Search results for: chronic HCV infection

Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

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Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

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Authors: Kun Hua O., Dong Woon Kim, Won Hyung Lee

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Introduction: Neuropathic pain induced by spinal or peripheral nerve injury is highly resistant to common painkillers, nerve blocks, and other pain management approaches. Recently, several new therapeutic drug candidates have been developed to control neuropathic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate the ability of intrathecal or intravenous Evans blue to decrease pain behavior and to study the relationship between Evans blue and the neural structure of pain transmission. Method: Neuropathic pain (allodynia) of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats(n=10) in each group. Evans blue (5, 15, 50μg/10μl) or phosphate buffer saline(PBS,10μl) was injected intrathecally at 3days post-ligation or intravenously(1mg/200 μl) 3days and 5days post-ligation . Mechanical sensitivity was assessed using Von Frey filaments at 3 days post-ligation and at 2 hours, days 1, 2, 3, 5,7 after intrathecal Evans blue injection, and on days 2, 4, 7, and 11 at 14 days after intravenous injection. In the intrathecal group, microglia and glutaminergic neurons in the dorsal horn and VNUT(vesicular nucleotide transporter) in the dorsal root ganglia were tested to evaluate co-staining with Evans blue. The experimental procedures were performed in accordance with the animal care guideline of the Korean Academy of Medical Science(Animal ethic committee of Chungnam National University Hospital: CNUH-014-A0005-1). Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw 3 days post-ligation. Intrathecal Evans blue most significantly(P＜0.001) alleviated allodynia at 2 days after intrathecal, but not an intravenous injection. Glutaminergic neurons in the dorsal horn and VNUT in the dorsal root ganglia were co-stained with Evans blue. On the other hand, microglia in the dorsal horn were partially co-stained with Evans blue. Conclusion: We confirmed that Evans blue might have an analgesic effect through the central nervous system, not another system in neuropathic pain of the SNL animal model. These results suggest Evans blue may be a potential new drug for the treatment of chronic pain. This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C100757512), funded by the Ministry of Education.

Keywords: neuropathic pain, Evas blue, intrathecal, intravenous

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Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Atefeh Abdollahi, Maryam Bahreini, Babak Choobi Anzali, Fatemeh Rasooli

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Introduction: Triage becomes the main part of organization of care in Emergency department (ED)s. It is used to describe the sorting of patients for treatment priority in ED. The accurate triage of injured patients has reduced fatalities and improved resource usage. Besides, the nurses’ knowledge and skill are important factors in triage decision-making. The ability to define an appropriate triage level and their need for intervention is crucial to guide to a safe and effective emergency care. Methods: This is a prospective cross-sectional study designed for emergency nurses working in four public university hospitals. Five triage workshops have been conducted every three months for emergency nurses based on a standard triage Emergency Severity Index (ESI) IV slide set - approved by Iranian Ministry of Health. Most influential items on triage performance were discussed through brainstorming in workshops which then, were peer reviewed by five emergency physicians and two head registered nurses expert panel. These factors that might distract nurse’ attention from proper decisions included patients’ past medical diseases, the natural tricks of triage and system failure. After permission had been taken, emergency nurses participated in the study and were given the structured questionnaire. Data were analysed by SPSS 21.0. Results: 92 emergency nurses enrolled in the study. 30 % of nurses reported the past history of chronic disease as the most influential confounding factor to ascertain triage level, other important factors were the history of prior admission, past history of myocardial infarction and heart failure to be 20, 17 and 11 %, respectively. Regarding the concept of difficulties in triage practice, 54.3 % reported that the discussion with patients and family members was difficult and 8.7 % declared that it is hard to stay in a single triage room whole day. Among the participants, 45.7 and 26.1 % evaluated the triage workshops as moderately and highly effective, respectively. 56.5 % reported overcrowding as the most important system-based difficulty. Nurses were mainly doubtful to differentiate between the triage levels 2 and 3 according to the ESI VI system. No significant correlation was found between the work record of nurses in triage and the uncertainty in determining the triage level and difficulties. Conclusion: The work record of nurses hardly seemed to be effective on the triage problems and issues. To correct the deficits, training workshops should be carried out, followed by continuous refresher training and supportive supervision.

Keywords: assessment, education, nurse, triage

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Authors: Rui Fonseca-Pinto, Emanuel Silva, Rui Rijo, Ricardo Martinho, Bruno Carreira

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The sedentary lifestyle is associated to the development of chronic noncommunicable diseases (obesity, hypertension, Diabetes Mellitus Type 2) and the World Health Organization, given the evidence that physical activity is determinant for individual and collective health, defined the Physical Activity Level (PAL) as a vital signal. Strategies for increasing the practice of physical activity in all age groups have emerged from the various social organizations (municipalities, universities, health organizations, companies, social groups) by increasingly developing innovative strategies to promote motivation strategies and conditions to the practice of physical activity. The adaptation of cities to the new paradigms of sustainable mobility has provided the adaptation of urban training circles and mobilized citizens to combat sedentarism. This adaptation has accompanied the technological evolution and makes possible the use of mobile technology to monitor outdoor training programs and also, through the network connection (IoT), use the training data to make personalized recommendations. This work presents a physical activity counseling platform to be used in the physical maintenance circuits of urban centers, the MOVIDA.polis. The platform consists of a back office for the management of circuits and training stations, and for a mobile application for monitoring the user performance during workouts. Using a QRcode, each training station is recognized by the App and based on the individual performance records (effort perception, heart rate variation) artificial intelligence algorithms are used to make a new personalized recommendation. The results presented in this work were obtained during the proof of concept phase, which was carried out in the PolisLeiria training circuit in the city of Leiria (Portugal). It was possible to verify the increase in adherence to the practice of physical activity, as well as to decrease the interval between training days. Moreover, the AI-based recommendation acts as a partner in the training and an additional challenging factor. The platform is ready to be used by other municipalities in order to reduce the levels of sedentarism and approach the weekly goal of 150 minutes of moderate physical activity. Acknowledgments: This work was supported by Fundação para a Ciência e Tecnologia FCT- Portugal and CENTRO2020 under the scope of MOVIDA project: 02/SAICT/2016 – 23878.

Keywords: physical activity, mHealth, urban training circuits, health promotion

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Authors: Kamrun Nahar Koly, Saimul Islam

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Overweight and obesity is increasing at an alarming rate and a leading risk factor for morbidity throughout the world. In a country like Bangladesh where under nutrition and overweight both co-exist at the same time, but this issue has been underexplored as expected. The aim of the present study was to assess the knowledge, attitudes and identify the barriers of the physicians regarding overweight and obesity management on an urban hospital of Dhaka city in Bangladesh. A simple cross sectional study was conducted at two selected government and two private hospital to assess the knowledge, attitude and common barriers regarding overweight and obesity management among healthcare professionals. One hundred and fifty five physicians were surveyed. A standard questionnaire was constructed in local language and interview was administrated. Among the 155 physicians, majority 53 (34.20%) were working on SMC, 36 (23.20%) from DMC, 33 (21.30%) were based on SSMC and the rest 33 (21.30%) were from HFRCMH. Mean age of the study physicians were 31.88±5.92. Majority of the physicians 80 (51.60%) were not able to answer the correct prevalence of obesity but also a substantial number of them 75(48.40%) could mark the right answer. Among the physicians 150 (96.77%) reported BMI as a diagnostic index for overweight and obesity, where as 43 (27.74%) waist circumference, 30 (19.35%) waist hip ratio and 26 (16.77%) marked mid-arm circumference. A substantial proportion 71 (46.70%) of the physicians thought that they do not have much to do controlling weight problem in Bangladesh context though it has been opposed by 42 (27.60%) of the physicians and 39(25.70%) was neutral to comment. The majority of them 147 (96.1%) thought that a family based education program would be beneficial followed by 145 (94.8%) physicians mentioned about raising awareness among mothers as she is the primary caregiver. The idea of a school based education program will also help to early intervene referred by 142 (92.8%) of the physicians. Community based education program was also appreciated by 136 (89.5%) of the physicians. About 74 (47.7%) of them think that the patients still lack in motivation to maintain their weight properly at the same time too many patients to deal with can be a barrier as well assumed by 73 (47.1%) of them. Lack of national policy or management guideline can act as an obstacle told by 60 (38.7%) of the physicians. The relationship of practicing as a part of the general examination and chronic disease management was statistically significant (p<0.05) with physician occupational status. As besides, perceived barriers like lack of parents support, lack of a national policy was statistically significant (p<0.05) with physician occupational status. For the young physician, more training programme will be needed to transform their knowledge and attitude into practice. However, several important barriers interface for the physician treatment efforts and need to address.

Keywords: obesity management, physician, awareness, barriers, Bangladesh

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Authors: Ibrahim Siddig Hamid, Ikram Mohamed Eltayeb

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Trachyspermum ammi belongs to the family Apiaceae, is used traditionally for the treatment of gastrointestinal ailments, lack of appetite and bronchial problems as well used as antiseptic, antimicrobial, antipyretic, febrifugal and in the treatment of typhoid fever. Peganum harmala belongs to the family Zygophyllaceae it has been reported to have an antibacterial activity and used to treat depression and recurring fevers. It also used to kill algae, bacteria, intestinal parasites and molds. In Sudan, the combination of two plants are traditionally used for the treatment of bacillary dysentery. Bacillary dysentery is caused by one or more types of Shigella species bacteria mainly Shigella dysenteri and shigella flexneri. Bacillary dysentery is mainly found in hot countries like Sudan with poor hygiene and sanitation. Bacillary dysentery causes sudden onset of high fever and chills, abdominal pain, cramps and bloating, urgency to pass stool, weight loss, and dehydration and if left untreated it can lead to serious complications including delirium, convulsions and coma. A serious infection like this can be fatal within 24 hours. The objective of this study is to investigate the in vitro susceptibility of Sh. flexneri and Sh. dysenteriae to the T. ammi and P. harmala. T. ammi and P. harmala were extracted by 96% ethanol using Soxhlet apparatus. The antimicrobial activity of the extracts was investigated according to the disc diffusion method. The discs were prepared by soaking sterilized filter paper discs in 20 microliter of serially diluted solutions of each plant extract with the concentrations (100, 50, 25, 12.5, 6.25mg/dl) then placing them on Muller Hinton Agar plates that were inoculated with bacterial suspension separately, the plates were incubated for 24 hours at 37c and the minimum inhibitory concentration of the extract which was the least concentration of the extract to inhibit fungal growth was determined. The results showed the high antimicrobial activity of T. ammi extract with an average diameter zone ranging from 18-20 mm and its minimum inhibitory concentration was found to be 25 mg/ml against the two shigella species. P. harmala extract was found to have slight antibacterial effect against the two bacteria. This result justified the Sudanese traditional use of Trachyspermum ammi plant for the treatment of bacillary dysentery.

Keywords: harmala, peganum, shigella, trachyspermum

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Authors: H. Akhloufi, M. Hulscher, J. M. Prins, I. H. Van Der Sijs, D. Melles, A. Verbon

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Background: A timely switch from intravenous to oral antibiotic therapy has many advantages, such as reduced incidence of IV-line related infections, a decreased hospital length of stay and less workload for healthcare professionals with equivalent patient safety. Additionally, numerous studies have demonstrated significant decreases in costs of a timely intravenous to oral antibiotic therapy switch, while maintaining efficacy and safety. However, a considerable variation in iv to oral antibiotic switch therapy criteria has been described in literature. Here, we report the development of a set of iv to oral switch criteria that are generally applicable in all hospitals. Material/methods: A RAND-modified Delphi procedure, which was composed of 3 rounds, was used. This Delphi procedure is a widely used structured process to develop consensus using multiple rounds of questionnaires within a qualified panel of selected experts. The international expert panel was multidisciplinary and composed out of clinical microbiologists, infectious disease consultants and clinical pharmacists. This panel of 19 experts appraised 6 major intravenous to oral antibiotic switch therapy criteria and operationalized these criteria using 41 measurable conditions extracted from the literature. The procedure to select a concise set of iv to oral switch criteria included 2 questionnaire rounds and a face-to-face meeting. Results: The procedure resulted in the selection of 16 measurable conditions, which operationalize 6 major intravenous to oral antibiotic switch therapy criteria. The following 6 major switch therapy criteria were selected: (1) Vital signs should be good or improving when bad. (2) Signs and symptoms related to the infection have to be resolved or improved. (3) The gastrointestinal tract has to be intact and functioning. (4) The oral route should not be compromised. (5) Absence of contra-indicated infections. (6) An oral variant of the antibiotic with good bioavailability has to exist. Conclusions: This systematic stepwise method which combined evidence and expert opinion resulted in a feasible set of 6 major intravenous to oral antibiotic switch therapy criteria operationalized by 16 measurable conditions. This set of early antibiotic iv to oral switch criteria can be used in daily practice in all adult hospital patients. Future use in audits and as rules in computer assisted decision support systems will lead to improvement of antimicrobial steward ship programs.

Keywords: antibiotic resistance, antibiotic stewardship, intravenous to oral, switch therapy

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Authors: H.C. Chen, S. W. C. Chan, K. Cheng, A. Vathsala, H. K. Sran, H. He

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Background: End-stage renal disease (ESRD) is the last stage of chronic kidney disease. The numbers of patients with ESRD have increased worldwide due to the growing number of aging, diabetes and hypertension populations. Patients with ESRD suffer from physical illness and psychological distress due to complex treatment regimens, which often affect the patients’ social and psychological functioning. As a result, the patients may fail to perform daily self-care and self-management, and consequently experience worsening conditions. Aims: The study aims to examine the effectiveness of a self-efficacy psychoeducational programme on primary outcome (self-efficacy) and secondary outcomes (psychological wellbeing, treatment adherence, and quality of life) in patients with ESRD and haemodialysis in Singapore. Methodology: A randomised controlled, two-group pretest and repeated posttests design will be carried out. A total of 154 participants (n=154) will be recruited. The participants in the control group will receive a routine treatment. The participants in the intervention group will receive a self-efficacy psychoeducational programme in addition to the routine treatment. The programme is a two-session of educational intervention in a week. A booklet, two consecutive sessions of face-to-face individual education, and an abdominal breathing exercise are adopted in the programme. Outcome measurements include Dialysis Specific Self-efficacy Scale, Kidney Disease Quality of Life- 36 Hospital Anxiety and Depression Scale, Renal Adherence Attitudes Questionnaire and Renal Adherence Behaviour Questionnaire. The questionnaires will be used to measure at baseline, 1- and 3- and 6-month follow-up periods. Process evaluation will be conducted with a semi-structured face to face interview. Quantitative data will be analysed using SPSS21.0 software. Qualitative data will be analysed by content analysis. Significance of the study: This study will identify a clinically useful and potentially effective approach to help patients with end-stage renal disease and haemodialysis by enhancing their self-efficacy in self-care behaviour, and therefore improving their psychological wellbeing, treatment adherence and quality of life. This study will provide information to develop clinical guidelines to improve patients’ disease self-management and to enhance health-related outcomes. Hopefully it will help reducing disease burden.

Keywords: end-stage renal disease (ESRD), haemodialysis, psychoeducation, self-efficacy

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Authors: Bharti Verma, Chandrajit Balomajumder

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Water pollution is escalated owing to industrialization and random ejection of one or more toxic heavy metal ions from the semiconductor industry, electroplating, metallurgical, mining, chemical manufacturing, tannery industries, etc., In semiconductor industry various kinds of chemicals in wafers preparation are used . Fluoride, toxic solvent, heavy metals, dyes and salts, suspended solids and chelating agents may be found in wastewater effluent of semiconductor manufacturing industry. Also in the chrome plating, in the electroplating industry, the effluent contains heavy amounts of Chromium. Since Cr(VI) is highly toxic, its exposure poses an acute risk of health. Also, its chronic exposure can even lead to mutagenesis and carcinogenesis. On the contrary, Cr (III) which is naturally occurring, is much less toxic than Cr(VI). Discharge limit of hexavalent chromium and trivalent chromium are 0.05 mg/L and 5 mg/L, respectively. There are numerous methods such as adsorption, chemical precipitation, membrane filtration, ion exchange, and electrochemical methods for the heavy metal removal. The present study focuses on the removal of Chromium ions by using flat sheet UF5kDa membrane. The Ultra filtration membrane process is operated above micro filtration membrane process. Thus separation achieved may be influenced due to the effect of Sieving and Donnan effect. Ultrafiltration is a promising method for the rejection of heavy metals like chromium, fluoride, cadmium, nickel, arsenic, etc. from effluent water. Benefits behind ultrafiltration process are that the operation is quite simple, the removal efficiency is high as compared to some other methods of removal and it is reliable. Polyamide membranes have been selected for the present study on rejection of Cr(VI) from feed solution. The objective of the current work is to examine the rejection of Cr(VI) from aqueous feed solutions by flat sheet UF5kDa membranes with different parameters such as pressure, feed concentration and pH of the feed. The experiments revealed that with increasing pressure, the removal efficiency of Cr(VI) is increased. Also, the effect of pH of feed solution, the initial dosage of chromium in the feed solution has been studied. The membrane has been characterized by FTIR, SEM and AFM before and after the run. The mass transfer coefficients have been estimated. Membrane transport parameters have been calculated and have been found to be in a good correlation with the applied model.

Keywords: heavy metal removal, membrane process, waste water treatment, ultrafiltration

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Authors: Nehir Nebioglu

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Chemotherapy is widely used for the treatment of cancer. Doxorubicin is an anti-cancer chemotherapy drug that is classified as an anthracycline antibiotic. Antitumor antibiotics consist of natural products produced by species of the soil fungus Streptomyces. These drugs act in multiple phases of the cell cycle and are known cell-cycle specific. Although DOX is a precious clinical antineoplastic agent, resistance is also a problem that limits its utility besides cardiotoxicity problem. The drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. The mechanism of resistance is thought to involve, in particular, ABCB1 (MDR1, Pgp) and ABCC1 (MRP1) as well as other transporters. Several studies on DOX-resistant cell lines have shown that resistance can be overcome by an inhibition of ABCB1, ABCC1, and ABCC2. This study attempts to understand the effects of different concentration levels of glucose treatment and starvation on the proliferation of Doxorubicin resistant cancer cells lines. To understand the effect of starvation, K562/Dox and K562 cell lines were treated with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM Dox concentrations in both starvation and normal medium conditions. In addition to this, to interpret the effect of glucose treatment, different concentrations (0, 1 mM, 5 mM, 25 mM) of glucose were applied to Dox-treated (with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM) K562/Dox and K652 cell lines. All results show significant decreasing in the cell count of K562/Dox, when cells were starved. However, while proliferation of K562/Dox lines decrease is associated with the increasingly applied Dox concentration, K562/Dox starved ones remain at the same proliferation level. Thus, the results imply that an amount of K562/Dox lines gain starvation resistance and remain resistant. Furthermore, for K562/Dox, there is no clear effect of glucose treatment in terms of cell proliferation. In the presence of a moderate level of glucose (5 mM), proliferation increases compared to other concentration of glucose for each different Dox application. On the other hand, a significant increase in cell proliferation in moderate level of glucose is only observed in 5 uM Dox concentration. The moderate concentration level of Dox can be examined in further studies. For the high amount of glucose (25 mM), cell proliferation levels are lower than moderate glucose application. The reason could be high amount of glucose may not be absorbable by cells. Also, in the presence of low amount of glucose, proliferation is decreasing in an orderly manner of increase in Dox concentration. This situation can be explained by the glucose depletion -Warburg effect- in the literature.

Keywords: drug resistance, cancer cells, chemotherapy, doxorubicin

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Authors: Felicia N. Obialo, Aliza Wingo, Thomas Wingo

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Psychosocial factors such as personality traits and social networks influence cognitive aging and dementia outcomes both positively and negatively. The inherent complexity of these factors makes defining the underlying mechanisms of their influence difficult; however, exploring their interactions affords promise in the field of cognitive aging. The objective of this study was to elucidate some of these interactions by determining the relationship between social network size and dementia outcomes and by determining whether personality traits mediate this relationship. The longitudinal Alzheimer’s Disease (AD) database provided by Rush University’s Religious Orders Study/Memory and Aging Project was utilized to perform retrospective regression and mediation analyses on 3,591 participants. Participants who were cognitively impaired at baseline were excluded, and analyses were adjusted for age, sex, common chronic diseases, and vascular risk factors. Dementia outcome measures included cognitive trajectory, clinical dementia diagnosis, and postmortem beta-amyloid plaque (AB), and neurofibrillary tangle (NT) accumulation. Personality traits included agreeableness (A), conscientiousness (C), extraversion (E), neuroticism (N), and openness (O). The results show a positive correlation between social network size and cognitive trajectory (p-value = 0.004) and a negative relationship between social network size and odds of dementia diagnosis (p = 0.024/ Odds Ratio (OR) = 0.974). Only neuroticism mediates the positive relationship between social network size and cognitive trajectory (p < 2e-16). Agreeableness, extraversion, and neuroticism all mediate the negative relationship between social network size and dementia diagnosis (p=0.098, p=0.054, and p < 2e-16, respectively). All personality traits are independently associated with dementia diagnosis (A: p = 0.016/ OR = 0.959; C: p = 0.000007/ OR = 0.945; E: p = 0.028/ OR = 0.961; N: p = 0.000019/ OR = 1.036; O: p = 0.027/ OR = 0.972). Only conscientiousness and neuroticism are associated with postmortem AD pathologies; specifically, conscientiousness is negatively associated (AB: p = 0.001, NT: p = 0.025) and neuroticism is positively associated with pathologies (AB: p = 0.002, NT: p = 0.002). These results support the study’s objectives, demonstrating that social network size and personality traits are strongly associated with dementia outcomes, particularly the odds of receiving a clinical diagnosis of dementia. Personality traits interact significantly and beneficially with social network size to influence the cognitive trajectory and future dementia diagnosis. These results reinforce previous literature linking social network size to dementia risk and provide novel insight into the differential roles of individual personality traits in cognitive protection.

Keywords: Alzheimer’s disease, cognitive trajectory, personality traits, social network size

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Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Sylvie Ekanga Lumumba

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Background and Significance of the Study: Over the past three decades, the perception of sexual violence has changed significantly, it is now recognized that men and boys are victims of sexual violence. However, the body of research on male victims and particularly on their attackers is much more limited. Research on the above is thus more than required. To contribute to the above quest for further studies, the researcher conducted this study on sexual violence perpetrated against men and boys by women, in the Municipality of Ibanda, Town of Bukavu, Province of South Kivu, Democratic Republic of Congo. The main study objectives were the following: to investigate on the statement of sexual violence perpetrated against men and boys in the Municipality of Ibanda, to investigate into its consequences and the statement of medical and psycho-social care given to victims. Methodology: Data were collected using valid and reliable Survey Questionnaire and Interview Schedule. Study population: the 85,882 men and boys from the Municipality of Ibanda. Sampling: led to 150 men and boys, received discreetly by the researcher during November-December 2015. Major findings: First, findings related to sexual abuse and its procedure: 74.2% of men and boys were victims of sexual violence perpetrated by a woman, more than a year ago. 13.3% however, were victims for less than a year now. 79.7% of victims have experienced sexual violence by a sexual act; 3.9% through the intention of the woman to cause the death of the victim, by serious injury to the genitals. The Second group of findings related to the consequences of sexual violence revealed that HIV/AIDS is the most important physical consequence experienced by 77.3 % of victims. Physical psychological consequences are: urinary or defecation problems (72.7%); while key psycho-emotional and behavioral consequence is: living a state of deep shame and humiliation: 68.8%. As for sexual consequences: 71.1% indicated a chronic avoidance of sexual activity and 57% reported sexual dysfunctions. The third group of findings is related to medical and psycho-social care: repetitively, more than 80% of male victims affirmed that with the help of friends and traditional healers, they took care of themselves for all the eight WHO phases of clinical care of rape victims, this was hence not effectively done. Concluding Statement: for this study, the statement of sexual violence of men and boys by women in the Eastern Congo and its consequences are not researched upon and are underestimated; the study also revealed that the care of male victims is grossly ill-conducted, as opposed to female victims care. It therefore calls for further research and further vulgarization of the research results, to convince other stakeholders (politicians for example) to immediately take action.

Keywords: sexual violence, men and boys, medical care, psycho-social care

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Authors: M. Turmanauli, T. Todua, O. Gvaberidze, R. Javakhadze, N. Chkhaidze, N. Khatiashvili

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Background: Mining process has the significant influence on human health and quality of life. In recent years the events in Georgia were reflected on the industry working process, especially minimal requirements of labor safety, hygiene standards of workplace and the regime of work and rest are not observed. This situation is often caused by the lack of responsibility, awareness, and knowledge both of workers and employers. The control of working conditions and its protection has been worsened in many of industries. Materials and Methods: For evaluation of the current situation the prospective epidemiological study by face to face interview method was conducted at Georgian “Manganese Zestafoni Ferroalloy Plant” in 2011-2013. 65.7% of employees (1428 bulletin) were surveyed and the incidence rates of temporary disability days were studied. Results: The average length of a temporary disability single accident was studied taking into consideration as sex groups as well as the whole cohort. According to the classes of harmfulness the following results were received: Class 2.0-10.3%; 3.1-12.4%; 3.2-35.1%; 3.3-12.1%; 3.4-17.6%; 4.0-12.5%. Among the employees 47.5% and 83.1% were tobacco and alcohol consumers respectively. According to the age groups and years of work on the base of previous experience ≥50 ages and ≥21 years of work data prevalence respectively. The obtained data revealed increased morbidity rate according to age and years of work. It was found that the bone and articulate system and connective tissue diseases, aggravation of chronic respiratory diseases, ischemic heart diseases, hypertension and cerebral blood discirculation were the leading among the other diseases. High prevalence of morbidity observed in the workplace with not satisfactory labor conditions from the hygienic point of view. Conclusion: According to received data the causes of morbidity are the followings: unsafety labor conditions; incomplete of preventive medical examinations (preliminary and periodic); lack of access to appropriate health care services; derangement of gathering, recording, and analysis of morbidity data. This epidemiological study was conducted at the JSC “Manganese Ferro Alloy Plant” according to State program “ Prevention of Occupational Diseases” (Program code is 35 03 02 05).

Keywords: occupational health, mining process, morbidity level, cerebral blood discirculation

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

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Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

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Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

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Authors: Kemal Kehan, Emine Aktas Bajalan

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This study was carried out to determine the burnout levels and related factors of teachers working in primary schools affiliated to the Turkish Republic of Northern Cyprus (TRNC) Ministry of National Education during the COVID-19 pandemic period. The research was conducted in descriptive cross-sectional design. The population of the research consists of 1071 teachers working in 93 primary schools in 6 central districts affiliated to the TRNC Ministry of National Education in the 2021-2022 academic year. When the sample size of the study was calculated by power analysis, it was determined that 202 teachers should be reached with 95% confidence (1-α), 95% test power (1-β) and d=0.5 effect size. Within the scope of the inclusion criteria of the research, the main sample of the study consisted of 300 teachers and the baist random sampling method was used. The data were collected using the Sociodemographic Data Form consisting of 34 questions, including the sociodemographic characteristics of the teachers and the 22-item Maslach Burnout Scale (MBS). The analysis of the data was carried out using descriptive and correlational analyzes in the SPSS 22 package program. In the study, it was determined that 65% of the teachers were women, 68% were married, 84% had a bachelor's degree, 70.33% had children, and 67.67% were dependents. Regarding how teachers evaluate the COVID-19 pandemic period; 90% of them said, “I am worried about my family's health and the risk of infection”, 80% of them, “I feel that my profession does not get the value it deserves”, 75.67% of them mentioned “My hopes for the future have started to wane”, 75.33% of them say “I am worried about my own health”. It was determined that they gave the answer of, “I am worried about the issue”. It was found that the teachers' MBS total score average was 48.63±8.01, the burnout level was moderate, and the average score they got from the sub-dimensions of the scale was also moderate. It has been found that there are negative correlations between the professional satisfaction scores of the teachers during and before the COVID-19 pandemic and the scores they received from the general and sub-dimensions of MBS. It was determined that there was a statistically significant difference (p<0.05) between the scores of teachers diagnosed with COVID-19 from the scale and its sub-dimensions. As a result, it is suggested that social activities should be increased and professional development and promotion opportunities should be offered in order to ensure that teachers are satisfied with their work areas, to reduce their burnout levels or to prevent them completely.

Keywords: teachers, burnout, maslach burnout scale, pandemic, online education

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Authors: Ibrahim Mohamed Ibrahim Hassanin, Hany Hassan Mostafa, Mona Mohamed Shaban, Ahlam El Said Kamel

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Background: New so-called minimally invasive devices have been developed to limit groin pain after sling placement for treatment of stress urinary incontinence (SUI) to minimize the risk of postoperative pain and organ perforation. A new generation of suburethral slings was described that avoided skin incision to pull out and tension the sling. Evaluation of this device through prospective short-term series has shown controversial results compared with other tension-free techniques. The aim of this study is to compare success rates and complications for tension-free vaginal tape secur (TVT secur) and trans-obturator sub urethral tape inside-out technique (TVT-O) for treatment of stress urinary incontinence (SUI). Materials and Methods: Fifty patients with genuine SUI were divided into two groups: group S (n=25) were operated upon using (TVT secur) and group O (n=25) were operated upon using trans-obturator suburethral tape inside-out technique (TVT-O). Success rate, quality of life and postoperative complications such as groin pain, urgency, urine retention and vaginal tape erosion were reported in both groups at one, three, and six months after surgery. Results: As regards objective cure rate at one, three, six months intervals; there was a significant difference between group S (56%, 64%, and 60%), and group O (80%, 88%, and 88%) respectively (P <0.05). As regards subjective cure rate at one, three, six months intervals; there was a significant difference between group S (44%, 44%, and 48%), and group O (76%, 80%, and 80%) respectively (P <0.05). Quality of life (QoL) parameters improved significantly in cured patients with no difference between both groups. As regards complications, group O had a higher frequency of complications than group S; groin pain (12% vs 12% p= 0.05), urgency (4% (1 case) vs 0%), urine retention (8% (2 cases) vs 0%), vaginal tape erosion (4% (1 case) vs 0%). No cases were complicated with wound infection. Conclusion: Compared to TVT secur, TVT-O showed higher subjective and objective cure rates after six months but higher rate of complications. Both techniques were comparable as regards improvement of quality of life after surgery.

Keywords: stress urinary incontinence, trans-vaginal tape-obturator, TVT Secur, TVT-O

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Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Pavana Basavakumar, Devadas Bhat

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Diabetes is a disease which often goes undiagnosed until its secondary effects are noticed. Early detection of the disease is necessary to avoid serious consequences which could lead to the death of the patient. Conventional invasive tests for screening of diabetes are mostly painful, time consuming and expensive. There’s also a risk of infection involved, therefore it is very essential to develop non-invasive methods to screen and estimate the level of blood glucose. Extensive research is going on with this perspective, involving various techniques that explore optical, electrical, chemical and thermal properties of the human body that directly or indirectly depend on the blood glucose concentration. Thus, non-invasive blood glucose monitoring has grown into a vast field of research. In this project, an attempt was made to device a prototype for screening of diabetes by measuring electrical impedance of the skin and building a model to predict a patient’s condition based on the measured impedance. The prototype developed, passes a negligible amount of constant current (0.5mA) across a subject’s index finger through tetra polar silver electrodes and measures output voltage across a wide range of frequencies (10 KHz – 4 MHz). The measured voltage is proportional to the impedance of the skin. The impedance was acquired in real-time for further analysis. Study was conducted on over 75 subjects with permission from the institutional ethics committee, along with impedance, subject’s blood glucose values were also noted, using conventional method. Nonlinear regression analysis was performed on the features extracted from the impedance data to obtain a model that predicts blood glucose values for a given set of features. When the predicted data was depicted on Clarke’s Error Grid, only 58% of the values predicted were clinically acceptable. Since the objective of the project was to screen diabetes and not actual estimation of blood glucose, the data was classified into three classes ‘NORMAL FASTING’,’NORMAL POSTPRANDIAL’ and ‘HIGH’ using linear Support Vector Machine (SVM). Classification accuracy obtained was 91.4%. The developed prototype was economical, fast and pain free. Thus, it can be used for mass screening of diabetes.

Keywords: Clarke’s error grid, electrical impedance of skin, linear SVM, nonlinear regression, non-invasive blood glucose monitoring, screening device for diabetes

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Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

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Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

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Authors: Choon Seong Ng, P. Petrick, C. L. Lau

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Background: Carbapenem-resistant isolates have been increasingly reported recently. Carbapenem stewardship is designed to optimize its usage particularly among medical wards with high prevalence of carbapenem prescriptions to combat such emerging resistance. Carbapenem stewardship programmes (CSP) can reduce antibiotic use but clinical outcome of such measures needs further evaluation. We examined this in a prospective manner using feedback mechanism. Methods: Our single-center prospective cohort study involved all carbapenem prescriptions across the medical wards (including medical patients admitted to intensive care unit) in a tertiary university hospital setting. The impact of such stewardship was analysed according to the accepted and the rejected groups. The primary endpoint was safety. Safety measure applied in this study was the death at 1 month. Secondary endpoints included length of hospitalisation and readmission. Results: Over the 19 months’ period, input from 144 carbapenem prescriptions was analysed on the basis of acceptance of our CSP recommendations on the use of carbapenems. Recommendations made were as follows : de-escalation of carbapenem; stopping the carbapenem; use for a short duration of 5-7 days; required prolonged duration in the case of carbapenem-sensitive Extended Spectrum Beta-Lactamases bacteremia; dose adjustment; and surgical intervention for removal of septic foci. De-escalation, shorten duration of carbapenem and carbapenem cessation comprised 79% of the recommendations. Acceptance rate was 57%. Those who accepted CSP recommendations had no increase in mortality (p = 0.92), had a shorter length of hospital stay (LOS) and had cost-saving. Infection-related deaths were found to be higher among those in the rejected group. Moreover, three rejected cases (6%) among all non-indicated cases (n = 50) were found to have developed carbapenem-resistant isolates. Lastly, Pitt’s bacteremia score appeared to be a key element affecting the carbapenem prescription’s behaviour in this trial. Conclusions: Carbapenem stewardship program in the medical wards not only saves money, but most importantly it is safe and does not harm the patients with added benefits of reducing the length of hospital stay. However, more time is needed to engage the primary clinical teams by formal clinical presentation and immediate personal feedback by senior Infectious Disease (ID) personnel to increase its acceptance.

Keywords: audit and feedback, carbapenem stewardship, medical wards, university hospital

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Authors: H. C. Chen, S. W. C. Chan, K. Cheng, A. Vathsala, H. K. Sran, H. He

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Background: End-stage renal disease (ESRD) is the last stage of chronic kidney disease. The numbers of patients with ESRD have increased worldwide due to the growing number of aging, diabetes and hypertension populations. Patients with ESRD suffer from physical illness and psychological distress due to complex treatment regimens, which often affect the patients’ social and psychological functioning. As a result, the patients may fail to perform daily self-care and self-management, and consequently experience worsening conditions. Aims: The study aims to examine the effectiveness of a self-efficacy psychoeducational programme on primary outcome (self-efficacy) and secondary outcomes (psychological wellbeing, treatment adherence, and quality of life) in patients with ESRD and haemodialysis in Singapore. Methodology: A randomised controlled, two-group pretest and repeated posttests design will be carried out. A total of 154 participants (n=154) will be recruited. The participants in the control group will receive a routine treatment. The participants in the intervention group will receive a self-efficacy psychoeducational programme in addition to the routine treatment. The programme is a two-session of educational intervention in a week. A booklet, two consecutive sessions of face-to-face individual education, and an abdominal breathing exercise are adopted in the programme. Outcome measurements include Dialysis Specific Self-efficacy Scale, Kidney Disease Quality of Life- 36 Hospital Anxiety and Depression Scale, Renal Adherence Attitudes Questionnaire and Renal Adherence Behaviour Questionnaire. The questionnaires will be used to measure at baseline, 1- and 3- and 6-month follow-up periods. Process evaluation will be conducted with a semi-structured face to face interview. Quantitative data will be analysed using SPSS21.0 software. Qualitative data will be analysed by content analysis. Significance of the study: This study will identify a clinically useful and potentially effective approach to help patients with end-stage renal disease and haemodialysis by enhancing their self-efficacy in self-care behaviour, and therefore improving their psychological well-being, treatment adherence and quality of life. This study will provide information to develop clinical guidelines to improve patients’ disease self-management and to enhance health-related outcomes and it will help reducing disease burden.

Keywords: end-stage renal disease (ESRD), haemodialysis, psychoeducation, self-efficacy

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Authors: Manami Masuda, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

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Objectives: Fatty acid salts are a type of anionic surfactant and are produced from fatty acids and alkali. Moreover, fatty acid salts are known to have potent antibacterial activities. Acanthamoeba is ubiquitously distributed in the environment including sea water, fresh water, soil and even from the air. Although generally free-living, Acanthamoeba can be an opportunistic pathogen, which could cause a potentially blinding corneal infection known as Acanthamoeba keratitis. So, in this study, we evaluated the anti-amoeba activity of fatty acid salts and fatty acids to Acanthamoeba castellanii ATCC 30010. Materials and Methods: The antibacterial activity of 9 fatty acid salts (potassium butyrate (C4K), caproate (C6K), caprylate (C8K), caprate (C10K), laurate (C12K), myristate (C14K), oleate (C18:1K), linoleate (C18:2K), linolenate (C18:3K)) tested on cells of Acanthamoeba castellanii ATCC 30010. Fatty acid salts (concentration of 175 mM and pH 10.5) were prepared by mixing the fatty acid with the appropriate amount of KOH. The amoeba suspension mixed with KOH with a pH adjusted solution was used as the control. Fatty acids (concentration of 175 mM) were prepared by mixing the fatty acid with Tween 80 (20 %). The amoeba suspension mixed with Tween 80 (20 %) was used as the control. The anti-amoeba method, the amoeba suspension (3.0 × 104 cells/ml trophozoites) was mixed with the sample of fatty acid potassium (final concentration of 175 mM). Samples were incubated at 30°C, for 10 min, 60 min, and 180 min and then the viability of A. castellanii was evaluated using plankton counting chamber and trypan blue stainings. The minimum inhibitory concentration (MIC) against Acanthamoeba was determined using the two-fold dilution method. The MIC was defined as the minimal anti-amoeba concentration that inhibited visible amoeba growth following incubation (180 min). Results: C8K, C10K, and C12K were the anti-amoeba effect of 4 log-unit (99.99 % growth suppression of A. castellanii) incubated time for 180 min against A. castellanii at 175mM. After the amoeba, the suspension was mixed with C10K or C12K, destroying the cell membrane had been observed. Whereas, the pH adjusted control solution did not exhibit any effect even after 180 min of incubation with A. castellanii. Moreover, C6, C8, and C18:3 were the anti-amoeba effect of 4 log-unit incubated time for 60 min. C4 and C18:2 exhibited a 4-log reduction after 180 min incubation. Furthermore, the minimum inhibitory concentration (MIC) was determined. The MIC of C10K, C12K and C4 were 2.7 mM. These results indicate that C10K, C12K and C4 have high anti-amoeba activity against A. castellanii and suggest C10K, C12K and C4 have great potential for antimi-amoeba agents.

Keywords: Fatty acid salts, anti-amoeba activities, Acanthamoeba, fatty acids

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Authors: Orkide Donma, Mustafa M. Donma

Abstract:

Obesity may lead to growing serious health problems throughout the world. Vitamin D appears to play a role in cardiovascular and metabolic health. Vitamin D deficiency may add to derangements in human metabolic systems, particularly those of children. Childhood obesity is associated with an increased risk of chronic and sophisticated diseases. The aim of this study is to investigate associations as well as possible differences related to parameters affected by obesity and their relations with vitamin D status in obese (OB) and morbid obese (MO) children. This study included a total of 78 children. Of them, 41 and 37 were OB and MO, respectively. WHO BMI-for age percentiles were used for the classification of obesity. The values above 99 percentile were defined as MO. Those between 95 and 99 percentiles were included into OB group. Anthropometric measurements were recorded. Basal metabolic rates (BMRs) were measured. Vitamin D status is determined by the measurement of 25-hydroxy cholecalciferol [25- hydroxyvitamin D3, 25(OH)D] using high-performance liquid chromatography. Vitamin D status was evaluated as deficient, insufficient and sufficient. Values < 20.0 ng/ml, values between 20-30 ng/ml and values > 30.0 ng/ml were defined as vitamin D deficient, insufficient and sufficient, respectively. Optimal 25(OH)D level was defined as ≥ 30 ng/ml. SPSSx statistical package program was used for the evaluation of the data. The statistical significance degree was accepted as p < 0.05. Mean ages did not differ between the groups. Significantly increased body mass index (BMI), waist circumference (C) and neck C as well as significantly decreased fasting blood glucose (FBG) and vitamin D values were observed in MO group (p < 0.05). In OB group, 37.5% of the children were vitamin D deficient, and in MO group the corresponding value was 53.6%. No difference between the groups in terms of lipid profile, systolic blood pressure (SBP), diastolic blood pressure (DBP) and insulin values was noted. There was a severe statistical significance between FBG values of the groups (p < 0.001). Important correlations between BMI, waist C, hip C, neck C and both SBP as well as DBP were found in OB group. In MO group, correlations only with SBP were obtained. In a similar manner, in OB group, correlations were detected between SBP-BMR and DBP-BMR. However, in MO children, BMR correlated only with SBP. The associations of vitamin D with anthropometric indices as well as some lipid parameters were defined. In OB group BMI, waist C, hip C and triglycerides (TRG) were negatively correlated with vitamin D concentrations whereas none of them were detected in MO group. Vitamin D deficiency may contribute to the complications associated with childhood obesity. Loss of correlations between obesity indices-DBP, vitamin D-TRG, as well as relatively lower FBG values, observed in MO group point out that the emergence of MetS components starts during obesity state just before the transition to morbid obesity. Aside from its deficiency state, associations of vitamin D with anthropometric measurements, blood pressures and TRG should also be evaluated before the development of morbid obesity.

Keywords: children, morbid obesity, obesity, vitamin D

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

Abstract:

Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Maryam Beiranvand

Abstract:

Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.

Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria

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