities, and improve their health behavior and behavior lifestyles.Keywords: first-generation immigrant Muslim women, telehealth, COVID-19 pandemic, health information technology, health and digital literacy
Procedia PDF Downloads 7647 The Effects of Circadian Rhythms Change in High Latitudes
Authors: Ekaterina Zvorykina
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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors
Procedia PDF Downloads 15246 Impact of Water Interventions under WASH Program in the South-west Coastal Region of Bangladesh
Authors: S. M. Ashikur Elahee, Md. Zahidur Rahman, Md. Shofiqur Rahman
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This study evaluated the impact of different water interventions under WASH program on access of household's to safe drinking water. Following survey method, the study was carried out in two Upazila of South-west coastal region of Bangladesh namely Koyra from Khulna and Shymnagar from Satkhira district. Being an explanatory study, a total of 200 household's selected applying random sampling technique were interviewed using a structured interview schedule. The predicted probability suggests that around 62 percent household's are out of year-round access to safe drinking water whereby, only 25 percent household's have access at SPHERE standard (913 Liters/per person/per year). Besides, majority (78 percent) of the household's have not accessed at both indicators simultaneously. The distance from household residence to the water source varies from 0 to 25 kilometer with an average distance of 2.03 kilometers. The study also reveals that the increase in monthly income around BDT 1,000 leads to additional 11 liters (coefficient 0.01 at p < 0.1) consumption of safe drinking water for a person/year. As expected, lining up time has significant negative relationship with dependent variables i.e., for higher lining up time, the probability of getting access for both SPHERE standard and year round access variables becomes lower. According to ordinary least square (OLS) regression results, water consumption decreases at 93 liters for per person/year of a household if one member is added to that household. Regarding water consumption intensity, ordered logistic regression (OLR) model shows that one-minute increase of lining up time for water collection tends to reduce water consumption intensity. On the other hand, as per OLS regression results, for one-minute increase of lining up time, the water consumption decreases by around 8 liters. Considering access to Deep Tube Well (DTW) as a reference dummy, in OLR, the household under Pond Sand Filter (PSF), Shallow Tube Well (STW), Reverse Osmosis (RO) and Rainwater Harvester System (RWHS) are respectively 37 percent, 29 percent, 61 percent and 27 percent less likely to ensure year round access of water consumption. In line of health impact, different type of water born diseases like diarrhea, cholera, and typhoid are common among the coastal community caused by microbial impurities i.e., Bacteria, Protozoa. High turbidity and TDS in pond water caused by reduction of water depth, presence of suspended particle and inorganic salt stimulate the growth of bacteria, protozoa, and algae causes affecting health hazard. Meanwhile, excessive growth of Algae in pond water caused by excessive nitrate in drinking water adversely effects on child health. In lieu of ensuring access at SPHERE standard, we need to increase the number of water interventions at reasonable distance, preferably a half kilometer away from the dwelling place, ensuring community peoples involved with its installation process where collectively owned water intervention is found more effective than privately owned. In addition, a demand-responsive approach to supply of piped water should be adopted to allow consumer demand to guide investment in domestic water supply in future.Keywords: access, impact, safe drinking water, Sphere standard, water interventions
Procedia PDF Downloads 21645 Determination of the Presence of Antibiotic Resistance from Vibrio Species in Northern Italy
Authors: Tramuta Clara, Masotti Chiara, Pitti Monica, Adriano Daniela, Battistini Roberta, Serraca Laura, Decastelli Lucia
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Oysters are considered filter organisms, and their raw consumption may increase health risks for consumers: it is often associated with outbreaks of gastroenteritis or enteric illnesses. Most of these foodborne diseases are caused by Vibrio strains, enteric pathogens also involved in the diffusion of genetic determinants of antibiotic resistance and their entrance along the food chain. The European Food Safety Authority (EFSA), during the European Union report on antimicrobial resistance in 2017, focused the attention about the role of food as a possible carrier of antibiotic-resistant bacteria or antibiotic-resistance genes that determine health risks for humans. This study wants to determine antibiotic resistance and antibiotic-resistance genes in Vibrio spp. isolated from Crassostrea gigas oysters collected in the Golfo della Spezia (Liguria, Italy). A total of 47 Vibrio spp. strains were isolated (ISO21872-2:2017) during the summer of 2021 from oysters of Crassostrea gigas. The strains were identified by MALDI-TOF (Bruker, Germany) mass spectrometry and tested for antibiotic susceptibility using a broth microdiluition method (ISO20776-1:2019) using Sensititre EUVSEC plates (Thermo-Fisher Scientific) to obtain the Minimum Inhibitory Concentration (MIC). The strains were tested with PCR-based biomolecular methods, according to previous works, to define the presence of 23 resistance genes of the main classes of antibiotics used in human and veterinary medicine: tet (B), tet (C), tet (D), tet (A), tet (E), tet (G ), tet (K), tet (L), tet (M), tet (O), tet (S) (tetracycline resistance); blaCTX-M, blaTEM, blaOXA, blaSHV (β-lactam resistance); mcr-1 and mcr-2 (colistin resistance); qnrA, qnrB, and qnrS (quinolone resistance); sul1, sul2 and sul3 (sulfonamide resistance). Six different species have been identified: V. alginolyticus 34% (n=16), V. harveyi 28% (n=13), V. fortis 15% (n=7), V. pelagius 8% (n=4), V. parahaemolyticus 11% (n=5) e V. chagasii 4% (n=2). The PCR assays showed the presence of the blaTEM gene on 40% of the strains (n=19). All the other genes were not detected, except for a V. alginolyticus positive for anrS gene. The broth microdiluition method results showed an high level of resistance for ciprofloxacin (62%; n=29), ampicillin (47%; n=22), and colistin (49%; n=23). Furthermore, 32% (n=15) of strains can be considered multiresistant bacteria for the simultaneous presence of resistance for three different antibiotic classes. Susceptibility towards meropenem, azithromycin, gentamicin, ceftazidime, cefotaxime, chloramphenicol, tetracycline and sulphamethoxazole reached 100%. The Vibrio species identified in this study are widespread in marine environments and can cause gastrointerstinal infections after the ingestion of raw fish products and bivalve molluscs. The level of resistance to antibiotics such as ampicillin, ciprofloxacin and colistin can be connected to anthropic factors (industrial, agricultural and domestic wastes) that promote the spread of resistance to these antibiotics. It can be also observed a strong correlation between phenotypic (resistant MIC) and genotypic (positive blaTEM gene) resistance for ampicillin on the same strains, probably due to the transfer of genetic material between bacterial strains. Consumption of raw bivalve molluscs can represent a risk for consumers heath due to the potentially presence of foodborne pathogens, highly resistant to different antibiotics and source of transferable antibiotic-resistant genes.Keywords: vibrio species, blaTEM genes, antimicrobial resistance, PCR
Procedia PDF Downloads 6944 Socio-Economic Determinants of Physical Activity of Non-Manual Workers, Including the Early Senior Group, from the City of Wroclaw in Poland
Authors: Daniel Puciato, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Michał Rozpara, Władysław Mynarski, Agnieszka Gawlik, Małgorzata Dębska, Soňa Jandová
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Physical activity as a part of people’s everyday life reduces the risk of many diseases, including those induced by lifestyle, e.g. obesity, type 2 diabetes, osteoporosis, coronary heart disease, degenerative arthritis, and certain types of cancer. That refers particularly to professionally active people, including the early senior group working on non-manual positions. The aim of the study is to evaluate the relationship between physical activity and the socio-economic status of non-manual workers from Wroclaw—one of the biggest cities in Poland, a model setting for such investigations in this part of Europe. The crucial problem in the research is to find out the percentage of respondents who meet the health-related recommendations of the World Health Organization (WHO) concerning the volume, frequency, and intensity of physical activity, as well as to establish if the most important socio-economic factors, such as gender, age, education, marital status, per capita income, savings and debt, determine the compliance with the WHO physical activity recommendations. During the research, conducted in 2013, 1,170 people (611 women and 559 men) aged 21–60 years were examined. A diagnostic poll method was applied to collect the data. Physical activity was measured with the use of the short form of the International Physical Activity Questionnaire with extended socio-demographic questions, i.e. concerning gender, age, education, marital status, income, savings or debts. To evaluate the relationship between physical activity and selected socio-economic factors, logistic regression was used (odds ratio statistics). Statistical inference was conducted on the adopted ex ante probability level of p<0.05. The majority of respondents met the volume of physical effort recommended for health benefits. It was particularly noticeable in the case of the examined men. The probability of compliance with the WHO physical activity recommendations was highest for workers aged 21–30 years with secondary or higher education who were single, received highest incomes and had savings. The results indicate the relations between physical activity and socio-economic status in the examined women and men. People with lower socio-economic status (e.g. manual workers) are physically active primarily at work, whereas those better educated and wealthier implement physical effort primarily in their leisure time. Among the investigated subjects, the youngest group of non-manual workers have the best chances to meet the WHO standards of physical activity. The study also confirms that secondary education has a positive effect on the public awareness on the role of physical activity in human life. In general, the analysis of the research indicates that there is a relationship between physical activity and some socio-economic factors of the respondents, such as gender, age, education, marital status, income per capita, and the possession of savings. Although the obtained results cannot be applied for the general population, they show some important trends that will be verified in subsequent studies conducted by the authors of the paper.Keywords: IPAQ, nonmanual workers, physical activity, socioeconomic factors, WHO
Procedia PDF Downloads 52743 Delicate Balance between Cardiac Stress and Protection: Role of Mitochondrial Proteins
Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan
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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.Keywords: aging heart, mitochondria, proteomics, redox state
Procedia PDF Downloads 16442 Prevalence of Chronic Diseases and Predictors of Mortality in Home Health Care Service: Data From Saudi Arabia
Authors: Walid A. Alkeridy, Arwa Aljasser, Khalid Mohammed Alayed, Saad Alsaad, Amani S. Alqahtani, Claire Ann Lim, Sultan H. Alamri, Doaa Zainhom Mekkawy, Mohammed Al-Sofiani
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Introduction: The history of publicly funded Home Health Care (HHC) service in Saudi Arabia dates back to 1991. The first HC program was launched to provide palliative home care services for patients with terminal cancer. Thereafter, more programs launched across Saudi Arabia most remarkably was launching the national program for HHC by the Ministry Of Health (MOH) in 2008. The national HHC MOH program is mainly providing long-term care home care services for over 40,000 Saudi citizens. The scope of the HHC service program provided by the Saudi MOH is quite diverse, ranging from basic nursing care to specialized care programs, e.g., home peritoneal dialysis, home ventilation, home infusion therapy, etc. Objectives: The primary aim of our study is to report the prevalence of chronic conditions among Saudi people receiving long-term HHC services. Secondary aims include identifying the predictors of mortality among individuals receiving long-term HHC services and studying the association between frailty and poor health outcomes among HHC users. Methods: We conducted a retrospective and cross-sectional data collection from participants receiving HHC services at King Saud University Medical City, Riyadh, Saudi Arabia. Data were collected from electronic health records (EHR), patient charts, and interviewing caregivers from the year 2019 to 2022. We assessed functional performance by Katz's activity of daily living and the Bristol Activity of Daily Living Scale (BADLS). A trained health care provider assessed frailty using the Clinical Frailty Scale (CFS). Mortality was assessed by reviewing the death certificates if patients were hospitalized through discharge status ascertainment from EHR. Results: The mean age for deceased individuals in HHC was 78.3 years. Over twenty percent of individuals receiving HHC services were readmitted to the hospital. The following variables were statistically significant between deceased and alive individuals receiving HHC services; clinical frailty scale, the total number of comorbid conditions, and functional performance based on the KATZ activity of daily living scale and the BADLS. We found that the strongest predictors for mortality were pressure ulcers which had an odds ratio of 3.75 and p-value of < 0.0001, and the clinical frailty scale, which had an odds ratio of 1.69 and p-value of 0.002, using multivariate regression analysis. In conclusion, our study found that pressure ulcers and frailty are the strongest predictors of mortality for individuals receiving home health care services. Moreover, we found a high rate of annual readmission for individuals enrolled in HHC, which requires further analysis to understand the possible contributing factors for the increased rate of hospital readmission and develop strategies to address them. Future studies should focus on designing quality improvement projects aimed at improving the quality of life for individuals receiving HHC services, especially those who have pressure ulcers at the end of life.Keywords: homecare, Saudi, prevalence, chronic
Procedia PDF Downloads 11241 Mean Nutrient Intake and Nutrient Adequacy Ratio in India: Occurrence of Hidden Hunger in Indians
Authors: Abha Gupta, Deepak K. Mishra
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The focus of food security studies in India has been on the adequacy of calories and its linkage with poverty level. India currently being undergoing a massive demographic and epidemiological transition has demonstrated a decline in average physical activity with improved mechanization and urbanization. Food consumption pattern is also changing with decreasing intake of coarse cereals and a marginal increase in the consumption of fruits, vegetables and meat products resulting into a nutrition transition in the country. However, deficiency of essential micronutrients such as vitamins and minerals is rampant despite their growing importance in fighting back with lifestyle and other modern diseases. The calorie driven studies can hardly tackle the complex problem of malnutrition. This paper fills these research lacuna and analyses mean intake of different major and micro-nutrients among different socio-economic groups and adequacy of these nutrients from recommended dietary allowance. For the purpose, a cross-sectional survey covering 304 households selected through proportional stratified random sampling was conducted in six villages of Aligarh district of the state of Uttar Pradesh, India. Data on quantity consumed of 74 food items grouped into 10 food categories with a recall period of seven days was collected from the households and converted into energy, protein, fat, carbohydrate, calcium, iron, thiamine, riboflavin, niacin and vitamin C using standard guidelines of National Institute of Nutrition. These converted nutrients were compared with recommended norms given by National Nutrition Monitoring Bureau. Per capita nutrient adequacy was calculated by dividing mean nutrient intake by the household size and then by comparing it with recommended norm. Findings demonstrate that source of both macro and micro-nutrients are mainly cereals followed by milk, edible oil and sugar items. Share of meat in providing essential nutrients is very low due to vegetarian diet. Vegetables, pulses, nuts, fruits and dry fruits are a poor source for most of the nutrients. Further analysis evinces that intake of most of the nutrients is higher than the recommended norm. Riboflavin is the only vitamin whose intake is less than the standard norm. Poor group, labour, small farmers, Muslims, scheduled caste demonstrate comparatively lower intake of all nutrients than their counterpart groups, though, they get enough macro and micro-nutrients significantly higher than the norm. One of the major reasons for higher intake of most of the nutrients across all socio-economic groups is higher consumption of monotonous diet based on cereals and milk. Most of the nutrients get their major share from cereals particularly wheat and milk intake. It can be concluded from the analysis that although there is adequate intake of most of the nutrients in the diet of rural population yet their source is mainly cereals and milk products depicting a monotonous diet. Hence, more efforts are needed to diversify the diet by giving more focus to the production of other food items particularly fruits, vegetables and pulse products. Awareness among the population, more accessibility and incorporating food items other than cereals in government social safety programmes are other measures to improve food security in India.Keywords: hidden hunger, India, nutrients, recommended norm
Procedia PDF Downloads 31140 Medicompills Architecture: A Mathematical Precise Tool to Reduce the Risk of Diagnosis Errors on Precise Medicine
Authors: Adriana Haulica
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Powered by Machine Learning, Precise medicine is tailored by now to use genetic and molecular profiling, with the aim of optimizing the therapeutic benefits for cohorts of patients. As the majority of Machine Language algorithms come from heuristics, the outputs have contextual validity. This is not very restrictive in the sense that medicine itself is not an exact science. Meanwhile, the progress made in Molecular Biology, Bioinformatics, Computational Biology, and Precise Medicine, correlated with the huge amount of human biology data and the increase in computational power, opens new healthcare challenges. A more accurate diagnosis is needed along with real-time treatments by processing as much as possible from the available information. The purpose of this paper is to present a deeper vision for the future of Artificial Intelligence in Precise medicine. In fact, actual Machine Learning algorithms use standard mathematical knowledge, mostly Euclidian metrics and standard computation rules. The loss of information arising from the classical methods prevents obtaining 100% evidence on the diagnosis process. To overcome these problems, we introduce MEDICOMPILLS, a new architectural concept tool of information processing in Precise medicine that delivers diagnosis and therapy advice. This tool processes poly-field digital resources: global knowledge related to biomedicine in a direct or indirect manner but also technical databases, Natural Language Processing algorithms, and strong class optimization functions. As the name suggests, the heart of this tool is a compiler. The approach is completely new, tailored for omics and clinical data. Firstly, the intrinsic biological intuition is different from the well-known “a needle in a haystack” approach usually used when Machine Learning algorithms have to process differential genomic or molecular data to find biomarkers. Also, even if the input is seized from various types of data, the working engine inside the MEDICOMPILLS does not search for patterns as an integrative tool. This approach deciphers the biological meaning of input data up to the metabolic and physiologic mechanisms, based on a compiler with grammars issued from bio-algebra-inspired mathematics. It translates input data into bio-semantic units with the help of contextual information iteratively until Bio-Logical operations can be performed on the base of the “common denominator “rule. The rigorousness of MEDICOMPILLS comes from the structure of the contextual information on functions, built to be analogous to mathematical “proofs”. The major impact of this architecture is expressed by the high accuracy of the diagnosis. Detected as a multiple conditions diagnostic, constituted by some main diseases along with unhealthy biological states, this format is highly suitable for therapy proposal and disease prevention. The use of MEDICOMPILLS architecture is highly beneficial for the healthcare industry. The expectation is to generate a strategic trend in Precise medicine, making medicine more like an exact science and reducing the considerable risk of errors in diagnostics and therapies. The tool can be used by pharmaceutical laboratories for the discovery of new cures. It will also contribute to better design of clinical trials and speed them up.Keywords: bio-semantic units, multiple conditions diagnosis, NLP, omics
Procedia PDF Downloads 6339 Benefits of Environmental Aids to Chronobiology Management and Its Impact on Depressive Mood in an Operational Setting
Authors: M. Trousselard, D. Steiler, C. Drogou, P. van-Beers, G. Lamour, S. N. Crosnier, O. Bouilland, P. Dubost, M. Chennaoui, D. Léger
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According to published data, undersea navigation for long periods (nuclear-powered ballistic missile submarine, SSBN) constitutes an extreme environment in which crews are subjected to multiple stresses, including the absence of natural light, illuminance below 1,000 lux, and watch schedules that do not respect natural chronobiological rhythms, for a period of 60-80 days. These stresses seem clearly detrimental to the submariners’ sleep, with consequences for their affective (seasonal affective disorder-like) and cognitive functioning. In the long term, there are abundant publications regarding the consequences of sleep disruption for the occurrence of organic cardiovascular, metabolic, immunological or malignant diseases. It seems essential to propose countermeasures for the duration of the patrol in order to reduce the negative physiological effects on the sleep and mood of submariners. Light therapy, the preferred treatment for dysfunctions of the internal biological clock and the resulting seasonal depression, cannot be used without data to assist knowledge of submariners’ chronobiology (melatonin secretion curve) during patrols, given the unusual characteristics of their working environment. These data are not available in the literature. The aim of this project was to assess, in the course of two studies, the benefits of two environmental techniques for managing chronobiological stress: techniques for optimizing potential (TOP; study 1)3, an existing programme to help in the psychophysiological regulation of stress and sleep in the armed forces, and dawn and dusk simulators (DDS, study 2). For each experiment, psychological, physiological (sleep) or biological (melatonin secretion) data were collected on D20 and D50 of patrol. In the first experiment, we studied sleep and depressive distress in 19 submariners in an operational setting on board an SSBM during a first patrol, and assessed the impact of TOP on the quality of sleep and depressive distress in these same submariners over the course of a second patrol. The submariners were trained in TOP between the two patrols for a 2-month period, at a rate of 1 h of training per week, and assigned daily informal exercises. Results show moderate disruptions in sleep pattern and duration associated with the intensity of depressive distress. The use of TOP during the following patrol improved sleep and depressive mood only in submariners who regularly practiced the techniques. In light of these limited benefits, we assessed, in a second experiment, the benefits of DDS on chronobiology (daily secretion of melatonin) and depressive distress. Ninety submariners were randomly allocated to two groups, group 1 using DDS daily, and group 2 constituting the control group. Although the placebo effect was not controlled, results showed a beneficial effect on chronobiology and depressive mood for submariners with a morning chronotype. Conclusions: These findings demonstrate the difficulty of practicing the tools of psychophysiological management in real life. They raise the question of the subjects’ autonomy with respect to using aids that involve regular practice. It seems important to study autonomy in future studies, as a cognitive resource resulting from the interaction between internal positive resources and “coping” resources, to gain a better understanding of compliance problems.Keywords: chronobiology, light therapy, seasonal affective disorder, sleep, stress, stress management, submarine
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