Search results for: cancer risks

Authors: Bryan M. Baltazar, Marjorie V. Remolador, Klathea H. Sevilla, Imee Saladaga, Loureal Camille Inocencio, Ma. Rosario Concepcion O. Ang

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Biomass energy is a traditional source of sustainable energy, which has been widely used in developing countries. The Philippines, specifically Central Luzon, has an abundant source of biomass. Hence, it could supply abundant agricultural residues (rice husks), as feedstock in a biomass power plant. However, locating a potential site for biomass development is a complex process which involves different factors, such as physical, environmental, socio-economic, and risks that are usually diverse and conflicting. Moreover, biomass distribution is highly dispersed geographically. Thus, this study develops an integrated method combining Geographical Information Systems (GIS) and methods for energy planning; Multi-Criteria Decision Analysis (MCDA) and Analytical Hierarchy Process (AHP), for locating suitable site for biomass power plant development in Central Luzon, Philippines by considering different constraints and factors. Using MCDA, a three level hierarchy of factors and constraints was produced, with corresponding weights determined by experts by using AHP. Applying the results, a suitability map for Biomass power plant development in Central Luzon was generated. It showed that the central part of the region has the highest potential for biomass power plant development. It is because of the characteristics of the area such as the abundance of rice fields, with generally flat land surfaces, accessible roads and grid networks, and low risks to flooding and landslide. This study recommends the use of higher accuracy resource maps, and further analysis in selecting the optimum site for biomass power plant development that would account for the cost and transportation of biomass residues.

Keywords: analytic hierarchy process, biomass energy, GIS, multi-criteria decision analysis, site suitability analysis

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Rajkumar Ghosh

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Urban flooding is a common occurrence throughout Asia. Almost every city is vulnerable to urban floods in some fashion, and city people are particularly vulnerable. Pluvial and fluvial flooding are the most prominent causes of urban flooding in the Gomti Nagar region of Lucknow, Uttar Pradesh, India. The pluvial flooding is regarded to be less damaging because it is caused by heavy rainfall, Seasonal rainfall fluctuations, water flows off concrete infrastructures, blockages of the drainage system, and insufficient drainage capacity or low infiltration capacity. However, this study considers pluvial flooding in Lucknow to be a significant source of cumulative damage over time, and the risks of such events are increasing as a result of changes in ageing infrastructure, hazard exposure, rapid urbanization, massive water logging and global warming. As a result, urban flooding has emerged as a critical field of study. The popularity of analytical approaches to project the spatial extent of flood dangers has skyrocketed. To address future urban flood resilience, more effort is needed to enhance both hydrodynamic models and analytical tools to simulate risks under present and forecast conditions. Proper urban planning with drainage system and ample space for high infiltration capacity are required to reduce urban flooding. A better India with no urban flooding is a pipe dream that can be realized by putting household rooftop rainwater collection systems in every structure. According to the current study, domestic RTRWHs are strongly recommended as an alternative source of water, as well as to prevent surface runoff and urban floods in this region of Lucknow, urban areas of India.

Keywords: rooftop rainwater harvesting, urban flood, pluvial flooding, fluvial flooding

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Anushaa A.

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In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Ga-Young Lee, Hyun-Man Kim

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The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

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Authors: Azadeh Yasari, Michael Ganzle, Stephen Strelkov, Nuanyi Liang, Jonathan Curtis, Nat N. V. Kav

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Pathogenic fungi cause significant yield losses and quality reductions to major crops including wheat, canola, and barley. Toxic metabolites produced by phytopathogenic fungi also pose significant risks to animal and human health. Extensive application of synthetic fungicides is not a sustainable solution since it poses risks to human, animal and environmental health. Unsaturated fatty acids may provide an environmentally friendly alternative because of their direct antifungal activity against phytopathogens as well as through the stimulation of plant defense pathways. The present study assessed the in vitro and in vivo efficacy of two hydroxy fatty acids, coriolic acid and ricinoleic acid, against the phytopathogens Fusarium graminearum, Pyrenophora tritici-repentis, Pyrenophora teres f. teres, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Antifungal activity of coriolic acid and ricinoleic acid was evaluated using broth micro-dilution method to determine the minimum inhibitory concentration (MIC). Results indicated that both ricinoleic acid and coriolic acid showed antifungal activity against phytopathogens, with the strongest inhibitory activity against L. maculans, but the MIC varied greatly between species. An antifungal effect was observed for coriolic acid in vivo against pathogenic fungi of wheat and barley. This effect was not correlated to the in vitro activity because ricinoleic acid with equivalent in vitro antifungal activity showed no protective effect in vivo. Moreover, neither coriolic acid nor ricinoleic acid controlled fungal pathogens of canola. In conclusion, coriolic acid inhibits some phytopathogens in vivo and may have the potential to be an effective crop protection agent.

Keywords: coriolic acid, minimum inhibitory concentration, pathogenic fungi, ricinoleic acid

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Authors: Kiyanoush Ghalavand

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Aquaculture production is inherently a risky business, and farmers face a variety of weather, pest, disease, inptut supply, and market related risks. There are many factors out farmers control and unpredictable. Insurance has an important role in aquaculture production and is a tool to support farmers against threats. Investigation of factors affecting aquaculture farmers' adoption of aquaculture insurance strategy was the objective of this study. The purpose of this study was determining the related factors to adoption of insurance by aquaculture farmers in Khuzestan province, Iran. The research design was a descriptive and correlation surveying method. Aquaculture farmers in Khuzestan province were the target population for this study. A random sample of aquaculture selected (N=1830, n =139). The main result of the study reveled that exist correlation between the level of education, knowledge about purpose of insurance, participation in extension course, visit with insurance organization, and contact with extension agents to the adoption of insurance by aquaculture farmers were significantly positive. By using Bartlett's test and KMO test, determine whether research variables are appropriate for factor analysis (Sig = 0.000, Bartlett test = 0.9724, KMO = 0.74). The number of factors was determined using a split plot, eigenvalue, and percent of variance. An examination of the items and their factors loadings was used to understand the nature of the nine factors. To reduce subjectivity, items with factor loading equal to or greater than 0.5 were considered most important when factors were labeled. The nine factors were labeled (1) Extension and education activities, (2) Economical characteristics, (3) Governmental support, (4) communicational channel, (5) local leaders, (6) Facilitate in given damage (7) Motivation establishing, (8) Given damage in appropriate methods and (9) Appropriate activities by insurance organization. The results obtained from the factors analysis reveal that the nine factors explain percentage75 of the variation of the adoption of insurance of the adoption of insurance by aquaculture farmers in Khuzestan province.

Keywords: aquaculture farmers, insurance, factorial analysis, Khuzestan province, risks

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Authors: Jamal Alasiri, Naif Hakeem, Saoud Almaslmani

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Background: Patients with humeral shaft fractures have two different treatment options. Surgical therapy has lesser risks of non-union, mal-union, and re-intervention than non-surgical therapy. These positive clinical outcomes of the surgical approach make it a preferable treatment option despite the risks of radial nerve palsy and additional surgery-related risk. We aimed to evaluate patients’ outcomes and return to work after surgical vs. non-surgical management of shaft humeral fracture. Methods: We used databases, including PubMed, Medline, and Cochrane Register of Controlled Trials, from 2010 to January 2022 to search for potential randomised controlled trials (RCTs) and cohort studies comparing the patients’ related outcome measures and return to work between surgical and non-surgical management of humerus fracture. Results: After carefully evaluating 1352 articles, we included three RCTs (232 patients) and one cohort study (39 patients). The surgical intervention used plate/nail fixation, while the non-surgical intervention used a splint or brace procedure to manage shaft humeral fracture. The pooled DASH effects of all three RCTs at six (M.D: -7.5 [-13.20, -1.89], P: 0.009) I2:44%) and 12 months (M.D: -1.32 [-3.82, 1.17], p:0.29, I2: 0%) were higher in patients treated surgically than in non-surgical procedures. The pooled constant Murley score at six (M.D: 7.945[2.77,13.10], P: 0.003) I2: 0%) and 12 months (M.D: 1.78 [-1.52, 5.09], P: 0.29, I2: 0%) were higher in patients who received non-surgical than surgical therapy. However, pooled analysis for patients returning to work for both groups remained inconclusive. Conclusion: Altogether, we found no significant evidence supporting the clinical benefits of surgical over non-surgical therapy. Thus, the non-surgical approach remains the preferred therapeutic choice for managing shaft humeral fractures due to its lesser side effects.

Keywords: shaft humeral fracture, surgical treatment, Patient-related outcomes, return to work, DASH

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Authors: Devadrita Dey Sarkar

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Regardless of the many technologic advances in the past decade, increased training and experience, and the obvious benefits of uniform standards, the false-negative rate in screening mammography remains unacceptably high .A computer aided neural network classification of regions of suspicion (ROS) on digitized mammograms is presented in this abstract which employs features extracted by a new technique based on independent component analysis. CAD is a concept established by taking into account equally the roles of physicians and computers, whereas automated computer diagnosis is a concept based on computer algorithms only. With CAD, the performance by computers does not have to be comparable to or better than that by physicians, but needs to be complementary to that by physicians. In fact, a large number of CAD systems have been employed for assisting physicians in the early detection of breast cancers on mammograms. A CAD scheme that makes use of lateral breast images has the potential to improve the overall performance in the detection of breast lumps. Because breast lumps can be detected reliably by computer on lateral breast mammographs, radiologists’ accuracy in the detection of breast lumps would be improved by the use of CAD, and thus early diagnosis of breast cancer would become possible. In the future, many CAD schemes could be assembled as packages and implemented as a part of PACS. For example, the package for breast CAD may include the computerized detection of breast nodules, as well as the computerized classification of benign and malignant nodules. In order to assist in the differential diagnosis, it would be possible to search for and retrieve images (or lesions) with these CAD systems, which would be reliable and useful method for quantifying the similarity of a pair of images for visual comparison by radiologists.

Keywords: CAD(computer-aided design), lesions, neural network, ROS(region of suspicion)

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

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Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

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Authors: Panrapee Suttiwan, Rewadee Watakakosol Arunya Tuicomepee, Sakkaphat T. Ngamake

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Alcohol consumption ranks among the top six of health-risk behaviors that lead to disability and death among Thai teenagers. Underage drinkers have higher health risks than their non-drinking peers do. This study, therefore, aimed to explore salient beliefs of Thai teenagers with alcohol reduction and cessation based on the Theory of Planned Behaviour theoretical framework. Participants were 225 high-school and vocational school students, most of whom (60.9%) consumed alcohol almost daily (5-6 times / week), and one-third of whom (33.8%) reported habitual moderate drink. The average age was 16.5 (SD = 0.9), and the average age of the first use of alcohol was 13.7 (SD = 2.2). Instrument was an open-ended questionnaire that elicited beliefs about having alcohol reduction / cessation in the past 12 months. Findings revealed salient benefit beliefs of alcohol reduction / cessation among the teens such as improved physical and mental health, accident and violence avoidance, less sexual risks, money and time saving, better academic performance, and improved relationships. In contrast, the teens identified several disadvantage beliefs such as deteriorating health, social awkwardness, lack of little fun, excitement, and experience, physical uneasiness, stress, and lack of self-confidence. Salient normative groups for alcohol reduction / cessation included parents, elder relatives, siblings, close friends, teachers, boy / girlfriends, and seniors / juniors at school. Situations influencing alcohol reduction / cessation included quarrels with boy / girlfriends, family conflicts, peer pressure, partying and socializing, festive holidays and anniversary celebration, and visiting entertainment places, etc. This study provides empirical evidence that help to identify normative attitudes towards alcohol reduction / cessation and may thus be an important knowledge for public health campaigns seeking to reduce alcohol consumption in this population.

Keywords: alcohol consumption reduction, cessation, salient belief, Thai teenagers

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Aliro Villacorta, Laura Rubio, Mohamed Alaraby, Montserrat López Mesas, Victor Fuentes-Cebrian, Oscar H. Moriones, Ricard Marcos, Alba Hernández.

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Micro and nano plastics (MNPLs) are emergent environmental pollutants requiring urgent information on their potential risks to human health. One of the problems associated with the evaluation of their undesirable effects is the lack of real samples matching those resulting from the environmental degradation of plastic wastes. To such end, we propose an easy method to obtain polyethylene terephthalate nano plastics from water plastic bottles (PET-NPLs) but, in principle, applicable to any other plastic goods sources. An extensive characterization indicates that the proposed process produces uniform samples of PET-NPLs of around 100 nm, as determined by using a multi-angle and dynamic light scattering methodology. An important point to be highlighted is that to avoid the metal contamination resulting from methods using metal blades/burrs for milling, trituration, or sanding, we propose to use diamond burrs to produce metal-free samples. To visualize the toxicological profile of the produced PET-NPLs, we have evaluated their ability to be internalized by cells, their cytotoxicity, and their ability to induce oxidative stress and induce DNA damage. In this preliminary approach, we have detected their cellular uptake, but without the induction of significant biological effects. Thus, no relevant increases in toxicity, reactive oxygen species (ROS) induction, or DNA damage -as detected with the comet assay- have been observed. The use of real samples, as produced in this study, will generate relevant data in the discussion about the potential health risks associated with MNPLs exposures.

Keywords: nanoplastics, polyethylene terephthalate, physicochemical characterization, cell uptake, cytotoxicity

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Authors: Samuel Odumu Ogana John, Stephen Friday Olukotun, Manny Mathuthu

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Radon-222 (²²²Rn), a naturally occurring radioactive gas, poses potential health risks due to its inhalation and ingestion, especially through drinking water. This study investigates the activity concentration levels of ²²²Rn in 21 brands of bottled water samples collected from the open market in South Africa. The samples were analyzed using a highly sensitive system consisting of the Ionization Chamber AlphaGUARD (PQ 2000), an AquaKIT set, and an AlphaPUMP, ensuring precise measurement of radon activity. The results revealed significant variations in radon concentrations across different brands, with values ranging from 0.062 ± 0.046 Bq/m³ to 0.198 ± 0.286 Bq/mv³, with a mean of 0.118 ± 0.034 Bq/m³. These measurements were then used to estimate the annual effective ingestion dose of radiation for consumers across various age groups based on the guidelines provided by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The mean effective doses were found to be 4.057 × 10⁻⁴ ± 1.188 × 10⁻⁴ mSv/y for infants (1–2 years), 2.428 × 10⁻⁴ ± 7.111 × 10⁻⁵ mSv/y for children (7–12 years), and 2.058 × 10⁻⁴ ± 6.026 × 10⁻⁵ mSv/y for adults, all of which are below the recommended international safety limits and are comparable to other published studies. These findings suggest that bottled drinking water in South Africa is safe for consumption and does not pose a significant health hazard from ²²²Rn radiation. The study underscores the importance of monitoring radon levels in bottled water to assess the associated radiological health risks, particularly in South Africa, where access to safe drinking water is essential. This research provides baseline data for future regulatory frameworks and policy development and can serve as a valuable reference for bottled water producers. Furthermore, it highlights the need for continued investigation into the regulation and mitigation of radon exposure in drinking water sources throughout the country.

Keywords: Radon-222, activity concentration levels, annual effective ingestion dose, bottled drinking water, South Africa

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Authors: Bar Y. Ainuz, Harry M. Salinas, Aleeza Ali, Eli B. Levitt, Austin J. Pourmoussa, Antoun Bouz, Miguel A. Medina

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Introduction: Breast conservation therapy remains the mainstay surgical treatment for early breast cancer. Oncoplastic techniques, in conjunction with lumpectomy and adjuvant radiotherapy, have been demonstrated to achieve good aesthetic results without adversely affecting cancer outcomes in the treatment of patients with macromastia or significant ptosis. In our patient population, many women present for breast conservation with pre-existing cosmetic implants or with breast volumes too small for soft tissue, only oncoplastic techniques. Our study evaluated a consecutive series of patients presenting for breast conservation undergoing concomitant oncoplastic-augmentation-mastopexy (OAM) with a contralateral augmentation-mastopexy for symmetry. Methods: OAM surgical technique involves simultaneous lumpectomy with exchange or placement of implants, oncoplastic mastopexy, and concomitant contralateral augmentation mastopexy for symmetry. Patients undergoing lumpectomy for breast conservation as outpatients were identified via retrospective chart review at a high volume private academic affiliated community-based cancer center. Patients with ptosis and either pre-existing breast implants or insufficient breast volume undergoing oncoplastic implant placement (or exchange) and mastopexy were included in the study. Operative details, aesthetic outcomes, and complications were assessed. Results: Over a continuous three-year period, with a two-surgeon cohort, 30 consecutive patients (56 breasts, 4 unilateral procedures) were identified. Patients had an average age of 52.5 years and an average BMI of 27.5, with 40% smokers or former smokers. The average operative time was 2.5 hours, the average implant size removed was 352 cc, and the average implant size placed was 300 cc. All new implants were smooth silicone, with the majority (92%) placed in a retropectoral fashion. 40% of patients received chemotherapy, and 80% of patients received whole breast adjuvant photon radiotherapy with a total radiation dose of either 42.56 or 52.56 Gy. The average and median length of follow-up were both 8.2 months. Of the 24 patients that received radiotherapy, 21% had asymmetry due to capsular contracture. A total of 7 patients (29.2%) underwent revisions for either positive margins (12.5%), capsular contracture (8.3%), implant loss (4.2%), or cosmetic concerns (4.2%). One patient developed a pulmonary embolism in the acute postoperative period and was treated with anticoagulant therapy. Conclusion: Oncoplastic augmentation mastopexy is a safe technique with good aesthetic outcomes and acceptable complication rates for ptotic patients with breast cancer and a paucity of breast volume or pre-existing implants who wish to pursue breast-conserving therapy. The revision rates compare favorably with single-stage cosmetic augmentation procedures as well as other oncoplastic techniques described in the literature. The short-term capsular contracture rates seem lower than the rates in patients undergoing radiation after mastectomy and implant-based reconstruction. Long term capsular contractures and revision rates are too early to know in this cohort.

Keywords: breast conserving therapy, oncoplastic augmentation mastopexy, capsular contracture, breast reconstruction

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 112

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

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Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

Procedia PDF Downloads 144

Authors: Asnakew Mulualem Tegegne, Tarun Kumar Lohani, , Abunu Atlabachew Eshete

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Groundwater quality has become deteriorated due to natural and anthropogenic activities. Poor water quality has a potential risk to human health and the environment. Therefore, the study aimed to assess the potential risk of groundwater quality contamination levels and public health risks in the Gunabay watershed. For this task, seventy-eight groundwater samples were collected from thirty-nine locations in the dry and wet seasons during 2022. The ground water contamination index was applied to assess the overall quality of groundwater. Six major driving forces (temperature, population density, soil, land cover, recharge, and geology) and their quantitative impact of each factor on groundwater quality deterioration were demonstrated using Geodetector. The results showed that low groundwater quality was detected in urban and agricultural land. Especially nitrate contamination was highly linked to groundwater quality deterioration and public health risks, and a medium contamination level was observed in the area. This indicates that the inappropriate application of fertilizer on agricultural land and wastewater from urban areas has a great impact on shallow aquifers in the study area. Furthermore, the major influencing factors are ranked as soil type (0.33–0.31)>recharge (0.17–0.15)>temperature (0.13–0.08)>population density (0.1–0.08)>land cover types (0.07– 0.04)>lithology (0.05–0.04). The interaction detector revealed that the interaction between soil ∩ recharge, soil ∩ temperature, and soil ∩ land cover, temperature ∩ recharge is more influential to deteriorate groundwater quality in both seasons. Identification and quantification of the major influencing factors may provide new insight into groundwater resource management.

Keywords: groundwater contamination index, geographical detectors, public health · influencing factors, and water resources management

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

Procedia PDF Downloads 233

Authors: Kamila Duś-Szachniewicz, Kinga M. Walaszek, Paweł Skiba, Paweł Kołodziej, Piotr Ziółkowski

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Cell adhesion is of fundamental importance in the cell communication, signaling, and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has greatly increased, and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. Unfortunately, most of the data regarding CAMs expression relates to study on cells maintained in standard oxygen condition of 21%, while the emerging evidence suggests that culturing cells in ambient air is far from physiological. In fact, oxygen in human tissues ranges from 1 to 11%. The aim of this study was to compare the effects of physiological lymph node normoxia (5% O2), and hyperoxia (21% O2) on the expression of cellular adhesion molecules of primary diffuse large B-cell lymphoma cells (DLBCL) isolated from 10 lymphoma patients. Quantitative RT-PCR and immunohistochemistry were used to confirm the differential expression of several CAMs, including ICAM, CD83, CD81, CD44, depending on the level of oxygen. Our findings also suggest that DLBCL cells maintained at ambient O2 (21%) exhibit reduced growth rate and migration ability compared to the cells growing in normoxia conditions. Taking into account all the observations, we emphasize the need to identify the optimal human cell culture conditions mimicking the physiological aspects of tumor growth and differentiation.

Keywords: adhesion molecules, diffuse large B-cell lymphoma, physiological normoxia, quantitative RT-PCR

Procedia PDF Downloads 279

Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

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Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

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Authors: O. R. Razanakoto, L. Temple

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Living in a least developed country, the Malagasy society has a weak capacity to internalize progress, including health concerns. Since the arrival in the fifteenth century of Arabic script, called Sorabe, that was mainly dedicated to the aristocracy, until the colonial era beginning at the end of the nineteenth century and that has popularized the current usual script of the occidental civilization, the upcoming manuscripts that deal with apparent scientific or at least academic issue have been slowly established. So that, the Malagasy communities’ way of life is not well documented yet to allow a precise understanding of the major concerns, reason, and purpose of the existence of the farmers that compose them. A question arises, according to literature, how does Malagasy community that is dominated by agrarian society conceive the conservation of its wellbeing? This study aims to emphasize the scope and the limits of the « One Health » concept or of the Health Integrated Approach (HIA) that evolves at global scale, with regard to the specific context of local Malagasy smallholder farms. It is expected to identify how this society represents linked risks and the mechanisms between human health, animal health, plant health, and ecosystem health within the last 100 years. To do so, the framework to conduct systematic review for agricultural research has been deployed to access available literature. This task has been coupled with the reading of articles that are not indexed by online scientific search engine but that mention part of a history of agriculture and of farmers in Madagascar. This literature review has informed the interactions between human illnesses and those affecting animals and plants (breeded or wild) with any unexpected event (ecological or economic) that has modified the equilibrium of the ecosystem, or that has disturbed the livelihoods of agrarian communities. Besides, drivers that may either accentuate or attenuate the devasting effects of these illnesses and changes were revealed. The study has established that the reasons of human worries are not only physiological. Among the factors that regulate global health, food system and contemporary medicine have helped to the improvement of life expectancy from 55 to 63 years in Madagascar during the last 50 years. However, threats to global health are still occurring. New human or animal illnesses and livestock / plant pathology or enemies may also appear, whereas ancient illnesses that are supposed to have disappeared may be back. This study has highlighted how much important are the risks associated to the impact of unmanaged externalities that weaken community’s life. Many risks, and also solutions, come from abroad and have long term effects even though those happen as punctual event. Thus, a constructivist strategy is suggested to the « One Health » global concept throughout the record of local facts. This approach should facilitate the exploration of methodological pathways and the identification of relevant indicators for research related to HIA.

Keywords: agrarian system, health integrated approach, history, madagascar, resilience, risk

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Authors: Sylvester S. Horvey, Jones Mensah

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The growing complexities and dynamics in the business environment have led to a new approach to risk management, known as enterprise risk management (ERM). ERM is a system and an approach to managing the risks of an organization in an integrated manner to achieve the corporate goals and strategic objectives. Regardless of the diversities in the business environment, ERM has become an essential factor in managing individual and business risks because ERM is believed to enhance shareholder value and firm growth. Despite the growing number of literature on ERM, the question about what factors drives ERM remains limited. This study provides a comprehensive literature review of the main factors that contribute to ERM implementation. Google Scholar was the leading search engine used to identify empirical literature, and the review spanned between 2000 and 2020. Articles published in Scimago journal ranking and Scopus were examined. Thirteen firm characteristics and sixteen articles were considered for the empirical review. Most empirical studies agreed that firm size, institutional ownership, industry type, auditor type, industrial diversification, earnings volatility, stock price volatility, and internal auditor had a positive relationship with ERM adoption, whereas firm size, institutional ownership, auditor type, and type of industry were mostly seen be statistically significant. Other factors such as financial leverage, profitability, asset opacity, international diversification, and firm complexity revealed an inconclusive result. The growing literature on ERM is not without limitations; hence, this study suggests that further research should examine ERM determinants within a new geographical context while considering a new and robust way of measuring ERM rather than relying on a simple proxy (dummy) for ERM measurement. Other firm characteristics such as organizational culture and context, corporate scandals and losses, and governance could be considered determinants of ERM adoption.

Keywords: enterprise risk management, determinants, ERM adoption, literature review

Procedia PDF Downloads 177