Search results for: Childhood Cancer

Authors: Nur Aimi Syairah Mohd Abdul Alim, Azilah Ajit, A. Z. Sulaiman

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The present study aimed to investigate the effects of ultrasound-assisted extraction (UAE) on the extraction of Vitexin and Iso-Vitexin from Ficus deltoidea plants. In recent years, ultrasound technology has been found to be a potential herbal extraction technique. The passage of ultrasound energy in a liquid medium generates mechanical agitation and other physical effects due to acoustic cavitation. The main goal is to optimised ultrasonic-assisted extraction condition providing the highest extraction yield with the most desirable antioxidant activity and stability. Thus, a series of experiments has been developed to investigate the effect of ultrasound energy on the vegetal material and the implemented parameters by using HPLC-photodiode array detection. The influences of several experimental parameters on the ultrasonic extraction of Ficus deltoidea leaves were investigated: extraction time (1-8 h), solvent-to-water ratio (1:10 to 1:50), temperature (50–100 °C), duty cycle (10–continuous sonication) and intensity. The extracts at the optimized condition were compared with those obtained by conventional boiling extraction, in terms of bioactive constituents yield and chemical composition. The compounds of interest identified in the extracts were Vitexin and Isovitexin, which possess anti-diabetic, anti-oxidant and anti-cancer properties. Results showed that the main variables affecting the extraction process were temperature and time. Though in less extent, solvent-to-water ratio, duty cycle and intensity are also demonstrated to be important parameters. The experimental values under optimal conditions were in good consistent with the predicted values, which suggested that ultrasonic-assisted extraction (UAE) is more efficient process as compared to conventional boiling extraction. It recommended that ultrasound extraction of Ficus deltoidea plants are feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable herbal medicine.

Keywords: Ficus, ultrasounds, vitexin, isovitexin

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Authors: Diwei Lin, Amanda Tan, Rajinder Singh-Rai

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We present the first reported case of a concomitant Leydig cell tumor (LCT) and paratesticular leiomyoma in an adult male with a known history of bilateral cryptorchidism. An 80-year-old male presented with a 2-month history of a left testicular lump associated with mild discomfort and a gradual increase in size on a background of bilateral cryptorchidism requiring multiple orchidopexy procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy and he proceeded to a left radical orchidectomy. Histopathological assessment of the left testis revealed a concomitant testicular LCT with malignant features and paratesticular leiomyoma. Leydig cell tumors (LCTs) are the most common pure testicular sex cord-stromal tumors, accounting for up to 3% of all testicular tumors. They can occur at almost any age, but are noted to have a bi-modal distribution, with a peak incidence at 6 to 10 and at 20 to 50 years of age. LCT’s are often hormonally active and can lead to feminizing or virilizing syndromes. LCT’s are usually regarded as benign but can rarely exhibit malignant traits. Paratesticular tumours are uncommon and their reported prevalence varies between 3% and 16%. They occur in a complex anatomical area which includes the contents of the spermatic cord, testicular tunics, epididymis and vestigial remnants. Up to 90% of paratesticular tumours are believed to originate from the spermatic cord, though it is often difficult to definitively ascertain the exact site of origin. Although any type of soft-tissue neoplasm can be found in the paratesticular region, the most common benign tumors reported are lipomas of the spermatic cord, adenomatoid tumours of the epididymis and leiomyomas of the testis. Genetic studies have identified potential mutations that could potentially cause LCTs, but there are no known associations between concomitant LCTs and paratesticular tumors. The presence of cryptorchidism in adults with both LCTs and paratesticular neoplasms individually has been previously reported and it appears intuitive that cryptorchidism is likely to be associated with the concomitant presentation in this case report. This report represents the first documented case in the literature of a unilateral concomitant LCT and paratesticular leiomyoma on a background of bilateral cryptorchidism.

Keywords: testicular cancer, leydig cell tumour, leiomyoma, paratesticular neoplasms

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: Sonja Djilas, Gordana Ćetković, Jasna Čanadanović-Brunet, Vesna Tumbas Šaponjac, Slađana Stajčić, Jelena Vulić, Milica Vinčić

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In recent years, interest in food rich in bioactive compounds, such as polyphenols, increased the advantages of the functional food products. Bioactive components help to maintain health and prevention of diseases such as cancer, cardiovascular and many other degenerative diseases. Recent research has shown that the fruit pomace, a byproduct generated from the production of juice, can be a potential source of valuable bioactive compounds. The use of fruit industrial waste in the processing of functional foods represents an important new step for the food industry. Sour cherries have considerable nutritional, medicinal, dietetic and technological value. According to the production volume of cherries, Serbia ranks seventh in the world, with a share of 7% of the total production. The use of sour cherry pomace has so far been limited to animal feed, even though it can be potentially a good source of polyphenols. For this study, local variety of sour cherry cv. ‘Feketićka’ was chosen for its more intensive taste and deeper red color, indicating high anthocyanin content. The contents of total polyphenols, flavonoids and anthocyanins, as well as radical scavenging activity on DPPH radicals and reducing power of sour cherry juice and pomace were compared using spectrophotometrical assays. According to the results obtained, 66.91% of total polyphenols, 46.77% of flavonoids, 46.77% of total anthocyanins and 47.88% of anthocyanin monomers from sour cherry fruits have been transferred to juice. On the other hand, 29.85% of total polyphenols, 33.09% of flavonoids, 53.23% of total anthocyanins and 52.12% of anthocyanin monomers remained in pomace. Regarding radical scavenging activity, 65.51% of Trolox equivalents from sour cherries were exported to juice, while 34.49% was left in pomace. However, reducing power of sour cherry juice was much stronger than pomace (91.28% and 8.72% of Trolox equivalents from sour cherry fruits, respectively). Based on our results it can be concluded that sour cherry pomace is still a rich source of natural antioxidants, especially anthocyanins with coloring capacity, therefore it can be used for dietary supplements development and food fortification.

Keywords: antioxidants, polyphenols, pomace, sour cherry

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Authors: John Masani Nduko, Joseph Wafula Matofari

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Many spontaneously fermented milk products are produced in Kenya, where they are integral to the human diet and play a central role in enhancing food security and income generation via small-scale enterprises. Fermentation enhances product properties such as taste, aroma, shelf-life, safety, texture, and nutritional value. Some of these products have demonstrated therapeutic and probiotic effects although recent reports have linked some to death, biotoxin infections, and esophageal cancer. These products are mostly processed from poor quality raw materials under unhygienic conditions resulting to inconsistent product quality and limited shelf-lives. Though very popular, research on their processing technologies is low, and none of the products has been produced under controlled conditions using starter cultures. To modernize the processing technologies for these products, our study aims at describing the microbiology and biochemistry of a representative Kenyan spontaneously fermented milk product, Mursik using modern biotechnology (DNA sequencing) and their chemical composition. Moreover, co-creation processes reflecting stakeholders’ experiences on traditional fermented milk production technologies and utilization, ideals and senses of value, which will allow the generation of products based on common ground for rapid progress will be discussed. Knowledge of the value of clean starting raw material will be emphasized, the need for the definition of fermentation parameters highlighted, and standard equipment employment to attain controlled fermentation discussed. This presentation will review the available information regarding traditional fermented milk (Mursik) and highlight our current research work on the application of molecular approaches (metagenomics) for the valorization of Mursik production process through starter culture/ probiotic strains isolation and identification, and quality and safety aspects of the product. The importance of the research and future research areas on the same subject will also be highlighted.

Keywords: lactic acid bacteria, high throughput biotechnology, spontaneous fermentation, Mursik

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Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

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Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

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Authors: Hassan Sheikh, Mehdi Nilipour, Amiraslan Fila

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Many conventional town planning processes do little to give children and young people a voice on what is important about the urban environment. As a result of paying little attention to the children, their physical, social and mental needs are hardly met in urban environments. Therefore, urban spaces are impotent to attract children, while their recreational space has been confined to home or virtual spaces. Since children are just taking the first steps to learn the world beyond house borders, their living environment will profoundly influence almost all aspects of their lives. This puts a great deal of responsibility on the shoulders of planners, who need to balance a number of different issues in urban design to make places more child-friendly. The main purpose of present research is to analyze and plan a child-friendly environment in an on-going urban settlement development for the benefit of all residents. Assessing children’s needs and regard them in development strategies and policies will help to “plan for children”. Following this purpose, based on child-friendly environment studies, indicators of child-friendly environments were collected. Then three distinct characteristics of case study, which are being under-construction, lack of social ties between dwellers and high-rise building, determined seven indicators included basic services, Urban and environmental qualities, Family, kin, peers and community, Sense of belonging and continuity, participation, Safety, security and freedom of movement and human scale. With the survey, Informal observation and participation in small communities, essential data has been collected and analyzed by SPSS software. The field study is Shahid-Keshvari town in Isfahan, Iran. Eighty-six middle childhood, children (ages 8-13) participated. The results show Children's satisfaction is correlated with basic services and the quality of the environment, social environment and the safety and security. The considerable number of children and youth (55%) like to live somewhere other than the town. Satisfaction and sense of belonging and continuity have a strong inverse correlation with age. In other words, as age increases, satisfaction and consequently a sense of belonging will be reduced; thus children and youth consider their future somewhere out of the town. The main reason for dissatisfaction was the basic services and social environment. More than half of children (55%) expressed their wish to develop basic services in terms of availability, hierarchy, and quality. Among all recreational places, children showed more interest to the parks. About three-quarters (76%) considered building a park as a crucial item for residents. The significant number of children (54%) want to have a relationship with more friends. This could be due to the serious shortage of the leisure spaces such as parks or playgrounds. Also, the space around the house or space between the apartments has not been designed for play or children’s activities. Moreover, the presence of strangers and construction workers have a negative impact on children's sense of peace and security; 60% of children are afraid of theft and 36% of children found strangers as a menace. The analysis of children’s issues and suggestions provides an insight to plan and design of child-friendly environment in new towns.

Keywords: child-friendly city (CFC), child-friendly environment, child participation, under-construction environment, Isfahan Shahid-Keshvari Town

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Authors: Suharni Mohamad Suharni Mohamad, Nurul Izzati Hamzan Nurul Izzati Hamzan, Norhayu Abdul Rahman Norhayu Abdul Rahman, Siti Suraiya Md Noor Siti Suraiya Md Noor

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Human papillomavirus (HPV) is an important risk factor for development of oral cancer. HPV16 is the most common type found in HPV-positive squamous cell carcinoma. In the present study, we established a real-time loop-mediated isothermal amplification (real-time LAMP) for detection of HPV16. A set of six primers was specially designed to recognize eight distinct sequences of HPV16-E6. Detection and quantification was achieved by real-time monitoring using a real-time turbidimeter based on threshold time required for turbidity in the LAMP reaction. LAMP reagents (MgSO4, dNTPs, Bst polymerase concentrations) and various incubation times and temperatures were optimized. The sensitivity was determined using 10-fold serial dilutions of HPV16 standard strain. The specificity of was evaluated using other HPV genotypes. The optimized method was established with specifically designed primers by real-time detection in approximately 30 min at 65°C. The limit of detection of HPV16 using the LAMP assay was 10 pg/ml that could be detected in 30 min. The LAMP assay was 10 times more sensitive than the conventional PCR in detecting HPV16. No cross-reactivity with other HPV genotypes was observed. This quantitative real-time LAMP assay may improve diagnostic potential for the detection and quantification of HPV16 in clinical samples and epidemiological studies due to its rapidity, simplicity, high sensitivity and specificity. This assay will be further evaluated with HPV DNAs of saliva from patients with oral squamous cell carcinoma. Acknowledgement: This study was financially supported by the ScienceFund Grant, Ministry of Science, Technology and Innovation (305/PPSG/6113219).

Keywords: Oral Squamous Cell Carcinoma (OSCC), Human Papillomavirus 16 (HPV16), Loop-Mediated Isothermal Amplification (LAMP), rapid detection

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Authors: Katherine Maurer

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Background and purpose: Violence that occurs within families is a global social problem. Children who are victims or witness to family violence are at risk for many negative effects both proximally and distally. One of the most disconcerting long-term effects occurs when child victims become adult perpetrators: the intergenerational transmission of family violence (ITFV). Early identification of those children most at risk for ITFV is needed to inform interventions to prevent future family violence perpetration and victimization. Only about 25-30% of child family violence victims become perpetrators of adult family violence (either child abuse, partner abuse, or both). Prior research has primarily been conducted using dichotomous measures of exposure (yes; no) to predict ITFV, given the low incidence rate in community samples. It is often assumed that exposure to greater amounts of violence predicts greater risk of ITFV. However, no previous longitudinal study with a community sample has tested a dose-response model of exposure to physical child abuse and parental physical intimate partner violence (IPV) using count data of frequency and severity of violence to predict adult ITFV. The current study used advanced statistical methods to test if increased childhood exposure would predict greater risk of ITFV. Methods: The study utilized 3 panels of prospective data from a cohort of 15 year olds (N=338) from the Project on Human Development in Chicago Neighborhoods longitudinal study. The data were comprised of a stratified probability sample of seven ethnic/racial categories and three socio-economic status levels. Structural equation modeling was employed to test a hurdle regression model of dose-response to predict ITFV. A version of the Conflict Tactics Scale was used to measure physical violence victimization, witnessing parental IPV and young adult IPV perpetration and victimization. Results: Consistent with previous findings, past 12 months incidence rates severity and frequency of interpersonal violence were highly skewed. While rates of parental and young adult IPV were about 40%, an unusually high rate of physical child abuse (57%) was reported. The vast majority of a number of acts of violence, whether minor or severe, were in the 1-3 range in the past 12 months. Reported frequencies of more than 5 times in the past year were rare, with less than 10% of those reporting more than six acts of minor or severe physical violence. As expected, minor acts of violence were much more common than acts of severe violence. Overall, regression analyses were not significant for the dose-response model of ITFV. Conclusions and implications: The results of the dose-response model were not significant due to a lack of power in the final sample (N=338). Nonetheless, the value of the approach was confirmed for the future research given the bi-modal nature of the distributions which suggest that in the context of both child physical abuse and physical IPV, there are at least two classes when frequency of acts is considered. Taking frequency into account in predictive models may help to better understand the relationship of exposure to ITFV outcomes. Further testing using hurdle regression models is suggested.

Keywords: intergenerational transmission of family violence, physical child abuse, intimate partner violence, structural equation modeling

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Abdulbaset Mazarzaei

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Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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Authors: Mohammad Mosaddik Rahman

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This study embarks on an exploratory journey to assess the pervasive issue of heavy metal contamination in the water bodies along Chittagong Coast, Bangladesh. Situated along the mesmerizing Bay of Bengal, known for its potential as an emerging tourist haven, economic zone, ship breaking yard, confronts significant environmental hurdles. The core of these challenges lies in the contamination from heavy metals such as lead, cadmium, chromium, and mercury, which detrimentally impact both the ecological integrity and public health of the region. This contamination primarily stems from industrial activities, particularly those involving metallurgical and chemical processes, which release these metals into the environment, leading to their accumulation in soil and water bodies. The study's primary aim is to conduct a thorough assessment of heavy metal pollution levels, alongside an analysis of nutrient variations, focusing on nitrates and nitrites. Methodologically, the study leverages systematic sampling and advanced analytical tools like the Hach 3900 spectrophotometer to ensure precise and reliable data collection. The implications of heavy metal presence are multifaceted, affecting microbial and aquatic life, and posing severe health risks to the local population, including respiratory problems, neurological disorders, and an increased risk of cancer. The results of this study highlight the urgent need for effective mitigation strategies and regulatory measures to address this critical issue. By providing a comprehensive understanding of the environmental and public health implications of heavy metal contamination in Chittagong Coast, this research endeavours to serve as a catalyst for change, emphasising the need for pollution control and advancements in water management policies. It is envisioned that the outcomes of this study will guide stakeholders in collaborating to develop and implement sustainable solutions, ultimately safeguarding the region’s environment and public health.

Keywords: heavy metal, environmental health, pollution control policies, shipbreaking yard

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Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

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Authors: Nurlan Smagulov, Aiman Konkabayeva, Akerke Sadykova, Arailym Serik

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Introduction. Adverse environmental factors do not immediately lead to pathological changes in the body. They can exert the growth of pre-pathology characterized by shifts in physiological, biochemical, immunological and other indicators of the body state. These disorders are unstable, reversible and indicative of body reactions. There is an opportunity to objectively judge the internal structure of the adaptive body reactions at the level of individual organs and systems. In order to obtain a stable response of the body to the chronic effects of unfavorable environmental factors of low intensity (compared to production environment factors), a time called the «lag time» is needed. The obtained results without considering this factor distort reality and, for the most part, cannot be a reliable statement of the main conclusions in any work. A technique is needed to reduce methodological errors and combine mathematical logic using statistical methods and a medical point of view, which ultimately will affect the obtained results and avoid a false correlation. Objective. Development of a methodology for assessing and predicting the environmental factors impact on the population health considering the «lag time.» Methods. Research objects: environmental and population morbidity indicators. The database on the environmental state was compiled from the monthly newsletters of Kazhydromet. Data on population morbidity were obtained from regional statistical yearbooks. When processing static data, a time interval (lag) was determined for each «argument-function» pair. That is the required interval, after which the harmful factor effect (argument) will fully manifest itself in the indicators of the organism's state (function). The lag value was determined by cross-correlation functions of arguments (environmental indicators) with functions (morbidity). Correlation coefficients (r) and their reliability (t), Fisher's criterion (F) and the influence share (R2) of the main factor (argument) per indicator (function) were calculated as a percentage. Results. The ecological situation of an industrially developed region has an impact on health indicators, but it has some nuances. Fundamentally opposite results were obtained in the mathematical data processing, considering the «lag time». Namely, an expressed correlation was revealed after two databases (ecology-morbidity) shifted. For example, the lag period was 4 years for dust concentration, general morbidity, and 3 years – for childhood morbidity. These periods accounted for the maximum values of the correlation coefficients and the largest percentage of the influencing factor. Similar results were observed in relation to the concentration of soot, dioxide, etc. The comprehensive statistical processing using multiple correlation-regression variance analysis confirms the correctness of the above statement. This method provided the integrated approach to predicting the degree of pollution of the main environmental components to identify the most dangerous combinations of concentrations of leading negative environmental factors. Conclusion. The method of assessing the «environment-public health» system (considering the «lag time») is qualitatively different from the traditional (without considering the «lag time»). The results significantly differ and are more amenable to a logical explanation of the obtained dependencies. The method allows presenting the quantitative and qualitative dependence in a different way within the «environment-public health» system.

Keywords: ecology, morbidity, population, lag time

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

Procedia PDF Downloads 153

Authors: Tarek Elnimr, Reda Morsy, Assem El Fert, Aziza Ismail

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Hepatitis is an inflammation of the liver. The condition can be self-limiting or can progress to fibrosis, cirrhosis or liver cancer. Disease caused by the hepatitis virus, the virus can cause hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. A growing body of evidence indicates that many trace elements play important roles in a number of carcinogenic processes that proceed with various mechanisms. To examine the status of trace elements during the development of hepatic carcinoma, we determined the iron, copper, zinc and selenium levels in some biological samples of patients at different stages of viral hepatic disease. We observed significant changes in the iron, copper, zinc and selenium levels in the biological samples of patients hepatocellular carcinoma, relative to those of healthy controls. The mean hair, nail, RBC, serum and whole blood copper levels in patients with hepatitis virus were significantly higher than that of the control group. In contrast the mean iron, zinc, and selenium levels in patients having hepatitis virus were significantly lower than those of the control group. On the basis of this study, we identified the impact of natural supplements to improve the treatment of viral liver damage, using the level of some trace elements such as, iron, copper, zinc and selenium, which might serve as biomarkers for increases survival and reduces disease progression. Most of the elements revealed diverse and random distribution in the samples of the donor groups. The correlation study pointed out significant disparities in the mutual relationships among the trace elements in the patients and controls. Principal component analysis and cluster analysis of the element data manifested diverse apportionment of the selected elements in the scalp hair, nail and blood components of the patients compared with the healthy counterparts.

Keywords: hepatitis, hair, nail, blood components, trace element, nutrition therapy, multivariate analysis, correlation, ICP-MS

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Gabriella Zarlenga, Martha L. Hall

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

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

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Authors: Suchithra V., Shreedhanya, Kavya Menon, Vidya Niranjan

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Skin metagenomics has a wide range of applications with direct relevance to the health of the organism. It gives us insight to the diverse community of microorganisms (the microbiome) harbored on the skin. In the recent years, it has become increasingly apparent that the interaction between skin microbiome and the human body plays a prominent role in immune system development, cancer development, disease pathology, and many other biological implications. Next Generation Sequencing has led to faster and better understanding of environmental organisms and their mutual interactions. This project is studying the human skin microbiome of different individuals having varied skin conditions. Bacterial 16S rRNA data of skin microbiome is downloaded from SRA toolkit provided by NCBI to perform metagenomics analysis. Twelve samples are selected with two controls, and 3 different categories, i.e., sex (male/female), skin type (moist/intermittently moist/sebaceous) and occlusion (occluded/intermittently occluded/exposed). Quality of the data is increased using Cutadapt, and its analysis is done using FastQC. USearch, a tool used to analyze an NGS data, provides a suitable platform to obtain taxonomy classification and abundance of bacteria from the metagenome data. The statistical tool used for analyzing the USearch result is METAGENassist. The results revealed that the top three abundant organisms found were: Prevotella, Corynebacterium, and Anaerococcus. Prevotella is known to be an infectious bacterium found on wound, tooth cavity, etc. Corynebacterium and Anaerococcus are opportunist bacteria responsible for skin odor. This result infers that Prevotella thrives easily in sebaceous skin conditions. Therefore it is better to undergo intermittently occluded treatment such as applying ointments, creams, etc. to treat wound for sebaceous skin type. Exposing the wound should be avoided as it leads to an increase in Prevotella abundance. Moist skin type individuals can opt for occluded or intermittently occluded treatment as they have shown to decrease the abundance of bacteria during treatment.

Keywords: bacterial 16S rRNA , next generation sequencing, skin metagenomics, skin microbiome, taxonomy

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar

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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure

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Authors: Kremena Ivanona, Bistra Kunovska, Jana Djunova, Desislava Djunakova, Zdenka Stojanovska

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In recent decades, the general public has become increasingly interested in the impact of air pollutions on their health. Currently, numerous studies are aimed at identifying pollutants in the indoor environment where they carry out daily activities. Internal pollutants can be of both natural and artificial origin. With regard to natural pollutants, special attention is paid to natural radioactivity. In recent years, radon has been one of the most studied indoor pollutants because it has the greatest contribution to human exposure to natural radionuclides. It is a known fact that lung cancer can be caused by radon radiation and it is the second risk factor after smoking for the onset of the disease. The main objective of the study under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018 is to evaluate the indoor radon as an important air pollutant in school buildings in order to reduce the exposure to children. The measurements were performed in 48 schools located in 55 buildings in one Bulgarian administrative district (Kardjaly). The nuclear track detectors (CR-39) were used for measurements. The arithmetic and geometric means of radon concentrations are AM = 140 Bq/m3, and GM = 117 Bq/m3 respectively. In 51 school rooms, the radon levels were greater than 200 Bq/m3, and in 28 rooms, located in 17 school buildings, it exceeded the national reference level of 300 Bq/m3, defined in the Bulgarian ordinance on radiation protection (or 30% of the investigated buildings). The statistically significant difference in the values of radon concentration by municipalities (KW, р < 0.001) obtained showed that the most likely reason for the differences between the groups is the geographical location of the buildings and the possible influence of the geological composition. The combined effect of the year of construction (technical condition of the buildings) and the energy efficiency measures was considered. The values of the radon concentration in the buildings where energy efficiency measures have been implemented are higher than those in buildings where they have not been performed. This result confirms the need for investigation of radon levels before conducting the energy efficiency measures in buildings. Corrective measures for reducing the radon levels have been recommended in school buildings with high radon levels in order to decrease the children's exposure.

Keywords: air pollution, indoor radon, children exposure, schools

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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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

Procedia PDF Downloads 283

Authors: J. Naalamle Amissah, Dorcas Osei‐Safo, C. M. Asare, Benjamin Missah‐Assihene, Eric. Y. Danquah, Ivan Addae‐Mensah

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Medicinal plants serve as a reservoir of active ingredients for the treatment of common ailments such as cancer, malaria and diabetes. With the recent wave of health consciousness and reliance on plant based medicines, the demand for medicinal plants has increased considerably. This surge in medicinal plant use has raised great concern amongst key players (herbalist, collectors, conservationist and researchers) along the value chain about the sustainability of the raw material. The over reliance on wild crafting as a means to obtain the raw material spells doom for several of Africa’s native medicinal plant species. In this study domestication protocols for the cultivation of Cryptolepis sanguinolenta (CS), a medicinal plant used in the treatment of malaria were developed. Initial surveys were conducted, using questionnaires comprising of open and close ended questions, to gather information that would inform the domestication and cultivation of the species. A field study was then conducted to determine the plant’s cropping cycle and the effect of staking and plant age on the active ingredient (cryptolepine) concentration in its roots. Results of the survey confirmed the demand for the raw material and threw more light on the harvesting methods and intensity of CS collection from the wild. Cryptolepine concentration was found to be highest (~1.84 mg/100 mg of root material) at 289 days after planting (DAP) which coincided with the peak of root dry weight (52.8 g), signifying the best time for root harvest. Staking was found to be important for seed production. The first 105 DAP were characterized by low yields of root dry weight (13.5 g), followed by a period of rapid growth in which the root dry weight increased almost linearly until 289 DAP. Although dry matter partitioned to the vines increased towards the end of the experimental period (60%), dry matter partitioned to the roots remained fairly constant (30%) throughout the experimental period. Cryptolepine was found to increase as the plant aged and the practice of staking CS promoted pod formation. A suitable cropping cycle for the cultivation of CS was also developed.

Keywords: domestication, staking, conservation, wild harvesting

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Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

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Authors: Shireen Ibish

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Physical inactivity and unhealthy diets have contributed to a global burden of disease with increased relation to non-communicable diseases, increased risk of colon and breast cancer, high prevalence of depression, reduced quality of life and early death. The World Health Organisation’s facts on Obesity show a tripling in prevalence across the European Region since the 1980s. This has lead to a huge public health burden, being responsible for and 10-13% of deaths (fourth largest cause of global mortality) and 2-8% of health costs in the Region. In the UK alone, the present cost of physical inactivity has been estimated to be £8.2 billion. In 2002 a paper published in the International Journal of Epidemiology on ‘sedentary’ lifestyle, put into figures the increasingly worrying statistics across European countries. “Percentages of sedentary lifestyles across European countries ranged between 43.3% (Sweden) and 87.8% (Portugal)”. This was especially so amongst obese subjects, less- educated people, and smokers. While in the UK’s “50% of adult population in the UK is predicted to be obese by 2050.” Sports and Exercise Medicine, as a specialty, has a lot to offer in targeting this globally increasing epidemic. The worrying figures and the increasing knowledge of combating and preventing this issue have lead to increased awareness amongst the medical profession and more targeted interventions to reduce the burden of disease. “The public health element of the specialty is critical – this is not simply a specialty for the management of elite athletes’ medical conditions – it is central to the promotion of exercise as a means of disease prevention, to enhance well-being and in the management of disease.” WHO advised on creating National policies, encouraging and providing opportunities for greater physical activity, and improve the affordability, availability and accessibility of healthy foods. In the UK various different movements have been established to target this problem. The Motivate2Move, Move Eat Treat and guidelines advising specialties on targeting and encouraging exercise in the population (Sport and Exercise Medicine A Fresh Approach).

Keywords: sedentary lifestyle, obesity, public health burden, medicine

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Authors: Kasun P. Wijayaratna, Lauren Gardner, Taha Hossein Rashidi

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Undergraduate students entering university across the last 2 to 3 years tend to be born during the middle years of the 1990s. This generation of students has been exposed to the internet and the desire and dependency on technology since childhood. Brains develop based on environmental influences and technology has wired this generation of student to be attuned to sophisticated complex visual imagery, indicating visual forms of learning may be more effective than the traditional lecture or discussion formats. Furthermore, post-millennials perspectives on career are not focused solely on stability and income but are strongly driven by interest, entrepreneurship and innovation. Accordingly, it is important for educators to acknowledge the generational shift and tailor the delivery of learning material to meet the expectations of the students and the needs of industry. In the context of transport engineering, effectively teaching undergraduate students the basic principles of transport planning, traffic engineering and highway design is fundamental to the progression of the profession from a practice and research perspective. Recent developments in technology have transformed the discipline as practitioners and researchers move away from the traditional “pen and paper” approach to methods involving the use of computer programs and simulation. Further, enhanced accessibility of technology for students has changed the way they understand and learn material being delivered at tertiary education institutions. As a consequence, blended learning approaches, which aim to integrate face to face teaching with flexible self-paced learning resources, have become prevalent to provide scalable education that satisfies the expectations of students. This research study involved the development of a series of ‘Blended Learning’ initiatives implemented within an introductory transport planning and geometric design course, CVEN2401: Sustainable Transport and Highway Engineering, taught at the University of New South Wales, Australia. CVEN2401 was modified by conducting interactive polling exercises during lectures, including weekly online quizzes, offering a series of supplementary learning videos, and implementing a realistic design project that students needed to complete using modelling software that is widely used in practice. These activities and resources were aimed to improve the learning environment for a large class size in excess of 450 students and to ensure that practical industry valued skills were introduced. The case study compared the 2016 and 2017 student cohorts based on their performance across assessment tasks as well as their reception to the material revealed through student feedback surveys. The initiatives were well received with a number of students commenting on the ability to complete self-paced learning and an appreciation of the exposure to a realistic design project. From an educator’s perspective, blending the course made it feasible to interact and engage with students. Personalised learning opportunities were made available whilst delivering a considerable volume of complex content essential for all undergraduate Civil and Environmental Engineering students. Overall, this case study highlights the value of blended learning initiatives, especially in the context of large class size university courses.

Keywords: blended learning, highway design, teaching, transport planning

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Authors: Nafiseh Mirabdolhosseini, Jerry Zhou, Vincent Ho

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The dramatic global rise in acid reflux has also led to oesophageal adenocarcinoma (OAC) becoming the fastest-growing cancer in developed countries. While gastroscopy with biopsy is used to diagnose OAC patients, this labour-intensive and expensive process is not suitable for population screening. This study aims to design, develop, and implement a minimally invasive system to capture optical data of the distal oesophagus for rapid screening of potential abnormalities. To develop the system and understand user requirements, a user-centric approach was employed by utilising co-design strategies. Target users’ segments were identified, and 38 patients and 14 health providers were interviewed. Next, the technical requirements were developed based on consultations with the industry. A minimally invasive optical system was designed and developed considering patient comfort. This system consists of the sensing catheter, controller unit, and analysis program. Its procedure only takes 10 minutes to perform and does not require cleaning afterward since it has a single-use catheter. A prototype system was evaluated for safety and efficacy for both laboratory and clinical performance. This prototype performed successfully when submerged in simulated gastric fluid without showing evidence of erosion after 24 hours. The system effectively recorded a video of the mid-distal oesophagus of a healthy volunteer (34-year-old male). The recorded images were used to develop an automated program to identify abnormalities in the distal oesophagus. Further data from a larger clinical study will be used to train the automated program. This system allows for quick visual assessment of the lower oesophagus in primary care settings and can serve as a screening tool for oesophageal adenocarcinoma. In addition, this system is able to be coupled with 24hr ambulatory pH monitoring to better correlate oesophageal physiological changes with reflux symptoms. It also can provide additional information on lower oesophageal sphincter functions such as opening times and bolus retention.

Keywords: endoscopy, MedTech, oesophageal adenocarcinoma, optical system, screening tool

Procedia PDF Downloads 64