Search results for: controlled drug delivery

Authors: Sagar Jitendra Mahendrakar

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Integrating quality assurance (QA) practices into DevOps culture has become increasingly important in modern software development environments. Collaboration, automation and continuous feedback characterize the seamless integration of DevOps development and operations teams to achieve rapid and reliable software delivery. In this context, quality assurance plays a key role in ensuring that software products meet the highest quality, performance and reliability standards throughout the development life cycle. This brief explores key principles, challenges, and best practices related to quality assurance in a DevOps culture. This emphasizes the importance of quality transfer in the development process, as quality control processes are integrated in every step of the DevOps process. Automation is the cornerstone of DevOps quality assurance, enabling continuous testing, integration and deployment and providing rapid feedback for early problem identification and resolution. In addition, the summary addresses the cultural and organizational challenges of implementing quality assurance in DevOps, emphasizing the need to foster collaboration, break down silos, and promote a culture of continuous improvement. It also discusses the importance of toolchain integration and capability development to support effective QA practices in DevOps environments. Moreover, the abstract discusses the cultural and organizational challenges in implementing QA within DevOps, emphasizing the need for fostering collaboration, breaking down silos, and nurturing a culture of continuous improvement. It also addresses the importance of toolchain integration and skills development to support effective QA practices within DevOps environments. Overall, this collection works at the intersection of QA and DevOps culture, providing insights into how organizations can use DevOps principles to improve software quality, accelerate delivery, and meet the changing demands of today's dynamic software. landscape.

Keywords: quality engineer, devops, automation, tool

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Authors: Danylo Brindak, Viktor Liashko, Olexander Chepurniy

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Despite considerable experience in implementation of the best international approaches and services within response to epidemy of multi-drug resistant tuberculosis, the results of situation analysis indicate the presence of faults in this area. In 2014, Ukraine (for the first time) was included in the world’s five countries with the highest level of drug-resistant tuberculosis. The effectiveness of its treatment constitutes only 35% in the country. In this context, the increase in allocation of funds to control the epidemic of multidrug-resistant tuberculosis does not produce perceptible positive results. During 2001-2016, only the Global Fund to fight AIDS, Tuberculosis, and Malaria allocated to Ukraine more than USD 521,3 million for programs of tuberculosis and HIV/AIDS control. However, current conditions in post-Semashko system create little motivation for rational use of resources or cost control at inpatient TB facilities. There is no motivation to reduce overdue hospitalization and to target resources to priority sectors of modern tuberculosis control, including a model of care focused on the patient. In the presence of a line-item budget at medical institutions, based on the input factors as the ratios of beds and staff, there is a passive disposal of budgetary funds by health care institutions and their employees who have no motivation to improve quality and efficiency of service provision. Outpatient treatment of tuberculosis is being implemented in Ukraine since 2011 and has many risks, namely creation of parallel systems, low consistency through dependence on funding for the project, reduced the role of the family doctor, the fragmentation of financing, etc. In terms of reforming approaches to health system financing, which began in Ukraine in late 2016, NGO Infection Control in Ukraine conducted piloting of a new, motivating method of remuneration of employees in primary health care. The innovative aspect of this funding mechanism is cost according to results of treatment. The existing method of payment on the basis of the standard per inhabitant (per capita ratio) was added with motivating costs according to results of work. The effectiveness of such treatment of TB patients at the outpatient stage is 90%, while in whole on the basis of a current system the effectiveness of treatment of newly diagnosed pulmonary TB with positive swab is around 60% in the country. Even though Ukraine has 5.24 TB beds per 10 000 citizens. Implemented pilot model of ambulatory treatment will be used for the creation of costs system according to results of activities, the integration of TB and primary health and social services and their focus on achieving results, the reduction of inpatient treatment of tuberculosis.

Keywords: health care reform, multi-drug resistant tuberculosis, outpatient treatment efficiency, tuberculosis

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Authors: Fahimeh Marefat, Marzieh Marefat

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The present research is inspired by the comment that “A substantive, thorough, sophisticated literature review is a precondition for doing substantive, thorough, sophisticated research”. This study is a report on an action research to solve my problem of preparing students to write a Literature Review (LR) that is more than mere cut and paste. More specifically, this study was initiated to discover whether there is an impact of equipping students with tools to write LR on the quality of research and on their view on LR significance. The participants were twenty-four Iranian TEFLers at Allameh Tabataba’i University. they were taking their advanced writing course with the lead researcher. We met once a week for 90 minutes for five weeks followed by individual consultations. Working through a process approach, and implementing tasks, the lead researcher ran workshops implementing different controlled assignments and subsequent activities to lead students to practice appropriate source use on multiple drafts: From choosing the topic, finding sources, forming questions, preparing quotation, paraphrase, and summary note cards, to outlining and most importantly introducing them the tools to evaluate prior research and offer their own take of it and finally synthesizing and incorporating the notes into the body of the LR section of their papers. The LR scoring rubric was implemented and a note was emailed to the students asking about their views. It was indicated that awareness raising and detailed explicit instruction improved the LR quality compared to their previous projects. Interestingly enough, they acknowledged how LR shaped all stages of their research, a further support for the notion of “being scholars before researchers”. The key to success is mastery over the literature which translates into extensive reading and critically appraising it.

Keywords: controlled tasks, critical evaluation, review of literature, writing synthesis

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Authors: Mehrnaz Mostafavi, Jalaledin Ghanavi

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This research investigates the production of nanoring structures through a chemical reduction approach, exploring gradual reduction processes assisted by reductant agents, leading to the formation of these specialized nanorings. The study focuses on the controlled reduction of metal atoms within these agents, crucial for shaping these nanoring structures over time. The paper commences by highlighting the wide-ranging applications of metal nanostructures across fields like Nanomedicine, Nanobiotechnology, and advanced spectroscopy methods such as Surface Enhanced Raman Spectroscopy (SERS) and Surface Enhanced Infrared Absorption Spectroscopy (SEIRA). Particularly, gold nanoparticles, especially in the nanoring configuration, have gained significant attention due to their distinctive properties, offering accessible spaces suitable for sensing and spectroscopic applications. The methodology involves utilizing human serum albumin as a reducing agent to create gold nanoparticles through a chemical reduction process. This process involves the transfer of electrons from albumin's carboxylic groups, converting them into carbonyl, while AuCl4− acquires electrons to form gold nanoparticles. Various characterization techniques like Ultraviolet–visible spectroscopy (UV-Vis), Atomic-force microscopy (AFM), and Transmission electron microscopy (TEM) were employed to examine and validate the creation and properties of the gold nanoparticles and nanorings. The findings suggest that precise and gradual reduction processes, in conjunction with optimal pH conditions, play a pivotal role in generating nanoring structures. Experiments manipulating optical properties revealed distinct responses in the visible and infrared spectrums, demonstrating the tunability of these nanorings. Detailed examinations of the morphology confirmed the formation of gold nanorings, elucidating their size, distribution, and structural characteristics. These nanorings, characterized by an empty volume enclosed by uniform walls, exhibit promising potential in the realms of Nanomedicine and Nanobiotechnology. In summary, this study presents a chemical synthesis approach using organic reducing agents to produce gold nanorings. The results underscore the significance of controlled and gradual reduction processes in crafting nanoring structures with unique optical traits, offering considerable value across diverse nanotechnological applications.

Keywords: nanoring structures, chemical reduction approach, gold nanoparticles, spectroscopy methods, nano medicine applications

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Authors: Kanduru Lokesh, Venkitasamy Kesavan

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The unique structural features of spiro-oxindoles with diverse biological activities have made them privileged structures in new drug discovery. The key structural characteristic of these compounds is the spiro ring fused at the C-3 position of the oxindole core with varied heterocyclic motifs. Structural diversification of heterocyclic scaffolds to synthesize new chemical entities as pharmaceuticals and agrochemicals is one of the important goals of synthetic organic chemists. Nitrogen and oxygen containing heterocycles are by far the most widely occurring privileged structures in medicinal chemistry. The structural complexity and distinct three-dimensional arrangement of functional groups of these privileged structures are generally responsible for their specificity against biological targets. Structurally diverse compound libraries have proved to be valuable assets for drug discovery against challenging biological targets. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance in drug discovery to improve the efficiency and efficacy of the drugs. The development of suitable methodology for the synthesis of spiro-oxindole compounds has attracted much interest often in response to the significant biological activity displayed by the both natural and synthetic compounds. So creating structural diversity of oxindole scaffolds is need of the decade and formidable challenge. A general way to improve synthetic efficiency and also to access diversified molecules is through the annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favorable way. These observations motivated us to develop the annulation reaction protocol to enable the synthesis of a new class of spiro-oxindole motifs which in turn would enable the enhancement of molecular diversity. As part of our enduring interest in the development of novel, efficient synthetic strategies to enable the synthesis of biologically important oxindole fused spirocarbocyclic systems, We have developed an efficient methodology for the construction of highly functionalized spirocarbocyclic oxindoles through [4+2] annulation of phthalides via Hauser annulation. functionalized spirocarbocyclic oxindoles was accomplished for the first time in the literature using Hauser annulation strategy. The reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate led to the access of new class of biologically important spiro[indoline-3,2'-naphthalene] derivatives in very good yields. The synthetic utility of the annulated product was further demonstrated by fluorination Using NFSI as a fluorinating agent to furnish corresponding fluorinated product.

Keywords: Hauser-Kraus annulation, spiro carbocyclic oxindoles, oxindole-ester, fluoridation

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Ran An, Dang Wang

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Background: Mechanical ventilation has been confirmed to increase the incidence of postoperative pulmonary complications (PPCs), and several studies have shown that low tidal volumes combined with positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) reduce the incidence of PPCs. However, the optimal lung-protective ventilatory strategy remains unclear. Methods: Multiple databases were searched for randomized controlled trials (RCTs) published prior to October 2023. The association between individual PEEP (iPEEP) or other forms of lung-protective ventilation and the incidence of PPCs was evaluated by Bayesian network meta-analysis. Results: We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low ventilation (LVt) combined with iPEEP and RM was associated with significantly lower incidences of PPCs [HVt: OR=0.38 95CrI (0.19, 0.75), LVt: OR=0.33, 95% CrI (0.12, 0.82)], postoperative atelectasis, and pneumonia than was HVt or LVt. In abdominal surgery, LVT combined with iPEEP or medium-to-high PEEP and RM were associated with significantly lower incidences of PPCs, postoperative atelectasis, and pneumonia. LVt combined with iPEEP and RM was ranked the highest, which was based on SUCRA scores. Conclusion: LVt combined with iPEEP and RM decreased the incidences of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. iPEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence was moderate.

Keywords: protection ventilation strategies, postoperative pulmonary complications, network meta-analysis, noncardiac surgery

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Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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Authors: Santram Lodhi, Alok Pal Jain, Awesh K. Yadav, Gopal Rai

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Rhodiola rosea L. (Crassulaceae) is commonly known as golden root or rose root. It is a perennial herbaceous plant and most investigated species of the genus Rhodiola. Rhodiola rosea contains flavonoids, terpenoids, phenylpropanoid glycosides and phenylethanol derivatives in the roots of the plant. The objective of present study was to investigate the protective effect of hydroalcoholic extract from Rhodiola rosea roots in DSS induced colitis in mice. The ulcerative colitis was induced by DSS (3%, w/v) in mice and estimated weight loss and stool consistency. Various parameters including Colon length, spleen weights and ulcer index were also measured. The histological observations were observed by H&E staining. Effect of hydroalcoholic extract on various antioxidant parameter of rat colon such as tissue myeloperoxidase (MPO), reduced GSH, SOD concentrations and lipid peroxidation were determined. Pro-inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and nitric oxide (NO) were determined by ELISA. In DSS induced group, mice body weight decreased gradually as compared to the control group. Redness and edema were observed in the colons intensely and scores representing inflammation in this group. The extract treated showed with tissue levels of TNF-α, IL-6 and MPO activity were significantly (p<0.05) increased. The mice treated with higher doses of hydroalcoholic extract (300 mg/kg) significantly reduced the activity compared with standard drug sulfasalazine (100 mg/kg. B.wt). Conclusion: Results of this study were suggested that the efficacy of hydroalcoholic extract, especially at the higher dose, was similar to that of standard drug, which concerned its potential application as a natural medicine for the treatment of ulcerative colitis.

Keywords: phenylpropanoid, Rhodiola rosea, sulfasalazin, ulcerative colitis

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Authors: Shilpee Jain, Sachin Latiyan, Kaushik Suneet

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Unlike traditional robots, medical microbots are not only smaller in size, but they also possess various unique properties, for example, biocompatibility, stability in the biological fluids, navigation opposite to the bloodstream, wireless control over locomotion, etc. The idea behind their usage in the medical field was to build a minimally invasive method for addressing the post-operative complications, including longer recovery time, infection eruption and pain. Herein, the present study demonstrates the fabrication of dual nature magneto-conducting Fe3O4 magnetic nanoparticles (MNPs) and SU8 derived carbon-based Janus microbots for the efficient intracellular delivery of biomolecules. The low aspect ratio with feature size 2-5 μm microbots were fabricated by using a photolithography technique. These microbots were pyrolyzed at 900°C, which converts SU8 into amorphous carbon. The pyrolyzed microbots have dual properties, i.e., the half part is magneto-conducting and another half is only conducting for sufficing the therapeutic payloads efficiently with the application of external electric/magnetic field stimulations. For the efficient intracellular delivery of the microbots, the size and aspect ratio plays a significant role. However, on a smaller scale, the proper control over movement is difficult to achieve. The dual nature of Janus microbots allowed to control its maneuverability in the complex fluids using external electric as well as the magnetic field. Interestingly, Janus microbots move faster with the application of an external electric field (44 µm/s) as compared to the magnetic field (18 µm/s) application. Furthermore, these Janus microbots exhibit auto-fluorescence behavior that will help to track their pathway during navigation. Typically, the use of MNPs in the microdevices enhances the tendency to agglomerate. However, the incorporation of Fe₃O₄ MNPs in the pyrolyzed carbon reduces the chances of agglomeration of the microbots. The biocompatibility of the medical microbots, which is the essential property of any biosystems, was determined in vitro using HeLa cells. The microbots were found to compatible with HeLa cells. Additionally, the intracellular uptake of microbots was higher in the presence of an external electric field as compared to without electric field stimulation. In summary, the cytocompatible Janus microbots were fabricated successfully. They are stable in the biological fluids, wireless controllable navigation with the help of a few Guess external magnetic fields, their movement can be tracked because of autofluorescence behavior, they are less susceptible to agglomeration and higher cellular uptake could be achieved with the application of the external electric field. Thus, these carriers could offer a versatile platform to suffice the therapeutic payloads under wireless actuation.

Keywords: amorphous carbon, electric/magnetic stimulations, Janus microbots, magnetic nanoparticles, minimally invasive procedures

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Authors: Nafsi K. Ashraf, C. V. Vipin, V. Anantha Subramanian

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This paper reports the design of a waterjet propulsion system for an amphibious vehicle based on circulation distribution over the camber line for the sections of the impeller and stator. In contrast with the conventional waterjet design, the inlet duct is straight for water entry parallel and in line with the nozzle exit. The extended nozzle after the stator bowl makes the flow more axial further improving thrust delivery. Waterjet works on the principle of volume flow rate through the system and unlike the propeller, it is an internal flow system. The major difference between the propeller and the waterjet occurs at the flow passing the actuator. Though a ducted propeller could constitute the equivalent of waterjet propulsion, in a realistic situation, the nozzle area for the Waterjet would be proportionately larger to the inlet area and propeller disc area. Moreover, the flow rate through impeller disk is controlled by nozzle area. For these reasons the waterjet design is based on pump systems rather than propellers and therefore it is important to bring out the characteristics of the flow from this point of view. The analysis is carried out using computational fluid dynamics. Design of waterjet propulsion is carried out adapting the axial flow pump design and performance analysis was done with three-dimensional computational fluid dynamics (CFD) code. With the varying environmental conditions as well as with the necessity of high discharge and low head along with the space confinement for the given amphibious vehicle, an axial pump design is suitable. The major problem of inlet velocity distribution is the large variation of velocity in the circumferential direction which gives rise to heavy blade loading that varies with time. The cavitation criteria have also been taken into account as per the hydrodynamic pump design. Generally, waterjet propulsion system can be parted into the inlet, the pump, the nozzle and the steering device. The pump further comprises an impeller and a stator. Analytical and numerical approaches such as RANSE solver has been undertaken to understand the performance of designed waterjet propulsion system. Unlike in case of propellers the analysis was based on head flow curve with efficiency and power curves. The modeling of the impeller is performed using rigid body motion approach. The realizable k-ϵ model has been used for turbulence modeling. The appropriate boundary conditions are applied for the domain, domain size and grid dependence studies are carried out.

Keywords: amphibious vehicle, CFD, impeller design, waterjet propulsion

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Authors: Thanusha D. Abeywickrama, Inoka C. Perera, Genji Kurisu

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Tuberculosis, considered being as the ninth leading cause of death worldwide, cause from a single infectious agent M. tuberculosis and the drug resistance nature of this bacterium is a continuing threat to the world. Therefore TB preventing treatment is expanding, where this study designed to analyze the regulatory mechanism of GntR transcriptional regulator gene Rv0792c, which lie between several genes codes for some hypothetical proteins, a monooxygenase and an oxidoreductase. The gene encoding Rv0792c was cloned into pET28a and expressed protein was purified to near homogeneity by Nickel affinity chromatography. It was previously reported that the protein binds within the intergenic region (BS region) between Rv0792c gene and monooxygenase (Rv0793). This resulted in binding of three protein molecules with the BS region suggesting tight control of monooxygenase as well as its own gene. Since monooxygenase plays a key role in metabolism, this gene may have a global regulatory role. The natural ligand for this regulator is still under investigation. In relation to the Rv0792 protein structure, a Circular Dichroism (CD) spectrum was carried out to determine its secondary structure elements. Percentage-wise, 17.4% Helix, 21.8% Antiparallel, 5.1% Parallel, 12.3% turn and 43.5% other were revealed from CD spectrum data under room temperature. Differential Scanning Calorimetry (DSC) was conducted to assess the thermal stability of Rv0792, which the melting temperature of protein is 57.2 ± 0.6 °C. The graph of heat capacity (Cp) versus temperature for the best fit was obtained for non-two-state model, which concludes the folding of Rv0792 protein occurs through stable intermediates. Peak area (∆HCal ) and Peak shape (∆HVant ) was calculated from the graph and ∆HCal / ∆HVant was close to 0.5, suggesting dimeric nature of the protein.

Keywords: CD spectrum, DSC analysis, GntR transcriptional regulator, protein structure

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Authors: L. B. Naves, L. Almeida

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The development of Drugs Delivery System (DDS), has been wildly investigated in the last decades. In this paper, first a general overview of traditional and modern wound dressing is presented. This is followed by a review of what scientist have done in the medical environment, focusing the possibility to develop a new alternative for DDS through transdermal pathway, aiming to treat melanoma skin cancer.

Keywords: cancer therapy, dressing polymers, melanoma, wound healing

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Authors: Akhtar Nawaz, Sahar Noor, Iftikhar Hussain

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This paper considers advanced hybrid manufacturing planning both push and pull system in which each customer order has a due date by demand forecast and customer orders. We present a tool for model for tool development that requires an absolute due dates and customer orders in a manufacturing supply chain. It is vital for the manufacturing companies to face the problem of variations in demands, increase in varieties by maintaining safety stock and to minimize components obsolescence and uselessness. High inventory cost and low delivery lead time is expected in push type of system and on contrary high delivery lead time and low inventory cost is predicted in the pull type. For this tool for model we need an MRP system for the push and pull environment and control of inventories in push parts and lead time in the pull part. To retain process data quickly, completely and to improve responsiveness and minimize inventory cost, a tool is required to deal with the high product variance and short cycle parts. In practice, planning and scheduling are interrelated and should be solved simultaneously with supply chain to ensure that the due dates of customer orders are met. The proposed tool for model considers alternative process plans for job types, with precedence constraints for job operations. Such a tool for model has not been treated in the literature. To solve the model, tool was developed, so a new technique was required to deal with the issue of high product variance and short life cycles in assemble to order.

Keywords: hybrid manufacturing system, supply chain system, make to order, make to stock, assemble to order

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Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

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The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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Authors: Selina Studer, Maria Kleinstäuber, Cornelia Weise

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Background: Finding words to report what you have been through may be challenging, especially when dealing with stressful or highly emotional experiences. Photovoice (PV) represents a possible way of facilitating experience reporting. In this approach, people take photos about a particular topic (in our study: worries about the future) and talk about the topic based on the photos. So far, the benefits of Photovoice have been quantitatively insufficiently tested. There is a lack of randomized controlled trials investigating PV in comparison to other methods. This study aimed to fill this research gap. Methods: 65 participants took part in the study and were randomly assigned to the PV group, the writing group (WG), or the control group (CG). The PV group received the task to take photos of worries regarding the future for one week and send max. 5 of them to the interviewer before the interview. The WG had to write down the worries about the future and send max. 5 of them to the interviewer before the interview. The control group did not receive a specific assignment. The semi-structured interview consisted of six open-ended questions and was applied to all future worries. The questions included the content of the future worries, the meaning, and how the worry expressed itself emotionally and physically. The interview was recorded and later transcribed. After the interview, online questionnaires were filled out. They covered a range of variables such as access to emotional content, ability to describe feelings, the extent of self-disclosure, and relationship quality. Results: Contrary to our hypotheses, one-way ANOVA revealed no differences between the three conditions concerning all variables (access to emotional content, ability to describe feelings, the extent of self-disclosure, and so on), all p's > 0.14, BF₀₁ = 1.78-7.66. In a subsequent step, the words in the transcribed interviews were analyzed. The LIWC program counted how many emotional words occurred in the text and assigned them to predefined categories. Planned contrasts revealed that the PV reported more negative emotional words compared to the two groups t(62) = 2.62, p = .011, and also compared to the WG only, t(62) = 2.36, p = .022, BF₀₁ = 0.62. Conclusions and implications: The applied self-report instruments did not reveal any differences between the groups. However, the PV group used more negative emotional words than the other two groups. The discrepancy between self-report and observation variables regarding emotionality is noticeable. It is suggested that the highly educated and above-average female sample may not have needed PV to access emotional content. It is possible that the approach would yield clearer results in a clinical sample. This and other approaches are currently being investigated in a follow-up study.

Keywords: photovoice, controlled randomized study, online intervention, emotional awareness, self-disclosure, data triangulation, interviews

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Authors: A. Fomujong, P. Mobit, A. Ndlovu, R. Teboh

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Purpose: Film’s unique qualities, such as tissue equivalence, high spatial resolution, near energy independence and comparatively less expensive dosimeter, ought to make it the preferred and widely used in radiotherapy centers in low and middle income countries (LMICs). This, however, is not always the case, as other factors that are often maybe taken for granted in advanced radiotherapy centers remain a challenge in LMICs. We explored the unique qualities of film dosimetry that can make it possible for one Institution to benefit from another’s protocols via collaboration. Methods: For simplicity, two Institutions were considered in this work. We used a single batch of films (EBT-XD) and established a calibration protocol, including scan protocols and calibration curves, using the radiotherapy delivery system at Institution A. We then proceeded and performed patient-specific QA for patients treated on system A (PSQA-A-A). Films from the same batch were then sent to a remote center for PSQA on radiotherapy delivery system B. Irradiations were done at Institution B and then returned to Institution A for processing and analysis (PSQA-B-A). The following points were taken into consideration throughout the process (a) A reference film was irradiated to a known dose on the same system irradiating the PSQA film. (b) For calibration, we utilized the one-scan protocol and maintained the same scan orientation of the calibration, PSQA and reference films. Results: Gamma index analysis using a dose threshold of 10% and 3%/2mm criteria showed a gamma passing rate of 99.8% and 100% for the PSQA-A-A and PSQA-B-A, respectively. Conclusion: This work demonstrates that one could use established film dosimetry protocols in one Institution, e.g., an advanced radiotherapy center and apply similar accuracies to irradiations performed at another institution, e.g., a center located in LMIC, which thus encourages collaboration between the two for worldwide patient benefits.

Keywords: collaboration, film dosimetry, LMIC, radiotherapy, calibration

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Milad Gholizadeh

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Asthma and chronic obstructive pulmonary disease (COPD) are very shared inflammatory diseases of the airlines. They togethercause airway tapering and are cumulative in occurrence throughout the world, imposing huge burdens on health care. It is currently recognized that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) temporary together with basophils. Patients who have plain asthma or are asthmatic patients who smoke with topographies of COPD-induced inflammation and might advantage from treatments targeting neutrophils, countingmacrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies in contradiction of IL-1 and IL-17.Viral and bacterial infections, not only reason acute exacerbations of COPD, but also intensify and continue chronic inflammation in steady COPD through pathogen-associated molecular patterns. Present treatment plans are absorbed on titration of inhaled therapies such as long-acting bronchodilators, with cumulative interest in the usage of beleaguered biologic therapies meant at the underlying inflammatory devices. Educationssuggest that the mucosal IgA reply is abridged in COPD, and a lacking conveyance of IgA across the bronchial epithelium in COPD has been recognized, perhaps involving neutrophil proteinases, which may damage the Ig receptor mediating this transepithelialdirection-finding. Future instructions for investigation will emphasis elucidating the diverse inflammatory signatures foremost to asthma and chronic obstrucive, the development of reliable analytic standards and biomarkers of illness, and refining the clinical organization with an eye toward targeted therapies.

Keywords: imminology, asthma, COPD, CXCR2 antagonists

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Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

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The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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Authors: Somayeh Abedian, Pirhossein Kolivand, Hamid Reza Lornejad, Amin Karampour, Ebrahim Keshavarz Safari

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For emergency and relief service providers such as pre-hospital emergencies, quick arrival at the scene of an accident or any EMS mission is one of the most important requirements of effective service delivery. Response time (the interval between the time of the call and the time of arrival on scene) is a critical factor in determining the quality of pre-hospital Emergency Medical Services (EMS). This is especially important for heart attack, stroke, or accident patients. Location-based e-services can be broadly defined as any service that provides information pertinent to the current location of an active mobile handset or precise address of landline phone call at a specific time window, regardless of the underlying delivery technology used to convey the information. According to research, one of the effective methods of meeting this goal is determining the location of the caller via the cooperation of landline and mobile phone operators in the country. The follow-up of the Communications Regulatory Authority (CRA) organization has resulted in the receipt of two separate secured electronic web services. Thus, to ensure human privacy, a secure technical architecture was required for launching the services in the pre-hospital EMS information management system. In addition, to quicken medics’ arrival at the patient's bedside, rescue vehicles should make use of an intelligent transportation system to estimate road traffic using a GPS-based mobile navigation system independent of the Internet. This paper seeks to illustrate the architecture of the practical national model used by the Iranian EMS organization.

Keywords: response time, geographic location inquiry service (GLIS), location-based service (LBS), emergency medical services information system (EMSIS)

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Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

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Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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Authors: Brian Moore, Stuart Woodcock, Dean Dudley

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Mental health problems have significant social and economic consequences; however, many individuals do not seek traditional assistance for mental health difficulties. Martial arts training may provide an inexpensive alternative to traditional psychological therapy. While limited research has suggested martial arts training may be an efficacious intervention, the validity and reliability of this are questionable given the small number of relevant studies and other methodological problems. The study examined the effects of 10-week martial arts-based psycho-social intervention which was evaluated using a randomized controlled trial. The intervention was delivered to 283 secondary school students, aged between 12-14 years, who were recruited from government and catholic secondary schools in New South Wales, Australia. The intervention was delivered in a group format onsite at participating schools and had an intervention dose of 10 x 50-60 minute sessions, once per week for 10 weeks. Data were collected at baseline, post-intervention, and 12-week follow-up. Results found a consistent pattern for strength based wellbeing outcomes. All primary and secondary measures relating to resilience and self-efficacy improved for the intervention group and declined for the control group. As these findings were derived from a robust design and rigorous evaluation, they provide valid and reliable evidence that martial arts-based psycho-social interventions can be considered as an efficacious method of improving strength and wellbeing outcomes.

Keywords: martial arts, mental health, resilience, self-efficacy

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Authors: Yau-Luen Ng, Nathan Banka, Santosh Devasia

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In this paper, a method based on soft artificial cilia is introduced to separate particles based on size and mass. In nature, cilia are used for fluid propulsion in the mammalian circulatory system, as well as for swimming and size-selective particle entrainment for feeding in microorganisms. Inspired by biological cilia, an array of artificial cilia was fabricated using Polydimethylsiloxane (PDMS) to simulate the actual motion. A row of four individually-controlled magnetic artificial cilia in a semi-circular channel are actuated by the magnetic fields from four permanent magnets. Each cilium is a slender rectangular cantilever approximately 13mm long made from a composite of PDMS and carbonyl iron particles. A time-varying magnetic force is achieved by periodically varying the out-of-plane distance from the permanent magnets to the cilia, resulting in large-amplitude deflections of the cilia that can be used to drive fluid motion. Previous results have shown that this system of individually-controlled magnetic cilia can generate effective mixing flows; the purpose of the present work is to apply the individual cilia control to a particle separation task. Based on the observed beating patterns of cilia arrays in nature, the experimental beating patterns were selected as a metachronal wave, in which a fixed phase lead or lag is imposed between adjacent cilia. Additionally, the beating frequency was varied. For each set of experimental parameters, the channel was filled with water and polyethylene microspheres introduced at the center of the cilia array. Two types of particles were used: large red microspheres with density 0.9971 g/cm³ and 850-1000 μm avg. diameter, and small blue microspheres with density 1.06 g/cm³ and diameter 30 μm. At low beating frequencies, all particles were propelled in the mean flow direction. However, the large particles were observed to reverse directions above about 4.8 Hz, whereas reversal of the small particle transport direction did not occur until 6 Hz. Between these two transition frequencies, the large and small particles can be separated as they move in opposite directions. The experimental results show that selecting an appropriate cilia beating pattern can lead to selective transport of neutrally-buoyant particles based on their size. Importantly, the separation threshold can be chosen dynamically by adjusting the actuation frequency. However, further study is required to determine the range of particle sizes that can be effectively separated for a given system geometry.

Keywords: magnetic cilia, particle separation, tunable separation, soft actutors

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Authors: Krishna Dahiya

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Introduction: Labour pain has been described as the most severe pain experienced by women in their lives. Pain management in labour is one of the most important challenges faced by the obstetrician. The opioids are the primary treatment for patients with moderate and severe pain but these drugs are not always tolerated and are associated with dose-dependent side effects. Nonsteroidal anti-inflammatory drugs, too, are associated with variable adverse effects. Considering these factors, our study compared the efficacy and side effect of intravenous tramadol and paracetamol. Objective: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of tramadol for intrapartum analgesia. Methods: In a randomized prospective study at Pt. BDS PGIMS, 200 women in active labor were allocated to received either paracetamol (n=100) or tramadol (n=100). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events. Results: The mean age of cases were 25.55 ± 3.849 years and 25.60 ± 3.655 years respectively As recorded by the VAS score, there was significant pain reduction at 30 minutes, and at 1 and 2 hours in both groups (P<0.01). In comparison, between group I and II, a significantly higher rate of nausea and vomiting in tramadol group (14% vs 8%; P < 0.03) patients. Similarly, drowsiness (0% vs 11%; P<0.01), dry mouth (0% vs 8%; P<0.04) and dizziness (0% vs 9%; P<0.02) was also significant in group II. Conclusion: Due to difficulty in administering epidural analgesia to all parturients, administration of paracetamol and tramadol infusion for analgesia is simple and less invasive alternative. In the present study, both paracetamol and tramadol were equally effective for labour analgesia but paracetamol has emerged as safe alternative as compared to tramadol due to a low incidence of side effects.

Keywords: paracetamol, tramadol, labor, analgesia

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Authors: Meenakshi Chaudhary, V .S. Randhawa, M. Jais, R. Dutta

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Introduction: An outbreak of Multi drug resistant S. Typhi (i.e. resistance to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) occurred in 1990's in India which peaked in 1992-93 and resulted in the change of drug of choice from chloramphenicol to ciprofloxacin for enteric fever. Currently an emergence of Ciprofloxacin susceptible S. Typhi isolates in the region is being reported which appears to be chromosomally mediated. Methodology: Six hundred sixty four strains were randomly selected from the time period between January 2008-December 2011 at the National Salmonella Phage Typing Centre, LHMC, New Delhi. The strains were representative of the north, central and south zones of India. All isolates were subjected to serotyping, biotyping, phage typing and then to antimicrobial susceptibility testing by CLSI disk diffusion (CLSI) technique to Ciprofloxacin, Cefotaxime, Ampicillin, Chloramphenicol, Trimethoprim-Sulfomethoxazole and Tetracycline. Subsequently MIC of the isolates was determined by E-test (AB-Biodisc). Results: More than 80% of the tested strains had intermediate susceptibility to ciprofloxacin. The E test revealed the MIC (Ciprofloxacin) of these strains to be in the range of 0.12 to 0.5 µg/ml. Sixty nine percent of ciprofloxacin intermediate susceptible strains belonged to Phage type E1 and fourteen percent of these were Vi- Negative i.e these could not be typed by the phage typing scheme of Craigie and Yen. All the strains remained susceptible to cefotaxime. Conclusion: Predominant isolation of intermediate susceptible S. Typhi strains from India would alter the recommendations of empiric treatment of enteric fever in the region. Alternative to the low cost ciprofloxacin will have to be sought or increased dosage and/or duration of ciprofloxacin will have to be recommended. The reasons for the trend of increase in percentage of intermediate susceptible S. Typhi strains are not clear but may be attributed partly to the revision of CLSI guidelines in 2013.

Keywords: salmonella typhi, decreased ciprofloxacin susceptibility, ciprofloxacin, minimum inhibitory concentration

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Authors: Rakesh Mishra

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India’s Demography has always amazed the world because of its unprecedented outcomes in the presence of multifaceted socioeconomic and geographical characteristics. Being the first one to implement family panning in 1952, it occupies 2nd largest population of the world, with some of its state like Uttar Pradesh contributing 5th largest population to the world population surpassing Brazil. Being the one with higher in number it is more prone to the demographic disparity persisting into its territories brought upon by the inequalities in availability, accessibility and attainability of socioeconomic and various other resources. Fifth goal of Millennium Development Goal emphasis to improve maternal and child health across the world as Children’s development is very important for the overall development of society and the best way to develop national human resources is to take care of children. The target is to reduce the infant deaths by three quarters between 1990 and 2015. Child health status depends on the care and delivery by trained personnel, particularly through institutional facilities which is further associated with the status of the mother. However, delivery in institutional facilities and delivery by skilled personnel are rising slowly in India. The main objective of the present study is to measure the child health status on based on the educational and occupational background of the women in India. Study indicates that women education plays a very crucial role in deciding the health of the new born care and access to family planning, but the women autonomy indicates to have mixed results in different states of India. It is observed that rural women are 1.61 times more likely to exclusive breastfed their children compared to urban women. With respect to Hindu category, women belonging to other religious community were 21 percent less likely to exclusive breastfed their child. Taking scheduled caste as reference category, the odds of exclusive breastfeeding is found to be decreasing in comparison to other castes, and it is found to be significant among general category. Women of high education status have higher odds of using family planning methods in most of the southern states of India. By and large, girls and boys are about equally undernourished. Under nutrition is generally lower for first births than for subsequent births and consistently increases with increasing birth order for all measures of nutritional status. It is to be noted that at age 12-23 months, when many children are being weaned from breast milk, 30 percent of children are severely stunted and around 21 percent are severely underweight. So, this paper presents the evidence on the patterns of prevailing child health status in India and its states with reference to the mother socioeconomics and biological characteristics and examines trends in these, and discusses plausible explanations.

Keywords: immunization, exclusive breastfeeding, under five mortality, binary logistic regression, ordinal regression and life table

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Authors: Keith T. S. Tung, Frederick K. Ho, Rosa S. Wong, Camilla K. M. Lo, Wilfred H. S. Wong, C. B. Chow, Patrick Ip

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Objectives: Underage drinking is an important public health problem both locally and globally. Conventional prevention/intervention relies on unidirectional knowledge transfer such as mail leaflets or health talks which showed mixed results in changing the target behaviour. Previously, we conducted a school internet-based intervention which was found to be effective in reducing alcohol use among adolescents, yet the underlying mechanisms have not been properly investigated. This study, therefore, examined the mechanisms that explain how the intervention produced a change in alcohol drinking behaviours among Chinese adolescent as observed in our previous clustered randomised controlled trial (RCT) study. Methods: This is a cluster randomised controlled trial with parallel group design. Participating schools were randomised to the Internet intervention or the conventional health education group (control) with a 1:1 allocation ratio. Secondary 1–3 students of the participating schools were enrolled in this study. The Internet intervention was a web-based quiz game competition, in which participating students would answer 1,000 alcohol-related multiple-choice quiz questions. Conventional health education group received a promotional package on equivalent alcohol-related knowledge. The participants’ alcohol-related attitude, knowledge, and perceived behavioural control were self-reported before the intervention (baseline) and one month and three months after the intervention. Results: Our RCT results showed that participants in the Internet group were less likely to drink (risk ratio [RR] 0.79, p < 0.01) as well as in lesser amount (β -0.06, p < 0.05) compared to those in the control group at both post-intervention follow-ups. Within the intervention group, regression analyses showed that high quiz scorer had greater improvement in alcohol-related knowledge (β 0.28, p < 0.01) and attitude (β -0.26, p < 0.01) at 1 month after intervention, which in turn increased their perceived behavioural control against alcohol use (β 0.10 and -0.26, both p < 0.01). Attitude, compared to knowledge, was found to be a stronger contributor to the intervention effect on perceived behavioural control. Conclusions: Our internet-based intervention has demonstrated effectiveness in reducing the risk of underage drinking when compared with conventional health education. Our study results further showed an attitude to be a more important factor than knowledge in changing health-related behaviour. This has an important implication for future prevention/intervention on an underage drinking problem.

Keywords: adolescents, internet-based intervention, randomized controlled trial, underage drinking

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Authors: Karem H. Alzoubi, Ahmad S. Alkofahi, Omar F. Khabour, Nizar M. Mhaidat

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Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. In here, selected medicinal plant extracts from Jordan with high antioxidative capacity were tested for their protective effect against oxidative DNA damage using in vitro 8-hydroxydeoxyguanisine and sister chromatid exchanges (SCEs) assays in cultured human lymphocytes. The following plant extracts were tested Cupressus sempervirens L., Psidium guajava (L.) Gaerth., Silybum marianum L., Malva sylvestris L., Varthemia iphionoides Boiss., Eminium spiculatum L. Blume, Pistachia palaestina Boiss., Artemisia herba-alba Asso, Ficus carica L., Morus alba Linn , Cucumis sativus L., Eucalyptus camaldulensis Dehnh., Salvia triloba L., Zizyphus spina-christi L. Desf., and Laurus nobilis L. A fractionation scheme for the active plant extracts of the above was followed. Plants extract fractions with best protective properties against DNA damage included hexane fraction of S. marianum L. (aerial parts), chloroform fractions of P. palaestina Boiss. (Fruits), ethanolic fractions of E. camaldulensis Dehnh (leaves), S. triloba L. (leaves), and ethanolic fractions of Z. spina-christi L. Desf. (Fruits/leaves). On the other hand, the ethanolic extracts of V. iphionoides Boiss was found to increase oxidative DNA damage. Results of the SCEs are undergoing. In conclusion, plant extracts with antioxidative DNA damage properties might have clinical applications in cancer prevention.

Keywords: medicinal plants extract, fractionation, oxidative DNA damage, 8-hydroxydeoxyguanisine, SCEs, Jordan

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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