Search results for: Breast Cancer

Authors: Petr Daniel Edward Kovarik, Malcolm Jackson, Charles Kelly, Rahul Patil, Shahid Iqbal

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Introduction: Recognition of the presence of extra capsular spread (ECS) has been a major change in the TNM 8th edition published by the American Joint Committee on Cancer in 2018. Irrespective of the size or number of lymph nodes, the presence of ECS makes N3b disease a stage IV disease. The objective of this retrospective observational study was to conduct a comparative analysis of survival outcomes in patients with lymph node-positive cutaneous head and neck squamous cell carcinoma (CHNSCC) based on their TNM 7th and TNM 8th editions classification. Materials and Methods: From January 2010 to December 2020, 71 patients with CHNSCC were identified from our centre’s database who were treated with radical surgery and adjuvant radiotherapy. All histopathological reports were reviewed, and comprehensive nodal mapping was performed. The data were collected retrospectively and survival outcomes were compared using TNM 7th and 8th editions. Results: The median age of the whole group of 71 patients was 78 years, range 54 – 94 years, 63 were male and 8 female. In total, 2246 lymph nodes were analysed; 195 were positive for cancer. ECS was present in 130 lymph nodes, which led to a change in TNM staging. The details on N-stage as per TNM 7th edition was as follows; pN1 = 23, pN2a = 14, pN2b = 32, pN2c = 0, pN3 = 2. After incorporating the TNM 8th edition criterion (presence of ECS), the details on N-stage were as follows; pN1 = 6, pN2a = 5, pN2b = 3, pN2c = 0, pN3a = 0, pN3b = 57. This showed an increase in overall stage. According to TNM 7th edition, there were 23 patients were with stage III and remaining 48 patients, stage IV. As per TNM 8th edition, there were only 6 patients with stage III as compared to 65 patients with stage IV. For all patients, 2-year disease specific survival (DSS) and overall survival (OS) were 70% and 46%. 5-year DSS and OS rates were 66% and 20% respectively. Comparing the survival between stage III and stage IV of the two cohorts using both TNM 7th and 8th editions, there is an obvious greater survival difference between the stages if TNM 8th staging is used. However, meaningful statistics were not possible as the majority of patients (n = 65) were with stage IV and only 6 patients were stage III in the TNM 8th cohort. Conclusion: Our study provides a comprehensive analysis on lymph node data mapping in this specific patient population. It shows a better differentiation between stage III and stage IV in the TNM 8th edition as compared to TNM 7th however meaningful statistics were not possible due to the imbalance of patients in the sub-cohorts of the groups.

Keywords: cutaneous head and neck squamous cell carcinoma, extra capsular spread, neck lymphadenopathy, TNM 7th and 8th editions

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Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa

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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.

Keywords: graduation, family planning, systems strengthening, sustainability

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Authors: Prodromos E. Atlamazoglou

Abstract:

The method of moments combined with the method of symmetrical components is used for the analysis of interstitial hyperthermia applicators. The basis and testing functions are both piecewise sinusoids, qualifying our technique as a Galerkin one. The dielectric coatings are modeled by equivalent volume polarization currents, which are simply related to the conduction current distribution, avoiding in that way the introduction of additional unknowns or numerical integrations. The results of our method for a four dipole circular array, are in agreement with those already published in literature for a same hyperthermia configuration. Apart from being accurate, our approach is more general, more computationally efficient and takes into account the coupling between the antennas.

Keywords: hyperthermia, integral equations, insulated antennas, method of symmetrical components

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Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin

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Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.

Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length

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Authors: Phomid Techi, L. N. Padmasini, Mohan Mathew

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Objective: To evaluate the effectiveness of co-parent support on the duration of exclusive breastfeeding by a randomized control trial. Introduction: The current rates of exclusive breastfeeding for 6 months in India is 46% (NFHS3 2008.). The purpose of the study is to evaluate the effectiveness of co-parenting support on duration of exclusive breastfeeding in primi mothers. Design: RCT: Willing parents of healthy TAGA babies born in our hospital were explained about the study purpose and randomly assigned to either trial or control group. The control group was given the usual care. The intervention group received usual care and in addition the trial intervention. Follow-up data was collected at the end of 6 mon. Intervention: Face to face 30-minute discussion in post partum unit on breast feeding benefits, techniques, and problem-solving information followed up by phone calls to mother every 4 weeks to answer questions/concerns. Outcome measures: Duration of exclusive breastfeeding Baseline demographic variables were measured. Results: After obtaining IEC approval a total of 100 couples were recruited, 100 is each group. In the intervention group, the rate of exclusive breastfeeding was 97.2% while in the control group it was 64% (p-value 0.00). Conclusion: Co-parenting support has an important role in promoting exclusive breastfeeding.

Keywords: co-parenting, exclusive breastfeeding, developing nation, randomised control trial

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Authors: Osama H. Elsayed, Mohsen M. S. Asker, Mahmoud A. Swelim, Ibrahim H. Abbas, Aziza I. Attwa, Mohamed E. El Awady

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Hydroxy marilone C is a bioactive metabolite was produced from the culture broth of Streptomyces badius isolated from Egyptian soil. hydroxy marilone C was purified and fractionated by silica gel column with a gradient mobile phase dicloromethane (DCM) : Methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many instruments as Infrared (IR), nuclear magnetic resonance (NMR), Mass spectroscopy (MS) and UV spectroscopy to the elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549) and human breast adenocarcinoma cell line (MCF-7) and antiviral activities; showed that the maximum antioxidant activity was 78.8 % at 3000 µg/ml after 90 min. and the IC50 value against DPPH radical found about 1500 µg/ml after 60 min. By Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells were 443 µg/ml and 147.9 µg/ml, respectively. While for detection of antiviral activity using Madin-Darby canine kidney (MDCK) cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1µg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50) was 33.25% for 80 µg/ml. This results indicated that the hydroxy marilone C has a potential antitumor and antiviral activities.

Keywords: hydroxy marilone C, production, bioactive compound, Streptomyces badius

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Authors: Mehrnaz Mostafavi

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Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.

Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy

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Authors: W. Hajuthman, R. Warner, S. Rahman, M. Abraham, H. Helliwell, D. Bodiwala

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Context: Prostate cancer is a prevalent cancer in males in Europe and the US, with diagnosis primarily relying on PSA testing, mpMRI, and subsequent biopsies. However, this diagnostic strategy may lead to complications for patients. Research Aim: The aim of this study is to assess compliance with trust guidelines for antibiotic prophylaxis in patients undergoing transperineal template biopsies of the prostate and evaluate the rate of post-procedure complications. Methodology: This study is conducted retrospectively over an 8-month period. Data collection includes patient demographics, compliance with trust guidelines, associated risk factors, and post-procedure complications such as infection, haematuria, and urinary retention. Findings: The audit includes 100 patients with a median age of 66.11. The compliance with pre-procedure antibiotics was 98%, while compliance with antibiotic prophylaxis recommended by trust guidelines was 68%. Among the patients, 3% developed post-procedure sepsis, with 2 requiring admission for intravenous antibiotics. No evident risk factors were identified in these cases. Additionally, post-procedure urinary retention occurred in 3% of patients and post-procedure haematuria in 2%. Theoretical Importance: This study highlights the increasing use of transperineal template biopsies across UK centres and suggests that having a standardized protocol and compliance with guidelines can reduce confusion, ensure appropriate administration of antibiotics, and mitigate post-procedure complications. Data Collection and Analysis Procedures: Data for this study is collected retrospectively, involving the extraction and analysis of relevant information from patient records over the specified 8-month period. Question Addressed: This study addresses the following research questions: (1) What is the compliance rate with trust guidelines for antibiotic prophylaxis in transperineal template biopsies of the prostate? (2) What is the rate of post-procedure complications, such as infection, haematuria, and urinary retention? Conclusion: Transperineal template biopsies are becoming increasingly prevalent in the UK. Implementing a standardized protocol and ensuring compliance with guidelines can reduce confusion, ensure proper administration of antibiotics, and potentially minimize post-procedure complications. Additionally, considering that studies show no difference in outcomes when prophylactic antibiotics are not used, the reminder to follow trust guidelines may prompt a re-evaluation of antibiotic prescribing practices.

Keywords: prostate, transperineal template biopsies of prostate, antibiotics, complications, microbiology, guidelines

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Authors: Areti Angeliki Veroniki, Sofia Tsokani, Evangelos Paraskevaidis, Dimitris Mavridis

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The plethora of diagnostic test accuracy (DTA) studies has led to the increased use of systematic reviews and meta-analysis of DTA studies. Clinicians and healthcare professionals often consult DTA meta-analyses to make informed decisions regarding the optimum test to choose and use for a given setting. For example, the human papilloma virus (HPV) DNA, mRNA, and cytology can be used for the cervical intraepithelial neoplasia grade 2+ (CIN2+) diagnosis. But which test is the most accurate? Studies directly comparing test accuracy are not always available, and comparisons between multiple tests create a network of DTA studies that can be synthesized through a network meta-analysis of diagnostic tests (DTA-NMA). The aim is to summarize the DTA-NMA methods for at least three index tests presented in the methodological literature. We illustrate the application of the methods using a real data set for the comparative accuracy of HPV DNA, HPV mRNA, and cytology tests for cervical cancer. A search was conducted in PubMed, Web of Science, and Scopus from inception until the end of July 2019 to identify full-text research articles that describe a DTA-NMA method for three or more index tests. Since the joint classification of the results from one index against the results of another index test amongst those with the target condition and amongst those without the target condition are rarely reported in DTA studies, only methods requiring the 2x2 tables of the results of each index test against the reference standard were included. Studies of any design published in English were eligible for inclusion. Relevant unpublished material was also included. Ten relevant studies were finally included to evaluate their methodology. DTA-NMA methods that have been presented in the literature together with their advantages and disadvantages are described. In addition, using 37 studies for cervical cancer obtained from a published Cochrane review as a case study, an application of the identified DTA-NMA methods to determine the most promising test (in terms of sensitivity and specificity) for use as the best screening test to detect CIN2+ is presented. As a conclusion, different approaches for the comparative DTA meta-analysis of multiple tests may conclude to different results and hence may influence decision-making. Acknowledgment: This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Extension of Network Meta-Analysis for the Comparison of Diagnostic Tests ” (MIS 5047640).

Keywords: colposcopy, diagnostic test, HPV, network meta-analysis

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Authors: V. Mathad, S. Shivprasad, P. Shivsharannappa, M. K. Patil

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Introduction: Non-communicable diseases are emerging diseases in India. Government of India launched National Programme for Prevention and Control of Cardiovascular Diseases, Cancer and Stroke (NPCDCS) during the year 2008. The aim of the programme was to reduce the burden of non communicable diseases by health promotion and prompt treatment. Objective: The present study was intended to assess the impact of National Program for prevention and control of Cardiovascular Diseases, Diabetes, Cancer and Stroke Programme on biochemical and physiological factors influencing Type 2 diabetes in Kalaburagi District. Material and Method: NCD Clinic was established at District Hospital during April 2016. All the patients attending District Hospital Kalaburagi above the age of 30 years are screened for Non Communicable Diseases under NPCDCS Programme. A total sample of 7447 patients attending NCD Clinic situated at Kalaburagi district was assessed in this study. Pre structured and pretested schedule seeking information was obtained from all the patients by the counselor working under NPCDCS programme. All the Patients attending District Hospital were screened for Diabetes using Glucometer at NCD clinic. The suspected cases were further confirmed through Biochemical investigations like Fasting Blood glucose, HBA1c, Urine Glucose, Kidney Function test. SPSS 20 version was used for analysis of data. Chi square test, P values and odds ratio was used to study the association of factors. Results: A Total of 7447 patients attended NCD clinic during the year 2017-18 were analyzed, Diabetes was seen among 3028 individuals were as comorbidities along with Hypertension was seen among 757 individuals. The mean age of the population was 50 ± 2.84. 3440(46.2%) were males whereas Female constituted 4007(53.8%) of population. The incidence and prevalence of Diabetes being 8.6 and 12.8 respectively. Diabetes was more commonly seen during the age group of 40 to 69 years. Diabetes was significantly associated with Age group 40 to 69 years, obesity and female gender (p < 0.05). The risk of developing Hypertension and comorbidity conditions of hypertension and Diabetes was 1.224 and 1.305 times higher among males, whereas the risk of diabetes was 1.127 higher among females as compared to males. Conclusion: The screening for NCD has significantly increased after launching of NPCDCS programme. NCD was significantly associated with obesity, female gender, increased age as well as comorbid conditions like hypertension and tuberculosis.

Keywords: non-communicable diseases, NPCDCS programme, type 2 Diabetes, physiological factors

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Authors: Ghazanfari Masoumeh, Hajimohammadi Bahador, Eskandari Soheyl, Karimian Khosroshahi Nader

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Consumption of ready to cook meat products such as hamburgers, sausages and etc is being increased in the worldwide specially in the big cities , so safety and quality required for food products is very important and vital for consumers with consideration of meat price and increasing demands for meat products, possibility of substitution of cheep and unauthorized textures such as undesirable enclosures animals (massacre, lung tissue, breast of spleen, the organs abdominal cavity, gizzard chicken, skin, etc. ) have increased in the recent years, in this study 30 industrial and 30 handmade hamburgers in fast food restaurants detected out of Iranian national standard for hamburger No. 2304 in using the unauthorized textures. The purpose of this study was to determine using of chicken skin in produced hamburgers from chicken meat in Tehran base on histology methods. The rates of skin used were, 2 % in industrial and 9 % in handmade formula samples. Statistically using the unauthorized textures had significant higher rate in handmade (P < 0.05) in compare with the industrial samples. The results showed the handmade hamburgers with higher adulteration rate and non-compliance with the hamburger national standard could be a potentially health hazard.

Keywords: histology, adulteration, unauthorized textures, undesirable enclosures animals

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Authors: Xiaoyuan Chen

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Background: This study aimed to characterize the epidemiological and clinical features of five rare subtypes of hepatocellular carcinoma (HCC) and to create a competing risk nomogram for predicting cancer-specific survival. Methods: This study used the Surveillance, Epidemiology, and End Results database to analyze the clinicopathological data of 50,218 patients with classic HCC and five rare subtypes (ICD-O-3 Histology Code=8170/3-8175/3) between 2004 and 2018. The annual percent change (APC) was calculated using Joinpoint regression, and a nomogram was developed based on multivariable competing risk survival analyses. The prognostic performance of the nomogram was evaluated using the Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical value of the models. Results: The incidence of scirrhous carcinoma showed a decreasing trend (APC=-6.8%, P=0.025), while the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality plateau in all subtypes during the period. Clear cell carcinoma was the most common subtype (n=551, 1.1%), followed by fibrolamellar (n=241, 0.5%), scirrhous (n=82, 0.2%), spindle cell (n=61, 0.1%), and pleomorphic (n=17, ~0%) carcinomas. Patients with fibrolamellar carcinoma were younger and more likely to have non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro clinical characteristics and outcomes as classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were identified as independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice. Conclusion: The rare subtypes of HCC had distinct clinicopathological features and biological behaviors compared with classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could accurately predict prognoses, which is beneficial for individualized management.

Keywords: hepatocellular carcinoma, pathological subtype, fibrolamellar carcinoma, scirrhous carcinoma, clear cell carcinoma, spindle cell carcinoma, pleomorphic carcinoma

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Authors: Kirsty Biggs, Peter Larsen-Disney

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Background: The UK cervical screening programme significantly reduces cancer mortality through the early detection of abnormal cells. Despite this, over a quarter of eligible women choose not to attend their appointment. Objective: To qualitatively explore patients’ barriers to attending cervical smear appointments and identify key trends of cervical screening behaviour, knowledge, and attitudes in primary and secondary care. Methods: A cross-sectional study was conducted to evaluate smear services in Brighton and Hove using questionnaires in general practice and colposcopy. 226 patients participated in the voluntary questionnaire between 10/11/2017 and 02/02/2018. 118 patients were recruited from general practice surgeries and 108 from the colposcopy department. Women were asked about their smear knowledge, self-perceived risks factors, prior experiences and reasons for non-attendance. Demographic data was also collected. Results: Approximately a third of women did not engage in smear testing services. This was consistent across primary and secondary care groups. Over 90% were aware of the role of the screening process in relation to cervical cancer; however, over two thirds believed the smear was also a tool to screen for other pathologies. The most commonly cited reasons for non-attendance were negative emotions or previous experiences. Inconvenient appointment times were also commonly described. In a comparison of attenders versus non-attenders previous negative experiences (p < 0.01) and number of identified risk factors (p = 0.02) were statistically significant with non-attenders describing more prior negative smears and identifying more risk factors. Smear knowledge, risk perception and perceived importance of screening were not significant. Negative previous experiences were described in relation to poor bedside manner, pain, embarrassment and staff competency. Conclusions: In contrary to the literature, our white Caucasian cohort experienced significant barriers to accessing smear services. Women’s prior negative experiences are overriding their perceived importance to attend the screening programme; therefore, efforts need to focus on improving clinical experiences through auditing tools, training and providing a supportive appointment setting. Positive changes can also be expected by improving appointment availabilities with extended hours and self-booking systems.

Keywords: barriers, cervical, Papanicolaou, screening, smear

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Authors: Supriya Chatla, Anjana Male, Srikala Kamireddy

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L-asparaginase (E.C.3.5.1.1) is an anti-cancer enzyme that has been purified and characterized for decades to study and evaluate its anti-carcinogenic activity against Hodgkin’s lymphoma. The present investigation deals with screening, isolation and optimization of L-asparaginase giving fungal strain of soil samples from different areas of AP, India. L-Aspariginase activity was estimated on the basis of the pink color surrounding the growing colony. A total of 132 colonies were screened and isolated from different samples. Based on the zone diameter, L-asparaginase activity is determined, L- asparaginase activity is optimized at 28oc and Immobilized Aspariginase had more potency than the free enzymes.

Keywords: aspariginase, anticancer enzyme, Isolation, optimization

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Authors: Moshiur Rahman, Tahmida Jakia

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Bangladesh, a densely populated South Asian country is home to more than 160 million people. In two decades ago, the people of this developing nation drank heavily contaminated surface water. Over the past thirty years, the country, and its development partners, has undertaken extensive efforts to provide microbiologically safe groundwater based drinking water through the use of tube-wells. About 85% of the people now drink tube-well water from about 11 million tube-wells/hand pumps. However, diarrhoeal and other water-related diseases are still reported among the major causes of morbidity and mortality among Bangladeshi children. This implies that the mode of transmission of pathogens through water and/or other modes continue. In addition, massive scale arsenic contamination has been recently reported in the ground water. Thirty five million people may be at risk of consuming arsenic contaminated water exceeding 0.05 mg/l in Bangladesh. Drinking of arsenic contaminated water has been linked with skin problems, cancer, cardiovascular diseases, neurological diseases, eye problems, cancer of the internal organs, and other diseases. In the study area, Narail district, recent investigations about existing water quality situations indicated presence of low to high levels of arsenic, salinity, iron, manganese and bacteriological contamination risks. As challenges for safe water exist; it is likely that sanitation and food hygiene practices are poor which lead threat to ensure food security.The main attempt of this study is to find out the challenges to ensure food security andprovide probable solutions to ensure food safety towards 0.7 million of people in study area. A survey has been conducted at Lohagara and Kalia sub district of Narail district with a pretested questionnaire. Primary data are collected through a questionnaire, while secondary data are collected from pertinent offices as well as academic journals. FGD has also been done to know the knowledge regarding water, sanitation as well as food preparation and consumption practice of community people in study area. The major focus of this study is to assess the state of sanitation and food hygiene condition of rural people. It is found that most of the villagers have lack of knowledge about food safety. Open defecation rate is high which lead threat to ensure food security.

Keywords: food safety, challenges, hygiene, Bangladesh

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Authors: Yousif Mohamed Y. Abdallah, Khalid H. Eltom

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This is an experimental study deals with measurement of the periodic physiological organ motion during lung external irradiation in order to reduce the exposure of healthy tissue during radiation treatments. The results showed for left lung displacement reading (4.52+1.99 mm) and right lung is (8.21+3.77 mm) which the radiotherapy physician should take suitable countermeasures in case of significant errors. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, the calculation of tumour mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a high resolution CT scan with a margin of 3-5 mm is appropriate.

Keywords: physiological motion, lung, external irradiation, radiation medicine

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Authors: Tzu-Ting Hu, Jung-Der Wang, Ming-Yeng Lin, Jin-Luh Chen, Perng-Jy Tsai

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The vinyl chloride monomer (VCM) has been classified as group 1 (human) carcinogen by the IARC. Workers exposed to VCM are known associated with the development of the liver cancer and hence might cause economical and health losses. Particularly, for those work for the petrochemical industry have been seriously concerned in the environmental and occupational health field. Considering assessing workers’ health risks and their resultant economical and health losses requires the establishment of long-term VCM exposure data for any similar exposure group (SEG) of interest, the development of suitable technologies has become an urgent and important issue. In the present study, VCM exposures for petrochemical industry workers were determined firstly based on the database of the 'Workplace Environmental Monitoring Information Systems (WEMIS)' provided by Taiwan OSHA. Considering the existence of miss data, the reconstruction of historical exposure techniques were then used for completing the long-term exposure data for SEGs with routine operations. For SEGs with non-routine operations, exposure modeling techniques, together with their time/activity records, were adopted for determining their long-term exposure concentrations. The Bayesian decision analysis (BDA) was adopted for conducting exposure and health risk assessments for any given SEG in the petrochemical industry. The resultant excessive cancer risk was then used to determine the corresponding loss of quality-adjusted life expectancy (QALE). Results show that low average concentrations can be found for SEGs with routine operations (e.g., VCM rectification 0.0973 ppm, polymerization 0.306 ppm, reaction tank 0.33 ppm, VCM recovery 1.4 ppm, control room 0.14 ppm, VCM storage tanks 0.095 ppm and wastewater treatment 0.390 ppm), and the above values were much lower than that of the permissible exposure limit (PEL; 3 ppm) of VCM promulgated in Taiwan. For non-routine workers, though their high exposure concentrations, their low exposure time and frequencies result in low corresponding health risks. Through the consideration of exposure assessment results, health risk assessment results, and QALE results simultaneously, it is concluded that the proposed method was useful for prioritizing SEGs for conducting exposure abatement measurements. Particularly, the obtained QALE results further indicate the importance of reducing workers’ VCM exposures, though their exposures were low as in comparison with the PEL and the acceptable health risk.

Keywords: exposure assessment, health risk assessment, petrochemical industry, quality-adjusted life years, vinyl chloride monomer

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Authors: Wangxu Xia

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BACKGROUND BI-RADS 4 lesions raise the possibility of malignancy that warrant further clinical and radiologic work-up. This study aimed to evaluate the predictive performance of diffusion-weighted imaging(DWI) and microcalcifications on mammography for predicting malignancy of BI-RADS 4 lesions. In addition, the predictive performance of DWI combined with microcalcifications was alsocompared with the Kaiser score. METHODS During January 2021 and June 2023, 144 patients with 178 BI-RADS 4 lesions underwent conventional MRI, DWI, and mammography were included. The lesions were dichotomized intobenign or malignant according to the pathological results from core needle biopsy or surgical mastectomy. DWI was performed with a b value of 0 and 800s/mm2 and analyzed using theapparent diffusion coefficient, and a Kaiser score > 4 was considered to suggest malignancy. Thediagnostic performances for various diagnostic tests were evaluated with the receiver-operatingcharacteristic (ROC) curve. RESULTS The area under the curve (AUC) for DWI was significantly higher than that of the of mammography (0.86 vs 0.71, P<0.001), but was comparable with that of the Kaiser score (0.86 vs 0.84, P=0.58). However, the AUC for DWI combined with mammography was significantly highthan that of the Kaiser score (0.93 vs 0.84, P=0.007). The sensitivity for discriminating malignant from benign BI-RADS 4 lesions was highest at 89% for Kaiser score, but the highest specificity of 83% can be achieved with DWI combined with mammography. CONCLUSION DWI combined with microcalcifications on mammography could discriminate malignant BI-RADS4 lesions from benign ones with a high AUC and specificity. However, Kaiser score had a better sensitivity for discrimination.

Keywords: MRI, DWI, mammography, breast disease

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Authors: Warsi A. Ibrahim, Qureshi A. Ambrina, Younus M. Anjum

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Introduction: Oral lesions related to commercially available Smokeless Tobacco (ST), such as, Pan, Gutka, Mahwa, Naswar is considered a serious challenge for dental health care providers in Pakistan. Majority of labored Pakistani population consume ST, where public transporters and drivers are no exception. It was necessary to identify individuals of this particular population group and screen their oral health and early signs of pre-cancerous lesions so that appropriate preventive measures could be taken to reduce the burden on health providers. Aim of Study: To estimate Prevalence of ST consumption and perception of use, and to evaluate Oral Health status among public drivers of Karachi. Material & methods: A cross-sectional study survey was conducted over duration of 2 months, through convenient sampling. Sample size (n=615) of public drivers (age > 18 years) all over Karachi was gathered. A structured proforma was used to record socio-demographics, addiction profile, perception of use and oral health status (oral lesions, oral sub-mucosal fibrosis and dental caries) of study participants. Data was entered and analyzed using SPSS version 16.0 using descriptive statistics only. Results: Prevalence of ST consumption among the study participants was figured to 92.5%. Out of these almost 70% suffered from one or the other form of oral lesion(s). Four major types of ST consumption were observed out of which 60 % of oral lesion were related to Gutka chewers showing early signs of oral cancer. In addition, occurrence of Oral sub-mucosal fibrosis (OSF) was found to be significantly high around 54.8%. Overall dental caries status was also high, showing on an average 5 teeth of an individual were decayed, missing or filled deviating from WHO normal criteria (mean < 3). It was thus proven from the study that public drivers relied on oral tobacco consumption because it helps them ‘Improve consciousness’ (p-value: < 0.01; using chi-square test). Multivariate analysis showed that there were higher prevalence of smokeless tobacco among highway drivers versus local drivers (A.O.R: 2.82 [0.83-9.61], p-value: < 0.01) Conclusion: Smokeless tobacco (ST) consumption has a direct effect on oral health. However, the type of ST, the duration of consumption are factors which are directly related to the severity. Moreover, Gutka may be considered as having most lethal effects on oral health which may lead to oral cancer and affect individual’s quality of life. Specific preventive programs must be undertaken to reduce the consumption of Gutka among public transporters and drivers.

Keywords: smokeless tobacco, oral lesions, drivers, public transporters

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Authors: Udeshika Yapa Bandara, Chamindri Witharana, Preethi Soysa

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Pomegranate fruits are used in cancer treatment in Ayurveda, Sri Lanka. Due to prevailing therapeutic effects of phytochemicals, this study was focus on anti-cancer properties of the constituents in the parts of Pomegranate fruit. Furthermore, the method of extraction, plays a crucial step of the phytochemical analysis. Therefore, this study was focus on different extraction methods. Five techniques were involved for the peel and the pericarp to evaluate the most effective extraction method; Boiling with electric burner (BL), Sonication (SN), Microwaving (MC), Heating in a 50°C water bath (WB) and Sonication followed by Microwaving (SN-MC). The presence of polyphenolic and flavonoid contents were evaluated to recognize the best extraction method for polyphenols. The total phenolic content was measured spectrophotometrically by Folin-Ciocalteu method and expressed as Gallic Acid Equivalents (w/w% GAE). Total flavonoid content was also determined spectrophotometrically with Aluminium chloride colourimetric assay and expressed as Quercetin Equivalents (w/w % QE). Pomegranate juice was taken as fermented juice (with Saccharomyces bayanus) and fresh juice. Powdered seeds were refluxed, filtered and freeze-dried. 2g of freeze-dried powder of each component was dissolved in 100ml of De-ionized water for extraction. For the comparison of antioxidant activity and total phenol content, the polyphenols were removed by the Polyvinylpolypyrrolidone (PVVP) column and fermented and fresh juice were tested for the 1, 1-diphenyl-2-picrylhydrazil (DPPH) radical scavenging activity, before and after the removal of polyphenols. For the peel samples of Pomegranate fruit, total phenol and flavonoid contents were high in Sonication (SN). In pericarp, total phenol and flavonoid contents were highly exhibited in method of Sonication (SN). A significant difference was observed (P< 0.05) in total phenol and flavonoid contents, between five extraction methods for both peel and pericarp samples. Fermented juice had a greatest polyphenolic and flavonoid contents comparative to fresh juice. After removing polyphenols of fermented juice and fresh juice using Polyvinyl polypyrrolidone (PVVP) column, low antioxidant activity was resulted for DPPH antioxidant activity assay. Seeds had a very low total phenol and flavonoid contents according to the results. Although, Pomegranate peel is the main waste component of the fruit, it has an excellent polyphenolic and flavonoid contents compared to other parts of the fruit, devoid of the method of extraction. Polyphenols play a major role for antioxidant activity.

Keywords: antioxidant activity, flavonoids, polyphenols, pomegranate

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Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

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Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

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Authors: R. Mehta, M. Ghogomu, B. Schoel

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Reports appeared in 2020 about China detecting SARS-Cov-2 (Covid-19) on frozen meat, shrimp, and food packaging material. In this study, we examined the use of swabs for the detection of Covid-19 on meat samples, and chicken breast (CB) was used as a model. Methods: Heat inactivated SARS-Cov-2 virus (IV) from Microbiologics was loaded onto the CB, swabbing was done, and the recovered inactivated virus was subjected to the Machery & Nagel NucleoSpin RNAVirus kit for RNA isolation according to manufacturer's instructions. For RT-PCR, the IDT 2019-nCoV RUO Covid-19 test kit was used with the Taqman Fast Virus 1-step master mix. The limit of detection (LOD) of viral load recovered from the CB was determined under various conditions: first on frozen CB where the IV was introduced on a defined area, then on frozen CB, with IV spread-out, and finally, on thawed CB. Results: The lowest amount of IV which can be reliably detected on frozen CB was a load of 1,000 - 2,000 IV copies where the IV was loaded on one spot of about 1 square inch. Next, the IV was spread out over a whole frozen CB about 16 square inches. The IV could be recovered at a lowest load of 4,000 to 8,000 copies. Furthermore, the effects of temperature change on viral load recovery was investigated i.e., if raw unfrozen meat became contaminated and remains for 1 hour at 4°C or gets refrozen. The amount of IV recovered successfully from CB kept at 4°C and the refrozen CB was similar to the recovery gotten from loading the IV directly on the frozen CB. In conclusion, an assay using swabs was successfully established for the detection of SARS-Cov-2 on frozen or raw (unfrozen) CB with a minimal load of up to 8,000 copies spread over 16 square inches.

Keywords: assay, COVID-19, meat, SARS-Cov-2

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Authors: Mei Li, Victor Meddalena

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Background: Newfoundland and Labrador (NL) has rapidly aging population and is characterized by its vast geography with high proportion of dispersed rural communities when compared to other provinces in Canada. Structural, demographic and geographic factors have created big gaps for rural residents across NL with respect to accessing various health and social services. While the barriers are well documented for patients’ access to cancer care in rural and remote areas, challenges faced by family caregivers are not fully recognized. Caregiving burden coupled with challenges associated with relocation and frequent travels create situations where caregivers are vulnerable physically, emotionally, financially and socially. This study examines the experiences of family caregivers living in rural NL through a social justice lens. It is expected to identify the gaps existing in social policy and support for rural family caregivers. It will make a novel contribution to the literature in this regard. Methods: Design: This qualitative study adopted the hermeneutic phenomenology to best describe and interpret rural-based family caregivers’ living experiences and explore the meaning, impact, and the influence of both individual experience and contextual factors shaping these experiences. Data Collection: In-depth interviews with key informants were conducted with 12 participants from various rural communities in NL. A case study was also used to explore an individual’s experience in complex social units consisting of multiple variables of in-depth understanding of the reality. Data Analysis: Thematic analysis guided by the Voice-Centred Relational (VCR) method was employed to explore the relationships and contexts of participants. Emerging Themes: Six major emerging themes were identified, namely, overwhelming caregiving burden on rural family caregivers, long existing financial hardship, separation from family and community, low level of social support and self-reliance coping strategies, and social vulnerability and isolation. Conclusion: Understanding the lived experiences of rural-based family caregivers is critical to inform the policy makers the gap of health and social service in NL. The findings of this study also have implications for family caregivers who are vulnerable in other similar contexts. This study adds innovative insights for policy making and service provision in this regard.

Keywords: family caregivers, policy, relocation, rural

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Authors: Sasidhar B., Bhaskar Rao N., Ramesh Babu D. R., Ravi Shankar M.

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Segmentation of lung pleura is a preprocessing step in Computer-Aided Diagnosis (CAD) which helps in reducing false positives in detection of lung cancer. The existing methods fail in extraction of lung regions with the nodules at the pleura of the lungs. In this paper, a new method is proposed which segments lung regions with nodules at the pleura of the lungs based on curvature analysis and morphological operators. The proposed algorithm is tested on 06 patient’s dataset which consists of 60 images of Lung Image Database Consortium (LIDC) and the results are found to be satisfactory with 98.3% average overlap measure (AΩ).

Keywords: curvature analysis, image segmentation, morphological operators, thresholding

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Authors: Azza T. Tahera, Eman M. Ahmeda, Nadia A. Khalila, Yassin M. Nissanb

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New 3-(pyridin-4-yl)-[1,2,4] triazolo [4,3-b] pyridazine derivatives 2a-i, 4a,b and 6a,b were designed, synthesized and evaluated as cytotoxic agents. All compounds were investigated for their in vitro cytotoxicity at a single dose 10-5M concentration towards 60 cancer cell lines according to USA NCI protocol. The preliminary screening results showed that the majority of tested compounds exhibited remarkable activity against SR (leukemia) cell panel. Molecular docking for all synthesized compounds was performed on the active site of c-Met kinase. The most active compounds, 2f and 4a were further evaluated at a seven dose level screening and their IC50 as a c-Met kinase inhibitors were determined in vitro.

Keywords: triazolopyridazines, pyridazines, cytotoxic activity, cell panel

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Authors: Agburuga Obi, Madumere Akuego Jane

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This paper explores the important role sports can play in the promotion of good health and prevention of diseases. Technological advancements in today’s world has come along with some difficulties to man. This is because work formally done by man has been taken over by machines, thus, man has become sedentary. This has created a lot of health problems to man such as cardiovascular diseases, diabetes, cancer, obesity, and osteoporosis. To nip this ugly situation in the bud, the following recommendations are made: specific measures should be taken to raise the awareness within the government, key sectors and the population of the diverse benefits or physical activity and sports and the risk and costs of inactivity, provision of equipment, facilities for sports and recreational activities in every community, participation in physical activities in sports if not on daily basis at least thrice a week.

Keywords: physical activities, sport, good health, prevention, diseases

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Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

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Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

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Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

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T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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Authors: Samantha Meyerholz

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MSKCC offers patients cutting edge cancer care with the highest quality standards. However, many patients and industry members do not realize that the operations of the Immunology Histology Lab (IHC) are the backbone for carrying out this mission. The IHC lab manufactures blocks and slides containing critical tissue samples that will be read by a Pathologist to diagnose and dictate a patient’s treatment course. The lab processes 200 requests daily, leading to the generation of approximately 2,000 slides and 1,100 blocks each day. Lab material is transported through labeling, cutting, staining and sorting manufacturing stations, while being managed by multiple techs throughout the space. The quality of the stain as well as wait times associated with processing requests, is directly associated with patients receiving rapid treatments and having a wider range of care options. This project aims to improve slide request turnaround time for rush and non-rush cases, while increasing the quality of each request filled (no missing slides or poorly stained items). Rush cases are to be filled in less than 24 hours, while standard cases are allotted a 48 hour time period. Reducing turnaround times enable patients to communicate sooner with their clinical team regarding their diagnosis, ultimately leading faster treatments and potentially better outcomes. Additional project goals included streamlining tech and material workflow, while reducing waste and increasing efficiency. This project followed a DMAIC structure with emphasis on lean and ergonomic principles that could be integrated into an evolving lab culture. Load times and batching processes were analyzed using process mapping, FMEA analysis, waste analysis, engineering observation, 5S and spaghetti diagramming. Reduction of lab technician movement as well as their body position at each workstation was of top concern to pathology leadership. With new equipment being brought into the lab to carry out workflow improvements, screen and tool placement was discussed with the techs in focus groups, to reduce variation and increase comfort throughout the workspace. 5S analysis was completed in two phases in the IHC lab, helping to drive solutions that reduced rework and tech motion. The IHC lab plans to continue utilizing these techniques to further reduce the time gap between tissue analysis and cancer care.

Keywords: engineering, ergonomics, healthcare, lean

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