Search results for: drug delivery

Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

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Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Arnold Missiame

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In Ghana, rural dwellers who depend primarily on agriculture for their livelihood constitute about 60% of the country’s population. This shows the critical role and potentials of the agricultural sector in helping to achieve Ghana’s vision 2030. With the current threat of climate change and advancements in technology, agricultural extension is not just about technology transfer and improvements in productivity, but it is also about improving the managerial and technical skills of farmers. In Ghana, the government of Ghana as well as other players in the sector like; non-governmental organizations, NGOs, local and international funding agencies, for decades now, have made capacity-building-investments in smallholder farmers by way of extension services delivery. This study sought to compare the technical efficiency of farmers who have access to agricultural extension and farmers who do not in Ghana. The study employed the stochastic meta-frontier model to analyze household survey data comprising 300 smallholder cassava farmers from the Fanteakwa district of Ghana. The farmers were selected through a two-stage sampling technique where 5 communities were purposively selected in the first stage and then 60 smallholder cassava farmers were randomly selected from each of the 5 communities. Semi-structured questionnaires were used to collect data on farmers’ socioeconomic and farm-level characteristics. The results showed that farmers who have access to agricultural extensions services have higher technical efficiencies (TE) and produce much closer to their meta-production frontiers (higher technology gap ratios (TGR) than farmers who do not have access to such extension services. Furthermore, experience in cassava cultivation and formal education significantly improves the technical efficiencies of farmers. The study recommends that the mode and scope of agricultural extension service delivery in the country should be enhanced to ensure that smallholder farmers have easy access to extension agents.

Keywords: agricultural extension, Ghana, smallholder farmers, stochastic meta-frontier model, technical efficiency

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Authors: Karimeh Alnuaimi, Manal Kassab, Reem Ali, Khitam Mohammad, Kholoud Shattnawi

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Aim: To compare pregnancy outcomes of Syrian refugee women and Jordanian women. Background and introduction: The current conflict in Syria continues to displace thousands to neighboring countries, including Jordan. Pregnant refugee women are therefore facing many difficulties are known to increase the prevalence of poor reproductive health outcomes and antenatal complications. However, there is very little awareness of whether Syrian refugee women have different risks of pregnancy outcomes than Jordanian women. Methods: Using a retrospective cohort design, we examined pregnancy outcomes for Syrian refugee (N = 616) and Jordanian women (N = 644) giving birth at two governmental Hospitals in the north of Jordan, between January 1, 2014, and December 31, 2014. A checklist of 13 variables was utilized. The primary outcome measures were delivery by Caesarean section, maternal complications, low birth weight (< 2500 g), Apgar score and preterm delivery (< 37 weeks' gestational age). Results: Statistical analysis revealed that refugee mothers had a significant increase in the rate of cesarean section and the higher rate of anemia, a lower neonates’ weight, and Apgar scores when compared to their Jordanian counterparts. Discussion and Conclusion: Results were congruent with findings from other studies in the region and worldwide. Minimizing inequalities in pregnancy outcomes between Syrian refugees and Jordan women is a healthcare priority. Implications for nursing and health policy: The findings could guide the planning and development of health policies in Jordan that would help to alleviate the situation regarding refugee populations. The action is required by the policy makers, specifically targeting public and primary health care services, to address the problem of adequately meeting the need for antenatal care of this vulnerable population.

Keywords: pregnancy, Syrian refugee, Jordanian women, comparative study

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Authors: Isaac Kofi Mensah

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E-government has been adopted and used by many governments/countries around the world including Ghana to provide citizens and businesses with more accurate, real-time, and high quality services and information. The objective of this paper is to present an overview of the Government of Ghana’s (GoG) adoption and implement of e-government and its usage by the Ministries, Departments and its agencies (MDAs) as well as other public sector institutions to deliver efficient public service to the general public i.e. citizens, business etc. Government implementation of e-government focused on facilitating effective delivery of government service to the public and ultimately to provide efficient government-wide electronic means of sharing information and knowledge through a network infrastructure developed to connect all major towns and cities, Ministries, Departments and Agencies and other public sector organizations in Ghana. One aim for the Government of Ghana use of ICT in public administration is to improve productivity in government administration and service by facilitating the exchange of information to enable better interaction and coordination of work among MDAs, citizens and private businesses. The study was prepared using secondary sources of data from government policy documents, national and international published reports, journal articles, and web sources. This study indicates that through the e-government initiative, currently citizens and businesses can access and pay for services such as renewal of driving license, business registration, payment of taxes, acquisition of marriage and birth certificates as well as application for passport through the GoG electronic service (eservice) and electronic payment (epay) portal. Further, this study shows that there is an enormous commitment from GoG to adopt and implement e-government as a tool not only to transform the business of government but also to bring efficiency in public services delivered by the MDAs. To ascertain this, a further study need to be carried out to determine if the use of e-government has brought about the anticipated improvements and efficiency in service delivery of MDAs and other state institutions in Ghana.

Keywords: electronic government, electronic services, electronic pay, MDAs

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Authors: Rahul Malhotra

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Fiber based access networks can deliver performance that can support the increasing demands for high speed connections. One of the new technologies that have emerged in recent years is Passive Optical Networks. This paper is targeted to show the simultaneous delivery of triple play service (data, voice and video). The comparative investigation and suitability of various data rates is presented. It is demonstrated that as we increase the data rate, number of users to be accommodated decreases due to increase in bit error rate.

Keywords: BER, PON, TDMPON, GPON, CWDM, OLT, ONT

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Authors: Naylya Djumaeva

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Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

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Authors: Sevdenur Onger, Ali Asram Sagiroglu

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Hyperpigmentation is a cosmetically unappealing skin problem caused by an overabundance of melanin in the skin. Its pathophysiology is caused by melanocytes being exposed to paracrine melanogenic stimuli, which can upregulate melanogenesis-related enzymes (such as tyrosinase) and cause melanosome formation. Tyrosinase is linked to the development of melanosomes biochemically, and it is the main target of hyperpigmentation treatment. therefore, decreasing tyrosinase activity to reduce melanosomes has become the main target of hyperpigmentation treatment. Niacinamide (NA) is a natural chemical found in a variety of plants that is used as a skin-whitening ingredient in cosmetic formulations. NA decreases melanogenesis in the skin by inhibiting melanosome transfer from melanocytes to covering keratinocytes. Furthermore, NA protects the skin from reactive oxygen species and acts as a main barrier with the skin, reducing moisture loss by increasing ceramide and fatty acid synthesis. However, it is very difficult for hydrophilic compounds such as NA to penetrate deep into the skin. Furthermore, because of the nicotinic acid in NA, it is an irritant. As a result, we've concentrated on strategies to increase NA skin permeability while avoiding its irritating impacts. Since nanotechnology can affect drug penetration behavior by controlling the release and increasing the period of permanence on the skin, it can be a useful technique in the development of whitening formulations. Liposomes have become increasingly popular in the cosmetics industry in recent years due to benefits such as their lack of toxicity, high penetration ability in living skin layers, ability to increase skin moisture by forming a thin layer on the skin surface, and suitability for large-scale production. Therefore, liposomes containing NA were developed for this study. Different formulations were prepared by varying the amount of phospholipid and cholesterol and examined in terms of particle sizes, polydispersity index (PDI) and pH values. The pH values of the produced formulations were determined to be suitable with the pH value of the skin. Particle sizes were determined to be smaller than 250 nm and the particles were found to be of homogeneous size in the formulation (pdi<0.30). Despite the important advantages of liposomal systems, they have low viscosity and stability for topical use. For these reasons, in this study, liposomal cream formulations have been prepared for easy topical application of liposomal systems. As a result, liposomal cream formulations containing NA have been successfully prepared and characterized. Following the in-vitro release and ex-vivo diffusion studies to be conducted in the continuation of the study, it is planned to test the formulation that gives the most appropriate result on the volunteers after obtaining the approval of the ethics committee.

Keywords: delivery systems, hyperpigmentation, liposome, niacinamide

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Authors: Antonia Harold-Barry, Eugene Dempsey

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Background: The objective is to examine the survival and outcome of infants born under 26 weeks gestation in an Irish tertiary maternity hospital from 2007-2016 and to describe the survival and neurodevelopmental outcomes of these extremely preterm infants. Method: The population is 132 infants born at 23, 24, and 25 weeks in Cork University Maternity Hospital from 2007 to 2016. Ethical approval was granted by the Cork Clinical Research Ethics Committee. Patient details were obtained from the Vermont Oxford and Badger Networks. Survival rates and Bayley scores were calculated to assess neurodevelopmental outcomes. Statistical analysis with SPSS included frequencies, distributions, and comparisons between data from 2007-2011 and 2012-2016. Results: Overall survival rate was 63%. Of the surviving babies, 61% had Bayley scores calculated. Survival stood at 39% for delivery at 23 weeks, 50% at 24 weeks, and 83% at 25 weeks. The 2012 to 2016 cohort has shown further increases in survival, with 50% of babies at 23 weeks, 58% at 24 weeks, and 89% at 25 weeks. Corresponding figures for 2007-2011 are 20%, 39%, and 75%. Gestational age and incidence of periventricular leukomalacia were statistically significant, with a p-value of 0.022. Gestational age and delivery room deaths had a p-value of 0.025, as did gestational age and birth weight. A comparison of the two cohorts (2007-2011 and 2012-2016) with the administration of antenatal steroids showed a statistically significant p-value of 0.044. Conclusion: There is less morbidity and mortality in infants born at 25 than at 23 or 24 weeks. Survival of extremely premature infants has increased significantly over the past ten years. Survival rates with normal neurodevelopmental outcomes are comparable with international standards and reflect positive changes in attitude and practices in neonatal intensive care. This study will inform parents about the potential outcomes of extreme prematurity and policy regarding the management of extreme prematurity.

Keywords: extreme of viability, neurodevelopmental outcome, periventricular leukomalacia, prematurity

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: C. W. F. Che Wan Putra, M. Alshawi, M. S. Al Ahbabi, M. Jabakhanji

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The construction industry is a multi-disciplinary and multi-national industry, which has an important role to play within the overall economy of any country. There are major challenges to an improved performance within the industry. Particularly lacking is, the ability to capture the large amounts of information generated during the life-cycle of projects and to make these available, in the right format, so that professionals can then evaluate alternative solutions based on life-cycle analysis. The fragmented nature of the industry is the main reason behind the unavailability and ill utilisation of project information. The lack of adequately engaging clients and managing their requirements contributes adversely to construction budget and schedule overruns. This is a difficult task to achieve, particularly if clients are not continuously and formally involved in the design and construction process, which means that the design intent is left to designers that may not always satisfy clients’ requirements. Client lead is strongly recognised in bringing change through better collaboration between project stakeholders. However, one of the major challenges is that collaboration is operated under conventional procurement methods, which hugely limit the stakeholders’ roles and responsibilities to bring about the required level of collaboration. A research has been conducted with a typical project in the UAE. A qualitative research work was conducted including semi-structured interviews with project partners to discover the real reasons behind this delay. The case study also investigated the real causes of the problems and if they can be adequately addressed by BIM and IPD. Special focus was also placed on the Client leadership and the role the Client can play to eliminate/minimize these problems. It was found that part of the ‘key elements’ from which the problems exist can be attributed to the client leadership and the collaborative environment and BIM.

Keywords: client leadership, building information modelling (BIM), integrated project delivery (IPD), case study

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Gadia Duhita, Noorhana, Tjhin Wiguna

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Background: ADHD is the most common behavioural disorder in Indonesia. A stimulant, specifically methylphenidate, has been the first drug of choice for an ADHD treatment more than half a century. During the last decade, non-stimulant therapy (atomoxetine) for ADHD treatment has been developing. Growing evidence of its efficacy and the difference in its side effects profile to stimulant therapy have made methylphenidate’s position as a first line therapy for ADHD in need of re-evaluation. Both methylphenidate and atomoxetine have proven themselves against placebos in reducing core symptoms of ADHD. More recent studies directly compare the efficacy of methylphenidate and atomoxetine. Objective: The objective of this paper is to find out if either methylphenidate or atomoxetine is superior to another. This paper will assess the validity, importance, and applicability of current available evidence which compare the effectivity, efficacy, and safety of methylphenidate to atomoxetine for treatment in children and adolescents with ADHD. Method: The articles were searched for through the PubMed and Cochrane databases with “attention deficit/hyperactivity disorder OR adhd”, “methylphenidate”, and “atomoxetine” as the search keywords. Two articles which were relevant and eligible were chosen by using inclusion and exclusion criterias to be critically appraised. Result: The study by Hazel et al. showed that the efficacy of methylphenidate and atomoxetine are comparable for treatment in child and adolescent ADHD. The result shows 53.6% (95% CI 48.5%-58.4%) of the patient responded to the treatment by atomoxetine and 54.4% (95% CI 47.6%-61.1%) patients responded to methylphenidate, with the difference in proportion of–0.9% (95% CI –9.2%-7.5%). The other study by Hanwella et al. also showed that the efficacy of atomoxetine was not inferior to metilphenidate (SMD = 0.09, 95% CI –0.08-0.26) (Z = 1.06, p = 0.29). However, the sub-group analysis showed that OROS methylphenidate is more effective compared to atomoxetine (SMD = 0.32, 95% CI 0.12-0.53) (Z = 3.05, p < 0.02). Conclusion: The efficacy of methylphenidate and atomoxetine in reducing symptoms of ADHD is comparable. None is proven inferior to another. The choice of pharmacological tratment children and adolescents with ADHD should be made based on contraindication and the side effects profile of each drug.

Keywords: attention deficit/hyperactivity disorder, ADHD, atomoxetine, methylphenidate

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Authors: Mikiyas Yonas Fufa

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- Maternal and child health service was a critical service which may have many risks and many maternal and newborn mortality is there if not managed properly. In middle and low countries like Ethiopia accessibility and quality of MCH service is low. During this COVID-19 Pandemics even the pervious access of MCH will be decreased. So many pregnant mothers are not attending their ANC, Delivery and other services in the hospital because they think they are more vulnerable to COVID-19. This condition may make an increase of maternal and neonatal morbidity and mortality. The innovation is an idea (which is development of a mobile app prepared by Maternity Foundation organization that focuses on midwifery care. The app has detailed videos on danger signs in pregnancy and procedures during labor and delivery). By telling this to clients it is planned to explore the perception, attitude towards this innovation and barriers to accepting it. What is planned to study is to explore the perceptions and barriers towards using of new idea which is innovation of mHealth on the MCH services. It is planned to interview the pregnant mothers who come for ANC at health facility and mothers who are absent from their appointment of services. In this way it is planned to explore how the mothers accept this idea and what barriers make them from accepting this idea. This is a phenomenological qualitative study and application of diffusion of innovation theory on the MCH services. The participant will be selected by using quota sampling methods for the mother who are interviewed at hospitals and snowball/quota sampling methods for the mother who are absent from their appointment/visits. Sample size of the participant depends on the saturation of data/idea. Each participant will be interviewed based the open-ended questionnaires, and the interview will be recorded then transcribed then finally analyzed by the open code 4.03. Beneficiaries: The federal ministry of health prepares them to develop the apk of mhealth. Health professionals in the MCH will have a low overload and accessibility and the quality of care will be increased during COVID-19 Different collaborations will be participated and promote the mother to enjoy the new idea.

Keywords: COVID-19, m health, MCH, diffusion of innovation

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Authors: Eun-Seop Kim, Eun-Ha Jang, Rana R. Kim, Sae-Byul Jang

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Objective: Preterm labor is the most common antecedent of preterm birth(PTB), which is characterized by regular uterine contraction before 37 weeks of pregnancy and cervical change. In acute preterm labor, tocolytics are administered as the first-line medication to suppress uterine contractions but rarely delay pregnancy to 37 weeks of gestation. On the other hand, according to the Korean Traditional Medicine, PTB is caused by the deficiency of Qi and unnecessary energy in the body of the mother. The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of PTB. Methods: It is a case report of a 38-year-old woman (0-0-6-0) hospitalized for irregular uterine contractions and cervical change at 33+3/7 weeks of gestation. Past history includes chemical pregnancies achieved by Artificial Rroductive Technology(ART), one stillbirth (at 7 weeks) and a laparoscopic surgery for endometriosis. After seven trials of IVF and articificial insemination, she had succeeded in conception via in-vitro fertilization (IVF) with help of Traditional Korean Medicine (TKM) treatments. Due to irregular uterine contractions and cervical changes, 2 TKM were prescribed: Gami-Dangguisan, and Antae-eum, known to nourish blood and clear away heat. 120ml of Gami-Dangguisan was given twice a day monring and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: On admission, the cervix of 15mm in length and cervical os with 0.5cm-dilated were observed via ultrasonography. 50% cervical effacement was also detected in physical examination. Tocolysis had been temporarily maintained. As a supportive therapy, TKM herbal preparations(gami-dangguisan and Antae-eum) were concomitantly given. As of 34+2/7 weeks of gestation, however intermittent uterine contractions appeared (5-12min) on cardiotocography and vaginal bleeding was also smeared at 34+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39+3/7 gestational weeks. Conclusions: This is the first successful case report about a preter labor patient administered with conventional tocolytic agents as well as TKM herbal decoctions, delaying delivery to term. This case deserves attention considering it is rare to maintain gestation to term only with tocolytic intervention. Our report implies the potential of herbal medicine as an adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.

Keywords: preterm labor, traditional Korean medicine, herbal medicine, integrative treatment, complementary and alternative medicine

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Authors: Ayla Roberta Galaco, Juliana Fonseca De Lima, Osvaldo Antonio Serra

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Coordination polymers, also known as metal-organic frameworks (MOFs) or lanthanoide organic frameworks (LOFs) have been reported due of their promising applications in gas storage, separation, catalysis, luminescence, magnetism, drug delivery, and so on. As a type of organic–inorganic hybrid materials, the properties of coordination polymers could be chosen by deliberately selecting the organic and inorganic components. LOFs have received considerable attention because of their properties such as porosity, luminescence, and magnetism. Methods such as solvothermal synthesis are important as a strategy to control the structural and morphological properties as well as the composition of the target compounds. In this work the first solvothermal synthesis was employed to obtain the compound [Y0.4,Yb0.4,Er0.2(dmf)(for)(H2O)(tft)], by using terephthalic acid (tft) and oxalic acid, decomposed in formate (for), as ligands; Yttrium, Ytterbium and, Erbium as metal centers, in DMF and water for 4 days under 160 °C. The semi-rigid terephthalic acid (dicarboxylic) coordinates with Ln3+ ions and also is possible to form a polyfunctional bridge. On the other hand, oxalate anion has no high-energy vibrational groups, which benefits the excitation of Yb3+ in upconversion process. It was observed that the compounds with water molecules in the coordination sphere of the lanthanoide ions cause lower crystalline properties and change the structure of the LOF (1D, 2D, 3D). In the FTIR, the bands at 1589 and 1500 cm-1 correspond to the asymmetric stretching vibration of –COO. The band at 1383 cm-1 is assigned to the symmetric stretching vibration of –COO. Single crystal X-ray diffraction study reveals an infinite 3D coordination framework that crystalizes in space group P21/c. The other three products, [TR(chel)(ofd)0,5(H2O)2], where TR= Eu3+, Y3, and Yb3+/Er3+ were obtained by using 1, 2-phenylenedioxydiacetic acid (ofd) and chelidonic acid (chel) as organic ligands. Thermal analysis shows that the lanthanoide organic frameworks do not collapse at temperatures below 250 °C. By the polycrystalline X-ray diffraction patterns (PXRD) it was observed that the compounds with Eu3+, Y3+, and Yb3+/Er3+ ions are isostructural. From PXRD patterns, high crystallinity can be noticed for the complexes. The final products were characterized by single X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA). The X-ray diffraction (XRD) is an effective method to investigate crystalline properties of synthesized materials. The solid crystal obtained in the synthesis show peaks at 2θ < 10°, indicating the MOF formation. The chemical composition of LOFs was also confirmed by EDS.

Keywords: isostructural, lanthanoids, lanthanoids organic frameworks (LOFs), metal organic frameworks (MOFs), thermogravimetry, X-Ray diffraction

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Authors: Mbuso Siwela

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Background: The Sub-Saharan Africa region has the greatest number of people eligible to receive antiretroviral treatment (ART). Multi-month Drug dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. In Eswatini, however, few children and adolescents are on MMD. Young Heroes is implementing an HIV program that aims to avert new HIV infections in children and youth and improve treatment outcomes for children and adolescents living with HIV (C/ALHIV: 0-19 Years) and OVC caregivers with HIV prevention and impact mitigation interventions that prevent new HIV infections and reduce vulnerability. Aim of the study: The study aimed to ascertain factors that are associated with the assignment of the MMD model on C/ALHIVs. Methodology: The project provides treatment adherence support through well-trained community cadres (Home Visitors - HVs) at both community and health facility levels. During door-to-door visits, HVs track all C/ALHIV enrolled in the project monthly and refer any who might have stopped or interrupted treatment. C/ALHIV with unsuppressed viral load is supported through case conferencing and teen clubs. A quantitative cross-sectional analysis was conducted using STATA for children and adolescents living with HIV enrolled in the project. Bivariate analysis was conducted, and the Logistic Regression model was used to ascertain the effects of duration on ART on the choice of MMD model. Results: Data for 544 C/ALHIV (0-19 Years) was analyzed in STATA. Results show a strong association between (duration on ART, Age, being in teen club) and enrolment in an MMD model. Duration on ART is a major predictor for the choice of MMD model at (95% CI: 0.0012905 – 0.0039812; P = <0.0001). C/ALHIV who have been on ART for less than a year are less likely to be on MMD. C/ALHIVs who are 1 or more years on ART are more likely to be in 3 months dispensing, while those who are 5 years or more are most likely to be in 6 months model.

Keywords: C/ALHIV, OVC, HIV, treatment

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Authors: Asawari Alok Pawaskar

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This study was aimed at investigating quality assurance (QA) done with IBA matrix, the discrepan­cies observed for helical tomotherapy plans. A selection of tomotherapy plans that initially failed the with Matrix process was chosen for this investigation. These plans failed the fluence analysis as assessed using gamma criteria (3%, 3 mm). Each of these plans was modified (keeping the planning constraints the same), beamlets rebatched and reoptimized. By increasing and decreasing the modula­tion factor, the fluence in a circumferential plane as measured with a diode array was assessed. A subset of these plans was investigated using varied pitch values. Factors for each plan that were examined were point doses, fluences, leaf opening times, planned leaf sinograms, and uniformity indices. In order to ensure that the treatment constraints remained the same, the dose-volume histograms (DVHs) of all the modulated plans were compared to the original plan. It was observed that a large increase in the modulation factor did not significantly improve DVH unifor­mity, but reduced the gamma analysis pass rate. This also increased the treatment delivery time by slowing down the gantry rotation speed which then increases the maximum to mean non-zero leaf open time ratio. Increasing and decreasing the pitch value did not substantially change treatment time, but the delivery accuracy was adversely affected. This may be due to many other factors, such as the complexity of the treatment plan and site. Patient sites included in this study were head and neck, breast, abdomen. The impact of leaf tim­ing inaccuracies on plans was greater with higher modulation factors. Point-dose measurements were seen to be less susceptible to changes in pitch and modulation factors. The initial modulation factor used by the optimizer, such that the TPS generated ‘actual’ modulation factor within the range of 1.4 to 2.5, resulted in an improved deliverable plan.

Keywords: dose volume histogram, modulation factor, IBA matrix, tomotherapy

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Authors: Ezinne K. Okoro, Takahiko Katoh, Yoko Kawamura, Stanley C. Meribe

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HIV infection in children is largely as a result of vertical transmission (mother to child transmission [MTCT]). Thus, elimination of mother to child transmission of HIV/AIDS is critical in eliminating HIV infection in children. In Nigeria, drawbacks such as; limited pediatric screening, limited human capital, insufficient advocacy and poor understanding of ART guidelines, have impacted efforts at combating the disease, even as treatment services are free. Prevention of Mother to Child Transmission (PMTCT) program relies on health workers who not only counsel pregnant women on first contact but can competently provide HIV-positive pregnant women with accurate information about the PMTCT program such as feeding techniques and drug adherence. In developing regions like Nigeria where health care delivery faces a lot of drawbacks, it becomes paramount to address these issues of poor PMTCT coverage by conducting a baseline assessment of the knowledge, practices and perceptions related to HIV prevention amongst healthcare workers in Nigeria. A descriptive cross-sectional study was conducted amongst 250 health workers currently employed in health facilities in Abuja, Nigeria where PMTCT services were offered with the capacity to carry out early infant diagnosis testing (EID). Data was collected using a self-administered, pretested, structured questionnaire. This study showed that the knowledge of PMTCT of HIV was poor (30%) among healthcare workers who offer this service day-to-day to pregnant women. When PMTCT practices were analyzed in keeping with National PMTCT guidelines, over 61% of the respondents reported observing standard practices and the majority (58%) had good attitudes towards caring for patients with HIV/AIDS. Although 61% of the respondents reported being satisfied with the quality of service being rendered, 63% reported not being satisfied with their level of knowledge. Predictors of good knowledge were job designation and level of educational attainment. Health workers who were more satisfied with their working conditions and those who had worked for a longer time in the PMTCT service were more likely to observe standard PMTCT practices. With over 62% of the healthcare workers suggesting that more training would improve the quality of service being rendered, this is a strong pointer to stakeholders to consider a ‘healthcare worker-oriented approach’ when planning and conducting PMTCT training for healthcare workers. This in turn will increase pediatric ARV coverage, the knowledge and effectiveness of the healthcare workers in carrying out appropriate PMTCT interventions and culminating in the reduction/elimination of HIV transmission to newborns.

Keywords: attitudes, HIV/AIDS, healthcare workers, knowledge, mother to child transmission, Nigeria, perceptions

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Authors: Enny Suswati, Supangat Supangat

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Background. Ready-to-eat food products are becoming increasingly popular because consumers are increasingly busy, competitive, and changing lifestyles. Examples of ready-to-eat foods include crispy fried chicken. Escherichia coli is one of the most important causes of food-borne diseases and the most frequent antibiotic-resistant pathogen globally. This study assessed the prevalence and antibiotic resistance profile of E. coli from ready-to-eat crispy fried chicken in Jember city, Indonesia. Methodology. This cross-sectional study was conducted from November 2020 to April 2021 by collecting 81crispy fried chicken samples from 27 food stalls in campus area using a simple random sampling method. Isolation and determination of E. coli use were performed by conventional culture method. An antibiotic susceptibility test was conducted using Kirby Bauer disk diffusion method on the Mueller–Hinton agar. Result. Out of 81crispy fried chicken samples, 77 (95.06%) were positive for E. coli. High E. coli drug resistance was observed on ampicillin, amoxicillin (100%) followed by cefixime (98.72%), erythromycin (97.59%), sulfamethoxazole (93.59%), azithromicin (83.33%), cefotaxime (78.28%), choramphenicol (75.64%), and cefixime (74.36%). On the other hand, there was the highest susceptibility for ciprofloxacin (64.10%). The multiple antibiotic resistance indexes of E. coli isolates varied from 0.4 to 1. The predominant antimicrobial resistance profiles of E. coli were CfmCroAmlAmpAzmCtxSxtCE (n=17), CfmCroAmlCipAmpAzmCtxSxtCE (n=16), and CfmAmlAmpAzmCtxSxtCE (n=5), respectively. Multidrug resistance was also found in the isolates' 76/77 (98.70%). Conclusion. The resistance pattern CfmCroAmlAmpAzmCtxSxtCE was the most common among the E. coli isolates, with 17 showing it. The multiple antibiotic index (MAR index) ranged from 0.4 to 1. Hygienic measures should be rigorously implemented and monitoring resistance of E. coli is required to reduce the risks related to the emergence of multi-resistant bacteria

Keywords: antibacterial drug, ready to eat, crispy fried chicken, escherichia coli

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Authors: Gbone Akou Sophie

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Lome state in Togo is considered to have the highest HIV prevalence in Togo according to NAIIS 2023, with the prevalence of 5.5%, Female Sex Workers (FSW) are one of the most vulnerable population, and they are vital in HIV programming. They have the highest HIV prevalence compared to others such as HRM, PWID and Transgender in lome State, Togo. Evidence from Integrated Biological Behavioral Surveillance Survey shows increasing burden of HIV infection from 13.7% in 20018 to 17.2% in 2020 and now 22.9% in 2021 among Female Sex Workers (FSW). This shows their HIV prevalence has been rising over time. The vulnerability status of the FSW in the riverine areas of lome is heightened because of cultural and economic issues where there is exchange of sex for commodities with cross border traders as well as limited access to HIV prevention information. Methods:A cross sectional study which recruited 120 FSW from two Riverine LGAs of Agoe and Kpehenou LGA of Lome State using both snowballing and simple random sampling technique. While semi-structured questionnaire was used as an instrument for data collection among the 120 FSW respondents. Additional information was also elicited from 10 FSW key opinion leaders and community members through in-depth interviews (IDI). Results: 44(36%) of respondents were willing to receive regular HIV care and services as well as visit for STI check-ups at any service point. However, 47(40%) were willing to receive services at private facilities alone, 10 (8%) were willing to receive services at public facilities, 6 (5%) were willing to access services in their homes rather than in the health facility. 13 (11%) were also willing to have peers assist in getting HIV testing services. Conclusion: integrated differentiated model of care for HIV services helps improve HIV services uptake among FSW community especially in the hard- to reach riverine areas which will further lead to epidemic control. Also targeted HIV information should be designed to suit the learning needs of the hard-to reach communities like the riverine areas. More peer educators should be engaged to ensure information and other HIV services reach the riverine communities.

Keywords: female sex workers ( FSW), human immuno-deficiency virus(HIV), prevanlence, service delivery

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Authors: Ikram Mohamed Eltayeb Elsiddig, Yacouba Amina Djamila, Amna El Hassan Hamad

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Hyperglycemia and diabetes have been treated with several medicinal plants for a long time, meanwhile reduce associated side effects than the synthetic ones. Therefore, the search for more effective and safer anti-diabetic agents derived from plants has become an interest area of active research. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol, and high blood pressure. The present study was carried out to investigate the anti-hyperglycemic effect of the extracts of A. sativum bulb growing in Sudan on glucose-loaded Wistar albino rats. A. sativum bulbs were collected from local vegetable market at Khourtoum/ Sudan in a fresh form, identified and authenticated by taxonomist, then dried, and extracted with solvents of increasing polarity: petroleum ether, chloroform, ethyl acetate and methanol by using Soxhlet apparatus. The effect of the extracts on glucose uptake was evaluated by using the isolated rats hemidiaphgrams after loading the fasting rats with glucose, and the anti-hyperglycemic effect was investigated on glucose-loaded Wistar albino rats. Their effects were compared to control rats administered with the vehicle and to a standard group administered with Metformin standard drug. The most active extract was analyzed chemically using GC-MS analysis compared to NIST library. The results showed significant anti-diabetic effect of extracts of A. sativum bulb growing in Sudan. Addition to the hypoglycemic activity of A. sativum extracts was found to be decreased with increase in the polarity of the extraction solvent; this may explain the less polarity of substance responsible for the activity and their concentration decreased with polarity increase. The petroleum ether extract possess anti-hyperglycemic activity more significant than the other extracts and the Metformin standard drug with p-value 0.000** of 400mg/kg at 1 hour, 2 hour and four hour; and p-value 0.019*, 0.015* and 0.010* of 200mg/kg at 1 hour, 2 hour and four hour respectively. The GC-MS analysis of petroleum ether extract, with highest anti -diabetes activity showed the presence of Methyl linolate (42.75%), Hexadecanoic acid, methyl ester (10.54%), Methyl α-linolenate (8.36%), Dotriacontane (6.83), Tetrapentacontane (6.33), Methyl 18-methylnonadecanoate (4.8), Phenol,2,2’-methylenebis[6-(1,1-dimethylethyl)-4-methyl] (3.25), Methyl 20-methyl-heneicosanoate (2.70), Pentatriacontane (2.13) and many other minor compounds. The most of these compounds are well known for their anti-diabetic activity. The study concluded that A. sativum bulbs extracts were found to enhanced the reuptake of glucose in the isolated rat hemidiaphragm and have antihyperglycemic effect when evaluated on glucose-loaded albino rats with petroleum ether extract activity more significant than the Metformin standard drug.

Keywords: Allium, anti-hyperglycemic, bulbs, sativum

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Authors: Antonio Marco Miotti, Antonella Ruffatto, Giampaola Basso, Antonio Madia, Giulia Zavatta, Emanuela Salvatico, Emanuela Zilli

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A National Action Plan to fight antimicrobial resistance was launched in Italy in 2017. In order to reduce inappropriate exposure to antibiotics and infections from multi-drug resistant bacteria, it is essential to set up a structured system of surveillance and monitoring of the implementation of National Action Plan standards, including antimicrobial consumption, with a special focus on quinolones, third generation cephalosporins and carbapenems. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Pharmaceutical Service to the Hospital of Cittadella, ULSS 6 Euganea – Health Trust (District of Padua) for the years 2019 (before the pandemic), 2020 and 2021 for all classes of antibiotics. Multidisciplinary meetings have been organized monthly by the local Antimicrobial Stewardship Group. Between 2019 and 2021, an increase in the consumption of carbapenems in the Intensive Care Unit (from 12.2 to 18.2 DDD, + 49.2%) and a decrease in Medical wards (from 5.3 to 2.6 DDD, - 50.9%) was reported; a decrease in the consumption of quinolones in Intensive Care Unit (from 17.2 to 10.8 DDD, - 37.2%), Medical wards (from 10.5 to 6.6 DDD, - 37.1%) and Surgical wards (from 10.2 to 9.3 DDD, - 8.8%) was highlighted; an increase in the consumption of third generation cephalosporins in Medical wards (from 18.1 to 22.6 DDD, + 24,1%) was reported. Finally, after an increase in the consumption of macrolides between 2020 and 2019, in 2021, a decrease was reported in the Intensive Care Unit (DDD: 8.0 in 2019, 18.0 in 2020, 6.4 in 2021) and Medical wards (DDD: 9.0 in 2019, 13.7 in 2020, 10.9 in 2021). Constant monitoring of antimicrobial consumption and timely identifying of warning situations that may need a specific intervention are the cornerstone of Antimicrobial Stewardship programs, together with analysing data on bacterial resistance rates and infections from multi-drug resistant bacteria.

Keywords: carbapenems, quinolones, antimicrobial, stewardship

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Authors: A. Kumar, D. Himanshu, Ak Vaish, K. Usman , A. Singh, R. Misra, V. Atam, S. P. Verma, S. Singhal

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Introduction: Resistant and uncontrolled hypertension offer great challenge, in terms of higher risk of morbidity, mortality and not the least, difficulty in diagnosis and management. Our study tries to identify the importance of two crucial aspects of hypertension management, i.e. drug compliance and optimum dosing and also the effect of spironolactone on blood pressure in cases of resistant hypertension. Methodology: A prospective study was carried out among patients, who were referred as case of resistant hypertension to Hypertension Clinic at Gandhi memorial and associated hospital, Lucknow, India from August, 2013 to July 2014. A total of 122 Subjects having uncontrolled BP with ≥3 antihypertensives were selected. After ruling out secondary resistance and with appropriate lifestyle modifications, effect of adherence and optimum doses was seen with monitoring of BP. Only those having blood pressure still uncontrolled were true resistant. These patients were given spironolactone to see its effect on BP over next 12 weeks. Results: Mean baseline BP of all (n=122) patients was 150.4±7.2 mmHg systolic and 92.1±5.7 mmHg diastolic. After promoting adherence to the regimen, there was reduction of 4.20±3.65 mmHg systolic and 2.08±4.74 mmHg Diastolic blood pressure, with 26 patients achieving target blood pressure goal. Further reduction of 6.66±5.99 mmHg in systolic and 2.59±3.67 mmHg in diastolic BP was observed after optimizing the drug doses with another 66 patients achieving target blood pressure goal. Only 30 patients were true resistant hypertensive and prescribed spironolactone. Over 12 weeks, mean reduction of 20.62±3.65 mmHg in systolic and 10.08 ± 6.46 mmHg in diastolic BP was observed. Out of these 30, BP was controlled in 24 patients. Side effects observed were hyperkalemia in 2 patients and breast tenderness in 2 patients. Conclusion: Improper adherence and suboptimal regimen appear to be the important reasons for uncontrolled hypertension. By virtue of maintaining proper adherence to an optimum regimen, target BP goal can be reached in many without adding much to the regimen. Spironolactone is effective in patients with resistant hypertension, in terms of blood pressure reduction with minimal side effects.

Keywords: resistant, hypertension, spironolactone, blood pressure

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Authors: Noel Smith

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To achieve professional registration, UK social workers need to complete a programme of education and training which meets standards set down by central government. When it comes to practice, social work in local authorities must fulfil requirements of national legislation but there is considerable local variation in the organisation and delivery of services. This presentation discusses the on-going reform of social work education by central government in the context of research of social work services in a local authority. In doing so it highlights that the ‘direction of travel’ of the national reform of social work education seems at odds with the trajectory of development of local social work services. In terms of education reform, the presentation cites key government initiatives including the knowledge and skills requirements which have been published separately for, respectively, child and family social work and adult social work. Also relevant is the Government’s new ‘teaching partnership’ pilot which focuses exclusively on social work in local government, in isolation from social work in NGOs. In terms of research, the presentation discusses two studies undertaken by Professor Smith in Suffolk County Council, a local authority in the east of England. The first is an equality impact analysis of the introduction of a new model for the delivery of adult and community services in Suffolk. This is based on qualitative research with local government representatives and NGOs involved in social work with older people and people with disabilities. The second study is an on-going, mixed method evaluation of the introduction of a new model of social care for children and young people in Suffolk. This new model is based on the international ‘Signs of Safety’ approach, which is applied in this model to a wide range of services from early intervention to child protection. While both studies are localised, the service models they examine are good illustrations of the way services are developing nationally. Analysis of these studies suggest that, if services continue to develop as they currently are, then social workers will require particular skills which are not be adequately addressed in the Government’s plans for social work education. Two issues arise. First, education reform concentrates on social work within local government while increasingly local authorities are outsourcing service provision to NGOs, expecting greater community involvement in providing care, and integrating social care with health care services. Second, education reform focuses on the different skills required for working with older and disabled adults and working with children and families, to the point where potentially the profession would be fragmented into two different classes of social worker. In contrast, the development of adult and children’s services in local authorities re-asserts the importance of common social work skills relating to personalisation, prevention and community development. The presentation highlights the importance for social work education in the UK to be forward looking, in terms of the changing design of service delivery, and outward looking, in terms of lessons to be drawn from international social work.

Keywords: adult social work, children and families social work, European social work, social work education

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Authors: Mahamad Yousif, Eoin Cunningham, Beatrice Smyth

Abstract:

Every year ~6 million tonnes of feathers are produced globally. Due to feathers’ low density and possible contamination with pathogens, their disposal causes health and environmental problems. The extraction of keratin, which represents >90% of feathers’ dry weight, could offer a solution due to its wide range of applications in the food, medical, cosmetics, and biopolymer industries. One of these applications is the production of biofilms which can be used for packaging, edible films, drug delivery, wound healing etc. Several studies in the last two decades investigated keratin film production and its properties. However, the effects of many parameters on the properties of the films remain to be investigated including the extraction method, crosslinker type and concentration, and the film production method. These parameters were investigated in this study. Keratin was extracted from chicken feathers using two methods, alkaline extraction with 0.5 M NaOH at 80 °C or sulphitolysis extraction with 0.5 M sodium sulphite, 8 M urea, and 0.25-1 g sodium dodecyl sulphate (SDS) at 100 °C. The extracted keratin was mixed with different types and concentrations of plasticizers (glycerol and polyethylene glycol) and crosslinkers (formaldehyde (FA), glutaraldehyde, cinnamaldehyde, glyoxal, and 1,4-Butanediol diglycidyl ether (BDE)). The mixtures were either cast in a mould or compression moulded to produce films. For casting, keratin powder was initially dissolved in water to form a 5% keratin solution and the mixture was dried in an oven at 60 °C. For compression moulding, 10% water was added and the compression moulding temperature and pressure were in the range of 60-120 °C and 10-30 bar. Finally, the tensile properties, solubility, and transparency of the films were analysed. The films prepared using the sulphitolysis keratin had superior tensile properties to the alkaline keratin and formed successfully with lower plasticizer concentrations. Lowering the SDS concentration from 1 to 0.25 g/g feathers improved all the tensile properties. All the films prepared without crosslinkers were 100% water soluble but adding crosslinkers reduced solubility to as low as 21%. FA and BDE were found to be the best crosslinkers increasing the tensile strength and elongation at break of the films. Higher compression moulding temperature and pressure lowered the tensile properties of the films; therefore, 80 °C and 10 bar were considered to be the optimal compression moulding temperature and pressure. Nevertheless, the films prepared by casting had higher tensile properties than compression moulding but were less transparent. Two optimal films, prepared by film casting, were identified and their compositions were: (a) Sulphitolysis keratin, 20% glycerol, 10% FA, and 10% BDE. (b) Sulphitolysis keratin, 20% glycerol, and 10% BDE. Their tensile strength, elongation at break, Young’s modulus, solubility, and transparency were: (a) 4.275±0.467 MPa, 86.12±4.24%, 22.227±2.711 MPa, 21.34±1.11%, and 8.57±0.94* respectively. (b) 3.024±0.231 MPa, 113.65±14.61%, 10±1.948 MPa, 25.03±5.3%, and 4.8±0.15 respectively. A higher value indicates that the film is less transparent. The extraction method, film composition, and production method had significant influence on the properties of keratin films and should therefore be tailored to meet the desired properties and applications.

Keywords: compression moulding, crosslinker, film casting, keratin, plasticizer, solubility, tensile properties, transparency

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