Search results for: preventable death

Authors: Khachen Kongpakwattana, Nathorn Chaiyakunapruk

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Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.

Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Vusala Amirbayova

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The science of modern musicology, based on the achievements of a number of neighboring science fields, has more deeply penetrated into the sphere of artistic content of the art of music and developed a new scientific methodology, methods and approaches for a comprehensive study of the problem. In this regard, a new theory developed by the famous Russian musician-scientist, professor V. Kholopova – the specific and non – specific content of music – draws the attention with its different philosophical foundation and covering historical periods of the art of composing. The scientist related her theory to the art of European composer’s creativity, and did not include musical professionalism and especially, folklore creativity existing in other continent in her circle of interest. The researcher made an effort to explain triad (the world of ideas, emotions and subjects) which is included in the general content of music in the example of composers’ works belonging to different periods and cultures. In this respect, the artistic content of works has been deeply and comprehensively analyzed new philosophical basis. The theme ‘Leyli and Majnun’ was developed by many poets as one of the ancient legends of the East, and each artist was able to give a unique artistic interpretation of the work. This literary source was successfully developed in cognominal opera of great U. Hajibeyli in Azerbaijani music and its embodiment with symphonic means required great skill and courage from Gara Garayev. Unlike opera, as there is the opportunity to show the plot of ‘Leyli and Majnun’ in the symphonic poem, the composer achieved to reflect the main purpose of its idea convincingly with pure musical means, and created a great work with tragic spirit having a great emotional impact. Though the artistic content and form of ‘Leyli and Majnun’ symphonic poem have been sufficiently analyzed by music theorists until now, in our opinion, it is for the first time that the work is considered from the point of specific music content. Therefore, we will make an effort to penetrate into a specific layer of its artistic content after firstly reviewing the poem with traditional methods in the general plan. The use of both national fret – intonations and the system of major – minor by G. Garayev is based on well-tempered root. The composer, widely using national fret – intonations and model harmonic means on this ground, achieved to express the spirit and content of the poem. It perfectly embodies the grandeur and immortality of divine love, and the struggle of powerful human personality with the forces of despotism. Gara Garayev said about this work: “My most sublime goal and desire is to explain the literary issue that love endures to all obstacles and overcomes even death”. The music of ‘Leyli and Majnun’ symphonic poem is rich with deep desires and sharp contradictions. G.Garayev reflected these wonderful ideas about the power of music in his book ‘Articles, schools and sayings’: “Music is the decoration of life and a powerful source of inspiration”.

Keywords: content, music, symphonic, theory

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

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Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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Authors: Tesfaye Dagne, Dagmawit Solomon, Firmaye Bogale, Yosef Gebreyohannes, Samson Mideksa, Mamuye Hadis, Desalegn Ararso, Ermias Woldie, Tsegaye Getachew, Sabit Ababor, Zelalem Kebede

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Globally, road traffic accident (RTA) is causing millions of deaths and injuries every year. It is one of the leading causes of death among people of all age groups and the problem is worse among young reproductive age group. Moreover the problem is increasing with an increasing number of vehicles. The majority of the problem happen in low and middle income countries (LMIC), even if the number of vehicles in these countries is low compared to their population. So, the objective of this paper is to summarize the best available evidence on interventions that can reduce road traffic accidents in low and middle income countries (LMIC). Method: A rapid evidence synthesis approach adapted from the SURE Rapid Response Service was applied to search, appraise and summarize the best available evidence on effective intervention in reducing road traffic injury. To answer the question under review, we searched for relevant studies from databases including PubMed, the Cochrane Library, TRANSPORT, Health system evidence, Epistemonikos, and SUPPORT summary. The following key terms were used for searching: Road traffic accident, RTA, Injury, Reduc*, Prevent*, Minimiz*, “Low and middle-income country”, LMIC. We found 18 articles through a search of different databases mentioned above. After screening for the titles and abstracts of the articles, four of them which satisfy the inclusion criteria were included in the final review. Then we appraised and graded the methodological quality of systematic reviews that are deemed to be highly relevant using AMSTAR. Finding: The identified interventions to reduce road traffic accidents were legislation and enforcement, public awareness/education, speed control/ rumble strips, road improvement, mandatory motorcycle helmet, graduated driver license, street lighting. Legislation and Enforcement: Legislation focusing on mandatory motorcycle helmet usage, banning cellular phone usage when driving, seat belt laws, decreasing the legal blood alcohol content (BAC) level from 0.06 g/L to 0.02 g/L bring the best result where enforcement is there. Public Awareness/Education: focusing on seat belt use, child restraint use, educational training in health centers and schools/universities, and public awareness with media through the distribution of videos, posters/souvenirs, and pamphlets are effective in the short run. Speed Control: through traffic calming bumps, or speed bumps, rumbled strips are effective in reducing accidents and fatality. Mandatory Motorcycle Helmet: is associated with reduction in mortality. Graduated driver’s license (GDL): reduce road traffic injury by 19%. Street lighting: is a low-cost intervention which may reduce road traffic accidents.

Keywords: evidence synthesis, injury, rapid review, reducing, road traffic accident

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Authors: Mark McGuire, Eric Shannon, John Parmigiani

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Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.

Keywords: chain shot, safety, testing, timber harvesters

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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

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

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

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

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Authors: Shpetim Rezniqi

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Financial Policies in the process of global crisis the current crisis has swept the world with special emphasis, most developed countries, those countries which have most gross -product world and you have a high level of living.Even those who are not experts can describe the consequences of the crisis to see the reality that is seen, but how far will it go this crisis is impossible to predict. Even the biggest experts have conjecture and large divergence, but agree on one thing: - The devastating effects of this crisis will be more severe than ever before and can not be predicted.Long time, the world was dominated economic theory of free market laws. With the belief that the market is the regulator of all economic problems. The market, as river water will flow to find the best and will find the necessary solution best. Therefore much less state market barriers, less state intervention and market itself is an economic self-regulation. Free market economy became the model of global economic development and progress, it transcends national barriers and became the law of the development of the entire world economy. Globalization and global market freedom were principles of development and international cooperation. All international organizations like the World Bank, states powerful economic, development and cooperation principles laid free market economy and the elimination of state intervention. The less state intervention much more freedom of action was this market- leading international principle. We live in an era of financial tragic. Financial markets and banking in particular economies are in a state of thy good, US stock markets fell about 40%, in other words, this time, was one of the darkest moments 5 since 1920. Prior to her rank can only "collapse" of the stock of Wall Street in 1929, technological collapse of 2000, the crisis of 1973 after the Yom Kippur war, while the price of oil quadrupled and famous collapse of 1937 / '38, when Europe was beginning World war II In 2000, even though it seems like the end of the world was the corner, the world economy survived almost intact. Of course, that was small recessions in the United States, Europe, or Japan. Much more difficult the situation was at crisis 30s, or 70s, however, succeeded the world. Regarding the recent financial crisis, it has all the signs to be much sharper and with more consequences. The decline in stock prices is more a byproduct of what is really happening. Financial markets began dance of death with the credit crisis, which came as a result of the large increase in real estate prices and household debt. It is these last two phenomena can be matched very well with the gains of the '20s, a period during which people spent fists as if there was no tomorrow. All is not away from the mouth of the word recession, that fact no longer a sudden and abrupt. But as much as the financial markets melt, the greater is the risk of a problematic economy for years to come. Thus, for example, the banking crisis in Japan proved to be much more severe than initially expected, partly because the assets which were based more loans had, especially the land that falling in value. The price of land in Japan is about 15 years that continues to fall. (ADRI Nurellari-Published in the newspaper "Classifieds"). At this moment, it is still difficult to çmosh to what extent the crisis has affected the economy and what would be the consequences of the crisis. What we know is that many banks will need more time to reduce the award of credit, but banks have this primary function, this means huge loss.

Keywords: globalisation, finance, crisis, recomandation, bank, credits

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Authors: Anantha S. Babbili

Abstract:

This paper analyzes the current media practices dominant in global journalistic practices within the framework of world press theories of Libertarian, Authoritarian, Communist, and Social Responsibility to evaluate their efficacy in addressing their role in the coverage of the coronavirus, also known as COVID-19. The global media flows, determinants of news coverage, and international awareness and the Western view of the world will be critically analyzed within the context of the prevalent news values that underpin free press and media coverage of the world. While evaluating the global discourse paramount to a sustained and dispassionate understanding of world events, this paper proposes an ethical framework that brings clarity devoid of sensationalism, partisanship, right-wing and left-wing interpretations to a breaking and dangerous development of a pandemic. As the world struggles to contain the coronavirus pandemic with death climbing close to 6,000 from late January to mid-March, 2020, the populations of the developed as well as the developing nations are beset with news media renditions of the crisis that are contradictory, confusing and evoking anxiety, fear and hysteria. How are we to understand differing news standards and news values? What lessons do we as journalism and mass media educators, researchers, and academics learn in order to construct a better news model and structure of media practice that addresses science, health, and media literacy among media practitioners, journalists, and news consumers? As traditional media struggles to cover the pandemic to its audience and consumers, social media from which an increasing number of consumers get their news have exerted their influence both in a positive way and in a negative manner. Even as the world struggles to grasp the full significance of the pandemic, the World Health Organization (WHO) has been feverishly battling an additional challenge related to the pandemic in what it termed an 'infodemic'—'an overabundance of information, some accurate and some not, that makes it hard for people to find trustworthy sources and reliable guidance when they need it.' There is, indeed, a need for journalism and news coverage in times of pandemics that reflect social responsibility and ethos of public service journalism. Social media and high-tech information corporations, collectively termed GAMAF—Google, Apple, Microsoft, Amazon, and Facebook – can team up with reliable traditional media—newspapers, magazines, book publishers, radio and television corporates—to ease public emotions and be helpful in times of a pandemic outbreak. GAMAF can, conceivably, weed out sensational and non-credible sources of coronavirus information, exotic cures offered for sale on a quick fix, and demonetize videos that exploit peoples’ vulnerabilities at the lowest ebb. Credible news of utility delivered in a sustained, calm, and reliable manner serves people in a meaningful and helpful way. The world’s consumers of news and information, indeed, deserve a healthy and trustworthy news media – at least in the time of pandemic COVID-19. Towards this end, the paper will propose a practical model for news media and journalistic coverage during times of a pandemic.

Keywords: COVID-19, international news flow, social media, social responsibility

Procedia PDF Downloads 82

Authors: Babak Forouraghi

Abstract:

A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

Procedia PDF Downloads 29

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

Abstract:

Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

Procedia PDF Downloads 149

Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

Abstract:

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

Procedia PDF Downloads 23

Authors: Shlomit Paz, Meir Broza

Abstract:

Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period and produces an enterotoxin that causes copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. In an epidemic, the source of the contamination is usually the feces of an infected person. The disease can spread rapidly in areas with poor treatment of sewage and drinking water. Cholera remains a global threat and is one of the key indicators of social development. An estimated 3-5 million cases and over 100,000 deaths occur each year around the world. The relevance of climatic events as causative factors for cholera epidemics is well known. However, the examination of the involvement of winds in intra-continental disease distribution is new. The study explore the hypothesis that the spreading of cholera epidemics may be related to the dominant wind direction over land by presenting the influence of the wind direction on windborn dissemination by flying insects, which may serve as vectors. Chironomids ("non-biting midges“) exist in the majority of freshwater aquatic habitats, especially in estuarine and organic-rich water bodies typical to Vibrio cholerae. Chironomid adults emerge into the air for mating and dispersion. They are highly mobile, huge in number and found frequently in the air at various elevations. The huge number of chironomid egg masses attached to hard substrate on the water surface, serve as a reservoir for the free-living Vibrio bacteria. Both male and female, while emerging from the water, may carry the cholera bacteria. In experimental simulation, it was demonstrated that the cholera-bearing adult midges are carried by the wind, and transmit the bacteria from one body of water to another. In our previous study, the geographic diffusions of three cholera outbreaks were examined through their linkage with the wind direction: a) the progress of Vibrio cholerae O1 biotype El Tor in Africa during 1970–1971 and b) again in 2005–2006; and c) the rapid spread of Vibrio cholerae O139 over India during 1992–1993. Using data and map of cholera dissemination (WHO database) and mean monthly SLP and geopotential data (NOAA NCEP-NCAR database), analysis of air pressure data at sea level and at several altitudes over Africa, India and Bangladesh show a correspondence between the dominant wind direction and the intra-continental spread of cholera. The results support the hypothesis that aeroplankton (the tiny life forms that float in the air and that may be caught and carried upward by the wind, landing far from their origin) carry the cholera bacteria from one body of water to an adjacent one. In addition to these findings, the current follow-up study will present new results regarding the possible involvement of winds in the spreading of cholera in recent outbreaks (2010-2013). The findings may improve the understanding of how climatic factors are involved in the rapid distribution of new strains throughout a vast continental area. Awareness of the aerial transfer of Vibrio cholerae may assist health authorities by improving the prediction of the disease’s geographic dissemination.

Keywords: cholera, Vibrio cholerae, wind direction, Vibrio cholerae dissemination

Procedia PDF Downloads 340

Authors: Omer Zvi Shaked, Amir Tirosh

Abstract:

Type 1 Diabetes (T1DM) is an incurable chronic illness with no known preventive measures. Excess to insulin therapy can lead to hypoglycemia with neuro-glycogenic symptoms such as shakiness, nausea, sweating, irritability, fatigue, excessive thirst or hunger, weakness, seizure, and coma. Severe Hypoglycemia (SH) is also considered a most aversive event since it may put patients at risk for injury and death, which matches the criteria of a traumatic event. SH has a ranging prevalence of 20%, which makes it a primary medical Issue. One of the results of SH is an intense emotional fear reaction resembling the form of post-traumatic stress symptoms (PTS), causing many patients to avoid insulin therapy and social activities in order to avoid the possibility of hypoglycemia. As a result, they are at risk for irreversible health deterioration and medical complications. Fear of Hypoglycemia (FOH) is, therefore, a major disturbance for T1DM patients. FOH differs from prevalent post-traumatic stress reactions to other forms of traumatic events since the threat to life continuously exists in the patient's body. That is, it is highly probable that orthodox interventions may not be sufficient for helping patients after SH to regain healthy social function and proper medical treatment. Accordingly, the current presentation will demonstrate the results of a study conducted among T1DM patients after SH. The study was designed in two stages. First, a preliminary qualitative phenomenological study among ten patients after SH was conducted. Analysis revealed that after SH, patients confuse between stress symptoms and Hypoglycemia symptoms, divide life before and after the event, report a constant sense of fear, a loss of freedom, a significant decrease in social functioning, a catastrophic thinking pattern, a dichotomous split between the self and the body, and internalization of illness identity, a loss of internal locus of control, a damaged self-representation, and severe loneliness for never being understood by others. The second stage was a two steps study of intervention among five patients after SH. The first part of the intervention included three months of therapeutic 3rd wave CBT therapy. The contents of the therapeutic process were: acceptance of fear and tolerance to stress; cognitive de-fusion combined with emotional self-regulation; the adoption of an active position relying on personal values; and self-compassion. Then, the intervention included a one-week practical real-time 24/7 support by trained medical personnel, alongside a gradual exposure to increased insulin therapy in a protected environment. The results of the intervention are a decrease in stress symptoms, increased social functioning, increased well-being, and decreased avoidance of medical treatment. The presentation will discuss the unique emotional state of T1DM patients after SH. Then, the presentation will discuss the effectiveness of the intervention for patients with chronic conditions after a traumatic event. The presentation will make evident the unique situation of illness-related PTSD. The presentation will also demonstrate the requirement for multi-professional collaboration between social work and medical care for populations with chronic medical conditions. Limitations of the study and recommendations for further research will be discussed.

Keywords: type 1 diabetes, chronic illness, post-traumatic stress, illness-related PTSD

Procedia PDF Downloads 143

Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

Abstract:

Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

Procedia PDF Downloads 264

Authors: Babak Forouraghi

Abstract:

A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

Procedia PDF Downloads 33

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

Abstract:

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 93

Authors: Mohamed Ahmed Tony, Mohamed Hamoud

Abstract:

The present study was conducted to determine the effect of commercially coated slow-release sodium butyrate (CM3000®) as a feed additive on zootechnical performance, immune status and Clostridium perfringens severity after experimental infection. Three hundred 1-d-old broiler chicks (Cobb 500) were randomly distributed into 3 treatment groups (4 replicates each) using 25 chicks per replicate on floor pens. Control (C) birds were offered non-supplemented basal diets. Treatments 1 and 2 (T1 and T2) were fed diets containing CM3000® at 300 and 500 g/ton feed, respectively, during the entire experimental period (35 days). Feed and water were offered ad-libitum. Feed consumption and body weight were recorded weekly to calculate body weight gain and feed conversion. Blood samples were collected to evaluate the immune status of the birds against Newcastle disease vaccines using HI test. At the end of the experimental period, 20 birds were chosen randomly from each group (5 birds from each pen) to compare carcass yield. At day 16 of age 20 birds from each group (5 birds/replicate) were bacteriologically examined and proved to be free from Clostridium perfringens. The isolated birds were challenged orally with 1 ml buffer containing 106 CFU/ml Clostridium perfringens local isolate and prepared from necrotic enteritis (NE) diseased farms. Birds were observed on a regular basis daily for any signs of NE. Birds that died in the challenged group were necropsied to determine the cause of death. On day 28 of age, the surviving chickens were killed by cervical dislocation and necropsied immediately. Intestinal tracts were removed and intestinal lesions were scored. Tissue samples of the duodenum, jejunum, ileum and cecum for histopathological examination were collected. All collected data were statistically analyzed using IBM SPSS® version 19 software for personal computers. Means were compared by one-way ANOVA (P<0.05) followed by the Duncan Post Hoc test. The results revealed that body weight gain was significantly (P<0.05) improved in chicks fed on both doses of CM3000® compared to the control one. Final body weight gain in T1 and T2 were 2064.94 and 2141.37 g/bird, respectively, while in the control group, the weight gain showed 1952.78 g/bird. In addition, supplementation of diets with CM3000® increased significantly feed intake (P<0.05). Total feed intake in T1 and T2 were 3186.32 and 3273.29 g/bird, respectively; however, feed intake in the control group recorded 3081.95 g/bird. The best feed conversion was recorded in T2 group (1.53). Feed conversion in the control and T1 groups were 1.58 and 1.54, respectively. Dressing percentage, liver weights and the other carcasses yields were not different between treatments. The butyrate significantly enhanced immune responses measured against Newcastle disease vaccines. Sodium butyrate significantly reduced NE lesions and healthy improved the intestinal tissues in the samples collected from T1 and T2-challenged chickens versus those collected from the control group. In conclusion, exogenous administration of slow-release butyrate (CM3000®) is capable of improving performance, enhancing immunity and NE disease resistance in broiler chickens.

Keywords: sodium butyrate, broiler chicken, zootechnical performance, immunity, necrotic enteritis

Procedia PDF Downloads 47

Authors: Biva Samadder, Samita Manna

Abstract:

India is a melting pot of races, tribes, castes and communities. The population of India can be roughly branched into the huge majority of “Civilized” Indians of the Plains and the minority of Tribal population of the hill area and the forest who constituting almost 16 percent of total population of India. The Kirat community composed of four ethnic tribes: Limbu, Lepcha, Dhimal, and Rai. These Kirat people were found to be rich in indigenous knowledge, skill and practices especially for the use on medicinal plants and livelihood purposes. The “Mundhum" is the oral scripture or the “Bible of the Limbus” which serves as the canon of the codes of the Limbu socialization, their moral values and the very orientation of their lifestyle. From birth till death the Limbus are disciplined in the life with full of religious rituals, traditions and culture governed by community norms with a rich legacy of indigenous knowledge and traditional practices. The present study has been conducted using both secondary as well as primary data by applying social methodology consisting of the social survey, questionnaire, interviews and observations in the Kalimpong Block-I of Darjeeling District of west Bengal of India, which is a heterogeneous zone in terms of its ethnic composition and where the Limbus are pre-dominantly concentrated. Due to their close contact with other caste and communities Limbus are now adjusted with the changing situation by borrowing some cultural traits from the other communities and changes that have taken place in their cultural practices, religious beliefs, economic aspects, languages and in social roles and relationships which is bringing the change in their material culture. Limbu language is placed in the Tibeto- Burman Language category. But due to the political and cultural domination of educationally sound and numerically dominant Bengali race, the different communities in this area forced to come under the one umbrella of the Nepali or Gorkhali nation (nation-people). Their respective identities had to be submerged in order to constitute as a strong force to resist Nepali domination and ensure their common survival. As Nepali is a lingua-franca of the area knowing and speaking Nepali language helps them in procuring economic and occupational facilities. Ironically, present day younger generation does not feel comfortable speaking in their own Limbu tongue. The traditional knowledge about medicinal plants, healing, and health culture is found to be wear away due to the lack of interest of young generation. Not only poverty, along with exclusion due to policies they are in the phase of extinction, but their capabilities are ignored and not documented and preserved especially in the case of Limbus who having a great cultural heritage of an oral tradition. Attempts have been made to discuss the persistence and changes in socioeconomic pattern of life in relation to the social structure, material culture, cultural practices, social relationships, indigenous technology, ethos and their values and belief system.

Keywords: changing social relationship, cultural transition, identity, indigenous knowledge, language

Procedia PDF Downloads 143

Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

Abstract:

Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Lakshmi Rao Kandukuri, Mamata Deenadayal, Suma Prasad, Bipin Sethi, Srinadh Buragadda, Lalji Singh

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Worldwide; at least 7.6 million children are born annually with severe genetic or congenital malformations and among them 90% of these are born in mid and low-income countries. Precise prevalence data are difficult to collect, especially in developing countries, owing to the great diversity of conditions and also because many cases remain undiagnosed. The genetic and congenital disorder is the second most common cause of infant and childhood mortality and occurs with a prevalence of 25-60 per 1000 births. The higher prevalence of genetic diseases in a particular community may, however, be due to some social or cultural factors. Such factors include the tradition of consanguineous marriage, which results in a higher rate of autosomal recessive conditions including congenital malformations, stillbirths, or mental retardation. Genetic diseases can vary in severity, from being fatal before birth to requiring continuous management; their onset covers all life stages from infancy to old age. Those presenting at birth are particularly burdensome and may cause early death or life-long chronic morbidity. Genetic testing for several genetic diseases identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use and more are being developed. Chromosomal abnormalities are the major cause of human suffering, which are implicated in mental retardation, congenital malformations, dysmorphic features, primary and secondary amenorrhea, reproductive wastage, infertility neoplastic diseases. Cytogenetic evaluation of patients is helpful in the counselling and management of affected individuals and families. We present here especially chromosomal abnormalities which form a major part of genetic disease burden in India. Different programmes on chromosome research and human reproductive genetics primarily relate to infertility since this is a major public health problem in our country, affecting 10-15 percent of couples. Prenatal diagnosis of chromosomal abnormalities in high-risk pregnancies helps in detecting chromosomally abnormal foetuses. Such couples are counselled regarding the continuation of pregnancy. In addition to the basic research, the team is providing chromosome diagnostic services that include conventional and advanced techniques for identifying various genetic defects. Other than routine chromosome diagnosis for infertility, also include patients with short stature, hypogonadism, undescended testis, microcephaly, delayed developmental milestones, familial, and isolated mental retardation, and cerebral palsy. Thus, chromosome diagnostics has found its applicability not only in disease prevention and management but also in guiding the clinicians in certain aspects of treatment. It would be appropriate to affirm that chromosomes are the images of life and they unequivocally mirror the states of human health. The importance of genetic counseling is increasing with the advancement in the field of genetics. The genetic counseling can help families to cope with emotional, psychological, and medical consequences of genetic diseases.

Keywords: India, chromosome abnormalities, genetic disorders, cytogenetic study

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Authors: Marco Frieslaar, Bing Chu, Eric Rogers

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Stroke is a devastating illness that is the second biggest cause of death in the world (after heart disease). Where it does not kill, it leaves survivors with debilitating sensory and physical impairments that not only seriously harm their quality of life, but also cause a high incidence of severe depression. It is widely accepted that early intervention is essential for recovery, but current rehabilitation techniques largely favor hospital-based therapies which have restricted access, expensive and specialist equipment and tend to side-step the emotional challenges. In addition, there is insufficient funding available to provide the long-term assistance that is required. As a consequence, recovery rates are poor. The relatively unexplored solution is to develop therapies that can be harnessed in the home and are formulated from technologies that already exist in everyday life. This would empower individuals to take control of their own improvement and provide choice in terms of when and where they feel best able to undertake their own healing. This research seeks to identify how effective post-stroke, rehabilitation therapy can be applied to upper limb mobility, within the physical context of a home rather than a hospital. This is being achieved through the design and construction of an automation scheme, based on iterative learning control and the Riener muscle model, that has the ability to adapt to the user and react to their level of fatigue and provide tangible physical recovery. It utilizes a SMART Phone and laptop to construct an iterative learning control (ILC) system, that monitors upper arm movement in three dimensions, as a series of exercises are undertaken. The equipment generates functional electrical stimulation to assist in muscle activation and thus improve directional accuracy. In addition, it monitors speed, accuracy, areas of motion weakness and similar parameters to create a performance index that can be compared over time and extrapolated to establish an independent and objective assessment scheme, plus an approximate estimation of predicted final outcome. To further extend its assessment capabilities, nerve conduction velocity readings are taken by the software, between the shoulder and hand muscles. This is utilized to measure the speed of response of neuron signal transfer along the arm and over time, an online indication of regeneration levels can be obtained. This will prove whether or not sufficient training intensity is being achieved even before perceivable movement dexterity is observed. The device also provides the option to connect to other users, via the internet, so that the patient can avoid feelings of isolation and can undertake movement exercises together with others in a similar position. This should create benefits not only for the encouragement of rehabilitation participation, but also an emotional support network potential. It is intended that this approach will extend the availability of stroke recovery options, enable ease of access at a low cost, reduce susceptibility to depression and through these endeavors, enhance the overall recovery success rate.

Keywords: home-based therapy, iterative learning control, Riener muscle model, SMART phone, stroke rehabilitation

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Authors: Anita Conti, Riccardo Ossanna, Lindsey A. Quintero, Giamaica Conti, Andrea Sbarbati

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Ischemia/reperfusion (IR) injury induces muscle fiber atrophy and skeletal muscle fiber death with subsequently functionality loss. The heterogeneous pool of cells, especially mesenchymal stem cells, contained in the stromal vascular fraction (SVF) of adipose tissue could promote muscle fiber regeneration. To prevent SVF dispersion, it has been proposed the use of injectable biopolymers that work as cells carrier. A significant element of the extracellular matrix is hyaluronic acid (HA), which has been widely used in regenerative medicine as a cell scaffold given its biocompatibility, degradability, and the possibility of chemical functionalization. Connective tissue micro-fragments enriched with SVF obtained from mechanical disaggregation of adipose tissue were evaluated for IR muscle injury regeneration using low molecular weight HA as a scaffold. IR induction. Hindlimb ischemia was induced in 9 athymic nude mice through the clamping of the right quadriceps using a plastic band. Reperfusion was induced by cutting the plastic band after 3 hours of ischemic period. Contralateral (left) muscular tissue was used as healthy control. Treatment. Twenty-four hours after the IR induction, animals (n=3) were intramuscularly injected with 100 µl of SVF mixed with HA (SVF-HA). Animals treated with 100 µl of HA (n=3) and 100 µl saline solution (n=3) were used as control. Treatment monitoring. All animals were in vivo monitored by magnetic resonance imaging (MRI) at 5, 7, 14 and 18 days post-injury (dpi). High-resolution morphological T2 weighed, quantitative T2 map and Dynamic Contrast-Enhanced (DCE) images were acquired in order to assess the regenerative potential of SVF-HA treatment. Ex vivo evaluation. After 18 days from IR induction, animals were sacrificed, and the muscles were harvested for histological examination. At 5 dpi T2 high-resolution MR images clearly reveal the presence of an extensive edematous area due to IR damage for all groups identifiable as an increase of signal intensity (SI) of muscular and surrounding tissue. At 7 dpi, animals of the SVF-HA group showed a reduction of SI, and the T2relaxation time of muscle tissue of the HA-SVF group was 29±0.5ms, comparable with the T2relaxation time of contralateral muscular tissue (30±0.7ms). These suggest a reduction of edematous overflow and swelling. The T2relaxation time at 7dpi of HA and saline groups were 84±2ms and 90±5ms, respectively, which remained elevated during the rest of the study. The evaluation of vascular regeneration showed similar results. Indeed, DCE-MRI analysis revealed a complete recovery of muscular tissue perfusion after 14 dpi for the SVF-HA group, while for the saline and HA group, controls remained in a damaged state. Finally, the histological examination of SVF-HA treated animals exhibited well-defined and organized fibers morphology with a lateralized nucleus, similar to contralateral healthy muscular tissue. On the contrary, HA and saline-treated animals presented inflammatory infiltrates, with HA slightly improving the diameter of the fibers and less degenerated tissue. Our findings show that connective tissue micro-fragments enriched with SVF induce higher muscle homeostasis and perfusion restoration in contrast to control groups.

Keywords: ischemia/reperfusion injury, regenerative medicine, resonance imaging, stromal vascular fraction

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Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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

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

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Authors: Ajay Ivan

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This paper focuses on the cultural politics of health-promotional and disease-preventive pedagogic practices in the context of the national tobacco control programme in India. Tobacco consumption is typically problematised as a paradox: tobacco poses objective health risks such as cancer and heart disease, but its production, sale and export contribute significantly to state revenue. A blanket ban on tobacco products, therefore, is infeasible though desirable. Instead, initiatives against tobacco use have prioritised awareness creation and behaviour change to reduce its demand. This paper argues that public health communication is not, as commonly assumed, an apolitical and neutral transmission of disease-preventive information. Drawing on Michel Foucault’s concept of governmentality, it examines such campaigns as techniques of disciplining people rather than coercing them to give up tobacco use, which would be both impractical and counter-productive. At the level of the population, these programmes constitute a security mechanism that reduces risks without eliminating them, so as to ensure an optimal level of public health without hampering the economy. Anti-tobacco pedagogy thus aligns with a contemporary paradigm of health that emphasises risk-assessment and lifestyle management as tools of governance, using pedagogic techniques to teach people how to be healthy. The paper analyses the pictorial health warnings on tobacco packets and anti-tobacco advertisements in movie theatres mandated by the state, along with awareness-creation messages circulated by anti-tobacco advocacy groups in India, to show how they discursively construct tobacco and its consumption as a health risk. Smoking is resignified from a pleasurable and sociable practice to a deadly addiction that jeopardises the health of those who smoke and those who passively inhale the smoke. While disseminating information about the health risks of tobacco, these initiatives employ emotional and affective techniques of persuasion to discipline tobacco users. They incite fear of death and of social ostracism to motivate behaviour change, complementing their appeals to reason. Tobacco is portrayed as a grave moral danger to the family and a detriment to the vitality of the nation, such that using it contradicts one’s duties as a parent or citizen. Awareness programmes reproduce prevailing societal assumptions about health and disease, normalcy and deviance, and proper and improper conduct. Pedagogy thus functions as an apparatus of public health governance, recruiting subjects as volunteers in their own regulation and aligning their personal goals and aspirations to the objectives of tobacco control. The paper links this calculated management of subjectivity and the self-responsibilisation of the pedagogic subject to a distinct mode of neoliberal civic governance in contemporary India. Health features prominently in this mode of governance that serves the biopolitical obligation of the state as laid down in Article 39 of the Constitution, which includes a duty to ensure the health of its citizens. Insofar as the health of individuals is concerned, the problem is how to balance this duty of the state with the fundamental right of the citizen to choose how to live. Public health pedagogy, by directing the citizen’s ‘free’ choice without unduly infringing upon it, offers a tactical solution.

Keywords: public health communication, pedagogic power, tobacco control, neoliberal governance

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

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

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

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Authors: K. C. Tanuja, Mamatha P. Raj

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"People have always lived on streets. They have been the places where children first learned about the world, where neighbours met, the social centres of towns and cities, the rallying points for revolts, the scenes of repression. The street has always been the scene of this conflict, between living and access, between resident and traveller, between street life and the threat of death.” Livable Streets by Donald Appleyard. Urbanisation is happening rapidly all over the world. As population increasing in the urban settlements, its required to provide quality of life to all the inhabitants who live in. Urban design is a place making strategic planning. Urban design principles promote visualising any place environmentally, socially and economically viable. Urban design strategies include building mass, transit development, economic viability and sustenance and social aspects. Cities are wonderful inventions of diversity- People, things, activities, ideas and ideologies. Cities should be smarter and adjustable to present technology and intelligent system. Streets represent the community in terms of social and physical aspects. Streets are an urban form that responds to many issues and are central to urban life. Streets are for livability, safety, mobility, place of interest, economic opportunity, balancing the ecology and for mass transit. Urban streets are places where people walk, shop, meet and engage in different types of social and recreational activities which make urban community enjoyable. Streets knit the urban fabric of activities. Urban streets become livable with the introduction of social network enhancing the pedestrian character by providing good design features which in turn should achieve the minimal impact of motor vehicle use on pedestrians. Livable streets are the spatial definition to the public right of way on urban streets. Streets in India have traditionally been the public spaces where social life happened or created from ages. Streets constitute the urban public realm where people congregate, celebrate and interact. Streets are public places that can promote social interaction, active living and community identity. Streets as potential contributors to a better living environment, knitting together the urban fabric of people and places that make up a community. Livable streets or complete streets are making our streets as social places, roadways and sidewalks accessible, safe, efficient and useable for all people. The purpose of this paper is to understand the concept of livable street and parameters of livability on urban streets. Streets to be designed as the pedestrians are the main users and create spaces and furniture for social interaction which serves for the needs of the people of all ages and abilities. The problems of streets like congestion due to width of the street, traffic movement and adjacent land use and type of movement need to be redesigned and improve conditions defining the clear movement path for vehicles and pedestrians. Well-designed spatial qualities of street enhances the street environment, livability and then achieves quality of life to the pedestrians. A methodology been derived to arrive at the typologies in street design after analysis of existing situation and comparing with livable standards. It was Donald Appleyard‟s Livable Streets laid out the social effects on streets creating the social network to achieve Livable Streets.

Keywords: livable streets, social interaction, pedestrian use, urban design

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