Search results for: cancer drug

Authors: Auj-E Taqaddas

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The use of proton beam therapy is increasing globally. It seems to offer dosimetric advantages, especially in paediatric central nervous system (CNS) and brain tumours. A short E-survey was conducted to assess the clinical, technical, and educational resources and strategies employed in the state of the art proton beam therapy (PBT) centres in the USA to determine the current status of proton beam therapy. The study also aimed at finding out which PBT skills are in demand as well as what improvements are needed to ensure efficient treatment planning, delivery, and dosimetry. The study resulted in identifying areas for future research and development and in identifying cancers for which PBT is most suitable compared to other modalities to facilitate the implementation and use of PBT in clinical settings for cancer treatment.

Keywords: cancer, intensity modulated proton therapy, proton beam therapy, single field uniform scanning

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Mazita Mohd Diah, Anton V. Dolzhenko, Tin Wui Wong

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Nanoparticles, being small with a large specific surface area, increase solubility, enhance bioavailability, improve controlled release and enable precision targeting of the entrapped compounds. In this study, chitosan as polymeric permeation enhancer was conjugated to a polar pro-drug, carboxymethyl-5-fluorouracil (CMFU) to increase the skin drug permeation. Chitosan-CMFU conjugate was synthesized using chemical conjugation process through succinate linker. It was then transformed into nanoparticles via spray drying method. The conjugation was elucidated using Fourier Transform Infrared and Proton Nuclear Magnetic Resonance techniques. The nanoparticle size, size distribution, zeta potential, drug content, skin permeation and retention profiles were characterized. The conjugation was denoted using 1H NMR by new peaks at signal δ = 4.184 ppm (singlet, 2H for CH2) and 7.676-7.688 ppm (doublet, 1H for C6) attributed to CMFU in chitosan-CMFU NMR spectrum. The nanoparticles had profiles of particle size: 93.97 ±35.11 nm, polydispersity index: 0.40 ± 0.14, zeta potential: +18.25 ±2.95 mV and drug content: 6.20 ± 1.98 % w/w. Almost 80 % w/w CMFU in the form of nanoparticles permeated through the skin in 24 hours and close to 50 % w/w permeation occurred in first 1-2 hours. Without conjugation to chitosan and nanoparticulation, less than 40 % w/w CMFU permeated through the skin in 24 hours. The skin drug retention likewise was higher with chitosan-CMFU nanoparticles (15.34 ± 5.82 % w/w) than CMFU (2.24 ± 0.57 % w/w). CMFU, through conjugation with chitosan permeation enhancer and processed in nanogeometry, had its skin permeation and retention degree promoted.

Keywords: carboxymethyl-5-fluorouracil, chitosan, conjugate, skin permeation, skin retention

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Marjan Moradi Fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism, genotypes

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Authors: Shakir H. Mohammed Al-Alwany, Saad Hasan M. Ali, Ibrahim Mohammed S. Shnawa

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The study was aimed to define the percentage of detection of high-oncogenic risk types of HPV and their genotyping in archival tissue specimens that ranged from apparently healthy tissue to invasive breast cancer by using one of the recent versions of In Situ Hybridization(ISH) 0.2. To find out rational significance of such genotypes as well as over expressed products of mutants P53 and RB genes on the severity of underlying breast cancers. The DNA of HPV was detected in 46.5 % of tissues from breast cancers while HPV DNA in the tissues from benign breast tumours was detected in 12.5%. No HPV positive–ISH reaction was detected in healthy breast tissues of the control group. HPV DNA of genotypes (16, 18, 31 and 33) was detected in malignant group in frequency of 25.6%, 27.1%, 30.2% and 12.4%, respectively. Over expression of p53 was detected by IHC in 51.2% breast cancer cases and in 50% benign breast tumour group, while none of control group showed P53- over expression. Retinoblastoma protein was detected by IHC test in 49.7% of malignant breast tumours, 54.2% of benign breast tumours but no signal was reported in the tissues of control group. The significance prevalence of expression of mutated p53 & Rb genes as well as detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

Keywords: human papilloma virus, P53, RB, breast cancer

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Authors: Elyce Cardonick, Shistri Dhar, Linsdey Seidman

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Background: When breast cancer is diagnosed during pregnancy, the prognosis is comparable to non-pregnant women matched for prognostic indicators when pregnant women receive treatment without delay. Chemotherapy, including taxanes, can be given during pregnancy with normal neonatal development in exposed fetuses. Methods: Cases of primary breast cancer were extracted from the Cancer and Pregnancy Registry and longitudinal study at Cooper Medical School, which collects cases of pregnant women diagnosed and treated for cancer into a single database. Obstetrical, oncology and pediatric records were reviewed, including annual neonatal developmental, behavioral and medical assessments. Results: 270 pregnant women were diagnosed with primary breast cancer at a mean gestational age of 14.7+9weeks. Mean maternal age at diagnosis 34.5+4.5 years. Receptor status is comparable to non-pregnant women of reproductive age. Forty-nine women were advised to terminate. Two hundred two women underwent surgery;244 women received chemotherapy in pregnancy after the first trimester; the majority of Doxorubucin/Cytoxan; 81 of the cases included a taxane. At a mean of 90 months, follow up obtained on 255 newborns.192/255 newborns are meeting developmental milestones. Respiratory illnesses, including asthma, and bronchiolitis, were reported in 64 newborns, the most common medical condition reported. Thirty-one children are undergoing treatment for GERD, 11 for urinary tract infections, and 7 are undergoing treatment for anemia. Twenty-six children with expressive or articulation language delays, 21/26 are mild. Eleven children with gross/ 7 with fine motor delays. Eight children are treated for ADHD, 4 for anxiety and 4 have social skill impairment. The majority of children with developmental, language or motor delays were born preterm. Conclusion: After chemotherapy exposure in utero for breast cancer, the majority of newborns are meeting developmental milestones and are medically healthy. The goal for treating pregnant women with breast cancer is to aim for delivery close to the term.

Keywords: breast cancer, pregnancy, chemotherapy, newborn

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Authors: Szu Mei Hsiao

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This study explores the spiritual needs of inpatients with advanced cancer and their family caregivers in one southern regional teaching hospital in Taiwan and elucidates the differences and similarities of spiritual needs between them. Little research reports the different phases of spiritual needs and the potential impact of Chinese cultural values on the spiritual needs. Qualitative inquiry was used. Twenty-one patients with advanced cancer and twenty-two family caregivers were recruited. During hospitalization, all participants identified spiritual needs both the palliative phase and the dying phase: (a) the need to foster faith/confidence and hope for medicine and/or God; (b) to understand the meaning and values of life; (c) to experience more reciprocal human love and forgiveness; and (d) to obey God’s/Heaven will. Furthermore, the differences of spiritual needs between patients with advanced cancer and their family caregivers are as follows: (a) family caregivers emphasized the need to inform relatives and say goodbye in order to die peacefully; (b) patients highlighted a need to maintain a certain physical appearance in order to preserve their dignity; nurture one’s willpower; learn about the experiences of cancer survivors; and identify one’s own life experience for understanding the meaning and values of life. Moreover, the dissimilarity of spiritual needs is that the patients pointed out the need to understand God’s will during the palliative treatment phase. However, the family caregivers identified the need to forgive each other, and inform relatives and say goodbye to patients in the dying phase. This research has shown that the needs of meaning/values of life and facing death peacefully are different between two groups. Health professionals will be encouraged to detect and to develop individualized care strategies to meet spiritual needs.

Keywords: advanced cancer, Chinese culture, family caregivers, qualitative research, spiritual needs

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: May Fadheel Estephan, Richard Perks

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Context: Cancer is a serious health concern that affects millions of people worldwide. Early detection and treatment are essential for improving patient outcomes. However, current methods for cancer detection have limitations, such as low sensitivity and specificity. Research Aim: The aim of this study was to develop an optical sensor for cancer detection using elastic light scattering spectroscopy (ELSS). ELSS is a noninvasive optical technique that can be used to characterize the size and concentration of particles in a solution. Methodology: An optical probe was fabricated with a 100-μm-diameter core and a 132-μm centre-to-centre separation. The probe was used to measure the ELSS spectra of polystyrene spheres with diameters of 2, 0.8, and 0.413 μm. The spectra were then analysed to determine the size and concentration of the spheres. Findings: The results showed that the optical probe was able to differentiate between the three different sizes of polystyrene spheres. The probe was also able to detect the presence of polystyrene spheres in suspension concentrations as low as 0.01%. Theoretical Importance: The results of this study demonstrate the potential of ELSS for cancer detection. ELSS is a noninvasive technique that can be used to characterize the size and concentration of cells in a tissue sample. This information can be used to identify cancer cells and assess the stage of the disease. Data Collection: The data for this study were collected by measuring the ELSS spectra of polystyrene spheres with different diameters. The spectra were collected using a spectrometer and a computer. Analysis Procedures: The ELSS spectra were analysed using a software program to determine the size and concentration of the spheres. The software program used a mathematical algorithm to fit the spectra to a theoretical model. Question Addressed: The question addressed by this study was whether ELSS could be used to detect cancer cells. The results of the study showed that ELSS could be used to differentiate between different sizes of cells, suggesting that it could be used to detect cancer cells. Conclusion: The findings of this research show the utility of ELSS in the early identification of cancer. ELSS is a noninvasive method for characterizing the number and size of cells in a tissue sample. To determine cancer cells and determine the disease's stage, this information can be employed. Further research is needed to evaluate the clinical performance of ELSS for cancer detection.

Keywords: elastic light scattering spectroscopy, polystyrene spheres in suspension, optical probe, fibre optics

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Authors: Yu-Mei Hsueh, Cheng-Shiuan Tsai, Chao-Yuan Huang

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Prostate Cancer (PC) is a malignant tumor originated in prostate and is a second common male’s cancer in the world. Incidence of PC in Asia countries, have still been rising over the past few decades. As an antioxidant, selenium can slow down prostate cancer tumor progression, but the association between plasma selenium levels and risk of aggressive prostate cancer may be modified by different genotype of selenoprotein. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinaty total arsenic, and prostate cancer. Two hundred ninety five pathologically-confirmed cases of PC and 295 cancer-free controls were individually matched to case subjects by age (± 5 years) were recruited from Department of Urology of National Taiwan University Hospital, Taipei Municipal Wan Fang Hospital and Taipei Medical University Hospital. Personal interview and biospeciment of urine and blood collection from participants were conducted by well-trained interviewers after participants’ informed consent was obtained. Plasma selenium was measured by an inductively coupled plasma mass. Urinary arsenic concentration was detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of SEPP1rs3797310 and SEP15 rs5859 were determined using polymerase chain reaction-restriction fragment length polymorphism method. The higher plasma selenium was the lower OR of PC with a dose-response relationship. Prostate cancer patients with high plasma selenium had low tumor stage and grade. Participants carried SEPP1rs3797310 CT+TT genotype compared to those with CC genotype had a lower OR of PC in crude model; then this relationship was disappeared after confounder was adjusted. Prostate cancer patients with high urinary total arsenic concentration had high tumor stage and grade. Urinary total arsenic concentration was significantly positively related with plasma selenium and prostate specific antigen concentration. Participants with lower plasma selenium concentration and higher urinary total arsenic concentration compared to those with higher plasma selenium concentration and lower urinary total arsenic concentration had a higher OR of PC with a dose-response relationship.

Keywords: prostate cancer, plasma selenium concentration, urinary arsenic concentration, prostate specific antigen

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Authors: Han Xiao

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The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: Chueh Chang, Chia-jung Hsieh, Fu-yu Yu, Yu-Hwa Lin

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Background:The majority of women diagnosed with breast cancer undergo treatment involving surgery and radiotherapy or chemotherapy, or both. With these major advances in breast cancer management, many patients still have to deal with short or long-term side effects and psychological distress related to the disease and treatment, which have a substantial impact on their quality of life. The Laughing Qigong Program (LQP) is an interactive laughter program that combines the physical and physiological benefits of laughter with the mental benefits of Chinese qigong. Purpose: In order to improve the quality of life for breast cancer women in the community as well as echoing the WHO 2004 “Promoting Mental Health” for every one. This study focused on how to promote the positive mental health for women of breast cancer through the “laughter program” in Taiwan. During the presentation, how to practice Laughing Qigong will be demonstrated. Method: Using nonequivalent pretest-posttest design, ix-one breast cancer patients were volunteered to enroll in this study from the Taiwan Breast Cancer Alliance (TBCA). Thirty patients were assigned to the experimental group and the other 31 patients were assigned to the control group. The women who were assigned to the experimental group received laughter program one hour per session, once a week, totally 12 sessions. All subjects were tested before and after the intervention on the following: Self-Esteem scale (RSE), Face Scale (FS), Anxiety and pain experience were measured as psychological markers; saliva cortisol (CS) as an immunological marker; blood pressure (BP), heart rate (HR),and heart rate variability (HRV) as physiological markers of the body’s response to stress. Results: After comparing the experimental and control groups, the results revealed that those breast cancer women with “laughing program” their sense of humor were improved, less uncomfortable on self report physical conditions, more positive attitudes toward stress management by using laughter, and had emotional improvement according to the face scale.

Keywords: mental health promotion, breast cancer, laughing Qigong, women

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

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Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

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Authors: Pooja Mongia Raj, Rakesh Raj, Alpana Ram

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Background: The use of multiparticulate drug delivery systems in preference to single unit dosage forms for colon targeting purposes dates back to 1985 when Hardy and co-workers showed that multiparticulate systems enabled the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. Methods: Site-specific colonic drug delivery system (nanoparticles) of 5-ASA were prepared and coated with pH sensitive polymer. Chitosan nanoparticles (CTNP) bearing 5-Amino salicylic acid (5-ASA) were prepared, by ionotropic gelation method. Nanoparticulate dosage form consisting of a hydrophobic core enteric coated with pH-dependent polymer Eudragit S-100 by solvent evaporation method, for the effective delivery of drug to the colon for treatment of ulcerative colitis. Results: The mean diameter of CTNP and ECTNP formulations were 159 and 661 nm, respectively. Also optimum value of polydispersity index was found to be 0.249 [count rate (kcps) was 251.2] and 0.170 [count rate (kcps) was 173.9] was obtained for both the formulations respectively. Conclusion: CTNP and Eudragit chitosan nanoparticles (ECTNP) was characterized for shape and surface morphology by scanning electron microscopy (SEM) appeared to be spherical in shape. The in vitro drug release was investigated using USP dissolution test apparatus in different simulated GIT fluids showed promising release. In vivo experiments are in further proceeding for fruitful results.

Keywords: colon targeting, nanoparticles, polymer, 5-amino salicylic acid, edragit

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Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

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Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

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Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

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Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

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Authors: R. R. Dewi Rahmawaty Aktyani Putri, Earmporn Thongkrajai, Dedy Purwito

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There were many instruments have been developed to assess social support which has the different dimension in breast cancer patients. The Issue of measurement is a challenge to determining the component of dimensional concept, defining the unit of measurement, and establishing the validity and reliability of the measurement. However, the instruments where need to know how much support which obtained and perceived among women with breast cancer who undergone chemotherapy which it can help nurses to prevent of non-adherence in chemotherapy. This study aimed to measure the reliability of BC-SSAS instrument among 30 Indonesian women with breast cancer aged 18 years and above who undergone chemotherapy for six cycles in the oncological unit of Outpatient Department (OPD), Margono Soekardjo Hospital, Central Java, Indonesia. Data were collected during October to December 2015 by using modified the Breast Cancer Social Support Assessment (BC-SSAS). The Cronbach’s alpha analysis was carried out to measure internal consistency for reliability test of BC-SSAS instrument. This study used five experts for content validity index. The results showed that for content validity, I-CVI was 0.98 and S-CVI was 0.98; Cronbach’s alpha value was 0.971 and the Cronbach’s alpha coefficients for the subscales were high, with 0.903 for emotional support, 0.865 for informational support, 0.901 for tangible support, 0.897 for appraisal support and 0.884 for positive interaction support. The results confirmed that the BC-SSAS instrument has high reliability. BC-SSAS instruments were reliable and can be used in health care services to measure the social support received and perceived among women with breast cancer who undergone chemotherapy so that preventive interventions can be developed and the quality of health services can be improved.

Keywords: BC-SSAS, women with breast cancer, chemotherapy, Indonesia

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Authors: Wantana Amatariyakul, Chumnong Amatariyakul

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The research aims to examine the spread of drugs in higher education, especially amphetamine which is rapidly increasing in Thai society, its causes and effects, including the sociological perspective, in order to explain, prevent, control, and solve the problems. The students who participated in this research are regular students of Rajamangala University of Technology Isan, Khon Kaen Campus. The data were collected using questionnaires, group discussions, and in-depth interviews. The quantity data were analyzed using frequency, percentage, mean and standard deviation and using content analysis to analyzed quality data. The result of the study showed that the students had the results of examination on level of knowledge and understanding on drug abuse projected that the majority of sample group attained their knowledge on drug abuse respectively. Despite their uncertainty, the majority of samples presumed that amphetamine, marijuana and grathom (Mitragyna Speciosa Korth) would most likely be abused. The reason for first drug abuse is because they want to try and their friends convince them, as well as, they want to relax or solve the problems in life, respectively. The bad effects appearing to the drug addicts shows that their health deteriorates or worsens, as well as, they not only lose their money but also face with worse mental states. The reasons that respondents tried to avoid using drugs or refused drugs offered by friends were: not wanting to disappoint or upset their family members, fear of rejection by family members, afraid of being arrested by the police, afraid of losing their educational opportunity and ruining their future respectively. Students therefore defended themselves against drug addiction by refusing to try all drugs. Besides this, the knowledge about the danger and the harm of drugs persuaded them to stay away from drugs.

Keywords: drugs, higher education, drug addiction, spread of drugs

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Authors: Mario Hanna Louis Hanna

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The use of CAD (pc Aided layout) generation is ubiquitous inside the structure, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of structure faculties in Nigeria as an important part of the training module. This newsletter examines the moral troubles involved in implementing CAD (pc Aided layout) content into the architectural training curriculum. Using current literature, this study begins with the advantages of integrating CAD into architectural education and the responsibilities of various stakeholders in the implementation process. It also examines issues related to the terrible use of records generation and the perceived bad effect of CAD use on design creativity. The use of a survey technique, information from the architecture department of Chukwuemeka Odumegwu Ojukwu Uli college changed into accumulated to serve as a case observe on how the problems raised have been being addressed. The object draws conclusions on what guarantees a hit moral implementation. Tens of millions of human beings around the sector suffer from hepatitis C, one of the international's deadliest sicknesses. Interferon (IFN) is a remedy alternative for patients with hepatitis C, but these treatments have their aspect outcomes. Our research targeted growing an oral small molecule drug that goals hepatitis C virus (HCV) proteins and has fewer facet effects. Our contemporary study targets to broaden a drug primarily based on a small molecule antiviral drug precise for the hepatitis C virus (HCV). Drug improvement and the use of laboratory experiments isn't always best high-priced, however also time-eating to behavior those experiments. instead, on this in silicon have a look at, we used computational strategies to recommend a particular antiviral drug for the protein domain names of discovered in the hepatitis C virus. This examines used homology modeling and abs initio modeling to generate the 3-D shape of the proteins, then figuring out pockets within the proteins. Proper lagans for pocket pills were advanced the usage of the de novo drug design method. Pocket geometry is taken into consideration while designing ligands. A few of the various lagans generated, a different for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, Hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication.

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Authors: Cuneyt Yucelbas, Seral Ozsen, Sule Yucelbas, Gulay Tezel

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Due to the fact that there exist only a small number of complex systems in artificial immune system (AIS) that work out nonlinear problems, nonlinear AIS approaches, among the well-known solution techniques, need to be developed. Gaussian function is usually used as similarity estimation in classification problems and pattern recognition. In this study, diagnosis of breast cancer, the second type of the most widespread cancer in women, was performed with different distance calculation functions that euclidean, gaussian and gaussian-euclidean hybrid function in the clonal selection model of classical AIS on Wisconsin Breast Cancer Dataset (WBCD), which was taken from the University of California, Irvine Machine-Learning Repository. We used 3-fold cross validation method to train and test the dataset. According to the results, the maximum test classification accuracy was reported as 97.35% by using of gaussian-euclidean hybrid function for fold-3. Also, mean of test classification accuracies for all of functions were obtained as 94.78%, 94.45% and 95.31% with use of euclidean, gaussian and gaussian-euclidean, respectively. With these results, gaussian-euclidean hybrid function seems to be a potential distance calculation method, and it may be considered as an alternative distance calculation method for hard nonlinear classification problems.

Keywords: artificial immune system, breast cancer diagnosis, Euclidean function, Gaussian function

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Authors: Catarina Grande, Barbara Mota

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The main goal of the present study was to understand the impact of childhood cancer on the quality of life of survivors and the extent to which oncologic disease affects the functionality and participation of survivors at the present time, compared to the time of diagnosis. Six survivors of pediatric cancer participated in the study. Participants were interviewed using a semi-structured interview, adapted from two instruments present in the literature - QALY and QLACS - and piloted through a previous study. This study is based on a qualitative approach using content analysis, allowing the identification of categories and subcategories. Subsequently, the correspondence between the units of meaning and the codes in the International Classification of Functioning, Disability, and Health for Children and Young, which contributed to a more detailed analysis of the impact on the quality of life of survivors in relation to the domains under study. The results showed significant changes between the moment of diagnosis and the present moment, concretely at the microsystem of the survivor. Regarding functionality and participation, the results show that the functions of the body are the most affected domain, emphasizing the emotional component that currently has a greater impact on the quality of life of survivors. The present study allowed identifying a set of codes for the development of a CIF-CJ core set for pediatric cancer survivors. He also indicated the need for future studies to validate and deepen these issues.

Keywords: cancer, participation, quality of life, survivor

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Authors: Shannon Hearney, Jeffrey Hoch

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While all cancers are costly to treat, pancreatic cancer is a notoriously costly and deadly form of cancer. Across the world there are a variety of treatment centers ranging from small clinics to large, high-volume hospitals as well as differing structures of payment and access. It has been noted that centers that treat a high volume of pancreatic cancer patients have higher quality of care, it is unclear if that care is cost-effective. In the US there is no clear consensus on the cost-effectiveness of high-volume centers for the surgical care of pancreatic cancer. Other European countries, like Finland and Italy have shown that high-volume centers have lower mortality rates and can have lower costs, there however, is still a gap in knowledge about these centers cost-effectiveness globally. This paper seeks to review the current literature in Europe and the US to gain a better understanding of the state of high-volume pancreatic surgical centers cost-effectiveness while considering the contextual differences in health system structure. A review of major reference databases such as Medline, Embase and PubMed will be conducted for cost-effectiveness studies on the surgical treatment of pancreatic cancer at high-volume centers. Possible MeSH terms to be included, but not limited to, are: “pancreatic cancer”, “cost analysis”, “cost-effectiveness”, “economic evaluation”, “pancreatic neoplasms”, “surgical”, “Europe” “socialized medicine”, “privatized medicine”, “for-profit”, and “high-volume”. Studies must also have been available in the English language. This review will encompass European scientific literature, as well as those in the US. Based on our preliminary findings, we anticipate high-volume hospitals to provide better care at greater costs. We anticipate that high-volume hospitals may be cost-effective in different contexts depending on the national structure of a healthcare system. Countries with more centralized and socialized healthcare may yield results that are more cost-effective. High-volume centers may differ in their cost-effectiveness of the surgical care of pancreatic cancer internationally especially when comparing those in the United States to others throughout Europe.

Keywords: cost-effectiveness analysis, economic evaluation, pancreatic cancer, scientific literature review

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Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

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This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

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Authors: Reuben Mugisha, Stella Bakibinga

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The cervical cancer burden is a global threat, but more so in low income settings where more than 85% of mortality cases occur due to lack of sufficient screening programs. There is consequently a lack of early detection of cancer and precancerous cells among women. Studies show that 3% to 35% of deaths could have been avoided through early screening depending on prognosis, disease progression, environmental and lifestyle factors. In this study, a systematic literature review is undertaken to understand potential barriers and facilitators as documented in previous studies that focus on the application of telehealth in cervical cancer screening programs for early detection of cancer and precancerous cells. The study informs future studies especially those from low income settings about lessons learned from previous studies and how to be best prepared while planning to implement telehealth for cervical cancer screening. It further identifies the knowledge gaps in the research area and makes recommendations. Using a specified selection criterion, 15 different articles are analyzed based on the study’s aim, theory or conceptual framework used, method applied, study findings and conclusion. Results are then tabulated and presented thematically to better inform readers about emerging facts on barriers and facilitators to telehealth implementation as documented in the reviewed articles, and how they consequently lead to evidence informed conclusions that are relevant to telehealth implementation for cervical cancer screening. Preliminary findings of this study underscore that use of low cost mobile colposcope is an appealing option in cervical cancer screening, particularly when coupled with onsite treatment of suspicious lesions. These tools relay cervical images to the online databases for storage and retrieval, they permit integration of connected devices at the point of care to rapidly collect clinical data for further analysis of the prevalence of cervical dysplasia and cervical cancer. Results however reveal the need for population sensitization prior to use of mobile colposcopies among patients, standardization of mobile colposcopy programs across screening partners, sufficient logistics and good connectivity, experienced experts to review image cases at the point-of-care as important facilitators to the implementation of mobile colposcope as a telehealth cervical cancer screening mechanism.

Keywords: cervical cancer screening, digital technology, hand-held colposcopy, knowledge-sharing

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Authors: Frederick Monyepao

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Crack cocaine first appeared on the scene in the form of cocaine freebasing in the late 1970s. Stockbrokers, investment bankers, rock stars, Hollywood elites, and a few pro athletes were regular users of the substance. As criminogenic factors associated with substance abuse began to surface, congress passed new legislation. The laws led to the increase of health coverage insurances and the expansion of hospitals. By the mid-1980s, crack use spread into America's inner cities among impoverished African Americans and Latinos. While substance abuse increased among minority communities, legislation pertaining to substance abuse evolved. The prison industry also expanded the number of cells available. A qualitative approach was taken, drawing from a range secondary sources for contextual analysis. This paper traces out the continued marginalisation and racist undertones towards minorities as perpetuated by certain drug policies. It was discovered that the new legislation on crack was instrumental in the largest incarcerations the United States ever faced. Drug offenders increased in prisons eightfold from 1986 to 2000. The paper concludes that American drug control policies are consistently irrational and ineffective when measured by levels of substance use and abuse. On the contrary, these policies have been successful as agents of social control in maintaining the stratification patterns of racial/ethnic minorities and women. To move beyond prohibition, radical law and policy reform may require a change in narratives on substance use.

Keywords: crack, drug policy, minorities, racism, substance abuse

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Authors: Cho-Liang Chung

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Uniform and rapid drug release are important for trauma dressing application. Low glass transition polymer system and non-woven nanofiber structures as the designs conduct rapid-release characteristics. In this study, polyvinylpyrrolidone, polysulfone, and polystyrene were dissolved in dimethylformamide to form precursor solution. These solutions were blended with vitamin C to form the electrospinning solutions. The non-woven nanofibers structures were successfully prepared using an electrospinning process. The following instruments were used to analyze the characteristics of non-woven nanofibers structures: Atomic force microscopy (AFM), Field Emission Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The AFM was used to scan the nanofibers. 3D Graphics were applied to explore the surface morphology of nanofibers. FE-SEM was used to explore the morphology of non-woven structures. XRD was used to identify crystal structures in the non-woven structures. The evolution of morphology of non-woven structures was changed dramatically in different durations, because of the moisture absorption and decreasing glass transition temperature; the non-woven nanofiber structures can be applied to uniform and rapid drug release for trauma dressing application.

Keywords: nanofibers, non-woven, electrospinning process, rapid drug releasing

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Authors: Timea Harmath-Tánczos

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Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

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Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

Procedia PDF Downloads 525