Search results for: poor outcome of delayed breast cancer treatment

Authors: Sabri Arik

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In this paper, we study the global asymptotic robust stability of delayed neural networks with norm-bounded uncertainties. By employing the Lyapunov stability theory and Homeomorphic mapping theorem, we derive some new types of sufficient conditions ensuring the existence, uniqueness and global asymptotic stability of the equilibrium point for the class of neural networks with discrete time delays under parameter uncertainties and with respect to continuous and slopebounded activation functions. An important aspect of our results is their low computational complexity as the reported results can be verified by checking some properties symmetric matrices associated with the uncertainty sets of network parameters. The obtained results are shown to be generalization of some of the previously published corresponding results. Some comparative numerical examples are also constructed to compare our results with some closely related existing literature results.

Keywords: neural networks, delayed systems, lyapunov functionals, stability analysis

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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

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

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Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud

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Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.

Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences

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Authors: Mohamed Ghoz, Hala Alsabeh

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Context: Macroscopic Nose Macroneedling (MNM) is a new non-surgical procedure for lifting and tightening the nose. It is a tissue-non-invasive technique that uses a needle to create micro-injuries in the skin. These injuries stimulate the production of collagen and elastin, which results in the tightening and lifting of the skin. Research Aim: The research aim of this study was to investigate the efficacy and safety of MNM for the treatment of nasal deformities. Methodology A total of 100 patients with nasal deformities were included in this study. The patients were randomly assigned to either the MNM group or the control group. The MNM group received a single treatment of MNM, while the control group received no treatment. The patients were evaluated at baseline, 6 months, and 12 months after treatment. Findings: The results of this study showed that MNM was effective in improving the appearance of the nose in patients with nasal deformities. At 6 months after treatment, the patients in the MNM group had significantly improved nasal tip projection, nasal bridge height, and nasal width compared to the patients in the control group. The improvements in nasal appearance were maintained at 12 months after treatment. Theoretical Importance: The findings of this study provide support for the use of MNM as a safe and effective treatment for nasal deformities. MNM is a non-surgical procedure that is associated with minimal downtime and no risk of scarring. This makes it an attractive option for patients who are looking for a minimally invasive treatment for their nasal deformities. Data Collection: Data was collected from the patients using a variety of methods, including clinical assessments, photographic assessments, and patient-reported outcome measures. Analysis Procedures: The data was analyzed using a variety of statistical methods, including descriptive statistics, inferential statistics, and meta-analysis. Question Addressed: The research question addressed in this study was whether MNM is an effective and safe treatment for nasal deformities. Conclusion: The findings of this study suggest that MNM is an effective and safe treatment for nasal deformities. MNM is a non-surgical procedure that is associated with minimal downtime and no risk of scarring. This makes it an attractive option for patients who are looking for a minimally invasive treatment for their nasal deformities.

Keywords: nose, surgery, tie, suture

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Authors: Anne Nattembo

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Cervical cancer remains a major public health problem in developing countries, especially in Africa. Effective cervical cancer prevention communication requires identification of behaviors, attitudes and increasing awareness of a given population; thus this study focused on investigating awareness, attitudes, and behavior among female university students towards cervical cancer messages. The study objectives sought to investigate the communication behavior of young adults towards cervical cancer, to understand female students recognition of cervical cancer as a problem, to identify the frames related to cervical cancer and their impact towards audience communication and participation behaviors, to identify the factors that influence behavioral intentions and level of involvement towards cervical cancer services and to make recommendations on how to improve cervical cancer communication towards female university students. The researcher obtained data using semi-structured interviews and focus group discussions targeting 90 respondents. The semi-structured in-depth interviews were carried out through one-on-one discussions basis using a set of prepared questions among 53 respondents. All interviews were audio-tape recorded. Each interview was directly typed into Microsoft Word. 4 focus group discussions were conducted with a total of 37 respondents; 2 female only groups with 10 respondents in one and 9 respondents in another, 1 mixed with 12 participants 5 of whom were male, and 1 male only group with 6 participants. The key findings show that the participants preferred to receive and access cervical cancer information from doctors although they were mainly receiving information from the radio. In regards to the type of public the respondents represent, majority of the respondents were non-publics in the sense that they did not have knowledge about cervical cancer, had low levels of involvement and had high constraint recognition their cervical cancer knowledge levels. The researcher identified the most salient audience frames among female university students towards cervical cancer and these included; death, loss, and fear. These frames did not necessarily make cervical cancer an issue of concern among the female university students but rather an issue they distanced themselves from as they did not perceive it as a risk. The study also identified the constraints respondents face in responding to cervical cancer campaign calls-to-action which included; stigma, lack of knowledge and access to services as well as lack of recommendation from doctors. In regards to sex differences, females had more knowledge about cervical cancer than the males. In conclusion the study highlights the importance of interpersonal communication in risk or health communication with a focus on health providers proactively sharing cervical cancer prevention information with their patients. Health provider’s involvement in cervical cancer is very important in influencing behavior and compliance of cervical cancer calls-to-action. The study also provides recommendations for designing effective cervical cancer campaigns that will positively impact on the audience such as packaging cervical cancer messages that also target the males as a way of increasing their involvement and more campaigns to increase awareness of cervical cancer as well as designing positive framed messages to counter the negative audience frames towards cervical cancer.

Keywords: cervical cancer communication, health communication, university students, risk communication

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: O. Davies, K. Veravalli, P. Panwalkar, M. Tofighi, P. Butterick, B. Healy, A. Mofidi

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Vancomycin resistant enterococcus infection is a condition that usually impacts ICUs, transplant, dialysis, and cancer units, often as a nosocomial infection. After an outbreak in the acute trauma and orthopaedic unit in Morriston hospital, we aimed to access the conditions that predispose VRE infections in our unit. Thirteen cases of VRE infection and five cases of VRE colonisations were identified in patients who were treated for orthopaedic care between 1/1/2020 and 1/11/2021. Cases were reviewed to identify predisposing factors, specifically looking at age, presenting condition and treatment, presence of infection and antibiotic care, active haemo-oncological condition, long term renal dialysis, previous hospitalisation, VRE predisposition, and clearance (PREVENT) scores, and outcome of care. The presenting condition, treatment, presence of postoperative infection, VRE scores, age was compared between colonised and the infected cohort. VRE type in both colonised and infection group was Enterococcus Faecium in all but one patient. The colonised group had the same age (T=0.6 P>0.05) and sex (2=0.115, p=0.74), presenting condition and treatment which consisted of peri-femoral fixation or arthroplasty in all patients. The infected group had one case of myelodysplasia and four cases of chronic renal failure requiring dialysis. All of the infected patient had sustained an infected complication of their fracture fixation or arthroplasty requiring reoperation and antibiotics. The infected group had an average VRE predisposition score of 8.5 versus the score of 3 in the colonised group (F=36, p<0.001). PREVENT score was 7 in the infected group and 2 in the colonised group(F=153, p<0.001). Six patients(55%) succumbed to their infection, and one VRE infection resulted in limb loss. In the orthopaedic cohort, VRE infection is a nosocomial condition that has peri-femoral predilection and is seen in association with immunosuppression or renal failure. The VRE infection cohort has been treated for infective complication of original surgery weeks prior to VRE infection. Based on our findings, we advise avoidance of infective complications, change of practice in use of antibiotics and use radical surgery and surveillance for VRE infections beyond infective precautions. PREVENT score shows that the infected group are unlikely to clear their VRE in the future but not the colonised group.

Keywords: surgical site infection, enterococcus, orthopaedic surgery, vancomycin resistance

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Authors: Sungsoo Na, Chanho Park

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Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.

Keywords: cancer DNA, resonance frequency, quartz crystal microbalance, lung cancer

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Authors: Ľudmila Ballová, Slavomír Kurhajec, Eva Petrovová, Jarmila Eftimová

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Angiogenesis, a formation of new blood vessels from a pre-existing vasculature, plays an important role in pathologic processes such as the growth and metastasis of tumours. Tumours cannot grow beyond a few millimetres without blood supply from the newly formed blood vessels from the host tissue, a process called tumour-induced angiogenesis. The successful research of antiangiogenic treatment of cancer has focused on nutraceuticals with angiogenesis-modulating properties. Berberine, as a major active component of the bark of Phellodendron amurense Rupr., has shown antitumour activity by intervening into different steps of carcinogenesis. The influence of ethanolic extract of Phellodendron amurese bark on the angiogenesis was tested in vivo on chick chorioallantoic membrane (CAM). The irritancy of the CAM after the application of the crude bark extract dissolved in normal saline (10 mg/mL) was investigated on embryonic day 7. No significant signs of the irritancy, such as vasoconstriction, hyperaemia, haemorrhage or coagulation were observed which indicates the harmless character of the extract. A significant reduction in vessel sprouting and higher percentage of avascular zone was observed in the case of CAM treated with the extract in comparison with non-treated CAM (control), which is a proof of the antiangiogenic potential of the extract. These results could contribute to the development of novel drugs for the treatment of cancer or other diseases, in which angiogenesis plays a significant role.

Keywords: angiogenesis, berberine, chorioallantoic membrane, irritancy, phellodendron amurense

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Authors: Farzaneh Badinlou, Reza Kormi-Nouri, Monika Knopf

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Studies of adults' episodic memory have found that enacted encoding not only improve recall performance but also retrieve faster during the recall period. The current study focused on exploring the temporal progression of different encoding conditions in younger and older school children. 204 students from two age group of 8 and 14 participated in this study. During the study phase, we studied action encoding in two forms; participants performed the phrases by themselves (SPT), and observed the performance of the experimenter (EPT), which were compared with verbal encoding; participants listened to verbal action phrases (VT). At test phase, we used immediate and delayed free recall tests. We observed significant differences in memory performance as function of age group, and encoding conditions in both immediate and delayed free recall tests. Moreover, temporal progression of recall was faster in older children when compared with younger ones. The interaction of age-group and encoding condition was only significant in delayed recall displaying that younger children performed better in EPT whereas older children outperformed in SPT. It was proposed that enactment effect in form of SPT enhances item-specific processing, whereas EPT improves relational information processing and this differential processes are responsible for the results achieved in younger and older children. The role of memory strategies and information processing methods in younger and older children were considered in this study. Moreover, the temporal progression of recall was faster in action encoding in the form of SPT and EPT compared with verbal encoding in both immediate and delayed free recall and size of enactment effect was constantly increased throughout the recall period. The results of the present study provide further evidence that the action memory is explained with an emphasis on the notion of information processing and strategic views. These results also reveal the temporal progression of recall as a new dimension of episodic memory in children.

Keywords: action memory, enactment effect, episodic memory, school-aged children, temporal progression

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Authors: A. Abubakar, A. Parsa, S. Walker

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Despite advances made in the diagnosis and management of drug-sensitive tuberculosis (TB) over the past decades, treatment of multidrug-resistant tuberculosis (MDR-TB) remains challenging and complex particularly in high burden countries including Nigeria. Treatment of MDR-TB is cost-prohibitive with success rate generally lower compared to drug-sensitive TB and if care is not taken it may become the dominant form of TB in future with many treatment uncertainties and substantial morbidity and mortality. Addressing these challenges requires collaborative efforts thorough sustained researches to evaluate the current treatment guidelines, particularly in high burden countries and prevent progression of resistance. To our best knowledge, there has been no research exploring the acceptability, effectiveness, and cost-effectiveness of community-based-MDR-TB treatment model in Nigeria, which is among the high burden countries. The previous similar qualitative study looks at the home-based management of MDR-TB in rural Uganda. This research aimed to explore patient’s views and acceptability of community-based-MDR-TB treatment model and to evaluate and compare the effectiveness and cost-effectiveness of community-based versus hospital-based MDR-TB treatment model of care from the Nigerian perspective. Knowledge of patient’s views and acceptability of community-based-MDR-TB treatment approach would help in designing future treatment recommendations and in health policymaking. Accordingly, knowledge of effectiveness and cost-effectiveness are part of the evidence needed to inform a decision about whether and how to scale up MDR-TB treatment, particularly in a poor resource setting with limited knowledge of TB. Mixed methods using qualitative and quantitative approach were employed. Qualitative data were obtained using in-depth semi-structured interviews with 21 MDR-TB patients in Nigeria to explore their views and acceptability of community-based MDR-TB treatment model. Qualitative data collection followed an iterative process which allowed adaptation of topic guides until data saturation. In-depth interviews were analyzed using thematic analysis. Quantitative data on treatment outcomes were obtained from medical records of MDR-TB patients to determine the effectiveness and direct and indirect costs were obtained from the patients using validated questionnaire and health system costs from the donor agencies to determine the cost-effectiveness difference between community and hospital-based model from the Nigerian perspective. Findings: Some themes have emerged from the patient’s perspectives indicating preference and high acceptability of community-based-MDR-TB treatment model by the patients and mixed feelings about the risk of MDR-TB transmission within the community due to poor infection control. The result of the modeling from the quantitative data is still on course. Community-based MDR-TB care was seen as the acceptable and most preferred model of care by the majority of the participants because of its convenience which in turn enhanced recovery, enables social interaction and offer more psychosocial benefits as well as averted productivity loss. However, there is a need to strengthen this model of care thorough enhanced strategies that ensure guidelines compliance and infection control in order to prevent the progression of resistance and curtail community transmission.

Keywords: acceptability, cost-effectiveness, multidrug-resistant TB treatment, community and hospital approach

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Gudakesh Yadav

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Uttar Pradesh is one of the poorest performing states of India in terms of child health. Using data from the three round of NFHS and two rounds of DLHS, this paper attempts to examine tempo-spatial change in child health and care practices in Uttar Pradesh and its regions. Rate-ratio, CI, multivariate, and decomposition analysis has been used for the study. Findings demonstrate that child health care practices have improved over the time in all regions of the state. However; western and southern region registered the lowest progress in child immunization. Nevertheless, there is no decline in prevalence of diarrhea and ARI over the period, and it remains critically high in the western and southern region. These regions also poorly performed in giving ORS, diarrhoea and ARI treatment. Public health services are least preferred for diarrhoea and ARI treatment. Results from decomposition analysis reveal that rural area, mother’s illiteracy and wealth contributed highest to the low utilization of the child health care practices consistently over the period of time. The study calls for targeted intervention for vulnerable children to accelerate child health care service utilization. Poor performing regions should be targeted and routinely monitored on poor child health indicators.

Keywords: Acute Respiratory Infection (ARI), decomposition, diarrhea, inequality, immunization

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Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

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Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

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Authors: Talat Ghomashchi, Zahra Akbari, Shirin Malekpour, Marjan Alimirzaee

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Mixing the waste water of industries with natural water has caused environmental pollution. So researcher try to obtain methods and optimum conditions for waste water treatment. One of important stage in waste water treatment is dissolved air flotation. DAF is used for the removal of suspended solids and oils from waste water. In this paper, the effect of several parameters on flotation efficiency with Cationic polyacrylamide as flocculant, was examined, namely, (a) concentration of cationic flocculants, (b) pH (c) fast mixing time, (d) fast mixing speed,(e) slow mixing time,(f) retention time and temperature. After design of experiment, in each trial turbidity of waste water was measured by spectrophotometer. Results show that contribution of pH and concentration of flocculant on flotation efficiency are 75% and 9% respectively. Cationic polyacrylamide led to a significant increase in the settling speed and effect of temperature is negligible. In the optimum condition, the outcome of the DAF unit is increased and amount of suspended solid and oil in waste water is decreased effectively.

Keywords: dissolved air flotation, oil industry, waste water, treatment

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Allyson Augusta Shrikhande, Alexa Rains, Tayyaba Ahmed, Marjorie Mamsaang, Rakhi Vyas, Janaki Natarajan, Erika Moody, Christian Reutter, Kimberlee Leishear, Yogita Tailor, Sandra Sandhu-Restaino, Lora Liu, Neha James, Rosemarie Filart

Abstract:

Characterized by consistent difficulty getting and keeping an erection firm enough for intercourse, Erectile Dysfunction may affect up to 15% of adult men. Although awareness and access to treatment have improved in recent years, many patients do not actively seek diagnosis or treatment due to the stigma surrounding this condition. Patients who do seek treatment are often dissatisfied by the efficacy of the medication. The condition inhibits patients’ quality of life by worsening mental health and relationships. The purpose of this study was to test the effectiveness of an outpatient neuromuscular treatment protocol in treating the symptoms of Chronic Pelvic Pain and Erectile Dysfunction, improving pain and function. 56 patients ages 20-79 presented to an outpatient clinic for treatment of pelvic pain and Erectile Dysfunction symptoms. These symptoms had persisted for an average of 4 years. All patients underwent external ultrasound-guided hydro-dissection technique targeted at pelvic peripheral nerves in combination with pelvic floor musculature trigger-point injections. To measure the effects of this treatment, a five question Erectile Dysfunction questionnaire was completed by each patient at their first visit to a clinic and three months after treatment began. Answers were summed for a total score of 5-25, with a higher score indicating optimal function. The average score before treatment was 14.125 (SD 5.411) (a=0.05; CI 12.708-15.542), which increased by 18% to an average of 16.625 (SD 6.423) (a=0.05; CI 14.943-18.307) after treatment (P=0.0004). Secondary outcome variables included a Visual Analogue Scale (VAS) to measure pelvic pain intensity and the Functional Pelvic Pain Scale (FPPS) to measure function across multiple areas. VAS scores reduced by 51% after three months. Before treatment, the mean VAS score was 5.87, and the posttreatment mean VAS score was 2.89. Pelvic pain functionality improved by 34% after three months. Pretreatment FPPS scores averaged at 7.48, decreasing to 4.91 after treatment. These results indicate that this unique treatment was very effective at relieving pain and increasing function for patients with Erectile Dysfunction.

Keywords: chronic pelvic pain, erectile dysfunction, nonsurgical, outpatient, trigger point injections

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Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea

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Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studies

Keywords: anastrazole, letrozole, liver, rats

Procedia PDF Downloads 343

Authors: S. Jonsson, D. Millard, C. Bokhove

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Smartphones are ubiquitous and frequently used as learning tools, which makes the design of educational apps an important area of research. A key issue is designing apps to encourage engagement while maintaining a focus on the educational aspects of the app. Flow experience is a promising method for addressing this issue, which refers to a mental state of cognitive absorption and positive emotion. Flow experience has been shown to be associated with positive emotion and increased learning performance. Studies have shown that immediate feedback is an antecedent to Flow. This experiment investigates the effect of immediate feedback on Flow experience. An app teaching Spanish phrases was developed, and 30 participants completed both a 10min session with immediate feedback and a 10min session with delayed feedback. The app contained a task where the user assembles Spanish phrases by pressing bricks with Spanish words. Immediate feedback was implemented by incorrect bricks recoiling, while correct brick moved to form part of the finished phrase. In the delayed feedback condition, the user did not know if the bricks they pressed were correct until the phrase was complete. The level of Flow experienced by the participants was measured after each session using the Flow Short Scale. The results showed that higher levels of Flow were experienced in the immediate feedback session. It was also found that 14 of the participants indicated that the demands of the task were ‘just right’ in the immediate feedback session, while only one did in the delayed feedback session. These results have implications for how to design educational technology and opens up questions for how Flow experience can be used to increase performance and engagement.

Keywords: feedback timing, flow experience, L2 language learning, mobile learning

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Authors: Awais Ali, Hesham Ali

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The absence of teeth through either premature loss or developmental absence is a common condition with potentially severe impact on affected individuals. Management of these cases presents a clinical challenge which may be difficult to resolve given the effects of tooth loss or hypodontia over the course of a patient’s lifetime. Treatment of such cases is often best provided by a multi-disciplinary team, where the patient’s expectations and care delivery can be optimally managed. Orthodontic treatment is often used to prepare the dentition in advance of restorative replacement of missing teeth. Conversely, the placement of implants may precede the delivery of orthodontic treatment and indeed may function as an adjunctive orthodontic procedure. We discuss the use of both approaches here and illustrate their clinical implementation with two case reports. The first case demonstrates the use of fixed appliances to prepare the mouth for an opposing implant-retained complete denture. A second case demonstrates the use of implant-retained crowns to provide orthodontic anchorage in a partially dentate patient. We propose that complex cases such as these should always be planned and treated by a multi-disciplinary team in order to optimise the delivery of care, patient experience, and treatment outcome. The presented cases add to the body of evidence in this area.

Keywords: orthodontics, dental implantology, hypodontia, multi-disciplinary

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Authors: Hritwik Ghosh, Irfan Sadiq Rahat, Sachi Nandan Mohanty, J. V. R. Ravindra

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In the rapidly evolving landscape of medical diagnostics, the early detection and accurate classification of skin cancer remain paramount for effective treatment outcomes. This research delves into the transformative potential of Artificial Intelligence (AI), specifically Deep Learning (DL), as a tool for discerning and categorizing various skin conditions. Utilizing a diverse dataset of 3,000 images representing nine distinct skin conditions, we confront the inherent challenge of class imbalance. This imbalance, where conditions like melanomas are over-represented, is addressed by incorporating class weights during the model training phase, ensuring an equitable representation of all conditions in the learning process. Our pioneering approach introduces a hybrid model, amalgamating the strengths of two renowned Convolutional Neural Networks (CNNs), VGG16 and ResNet50. These networks, pre-trained on the ImageNet dataset, are adept at extracting intricate features from images. By synergizing these models, our research aims to capture a holistic set of features, thereby bolstering classification performance. Preliminary findings underscore the hybrid model's superiority over individual models, showcasing its prowess in feature extraction and classification. Moreover, the research emphasizes the significance of rigorous data pre-processing, including image resizing, color normalization, and segmentation, in ensuring data quality and model reliability. In essence, this study illuminates the promising role of AI and DL in revolutionizing skin cancer diagnostics, offering insights into its potential applications in broader medical domains.

Keywords: artificial intelligence, machine learning, deep learning, skin cancer, dermatology, convolutional neural networks, image classification, computer vision, healthcare technology, cancer detection, medical imaging

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Authors: Michael Menberu

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Housing affordability is a crucial policy objective. Incorporating economic sustainability in affordable housing in the development of the poorest of the poor's housing programs has become a major concern. This paper examines the affordability and economic sustainability of the poorest of the poor affordable housing in Debre Markos city. To address this, this study uses both quantitative and qualitative methods, Using a questionnaire survey, Interviews, field observation, household survey, and Pearson correlation analysis. The findings show that households in the expansion area have lower monthly incomes than in the past, but they are satisfied with the housing quality, rental pricing, and tenure security of their homes. This demonstrates in providing affordable housing for the poorest of the poor the location of the houses must be considered in order to have affordable and economically sustainable development. The findings show that housing is not truly affordable if it is in an inaccessible place with a long commute to work, high transportation expenditures, and land use that is homogeneous. Increasing the supply of affordable housing in accessible locations helps the poorest of the poor achieve multiple planning objectives: it reduces transportation costs, improves incomes, provides infrastructure, and reduces the distance to the work area.

Keywords: housing, affordable housing, economic sustainability, the poorest of the poor housing

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Authors: Bouharati Lokman, Bouharati Imen, Bouharati Khaoula, Bouharati Oussama, Bouharati Saddek

Abstract:

Ionizing radiation exposure is an established cancer risk factor. Compared to other common environmental carcinogens, it is relatively easy to determine organ-specific radiation dose and, as a result, radiation dose-response relationships tend to be highly quantified. Nevertheless, there can be considerable uncertainty about questions of radiation-related cancer risk as they apply to risk protection and public policy, and the interpretations of interested parties can differ from one person to another. Examples of tools used in the analysis of the risk of developing cancer due to radiation are characterized by uncertainty. These uncertainties are related to the history of exposure and different assumptions involved in the calculation. We believe that the results of statistical calculations are characterized by uncertainty and imprecision. Having regard to the physiological variation from one person to another. In this study, we develop a tool based on fuzzy logic inference. As fuzzy logic deals with imprecise and uncertain, its application in this area is adequate. We propose a fuzzy system with three input variables (age, sex and body attainable cancer). The output variable expresses the risk of infringement rate of each organ. A base rule is established from recorded actual data. After successful simulation, this will instantly predict the risk of infringement rate of each body following chronic exposure to 0.1 Gy.

Keywords: radiation exposure, cancer, modeling, fuzzy logic

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