Search results for: common drug combinations

Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Nouf Al Harthi

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Venous thromboembolism (VTE) is one of the most common causes of hospital-related deaths in critically ill patients. Guidelines recommended VTE prophylaxis with standardized, fixed doses for most patients. The underweight population has limited data to guide the appropriate drug and dosing regimen. The aim of this study was to describe the pattern of VTE prophylaxis dose regimens for underweighted critically ill adult patients and the prevalence of associated VTE and bleeding. This study is a retrospective cohort study, conducted in King Abdulaziz Medical City, Saudi Arabia. It included all critical patients admitted to the intensive care units and were above 14 years old with weight less than 50 kg or BMI of 18.5 kg/m2 or less and were on heparin as VTE prophylaxis for more than 72 hours from January 2016 until January 2020. After screening 270 patients, only 40 patients were included in this study according to our inclusion and exclusion criteria. Only 6 patients (15%) received VTE prophylaxis as an adjusted dose of heparin 2500 U Q12, while the rest of the patients were taking standard dosing of heparin, 5000 U Q12 was given to 21 (52.50%) patients and 5000 U Q8 was given to 13 (32.50%) patients. None of the adjusted doses developed any complications such as VTE or bleeding. There was no significant difference compared with the standard dose group. This study focused on describing the pattern of heparin doses as VTE prophylaxis in underweight patients. We also compared the standard dosing and adjusted dosage of VTE prophylaxis on underweight patients and any complications. There was no significant difference in the complication’s outcome or benefits between the two groups.

Keywords: venous thromboembolism prophylaxis, heparin, underweight patients, adult, critical care units

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Authors: Mustapha Kamel Mihoubi, Essadik Kerkar, Abdelhamid Hebbouche

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According to the randomness of most of the factors affecting the stability of a gravity dam, probability theory is generally used to TESTING the risk of failure and there is a confusing logical transition from the state of stability failed state, so the stability failure process is considered as a probable event. The control of risk of product failures is of capital importance for the control from a cross analysis of the gravity of the consequences and effects of the probability of occurrence of identified major accidents and can incur a significant risk to the concrete dam structures. Probabilistic risk analysis models are used to provide a better understanding the reliability and structural failure of the works, including when calculating stability of large structures to a major risk in the event of an accident or breakdown. This work is interested in the study of the probability of failure of concrete dams through the application of the reliability analysis methods including the methods used in engineering. It is in our case of the use of level II methods via the study limit state. Hence, the probability of product failures is estimated by analytical methods of the type FORM (First Order Reliability Method), SORM (Second Order Reliability Method). By way of comparison, a second level III method was used which generates a full analysis of the problem and involving an integration of the probability density function of, random variables are extended to the field of security by using of the method of Mont-Carlo simulations. Taking into account the change in stress following load combinations: normal, exceptional and extreme the acting on the dam, calculation results obtained have provided acceptable failure probability values which largely corroborate the theory, in fact, the probability of failure tends to increase with increasing load intensities thus causing a significant decrease in strength, especially in the presence of combinations of unique and extreme loads. Shear forces then induce a shift threatens the reliability of the structure by intolerable values of the probability of product failures. Especially, in case THE increase of uplift in a hypothetical default of the drainage system.

Keywords: dam, failure, limit state, monte-carlo, reliability, probability, sliding, Taylor

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Authors: Ahmed Saeed, Sadok Sassi, Mohammad Roshun

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Gears are important components with a vital role in many rotating machines. One of the common gear failure causes is tooth fatigue crack; however, its early detection is still a challenging task. The objective of this study is to develop a numerical model that simulates the effect of teeth cracks on the resulting gears vibrations and permits consequently to perform an early fault detection. In contrast to other published papers, this work incorporates the possibility of multiple simultaneous cracks with different depths. As cracks alter significantly the stiffness of the tooth, finite element software is used to determine the stiffness variation with respect to the angular position, for different combinations of crack orientation and depth. A simplified six degrees of freedom nonlinear lumped parameter model of a one-stage spur gear system is proposed to study the vibration with and without cracks. The model developed for calculating the stiffness with the crack permitted to update the physical parameters of the second-degree-of-freedom equations of motions describing the vibration of the gearbox. The vibration simulation results of the gearbox were by obtained using Simulink/Matlab. The effect of one crack with different levels was studied thoroughly. The change in the mesh stiffness and the vibration response were found to be consistent with previously published works. In addition, various statistical time domain parameters were considered. They showed different degrees of sensitivity toward the crack depth. Multiple cracks were also introduced at different locations and the vibration response along with the statistical parameters were obtained again for a general case of degradation (increase in crack depth, crack number and crack locations). It was found that although some parameters increase in value as the deterioration level increases, they show almost no change or even decrease when the number of cracks increases. Therefore, the use of any statistical parameters could be misleading if not considered in an appropriate way.

Keywords: Spur gear, cracked tooth, numerical simulation, time-domain parameters

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Keunhong Chae, Seokho Yoon

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This paper proposes a cooperative Alamouti space time transmission scheme with low relay complexity for the cooperative communication systems. In the proposed scheme, the source node combines the data symbols to construct the Alamouti-coded form at the destination node, while the conventional scheme performs the corresponding operations at the relay nodes. In simulation results, it is shown that the proposed scheme achieves the second order cooperative diversity while maintaining the same bit error rate (BER) performance as that of the conventional scheme.

Keywords: Space-time transmission, cooperative communication system, MIMO.

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Authors: A. Bhandari, S. Mukherjee

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Two frames in a Hilbert space are called woven or weaving if all possible merge combinations between them generate frames of the Hilbert space with uniform frame bounds. Weaving frames are powerful tools in wireless sensor networks which require distributed data processing. Considering the practical applications, this article deals with finite woven frames. We provide methods of constructing finite woven frames, in particular, bounded linear operators are used to construct woven frames from a given frame. Several examples are discussed. We also introduce the notion of woven frame sequences and characterize them through the concepts of gaps and angles between spaces.

Keywords: frames, woven frames, gap, angle

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Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

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Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: Nisa Mohan

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Clinical coding is a feasible method for estimating the national prevalence of adverse drug event (ADE) admissions. However, under-coding of ADE admissions is a limitation of this method. Whilst the under-coding will impact the accurate estimation of the actual burden of ADEs, the feasibility of the coded data in estimating the adverse drug event admissions goes much further compared to the other methods. Therefore, it is necessary to know the reasons for the under-coding in order to improve the clinical coding of ADE admissions. The ability to identify the reasons for the under-coding of ADE admissions rests on understanding the decision-making process of coding ADE admissions. Hence, the current study aimed to explore the decision-making process of clinical coders when coding cases of ADE admissions. Clinical coders from different levels of coding job such as trainee, intermediate and advanced level coders were purposefully selected for the interviews. Thirteen clinical coders were recruited from two Auckland region District Health Board hospitals for the interview study. Semi-structured, one-on-one, face-to-face interviews using open-ended questions were conducted with the selected clinical coders. Interviews were about 20 to 30 minutes long and were audio-recorded with the approval of the participants. The interview data were analysed using a general inductive approach. The interviews with the clinical coders revealed that the coders have targets to meet, and they sometimes hesitate to adhere to the coding standards. Coders deviate from the standard coding processes to make a decision. Coders avoid contacting the doctors for clarifying small doubts such as ADEs and the name of the medications because of the delay in getting a reply from the doctors. They prefer to do some research themselves or take help from their seniors and colleagues for making a decision because they can avoid a long wait to get a reply from the doctors. Coders think of ADE as a small thing. Lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing may contribute to the under-coding of the ADE admissions. These findings suggest that further work is needed on interventions to improve the clinical coding of ADE admissions. Providing education to coders about the importance of ADEs, educating clinicians about the importance of clear and confirmed medical records entries, availing pharmacists’ services to improve the detection and clear documentation of ADE admissions, and including a mandatory field in the discharge summary about external causes of diseases may be useful for improving the clinical coding of ADE admissions. The findings of the research will help the policymakers to make informed decisions about the improvements. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. This country-specific research conducted in New Zealand may also benefit other countries by providing insight into the clinical coding of ADE admissions and will offer guidance about where to focus changes and improvement initiatives.

Keywords: adverse drug events, clinical coders, decision making, hospital admissions

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Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni

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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.

Keywords: adherence, antiretroviral therapy, second line, treatment failure

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Authors: M. Liebherr, P. Schubert, S. Kersten, C. Dietz, L. Franz, C. T. Haas

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With a long history, dual-task has become one of the most intriguing research fields regarding human brain functioning and cognition. However, findings considering effects of task-interrelations are limited (especially, in combined motor and cognitive tasks). Therefore, we aimed at developing a measurement system in order to analyse interrelation effects of cognitive and motor tasks. On the one hand, the present study demonstrates the applicability of the measurement system and on the other hand first results regarding a systematization of different task combinations are shown. Future investigations should combine imagine technologies and this developed measurement system.

Keywords: dual-task, interference, cognition, measurement

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Authors: Hanjun Zhao, Ke Zhang, Bojian Zheng

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Background: So far, there is no universal antiviral agent which can inhibit multiple viral infections. More and more drug-resistant viral strains emerge after the antiviral drug application for treatment. Defensins are the front line of host innate immunity and have broad spectrum antibacterial and antiviral effects. However, there is limited data to show if these defensins have good antiviral activity in vivo and what the antiviral mechanism is. Subjects: To investigate a peptide with widespread antivirus activity in vitro and in vivo and illustrate the antiviral mechanism. Methods: Antiviral peptide library designed from mouse beta defensins was synthesized by the company. Recombinant beta defensin was obtained from E. coli. Antiviral activity in vitro was assayed by plaque assay, qPCR. Antiviral activity in vivo was detected by animal challenge with 2009 pandemic H1N1 influenza A virus. The antiviral mechanism was assayed by western blot, ELISA, and qPCR. Conclusions: We identify a new peptide which has widespread effects against multiple viruses (H1N1, H5N1, H7N9, MERS-CoV) in vitro and has efficient antivirus activity in vivo. This peptide inhibits viral entry into target cells and subsequently blocks viral replication. The in vivo study of the antiviral peptide against other viral infections and the investigation of its more detail antiviral mechanism are ongoing.

Keywords: antiviral peptide, defensin, Influenza A virus, mechanism

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Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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Authors: Kazunari Ozaki, Mitsuru Kageyama, Kenki Miyazawa, Yoshio Nakamura

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Background: Kampo (Japanese Traditional medicine) is a medicine traditionally practiced in Japan, based on ancient Chinese medicine. Most Kampo doctors have used decoction of crude drug pieces for treatment. 93% of the Kampo drugs sold in Japan are Kampo products nowadays. Of all Kampo products, 81% of them are Kampo extract formulations for prescription, which is prepared in powdered or granulated form from medicinal crude drug extracts mixed with appropriate excipient. Physicians with medical license for Western medicine prescribe these Kampo extract formulations for prescription in Japan. Objectives: Our study aims at presenting a brief history of Kampo extract formulations for prescription in Japan. Methods: Systematic searches for relevant studies were conducted using not only printed journals but also electronic journals from the bibliographic databases, such as PubMed/Medline, Ichushi-Web, and university/institutional websites, as well as search engines, such as Google and Google Scholar. Results: The first commercialization of Kampo extract formulations for general use (or OTC (over-the-counter) Kampo extract formulation) was achieved after 1957. The number of drugs has been subsequentially increased, reaching 148 Kampo extract formulation for prescription currently. Conclusion: We provide a history of Kampo extract formulations for prescription in Japan. The originality of this research is that it analyzes the background history of Kampo in parallel with relevant transitions in the government and insurance systems.

Keywords: health insurance system, history, Kampo, Kampo extract formulation for prescription, OTC Kampo extract formulation, pattern corresponding prescription (Ho-sho-so-tai) system

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Authors: Janneth González, George Barreto, Ludis Morales, Angélica Sabogal

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Sea anemone neurotoxins are peptides that interact with Na+ and K+ channels, resulting in specific alterations on their functions. Some of these neurotoxins (1ROO, 1BGK, 2K9E, 1BEI) are important for the treatment of nearly eighty autoimmune disorders due to their specificity for Kv1.3 channel. The aim of this study was to identify the common residues among these neurotoxins by computational methods, and establish whether there is a pattern useful for the future generation of a treatment for autoimmune diseases. Our results showed eight new key common residues between the studied neurotoxins interacting with a histidine ring and the selectivity filter of the receptor, thus showing a possible pattern of interaction. This knowledge may serve as an input for the design of more promising drugs for autoimmune treatments.

Keywords: neurotoxins, potassium channel, Kv1.3, computational methods, autoimmune diseases

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Authors: Neelam Taneja, Abhishek Mewara, Ajay Kumar

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Multidrug resistant shigellae have emerged as a therapeutic challenge in India. At our 2000 bed tertiary care referral centre in Chandigarh, North India, which caters to a large population of 7 neighboring states, antibiotic resistance in Shigella is being constantly monitored. Shigellae are isolated from 3 to 5% of all stool samples. In 1990 nalidixic acid was the drug of choice as 82%, and 63% of shigellae were resistant to ampicillin and cotrimoxazole respectively. Nalidixic acid resistance emerged in 1992 and rapidly increased from 6% during 1994-98 to 86% by the turn of 21st century. In the 1990s, the WHO recommended ciprofloxacin as the drug of choice for empiric treatment of shigellosis in view of the existing high level resistance to agents like chloramphenicol, ampicillin, cotrimoxazole and nalidixic acid. First resistance to ciprofloxacin in S. flexneri at our centre appeared in 2000 and rapidly rose to 46% in 2007 (MIC>4mg/L). In between we had an outbreak of ciprofloxacin resistant S.dysenteriae serotype 1 in 2003. Therapeutic failures with ciprofloxacin occurred with both ciprofloxacin-resistant S. dysenteriae and ciprofloxacin-resistant S. flexneri. The severity of illness was more with ciprofloxacin-resistant strains. Till 2000, elsewhere in the world ciprofloxacin resistance in S. flexneri was sporadic and uncommon, though resistance to co-trimoxazole and ampicillin was common and in some areas resistance to nalidixic acid had also emerged. Fluoroquinolones due to extensive use and misuse for many other illnesses in our region are thus no longer the preferred group of drugs for managing shigellosis in India. WHO presently recommends ceftriaxone and azithromycin as alternative drugs to fluoroquinolone-resistant shigellae, however, overreliance on this group of drugs also seems to soon become questionable considering the emerging cephalosporin-resistant shigellae. We found 15.1% of S. flexneri isolates collected over a period of 9 years (2000-2009) resistant to at least one of the third-generation cephalosporins (ceftriaxone/cefotaxime). The first isolate showing ceftriaxone resistance was obtained in 2001, and we have observed an increase in number of isolates resistant to third generation cephalosporins in S. flexneri 2005 onwards. This situation has now become a therapeutic challenge in our region. The MIC values for Shigella isolates revealed a worrisome rise for ceftriaxone (MIC90:12 mg/L) and cefepime (MIC90:8 mg/L). MIC values for S. dysenteriae remained below 1 mg/L for ceftriaxone, however for cefepime, the MIC90 has raised to 4 mg/L. These infections caused by ceftriaxone-resistant S. flexneri isolates were successfully treated by azithromycin at our center. Most worrisome development in the present has been the emergence of DSA(Decreased susceptibility to azithromycin) which surfaced in 2001 and has increased from 4.3% till 2011 to 34% thereafter. We suspect plasmid-mediated resistance as we detected qnrS1-positive Shigella for the first time from the Indian subcontinent in 2 strains from 2010, indicating a relatively new appearance of this PMQR determinant among Shigella in India. This calls for a continuous and strong surveillance of antibiotic resistance across the country. The prevention of shigellosis by developing cost-effective vaccines is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country

Keywords: Shigella, antimicrobial, resistance, India

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Authors: George Hanna Abdelmelek Henien

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Quality and safety issues are common in Ethiopia's food processing industry, which can negatively impact consumers' health and livelihoods. The country is known for its various agricultural products that are important to the economy. However, food quality and safety policies and management practices in the food processing industry have led to many health problems, foodborne illnesses and economic losses. This article aims to show the causes and consequences of food safety and quality problems in the food processing industry in Ethiopia and discuss possible solutions to solve them. One of the main reasons for food quality and safety in Ethiopia's food processing industry is the lack of adequate regulation and enforcement mechanisms. Inadequate food safety and quality policies have led to inefficiencies in food production. Additionally, the failure to monitor and enforce existing regulations has created a good opportunity for unscrupulous companies to engage in harmful practices that endanger the lives of citizens. The impact on food quality and safety is significant due to loss of life, high medical costs, and loss of consumer confidence in the food processing industry. Foodborne diseases such as diarrhoea, typhoid and cholera are common in Ethiopia, and food quality and safety play an important role in . Additionally, food recalls due to contamination or contamination often cause significant economic losses in the food processing industry. To solve these problems, the Ethiopian government began taking measures to improve food quality and safety in the food processing industry. One of the most prominent initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to monitor and control the quality and safety of food and beverage products in the country. EFDA has implemented many measures to improve food safety, such as carrying out routine inspections, monitoring the import of food products and implementing labeling requirements. Another solution that can improve food quality and safety in the food processing industry in Ethiopia is the implementation of food safety management system (FSMS). FSMS is a set of procedures and policies designed to identify, assess and control food safety risks during food processing. Implementing a FSMS can help companies in the food processing industry identify and address potential risks before they harm consumers. Additionally, implementing an FSMS can help companies comply with current safety and security regulations. Consequently, improving food safety policy and management system in Ethiopia's food processing industry is important to protect people's health and improve the country's economy. . Addressing the root causes of food quality and safety and implementing practical solutions that can help improve the overall food safety and quality in the country, such as establishing regulatory bodies and implementing food management systems.

Keywords: food quality, food safety, policy, management system, food processing industry food traceability, industry 4.0, internet of things, block chain, best worst method, marcos

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Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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Authors: B. Ben Amara, H. Mhiri Sellami

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Serious games adoption is increasing in multiple fields, including health, education, and business. In the same way, many research studied serious games (SGs) for various purposes such as classification, positive impacts, or learning outcomes. Although most of these research examine SG characteristics (SGCs) for conducting their studies, to author’s best knowledge, there is no consensus about features neither in number not in the description. In this paper, we conduct a literature review to collect essential game attributes regardless of the application areas and the study objectives. Firstly, we aimed to define Common SGCs (CSGCs) that characterize the game aspect, by gathering features having the same meanings. Secondly, we tried to identify specific features related to the application area or to the study purpose as a serious aspect. The findings suggest that any type of SG can be defined by a number of CSGCs depicting the gaming side, such as adaptability and rules. In addition, we outlined a number of specific SGCs describing the 'serious' aspect, including specific needs of the domain and indented outcomes. In conclusion, our review showed that it is possible to bridge the research gap due to the lack of consensus by using CSGCs. Moreover, these features facilitate the design and development of successful serious games in any domain and provide a foundation for further research in this area.

Keywords: serious game characteristics, serious games common aspects, serious games features, serious games outcomes

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Authors: Hyein Ko

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In 2017, many signs of populism occurred around the world. This paper suggests that populism is not a sudden phenomenon, but a manifestation of common people’s will. By analyzing previous research, this paper proposes three factors related to populism: Inequality, experience of economic crisis, and rapid cultural change. With these three elements, four cases will be investigated in this article; two countries experienced populism, and the other two countries did not experience it. Comparing four cases by using three elements will give a fruitful foundation for further analysis regarding populism. In sum, aforementioned three elements are highly related to the occurrence of populism. However, there is one hidden factor: dissatisfaction with established politics. Thus, populism is not a temporal phenomenon. It is a red alert for democratic crisis.

Keywords: common people, democratic crisis, populism, Trump phenomenon

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Authors: Maha Al-Ali, Selvakannan Periasamy, Rajarathinam Parthasarathy

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Drying temperature is an important factor impacting the physicochemical properties of the dried materials, particularly the pharmaceutical powders. Drying of pharmaceuticals by using microwave radiation is very limited, and the available information about the interaction between the electromagnetic radiations and the pharmaceutical material is still scarce. Therefore, microwave drying process is employed in this work to dry the wet (moisturised) granules of the formulated naproxen-sodium drug. This study aims to investigate the influences of the microwave radiation temperatures on the moisture removal, the crystalline structure, the size and morphology of the dried naproxen-sodium particles, and identify any potential changes in the chemical groups of the drug. In this work, newly formulated naproxen-sodium is prepared and moisturized by wet granulation process and hence dried by using microwave radiation at different temperatures. Moisture analyzer, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and scanning electron microscope are used to characterise the non-moisturised powder (reference powder), the moisturised granules, and the dried particles. The results show that microwave drying of naproxen-sodium at high drying temperature is more efficient than that at low temperatures in terms of the moisture removal. Although there is no significant change in the chemical structure of the dried particles, the particle size, crystallinity and morphology are relatively changed with changing of heating temperature.

Keywords: heating temperature, microwave drying, naproxen-sodium, particle size

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Authors: Y. V. S. Annapurna, V. V. Lakshmi

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Urinary tract infection (UTI) is one of the most common infectious diseases at the community level with a high rate of morbidity . This is further augmented by increase in the number of resistant and multi resistant strains of bacteria particularly by those producing Extended spectrum of beta lactamases. The present study was aimed at analysis of antibiograms of E.coli and Klebsiella sp causing urinary tract infections. Between November 2011 and April 2013, a total of 1120 urine samples were analyzed,. Antibiotic sensitivity testing was done with 542(48%) isolates of E.coli and 446(39%) of Klebsiella sp using the standard disc diffusion method against eleven commonly used antibiotics .Organisms showed high susceptibility to Amikacin and Netilimicin and low susceptibility to Cephalosporins. MAR index was calculated for the multidrug resistant strains. Maximum MAR index detected among the isolates was 0.9. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) according to CLSI guidelines. Plasmid profile of the isolates was carried out using alkaline hydrolysis method. Agarose-gel electrophoresis showed presence of high-molecular weight plasmid DNA among the ESBL strains. This study emphasizes the importance of indiscriminate use of antibiotics which if discontinued, in turn would prevent further development of bacterial drug resistance. For this, a proper knowledge of susceptibility pattern of uropathogens is necessary before prescribing empirical antibiotic therapy and it should be made mandatory.

Keywords: escherichia coli, extended spectrum of beta lactamase, Klebsiella spp, Uropathogens

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

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

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

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Authors: C. Brandt, R. Christopher, N. Damons

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Background: Soccer is one of the most common sports in the world. It is associated with a significant chance of injury either during training or during the course of an actual match. Studies on the epidemiology of soccer injuries have been widely conducted, but methodological appraisal is lacking to make evidence-based decisions. Objectives: The purpose of this study was to conduct a systematic review of common injuries in soccer and their risk factors. Methods: A systematic review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were searched. The quality of selected studies was rated, and data extracted and tabulated. Plot data analysis was done, and incidence rates and odds ratios were calculated, with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The search yielded 62 studies, of which 21 were screened for inclusion. A total of 16 studies were included for the analysis, ten for qualitative and six for quantitative analysis. The included studies had, on average, a low risk of bias and good methodological quality. The heterogeneity amongst the pooled studies was, however, statistically significant (χ²-p value < 0.001). The pooled results indicated a high incidence of soccer injuries at an incidence rate of 6.83 per 1000 hours of play. The pooled results also showed significant evidence of risk factors and the likelihood of injury occurrence in relation to these risk factors (OR=1.12 95% CI 1.07; 1.17). Conclusion: Although multiple studies are available on the epidemiology of soccer injuries and risk factors, only a limited number of studies were of sound methodology to be included in a review. There was also significant heterogeneity amongst the studies. The incidence rate of common soccer injuries was found to be 6.83 per 1000 hours of play. This incidence rate is lower than the values reported by the majority of previous studies on the occurrence of common soccer injuries. The types of common soccer injuries found by this review support the soccer injuries pattern reported in existing literature as muscle strain and ligament sprain of varying severity, especially in the lower limbs. The risk factors that emerged from this systematic review are predominantly intrinsic risk factors. The risk factors increase the risk of traumatic and overuse injuries of the lower extremities such as hamstrings and groin strains, knee and ankle sprains, and contusion.

Keywords: incidence, prevalence, risk factors, soccer injuries

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Authors: Orathai Srithongtham, Ubonsri Thabuddha

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The youth with HIV positive is not difference from the general youth in term of sexual needs. Sexual health is crucial the most to support the youth with HIV positive to be sexual well-being. This study aims to elucidate the sexual health on protection from STDs (Sexual Transmitted Diseases) and HIV transmission and to explain sexual risk behavior of the youth with HIV positive. The target group was the youth with HIV positive about 23 cases from two provinces in northeastern part of Thailand. Qualitative method was applied for collecting data by in-depth interview. Content analysis was use for data analysis. The youth with HIV positive was protection from STDs and HIV transmission by using the condom during sexual activity. The reason to deny the condom use were ashamed, condom is not a part of life, no have fit size, and the youth fear to stigmatized as a mental disorder and fear to stigmatized as going to fuck someone. The youth who trust with nurse in clinic was dare to request the condom by face. Sexual activity without condom use is sexual risk behavior. The major causes were couple trust and the sexual enjoyment first and sexual active competition with friend without condom use. The concern on HIV was the boyfriend or girlfriend not accepts the HIV positive people, worry about the HIV transmutation, and finally not compliance to ARV drug. The youth with HIV positive was lacking of the knowledge on sexual health on the issues of access to condom and the concern to keep on relationship with the boyfriend or girlfriend. This concern issues was led to the non-adherence of ARV drug and HIV distribution. To provide the sexual health service is more essential to the youth with HIV positive.

Keywords: sexual health, sexual risk behavior, youth, HIV

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Authors: Jannes Quer, Amir Niknejad, Marcus Weber

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Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

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