Search results for: cancer screening

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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Authors: Lanlan Xiao, Yang Liu, Shuo Chen, Bingmei Fu

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Most cancer-related deaths are due to metastasis. Metastasis is a complex, multistep processes including the detachment of cancer cells from the primary tumor and the migration to distant targeted organs through blood and/or lymphatic circulations. During hematogenous metastasis, the emigration of tumor cells from the blood stream through the vascular wall into the tissue involves arrest in the microvasculature, adhesion to the endothelial cells forming the microvessel wall and transmigration to the tissue through the endothelial barrier termed as extravasation. The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used Dissipative Particle Dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape and cell surface area increase, and slit size on the cell transmigration through the slit were investigated. Under a fixed driven force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area only by 3% can enable the cell to pass the narrow slit. Therefore the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entry but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

Keywords: dissipative particle dynamics, deformability, surface area increase, cell migration

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Authors: Nagia Ali, R. S. R. El-Mohamedy

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The purpose of this paper is to irradiate the dyes biologically through the use of Moreinga oleifera. The study confirms the potential use of Moringa oleifera in decolourization of dyes and thus opens up a scope for future analysis pertaining to its performance in treatment of textile effluent. In this paper, the ability of natural products in removing dyes was tested using two reactive dyes and one acid dye. After a preliminary screening for dye removal capacity, a vegetal protein extract derived from Moeringa oleifera seed was fully studied. The influences of several parameters such as pH, temperature or initial dye concentration were tested and the behavior of coagulants was compared. It was found that dye removal decreased as pH increased. Temperature did not seem to have a considerable effect, while initial dye concentration appeared to be a very important variable.

Keywords: Moreinga oleifera, decolourization, waste water, reactive dyes, acid dyes

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Authors: Chiu-Wen Chang, I-Yun Chang, Wei-Ting Chen, Hui-Ping Ho, Ruei-Hun Chang, Joh-Jong Huang

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Kaohsiung City is located in the tropical region where has Aedes aegypti and Aedes albopictus distributed; once the virus invades, it’s can easily trigger local epidemic. Besides, Kaohsiung City has a world-class airport and harbor, trade and tourism are close and frequently with every country, especially with the Southeast Asian countries which also suffer from dengue. Therefore, Kaohsiung City faces the difficult challenge of dengue every year. The objectives of this study was to enhance dengue clinical care, border management and vector surveillance in Kaohsiung City by establishing an larger scale, innovatively and more coordinated dengue prevention and control strategies in 2016, including (1) Integrated medical programs: facilitated 657 contract medical institutions, widely set up NS1 rapid test in clinics, enhanced triage and referrals system, dengue case daily-monitoring management (2) Border quarantine: comprehensive NS1 screening for foreign workers and fisheries when immigration, hospitalization and isolation for suspected cases, health education for high risk groups (foreign students, other tourists) (3) Mosquito control: Widely use Gravitrap to monitor mosquito density in environment, use NS1 rapid screening test to detect community dengue virus (4) Health education: create a dengue app for people to immediately inquire the risk map and nearby medical resources, routine health education to all districts to strengthen public’s dengue knowledge, neighborhood cleaning awards program. The results showed that after new integration of dengue prevention and control strategies fully implemented in Kaohsiung City, the number of confirmed cases in 2016 declined to 342 cases, the majority of these cases are the continuation epidemic in 2015; in fact, only two cases confirmed after the 2016 summer. Besides, the dengue mortality rate successfully decreased to 0% in 2016. Moreover, according to the reporting rate from medical institutions in 2014 and 2016, it dropped from 27.07% to 19.45% from medical center, and it decreased from 36.55% to 29.79% from regional hospital; however, the reporting rate of district hospital increased from 11.88% to 15.87% and also increased from 24.51% to 34.89% in general practice clinics. Obviously, it showed that under the action of strengthening medical management, it reduced the medical center’s notification ratio and improved the notification ratio of general clinics which achieved the great effect of dengue clinical management and dengue control.

Keywords: dengue control, integrated control strategies, clinical management, NS1

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Authors: Anne N. Heirman, Song Duimel, Rob van Son, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Julia van Weert, Michiel W.M. van den Brekel

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Objectives: Treatments for head-neck cancer are drastic and often significantly impact the quality of life and appearance of patients. Shared decision-making (SDM) beholds a collaboration between patient and doctor in which the most suitable treatment can be chosen by integrating patient preferences, values, and medical information. SDM has a lot of advantages that would be useful in making difficult treatment choices. The objective of this study was to determine the current level of SDM among patients and head-and-neck surgeons. Methods: Consultations of patients with a non-cutaneous head-and-neck malignancy facing a treatment decision were selected and included. If given informed consent, the consultation was recorded with an audio recorder, and the patient and surgeon filled in a questionnaire immediately after the consultation. The SDM level of the consultation was scored objectively by independent observers who judged audio recordings of the consultation using the OPTION5-scale, ranging from 0% (no SDM) to 100% (optimum SDM), as well as subjectively by patients (using the SDM-Q-9 and Control preference scale) and clinicians (SDM-Q-Doc, modified control preference scale) percentages. Preliminary results: Five head-neck surgeons have each at least seven recorded conversations with different patients. One of them was trained in SDM. The other four had no experience with SDM. Most patients were male (74%), and oropharyngeal carcinoma was the most common diagnosis (41%), followed by oral cancer (33%). Five patients received palliative treatment of which two patients were not treated recording guidelines. At this moment, all recordings are scored by the two independent observers. Analysis of the results will follow soon. Conclusion: The current study will determine to what extent there is a discrepancy between the objective and subjective level of shared decision-making (SDM) during a doctor-patient consultation in Head-and-Neck surgery. The results of the analysis will follow shortly.

Keywords: head-and-neck oncology, patient involvement, physician-patient relations, shared decision making

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Authors: Zohre Shahhosseini, Mehdi Pourasghar, AliReza Khalilian, Fariba Salehi

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Objective: The prevalence of anxiety during pregnancy, particularly in developing countries, and its adverse effects on mother and baby, can make pregnancy unpleasant for pregnant women. The effect of anxiety during pregnancy on birth outcomes and children can be a justification for screening of anxious pregnant women in periodic pregnancy care and helping them. In this study, researchers have investigated effects and comparison of group counseling (Cognitive therapy) and interactive lectures on anxiety during pregnancy of primiparas. Methods: The population studied in this semi-experimental trail was nulliparous pregnant women with backgrounds in health care centers in Sari city .They were studied during a period of 3 months from early March to end May 2016. Sample size in this study was 91 patients, who were randomly assigned to three groups: group counseling, interactive lecture, and control group. Demographic questionnaire and Speilberger State –Trait Anxiety Inventory (SPAI) was completed for all three groups after obtaining letter of consent and completing the initial checklist. Then interventions included 4 sessions for group counseling and 4 sessions for interactive lecture which were implemented in two sessions a week. 4 weeks after interventions, Speilberger State – Trait Anxiety Inventory (SPAI), completed by both group counseling and interactive lectures groups again. In control group, the second questionnaire was also completed 4 weeks after completing the initial questionnaire. Data analysis was performed using spss software version 18. At first, the Kalmogorov-Smiranov test was carried out and then chi square tests, Independent t-test, paired t-test, ANOVA test, and Dunnett's post hoc test were applied. Results: Findings show that group counseling and interactive lecture with reducing state and trait anxiety in significant level of P=0/000 contribute to reduction of anxiety in nulliparous pregnant mothers. However, in this study, group counseling was more effective than an interactive lecture in reducing participants' anxiety, but this difference was not significant (P≥0/05). Conclusions: According to the results of this study, it is suggested that by screening of psychological - mental problems of pregnant women in periodic care during pregnancy be considered by revised prenatal care plans and creation of counseling and training units at health centers. Besides owing to the fact that both interactive lecture and group counseling method were effective in reducing anxiety, these methods should be used proportionate to situations and facilities.

Keywords: anxiety, group counseling, cognitive therapy, interactive lecture, nulliparous

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Authors: Sahar Jami, Iman Valizadeh

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The purpose of the study: The aim of this study was to evaluate the influence of culture on the choice of capital structure management companies are listed in the Tehran Stock Exchange. Methods: This study was a cross-document using data after the event (Retrospective) in 1394 was performed. To select a sample of elimination sampling (screening) is used to determine the sample size was 123 companies. Results: The results showed that the variables of culture, return on equity, a significant positive impact on the capital structure (ROA, QTobins) and financial leverage and firm size variables and a significant negative impact on the capital structure (ROA, QTobins).

Keywords: culture management, capital structure, ROA, QTobins, variables of culture

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

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In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

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We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: It is well known that patients with Head and Neck Cancer (HNC) are at increased risk of subsequent head and neck cancers due to various aetiologies. Aim: We sought to determine the factors contributing to an increased risk of subsequent HNC primaries, and also to evaluate whether Aboriginal patients are at increased risk. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. We collected patient data including smoking and alcohol consumption, tumour and treatment data, and data on subsequent HNC primaries. Results: A subsequent HNC primary was seen in 37 patients (11.6%) overall. There was no significant difference in the rate of second primary HNCs between Aboriginal patients (12.5%) and nonAboriginal patients (11.2%) (p=0.408). Subsequent HNCs, were strongly associated with smoking and alcohol consumption however, with 95% of patients with a second primary being ever-smokers, and 54% of patients with a second primary having a history of excessive alcohol consumption. In the 37 patients with multiple HNC primaries, there were a total of 57 HNCs, with 29 patients having two primaries, six patients having 3 HNC primaries, one patient with four, and one with six. 54 out of the 57 cancers were in ever smokers (94.7%). There were only two multiple HNC primaries in a never smoker, non-drinker, and these cases were of unknown etiology with HPV/p16 status unknown in both cases. In the whole study population, there were 32 HPV-positive HNCs, and 67 p16-positive HNCs, with only two 2 nd HNCs in a p16-positive case, giving a rate of 3% in the p16+ population, which is actually much lower than the rate of second primaries seen in the overall population (11.6%), and was highest in the p16-negative population (15.7%). This suggests that p16-positivity is not a strong risk factor for subsequent primaries, and in fact p16-negativity appeared to be associated with increased risk, however this data is limited by the large number of patients without documented p16 status (45.3% overall, 12% for oropharyngeal, and 59.6% for oral cavity primaries had unknown p16 status). Summary: Subsequent HNC primaries were strongly associated with smoking and alcohol excess. Second and later HNC primaries did not appear to occur at increased rates in Aboriginal patients compared with non-Aboriginal patients, and p16-positivity did not predict increased risk, however p16-negativity was associated with an increased risk of subsequent HNCs.

Keywords: head and neck cancer, multiple primaries, aboriginal, p16 status, smoking, alcohol

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Authors: Akbar Esmaeili, Mahnoosh Aliahmadi

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This study synthesized a modified imaging of gallium@deferoxamine/folic acid/chitosan/polyaniline/polyvinyl alcohol (Ga@DFA/FA/CS/PANI/PVA). It contains Morus nigra extract by selenium nanoparticles prepared from Lactobacillus acidophilus. Using the impregnation method, Se nanoparticles were then deposited on (Ga@DFA/FA/ CS/PANI/PVA). The modified contrast agents were mixed with M. nigra extract, and investigated their antibacterial activities by applying to L929 cell lines. The influence of variable factors, including 1. surfactant, 2. solvent, 3. aqueous phase, 4. pH, 5. buffer, 6. minimum Inhibitory concentration (MIC), 7. minimum bactericidal concentration (MBC), 8. cytotoxicity on cancer cells., 9. antibiotic, 10. antibiogram, 11. release and loading, 12. the emotional effect, 13. the concentration of nanoparticles, 14. olive oil, and 15. they have investigated thermotical methods. The structure and morphology of the synthesized contrast agents were characterized by zeta potential sizer analysis (ZPS), X-Ray diffraction (XRD), Fourier-transform infrared (FT-IR), energy dispersive X-ray (EDX), ultraviolet–visible (UV–Vis) spectra, and scanning electron microscope (SEM). The experimental section was conducted and monitored by response surface methods (RSM), MTT, MIC, MBC, and cancer cytotoxic conversion assay. Antibiogram testing of NCs on Pseudomonas aeruginosa bacteria was successful and obtained MIC = 2 factors with less harmful effect. All experimental sections confirmed that our synthesized particles have potent antioxidant properties. Antibiogram testing revealed that NPS could kill P. aeruginosa and P. aeruginosa. A variety of synthetic conditions were done by diffusion emulsion method by varying parameters, the optimum state of DFA release Ga@DFA/FA/CS/PANI/PVA NPs (6 ml) with pH = 5.5, time = 3 h, NCs and DFA (3 mg), and achieved buffer (20 ml). DFA in Ga@DFA/FA/ CS/PANI/PVA was released and showed an absorption peak at 378 nm by applying a 300-rpm magnetic rate. In this report, Ga decreased the harmful effect on the human body.

Keywords: nanocapsules, technolgy, biology, nano

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Authors: Richard Vuijk, Arnoud Arntz

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Rationale: To our knowledge treatment of personality disorder comorbidity in adults with autism spectrum disorder (ASD) is understudied and is still in its infancy: We do not know if treatment of personality disorders may be applicable to adults with ASD. In particular, it is unknown whether patients with ASD benefit from experiential techniques that are part of schema therapy developed for the treatment of personality disorders. Objective: The aim of the study is to investigate the efficacy of a schema mode focused treatment with adult clients with ASD and comorbid personality pathology (i.e. at least one personality disorder). Specifically, we investigate if they can benefit from both cognitive-behavioral, and experiential interventions. Study design: A multiple baseline case series study. Study population: Adult individuals (age > 21 years) with ASD and at least one personality disorder. Participants will be recruited from Sarr expertise center for autism in Rotterdam. The study requires 12 participants. Intervention: The treatment protocol consists of 35 weekly offered sessions, followed by 10 monthly booster sessions. A multiple baseline design will be used with baseline varying from 5 to 10 weeks, with weekly supportive sessions. After baseline, a 5-week exploration phase follows with weekly sessions during which current and past functioning, psychological symptoms, schema modes are explored, and information about the treatment will be given. Then 15 weekly sessions with cognitive-behavioral interventions and 15 weekly sessions with experiential interventions will be given. Finally, there will be a 10-month follow-up phase with monthly booster sessions. Participants are randomly assigned to baseline length, and respond weekly during treatment and monthly at follow-up on Belief Strength of negative core beliefs (by VAS), and fill out SMI, SCL-90 and SRS-A 7 times during screening procedure (i.e. before baseline), after baseline, after exploration, after cognitive and behavioral interventions, after experiential interventions, and after 5- and 10- month follow-up. The SCID-II will be administered during screening procedure (i.e. before baseline), at 5- and at 10-month follow-up. Main study parameters: The primary study parameter is negative core beliefs. Secondary study parameters include schema modes, personality disorder manifestations, psychological symptoms, and social interaction and communication. Discussion: To the best of author’s knowledge so far no study has been published on the application of schema mode focused interventions in adult patients with ASD and comorbid PD(s). This study offers the first systematic test of application of schema therapy for adults with ASD. The results of this study will provide initial evidence for the effectiveness of schema therapy in treating adults with both ASD and PD(s). The study intends to provide valuable information for future development and implementation of therapeutic interventions for adults with both ASD and PD(s).

Keywords: adults, autism spectrum disorder, personality disorder, schema therapy

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Authors: Rosemary Anibogwu, Kavita Sharma, Karl De Jesus

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Sagebrush is an abundant and naturally occurring plant in the Intermountain West region of the United States. The plant contains an array of bioactive compounds such as flavonoids, terpenoids, sterols, and phenolic acids. It is important to identify and characterize these compounds because Native Americans use sagebrush as herbal medicine. These compounds are also utilized for preventing infection in wounds, treating headaches and colds, and possess antitumor properties. This research is an exploratory study on the sesquiterpene present in the leaves of sagebrush. The leaf foliage was extracted with 100 % chloroform and 100 % methanol. The percentage yield for the crude was considerably higher in chloroform. The Thin Layer Chromatography (TLC) analysis of the crude extracted unveiled a brown band at Rf = 0.25 and a dark brown band at Rf = 0.74, along with three unknown faint bands the 254 nm UV lamp. Furthermore, the two distinct brown (Achillin) and dark brown band (Hydroxyachillin) in TLC were further utilized in the isolation of pure compounds with column chromatography. The structures of Achillin and Hydroxyachillin were elucidated based on extensive spectroscopic analysis, including TLC, High-Performance Liquid Chromatography (HPLC), 1D- and 2D-Nuclear Magnetic Resonance (NMR), and Mass Spectroscopy (MS). The antioxidant activities of crude extract and three pure compounds were evaluated in terms of their peroxyl radical scavenging by Ferric Reducing Ability of Plasma (FRAP) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude extract showed the antioxidant activity of 18.99 ± 0.51 µmol TEg -1 FW for FRAP and 11.59 ± 0.38 µmol TEg -1 FW for DPPH. The activities of Achillin, Hydroxyachillin, and Quercetagetin trimethyl ether were 13.03, 15.90 and 14.02 µmol TEg -1 FW respectively for the FRAP assay. The three purified compounds have been submitted to the National Cancer Institute 60 cancer cell line for further study.

Keywords: HPLC, nuclear magnetic resonance spectroscopy, sagebrush, sesquiterpene lactones

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Authors: Robert Krause

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Primary progressive aphasia (PPA) is a neurodegenerative disease similar to frontotemporal and semantic dementia, while having a different clinical image and anatomic pathology topography. Nonetheless, they are often included under an umbrella term: frontotemporal lobar degeneration (FTLD). In the study, examples of diagnosing PPA are presented through the multidisciplinary lens of specialists from different fields (neurologists, psychiatrists, clinical speech therapists, clinical neuropsychologists and others) using a variety of diagnostic tools such as MR, PET/CT, genetic screening and neuropsychological and logopedic methods. Thanks to that, specialists can get a better and clearer understanding of PPA diagnosis. The study summarizes the concrete procedures and results of different specialists while diagnosing PPA in a patient of younger middle age and illustrates the importance of multidisciplinary approach to differential diagnosis of PPA.

Keywords: primary progressive aphasia, etiology, diagnosis, younger middle age

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Authors: M. Marsadek, A. Mohamed

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Power system security analysis is the most time demanding process due to large number of possible contingencies that need to be analyzed.  In a power system, any contingency resulting in security violation such as line overload or low voltage may occur for a number of reasons at any time.  To efficiently rank a contingency, both probability and the extent of security violation must be considered so as not to underestimate the risk associated with the contingency. This paper proposed a contingency ranking method that take into account the probabilistic nature of power system and the severity of contingency by using a newly developed method based on risk factor.  The proposed technique is implemented on IEEE 24-bus system.

Keywords: line overload, low voltage, probability, risk factor, severity

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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Authors: K. Bengango, H. Mesahsah, F. Haseb-Reho, J. M. Tafrate

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This present work was conducted to explore the micro-morphology and phytochemical characterization of the endemic medicinal plant Tekchebilium arvensis Linn (Asteraceae). Macroscopy, microscopy, physicochemical analysis and WHO recommended parameters for standardizations were performed. Microscopic evaluation revealed the presence of abaxial epidermis with paracytic stomata. Petiole showed epidermis, vascular strands, ground tissue and secretary cavities. Physico-chemical tests like ash values, loss on drying, extractive values were determined. Preliminary phytochemical screening showed the presence of sterols, tannins, flavonoids, glycosides, volatile oil, terpenoids, saponin and alkaloids.

Keywords: Tekchebilium arvensis Linn, Asteraceae, microscopical evaluation, phytochemical, powder microscopy, standardization

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain

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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.

Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children

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Authors: Ahmed Elhussein, Hossam El-Zomor, Adel Alieldin, Mahmoud A. Afifi, Abdullah Elhusseiny, Hala Taha, Amal Refaat, Soha Ahmed, Mohamed S. Zagloul

Abstract:

Background: A majority of children with retinoblastoma (60%) have a disease in one eye only (unilateral disease). This is a retrospective study to evaluate two different treatment modalities in those patients for saving their lives and vision. Methods: Four hundred and four patients were diagnosed with unilateral intraocular retinoblastoma at Children’s Cancer, Hospital Egypt (CCHE) through the period of July/2007 until December/2017. Management strategies included primary enucleation versus ocular salvage treatment. Results: Patients presented with mean age 24.5 months with range (1.2-154.3 months). According to the international retinoblastoma classification, Group D (n=172, 42%) was the most common, followed by group E (n=142, 35%), group C (n=63, 16%), and group B (n=27, 7%). All patients were alive at the end of the study except four patients who died, with 5-years overall survival 98.3% [CI, (96.5-100%)]. Patients presented with advanced disease and poor visual prognosis (n=241, 59.6%) underwent primary enucleation with 6 cycles adjuvant chemotherapy if they had high-risk features in the enucleated eye; only four patients out of 241 ended-up either with extraocular metastasis (n=3) or death (n=1). While systemic chemotherapy and focal therapy were the primary treatment for those who presented with favorable disease status and good visual prognosis (n=163, 40.4%); seventy-seven patients of them (47%) ended up with a pre-defined event (enucleation, EBRT, off protocol chemotherapy or 2ry malignancy). Ocular survival for patients received primary chemotherapy + focal therapy was [50.9% (CI, 43.5-59.6%)] at 3 years and [46.9% (CI,39.3-56%)] at 5 years. Comparison between upfront enucleation and primary chemotherapy for occurrence of extraocular metastasis revealed that there was no statistical difference between them except in group D (p value). While for occurrence of death, no statistical difference in all classification groups. Conclusion: In retinoblastoma, primary chemotherapy is a reasonable option and has a good probability for ocular salvage without increasing the risk of metastasis in comparison to upfront enucleation except in group D.

Keywords: CCHE, chemotherapy, enucleation, retinoblastoma

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Authors: Mamta Kumari, Shashi Jain

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Tannins are a unique category of plant phytochemicals especially in terms of their vast potential health-benefiting properties. Researchers have described the capacity of tannins to enhance glucose uptake and inhibit adipogenesis, thus being potential drugs for the treatment of non-insulin dependent diabetes mellitus. Thus, the present research was conducted to find out tannin content of food products. The percentage of tannin in various analyzed sources ranged from 0.0 to 108.53%; highest in kathaa and lowest in ker and mango bark. The percentage of tannins present in the plants, however, varies. Numerous studies have confirmed that the naturally occurring polyphenols are key factor for the beneficial effects of the herbal medicines. Isolation and identification of active constituents from plants, preparation of standardized dose & dosage regimen can play a significant role in improving the hypoglycaemic action.

Keywords: tannins, diabetes, polyphenols, antioxidant, hypoglycemia

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Goutam Kumar Ghorai, Sandip Sadhukhan, Arpita Sarkar, Debprasad Sinha, G. Sarkar, Ashis K. Dhara

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Diabetes mellitus is one of the most common chronic diseases in all countries and continues to increase in numbers significantly. Diabetic retinopathy (DR) is damage to the retina that occurs with long-term diabetes. DR is a major cause of blindness in the Indian population. Therefore, its early diagnosis is of utmost importance towards preventing progression towards imminent irreversible loss of vision, particularly in the huge population across rural India. The barriers to eye examination of all diabetic patients are socioeconomic factors, lack of referrals, poor access to the healthcare system, lack of knowledge, insufficient number of ophthalmologists, and lack of networking between physicians, diabetologists and ophthalmologists. A few diabetic patients often visit a healthcare facility for their general checkup, but their eye condition remains largely undetected until the patient is symptomatic. This work aims to focus on the design and development of a fully automated intelligent decision system for screening retinal fundus images towards detection of the pathophysiology caused by microaneurysm in the early stage of the diseases. Automated detection of microaneurysm is a challenging problem due to the variation in color and the variation introduced by the field of view, inhomogeneous illumination, and pathological abnormalities. We have developed aconvolutional neural network for efficient detection of microaneurysm. A loss function is also developed to handle severe class imbalance due to very small size of microaneurysms compared to background. The network is able to locate the salient region containing microaneurysms in case of noisy images captured by non-mydriatic cameras. The ground truth of microaneurysms is created by expert ophthalmologists for MESSIDOR database as well as private database, collected from Indian patients. The network is trained from scratch using the fundus images of MESSIDOR database. The proposed method is evaluated on DIARETDB1 and the private database. The method is successful in detection of microaneurysms for dilated and non-dilated types of fundus images acquired from different medical centres. The proposed algorithm could be used for development of AI based affordable and accessible system, to provide service at grass root-level primary healthcare units spread across the country to cater to the need of the rural people unaware of the severe impact of DR.

Keywords: retinal fundus image, deep convolutional neural network, early detection of microaneurysms, screening of diabetic retinopathy

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Authors: Varsha Chorsiya, Pooja Aneja, Dhananjay Kaushik, Abhinav Yadav

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Intoduction: Women’s Health Initiatives (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of obesity, heart disease, breast cancer and colorectal cancer, and fractures in menopause women. The utility of the present research work determines to find the role of Hormone Replacement Therapy (HRT) in changing the different component of body composition during perimenopause period. Methods: A comparative cross-sectional study included 30 subjects, aged between 40 and 50 years which were assigned into 2 groups i.e. 15 subjects in HRT (Group A) and 15 subjects in non-HRT (Group B). The subjects were taken from the hospitals and clinics of Faridabad undergoing HRT in supervision of the consultant gynecologist. The informed consents were signed before including the participants in the study. The body composition and lipid profile were evaluated for all the subjects. Result and Discussion: The BMI, body density, percent body fats and fat mass in both groups showed statistically significant differences i.e. p < 0.05. Our study did not reveal any statistically significant difference between non-HRT and HRT for lipid profile composition of HDL, LDL, VLDL, ratio, triglycerides and total cholesterol although these indicators (LDL, VLDL, ratio, triglycerides and total cholesterol) showed difference clinically with a higher mean values for non-HRT as compared to HRT group. The mean value for HDL was higher for HRT group in contrast to non-HRT group. The result clearly showed that HRT group has a good lipid profile composition. Conclusion: In conclusion, our data show that HRT has statistically significant role in determining BMI, fat percent mass and fat mass. The lipid profile including LDL, HDL, VLDL, ratio, triglycerides and total cholesterol found to be clinically better in HRT group as compared to the non-HRT group. The rationale for non-significant lipid profile probably lie in the fact that hormonal changes need a particular time period and might become significant in post-menopausal period.

Keywords: body composition, hormone replacement therapy, perimenopause, women health

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Authors: Annika Stechemesser, Rachel Pounds, Emma Lucas, Chris Dawson, Julia Lipecki, Pavle Vrljicak, Jan Brosens, Sean Kehoe, Jason Yap, Lawrence Young, Sascha Ott

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Advances in technology make it now possible to retrieve the genetic information of thousands of single cancerous cells. One of the key challenges in single cell analysis of cancerous tissue is to determine the number of different cell types and their characteristic genes within the sample to better understand the tumors and their reaction to different treatments. For this analysis to be possible, it is crucial to filter out background noise as it can severely blur the downstream analysis and give misleading results. In-depth analysis of the state-of-the-art filtering methods for single cell data showed that they do, in some cases, not separate noisy and normal cells sufficiently. We introduced an algorithm that filters and clusters single cell data simultaneously without relying on certain genes or thresholds chosen by eye. It detects communities in a Shared Nearest Neighbor similarity network, which captures the similarities and dissimilarities of the cells by optimizing the modularity and then identifies and removes vertices with a weak clustering belonging. This strategy is based on the fact that noisy data instances are very likely to be similar to true cell types but do not match any of these wells. Once the clustering is complete, we apply a set of evaluation metrics on the cluster level and accept or reject clusters based on the outcome. The performance of our algorithm was tested on three datasets and led to convincing results. We were able to replicate the results on a Peripheral Blood Mononuclear Cells dataset. Furthermore, we applied the algorithm to two samples of ovarian cancer from the same patient before and after chemotherapy. Comparing the standard approach to our algorithm, we found a hidden cell type in the ovarian postchemotherapy data with interesting marker genes that are potentially relevant for medical research.

Keywords: cancer research, graph theory, machine learning, single cell analysis

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