Search results for: oral cancer

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: 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: Tahera Begum, Sabina Yeasmin, Jalal Uddin

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Ten slums of ten wards of Chittagong city corporation of Bangladesh were conveniently selected to know about modern contraceptive use by the slum dwellers. Total 300 family heads or their wives were interviewed with a questionnaire in February 2014. Family size was 4.62. Among 300 families 248 eligible couples were found. 57% eligible couples use different modern contraceptive measures. Remaining 43% eligible couples do not use modern contraceptive measures. Among the users 58% use oral pill, 30% injectables, 8% use condom, 3% were found with ligation and only 1% with vasectomy. Contraceptive prevalence rate has been increased and pattern as changed. A discussion is made with literature review.

Keywords: conraceptive, Bangladesh, family, pill

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Authors: Hatice Guzel, Imran Oral, Huseyin Isler

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In this study, elastic constants, Young’s modulus, Poisson’s ratios, and shear moduli of orthotropic composite materials, consisting of E-glass/epoxy and carbon/epoxy, were calculated by ultrasonic velocities which were measured using ultrasonic pulse-echo method. 35 MHz computer controlled analyzer, 60 MHz digital oscilloscope, 5 MHz longitudinal probe, and 2,25 MHz transverse probe were used for the measurements of ultrasound velocities, the measurements were performed at ambient temperature. It was understood from the data obtained in this study that, measured ultrasound velocities and the calculated elasticity coefficients were depending on the fiber orientations.

Keywords: composite materials, elastic constants, orthotropic materials, ultrasound

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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: 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: 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: 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: Olusola Abiodun Arinde

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This research work was prompted by the very important role e-commerce plays in every organization, be it private or public. The underlying objective of this study is to have a critical appraisal of the extent to which e-commerce impacts on organizational effectiveness. This research was carried out using Zenith Bank Plc as a case study. Relevant data were collected through structured questionnaire, oral interview, journals, newspapers, and textbooks. The data collected were analyzed and hypotheses were tested. Based on the result of the hypotheses, it was observed that e-commerce is significant to every organization. Through e-commerce, fast services delivery would be guaranteed to customers, this would lead to higher productivity and profit for organizations. E-commerce should be managed in such a way that it does not alienate customers; it should also prevent enormous risks that are associated with e-commerce.

Keywords: e-commerce, fast service, productivity, profit

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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

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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: Alessandra Panico, Francesco Bagordo, Tiziana Grassi, Adele Idolo, Marcello Guido, Francesca Serio, Mattia De Giorgi, Antonella De Donno

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In the Province of Lecce (Southeastern Italy) an area with unusual high incidence of chronic respiratory diseases, including lung cancer, was recently identified. The causes of this health emergency are still not entirely clear. In order to determine the risk profile of children living in five municipalities included in this area an epidemiological-molecular study was performed in the years 2014-2016: the IMP.AIR. (Impact of air quality on health of residents in the Municipalities of Sternatia, Galatina, Cutrofiano, Sogliano Cavour and Soleto) study. 122 children aged 6-8 years attending primary school in the study area were enrolled to evaluate the frequency of micronuclei (MNs) in their buccal exfoliated cells. The samples were collected in May 2015 by rubbing the oral mucosa with a soft bristle disposable toothbrush. At the same time, a validated questionnaire was administered to parents to obtain information about health, lifestyle and eating habits of the children. In addition, information on airborne pollutants, routinely detected by the Regional Environmental Agency (ARPA Puglia) in the study area, was acquired. A multivariate analysis was performed to detect any significant association between frequency of MNs (dependent variable) and behavioral factors (independent variables). The presence of MNs was highlighted in the buccal exfoliated cells of about 42% of recruited children with a mean frequency of 0.49 MN/1000 cells, greater than in other areas of Salento. The survey on individual characteristics and lifestyles showed that one in three children was overweight and that most of them had unhealthy eating habits with frequent consumption of foods considered ‘risky’. Moreover many parents (40% of fathers and 12% of mothers) were smokers and about 20% of them admitted to smoking in the house where the children lived. Information regarding atmospheric contaminants was poor. Of the few substances routinely detected by the only one monitoring station located in the study area (PM2.5, SO2, NO2, CO, O3) only ozone showed high concentrations exceeding the limits set by the legislation for 67 times in the year 2015. The study showed that the level of early biological effect markers in children was not negligible. This critical condition could be related to some individual factors and lifestyles such as overweight, unhealthy eating habits and exposure to passive smoking. At present, no relationship with airborne pollutants can be established due to the lack of information on many substances. Therefore, it would be advisable to modify incorrect behaviors and to intensify the monitoring of airborne pollutants (e.g. including detection of PM10, heavy metals, aromatic polycyclic hydrocarbons, benzene) given the epidemiology of chronic respiratory diseases registered in this area.

Keywords: chronic respiratory diseases, environmental pollution, lifestyle, micronuclei

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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: ShuPei Wang, Yina Patterson

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This article outlines strategies for improving oral expression to advance proficiency in speaking and listening skills through structured argumentation. The objective is to empower students to effectively use the target language to express opinions and construct compelling arguments. This empowerment is achieved by honing learners' debating and questioning skills, which involves increasing their familiarity with vocabulary and phrases relevant to debates and deepening their understanding of the cultural context surrounding pertinent issues. Through this approach, students can enhance their ability to articulate complex concepts and discern critical points, surpassing superficial comprehension and enabling them to engage in the target language actively and competently.

Keywords: debate, teaching and materials design, spoken expression, listening proficiency, critical thinking

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Aneesha Fonseca, Arij Daas, Muhammed Abdulkader

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Transient intraocular pressure (IOP) rise is a common occurrence after glaucoma laser procedures. However, this pressure spike usually lasts only a few days. We describe a case of a 60-year-old Caucasian gentleman who underwent selective laser trabeculoplasty (SLT) in both eyes for ocular hypertension previously treated with Bimatoprost and Timolol and developed a sustained raised IOP. His IOP rose from 34 and 33 mmHg pre-laser to 48 and 42 mmHg after SLT in the right and left eye, respectively. Even after maximum medical therapy (Bimatoprost, Timolol, Brinzolamide Apraclonidine, and oral Acetozolamide), his IOP remained at 32 and 28mmHg. A provisional diagnosis of trabeculitis was made, and topical Ketorolac was commenced in addition to the IOP-lowering medications. Within a week, his IOP came down to 21 and 18mmHg in the right and left eye, respectively.

Keywords: complications, selective laser trabeculoplasty, sustained pressure rise, trabeculitis

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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: Dario Rajmilovich

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The tax system represents a multidisciplinary cosmos whose main purpose is to provide financial resources to the government of a given political jurisdiction in order to apply them to the public purposes outlined by that government. Not withstanding this basic external configuration of a finalistic order, its internal structure essentially responds to a series of principles or axes whose roots can be traced in the Old Testament (written Torah) and in oral sources (especially the KaBaLáh or Cábala compiled in the second century of the Common era in the book called "the Zóhar" (Book of Splendor) attributed to Rabi Shimón bar Iojái). The purpose of this work is to outline a general theory of taxation based on the biblical principles inherent to taxation and to project its effects in the configuration of a just tax system designated as "Virtuous Taxation".

Keywords: principles of taxation, kabaláh and taxation, old testament taxation, virtuous taxation

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Authors: Susanne Shunnaq

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During the past decade, an increasing number of higher education institutions in Oman have sought accreditation in an attempt to assure the quality of their programs. Sultan Qaboos University (SQU), the only public university in the country, has also been seeking accreditation. Hence, the university administration has been encouraging departments to evaluate their programs for development purposes. The Department of English, where 100% of the students are learners of English as a foreign language, already produced a self-study report that outlined the strength and weaknesses of the current program. The department came to the realization that due to a changing local and regional job market, transferrable communication skills are high in demand among stakeholders in the public and private sectors. Failure to equip English literature students, for example, with excellent verbal communicative skills in English may have detrimental effects for undergraduate job-seekers who have to compete for jobs in employment sectors with a predominantly English-speaking workforce. Ongoing extensive discussions about restructuring the current literature program by means of partially replacing literature courses with skills courses, hoping to produce higher quality graduates who are equipped with effective communication skills for local and regional markets, have sparked the idea for this research. The researcher, who is an American Literature specialist at SQU, has set out to investigate to what extent senior American literature students have been able to apply transferable communication skills in an advanced literature course. The study also attempts to unearth performance inhibitors and causes for communication breakdown. The primary data source for the study were audio-recordings of 6 in-class peer-group discussions in an advanced contemporary American literature course during the academic year 2016/2017. The significance of this research lies in the rarity of studies focusing on verbal communication skills in Omani higher education literature classrooms at a time when English programs are in the process of being re-visited and revamped both for accreditation purposes and for meeting job-market demands. The results showed a considerable variation in Omani students' verbal communicative abilities and English proficiency levels. The study also raises crucial questions and provides important recommendations for administrators and teachers alike who are in the process of restructuring English programs in the region and in non-English speaking countries worldwide.

Keywords: job-market, literature, Oman, tertiary education, oral communication skills

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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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Authors: Shekoufeh Behdad, Amirhossein Yadegari, Leila Ghodrati, Saman Yadegari

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Context: Preoperative anxiety is a common psychological reaction experienced by all patients undergoing surgery. It can have negative effects on the patient's well-being and even impact surgical outcomes. Therefore, finding effective interventions to reduce preoperative anxiety is important in improving patient care. Research Aim: The aim of this study is to compare the effects of oral administration of zaleplon (5 mg) and alprazolam (0.5 mg) on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Methodology: This study is a double-blind, randomized clinical trial conducted after receiving approval from the university's ethics committee and obtaining written informed consent from the patients. The night before the surgery, patients were randomly assigned to receive either 0.5 mg of alprazolam or 5 mg of zaleplon orally. Anxiety levels, measured using a 10-cm visual analog scale, and hemodynamic variables (blood pressure and heart rate) were assessed before drug administration and on the morning of the operation after the patient entered the pre-operation room. Findings: The study found that there were no significant differences in mean anxiety levels or hemodynamic variables before and after administration of either drug in both groups (P value > 0.05). This suggests that both 0.5 mg of alprazolam and 5 mg of zaleplon effectively reduce preoperative anxiety in women undergoing abdominal surgery without serious side effects. Theoretical Importance: This study contributes to the understanding of the effectiveness of alprazolam and zaleplon in reducing preoperative anxiety. It adds to the existing literature on pharmacological interventions for anxiety management, specifically in the context of gynecological abdominal surgery. Data Collection: Data for this study were collected through the assessment of anxiety levels using a visual analog scale and measuring hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate. These measurements were taken before drug administration and on the morning of the surgery. Analysis Procedures: Statistical analysis was performed to compare the mean anxiety levels and hemodynamic variables before and after drug administration in the two groups. The significance of the differences was determined using appropriate statistical tests. Questions Addressed: This study aimed to answer the question of whether there are differences in the effects of alprazolam and zaleplon on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Conclusion: The oral administration of both 0.5 mg of alprazolam and 5 mg of zaleplon the night before surgery effectively reduces preoperative anxiety in women undergoing abdominal surgery. These findings have important implications for the management of preoperative anxiety and can contribute to improving the overall surgical experience for patients.

Keywords: zaleplon, alprazolam, premedication, abdominal surgery

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Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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Authors: Anil Koklu, Amin Mansoorifar, Ali Beskok

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Dielectric spectroscopy (DS) is a noninvasive, label free technique for a long term real-time measurements of the impedance spectra of biological cells. DS enables characterization of cellular dielectric properties such as membrane capacitance and cytoplasmic conductivity. We have developed a lab-on-a-chip device that uses an electro-activated microwells array for loading, DS measurements, and unloading of biological cells. We utilized from dielectrophoresis (DEP) to capture target cells inside the wells and release them after DS measurement. DEP is a label-free technique that exploits differences among dielectric properties of the particles. In detail, DEP is the motion of polarizable particles suspended in an ionic solution and subjected to a spatially non-uniform external electric field. To the best of our knowledge, this is the first microfluidic chip that combines DEP and DS to analyze biological cells using electro-activated wells. Device performance is tested using two different cell lines of prostate cancer cells (RV122, PC-3). Impedance measurements were conducted at 0.2 V in the 10 kHz to 40 MHz range with 6 s time resolution. An equivalent circuit model was developed to extract the cell membrane capacitance and cell cytoplasmic conductivity from the impedance spectra. We report the time course of the variations in dielectric properties of PC-3 and RV122 cells suspended in low conductivity medium (LCB), which enhances dielectrophoretic and impedance responses, and their response to sudden pH change from a pH of 7.3 to a pH of 5.8. It is shown that microfluidic chip allowed online measurements of dielectric properties of prostate cancer cells and the assessment of the cellular level variations under external stimuli such as different buffer conductivity and pH. Based on these data, we intend to deploy the current device for single cell measurements by fabricating separately addressable N × N electrode platforms. Such a device will allow time-dependent dielectric response measurements for individual cells with the ability of selectively releasing them using negative-DEP and pressure driven flow.

Keywords: microfluidic, microfabrication, lab on a chip, AC electrokinetics, dielectric spectroscopy

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Authors: Sardar Khana, Zar Ali Khana

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Rapid industrial development and urbanization contribute a lot to wastewater discharge. The wastewater enters into natural aquatic ecosystems from industrial activities and considers as one of the main sources of water pollution. Discharge of effluents loaded with heavy metals into the surrounding environment has become a key issue regarding human health risk, environment, and food chain contamination. Nickel causes fatigue, cancer, headache, heart problems, skin diseases (Nickel Itch), and respiratory disorders. Nickel compounds such as Nickel Sulfide and Nickel oxides in industrial environment, if inhaled, have an association with an increased risk of lung cancer. Therefore the removal of Nickel from effluents before discharge is necessary. Removal of Nickel by low-cost biosorbents is an efficient method. This study was aimed to investigate the efficiency of activated carbon and Pinusroxburgiisaw dust for the removal of Nickel from industrial effluents using commercial Activated Carbon, and raw P.roxburgii saw dust. Batch and column adsorption experiments were conducted for the removal of Nickel. The study conducted indicates that removal of Nickel greatly dependent on pH, contact time, Nickel concentration, and adsorbent dose. Maximum removal occurred at pH 9, contact time of 600 min, and adsorbent dose of 1 g/100 mL. The highest removal was 99.62% and 92.39% (pH based), 99.76% and 99.9% (dose based), 99.80% and 100% (agitation time), 92% and 72.40% (Ni Conc. based) for P.roxburgii saw dust and activated Carbon, respectively. Similarly, the Ni removal in column adsorption was 99.77% and 99.99% (bed height based), 99.80% and 99.99% (Concentration based), 99.98%, and 99.81% (flow rate based) during column studies for Nickel using P.Roxburgiisaw dust and activated carbon, respectively. Results were compared with Freundlich isotherm model, which showed “r2” values of 0.9424 (Activated carbon) and 0.979 (P.RoxburgiiSaw Dust). While Langmuir isotherm model values were 0.9285 (Activated carbon) and 0.9999 (P.RoxburgiiSaw Dust), the experimental results were fitted to both the models. But the results were in close agreement with Langmuir isotherm model.

Keywords: nickel removal, batch, and column, activated carbon, saw dust, plant uptake

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

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The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Hao Huang

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INTRODUCTION: The Association of American Colleges and Universities (AACU) recommends the development of ‘high-impact practices,’ in an effort to increase rates of student retention and student engagement at undergraduate institutions. To achieve these goals, the Scripps College Humanities Institute and HI Fellows Seminar not only featured distinguished academics presenting their scholarship about current immigration policy and its consequences in the USA and around the world but integrated socially significant community leaders and creative activists/artivists in public talks, student workshops and collaborative art events. Students participated in experiential learning that involved guest personal presentations and discussions, oral history interviews that applied standard oral history methodologies, detailed cultural documentation, collaborative artistic interventions, and weekly posts in Internet Digital Learning Environment Sakai collaborative course forums and regular responses to other students’ comments. Our teaching pedagogies addressed the four learning styles outlined in Kolb’s Learning Style Inventory. PROJECT DESCRIPTION: Over the academic year 2017-18, the Scripps College Humanities Institute and HI Fellows Seminar presented a Fall 2017 topic, ‘The World at Our Doorsteps: Immigration and Deportation in Los Angeles’. Our purpose was to address how current federal government anti-immigration measures have affected many students of color, some of whom are immigrants, many of whom are related to and are friends with people who are impacted by the attitudes as well as the practices of the U.S. Citizenship and Immigration Services. In Spring 2018, we followed with the topic, ‘Exclusive Nationalisms: Global Migration and Immigration’. This addresses the rise of white supremacists who have ascended to position of power worldwide, in America, Europe, Russia, and xenophobic nationalisms in China, Myanmar and the Philippines. Recent scholarship has suggested the existence of categories of refugees beyond the political or social, who fit into the more inclusive category of migrants. ASSESSMENT METHODOLOGIES: Assessment methodologies not only included qualitative student interviews and quantitative student evaluations in standard rubric format, but also Outcome Assessments, Formative Evaluations, and Outside Guest Teacher feedback. These indicated that the most effective educational practices involved collaborative inquiry in undergraduate research, community-based learning, and capstone projects. Assessments of E-portfolios, written and oral coursework, and final creative projects with associated 10-12 page analytic paper revealed that students developed their understanding of how government and social organizations work; they developed communication skills that enhanced working with others from different backgrounds; they developed their ability to thoughtfully evaluate their course performance by adopting reflective practices; they gained analytic and interpretive skills that encouraged self-confidence and self- initiative not only academically, but also with regards to independent projects. CONCLUSION: Most importantly, the Scripps Humanities Institute experiential learning project spurred on real-world actions by our students, such as a public symposium on how to cope with bigots, a student tutoring program for immigrant staff children, student negotiations with the administration to establish meaningful, sustainable diversity and inclusion programs on-campus. Activism is not only to be taught to and for our students– it has to be enacted by our students.

Keywords: immigration, migration, human rights, learning assessment

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